Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation.

PubMed

Chowdhury, Indrajit; Thomas, Kelwyn; Zeleznik, Anthony; Thompson, Winston E

2016-05-01

Published results from our laboratory identified prohibitin (PHB), a gene product expressed in granulosa cells (GCs) that progressively increases during follicle maturation. Our current in vitro studies demonstrate that follicle-stimulating hormone (FSH) stimulates Phb expression in rat primary GCs. The FSH-dependent expression of PHB was primarily localized within mitochondria, and positively correlates with the morphological changes in GCs organelles, and synthesis and secretions of estradiol (E2) and progesterone (P4). In order to confirm that PHB plays a regulatory role in rat GC differentiation, endogenous PHB-knockdown studies were carried out in undifferentiated GCs using adenoviral (Ad)-mediated RNA interference methodology. Knockdown of PHB in GCs resulted in the suppression of the key steroidogenic enzymes including steroidogenic acute regulatory protein (StAR), p450 cholesterol side-chain cleavage enzyme (p450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), and aromatase (Cyp19a1); and decreased E2 and P4 synthesis and secretions in the presence of FSH stimulation. Furthermore, these experimental studies also provided direct evidence that PHB within the mitochondrial fraction in GCs is phosphorylated at residues Y249, T258, and Y259 in response to FSH stimulation. The observed levels of phosphorylation of PHB at Y249, T258, and Y259 were significantly low in GCs in the absence of FSH stimulation. In addition, during GC differentiation FSH-induced expression of phospho-PHB (pPHB) requires the activation of MEK1-ERK1/2 signaling pathway. Taken together, these studies provide new evidence supporting FSH-dependent PHB/pPHB upregulation in GCs is required to sustain the differentiated state of GCs. © 2016 The authors.

Discordances between follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) in female infertility

PubMed Central

2010-01-01

Background Follicle stimulating hormone (FSH) and anti-Müllerian hormone (AMH) represent the two most frequently utilized laboratory tests in determining ovarian reserve (OR). This study determined the clinical significance of their concordance and discordance in female infertility patients. Methods We investigated 366 consecutive infertility patients (350 reached IVF), excluding women with polycystic ovarian syndrome (PCOS). They were considered to have normal FSH and AMH if values fell within age-specific (as-) 95% confidence intervals (CI), and to suffer from diminished ovarian reserve (DOR) if FSH exceeded and/or AMH fell below those. The two hormones, thus, could be concordant (Group I), both normal (IA) or abnormal (IB), show normal AMH/abnormal FSH (Group II) or normal FSH/abnormal AMH (Group III). Oocyte yields, stratified for age categories, were then studied in each group as reflection of OR. Results Oocyte yields significantly decreased from groups IA to II to III and IB. Predictive values of as-FSH/AMH patterns changed, however, at different ages. Except at very young and very old ages, normal as-AMH better predicted higher oocytes yields than normal as-FSH, though above age 42 years normal as-FSH predicts good oocyte yields even with abnormally low AMH. Under age 42 discrepancies between as- FSH and as-AMH remain similarly predictive of oocyte yields at all ages. Discussion Concordances and discordances between as-FSH and as-AMH improve OR assessments and predictability of oocyte yields in IVF. PMID:20565808

A cost per live birth comparison of HMG and rFSH randomized trials.

PubMed

Connolly, Mark; De Vrieze, Kathleen; Ombelet, Willem; Schneider, Dirk; Currie, Craig

2008-12-01

To help inform healthcare treatment practices and funding decisions, an economic evaluation was conducted to compare the two leading gonadotrophins used for IVF in Belgium. Based on the results of a recently published meta-analysis, a simulated decision tree model was constructed with four states: (i) fresh cycle, (ii) cryopreserved cycle, (iii) live birth and (iv) treatment withdrawal. Gonadotrophin costs were based on highly purified human menopausal gonadotrophin (HP-HMG; Menopur) and recombinant FSH (rFSH) alpha (Gonal-F). After one fresh and one cryopreserved cycle the average treatment cost with HP-HMG was lower than with rFSH (HP-HMG euro3635; rFSH euro4103). The average cost saving per person started on HP-HMG when compared with rFSH was euro468. Additionally, the average costs per live birth of HP-HMG and rFSH were found to be significantly different: HP-HMG euro9996; rFSH euro13,009 (P < 0.0001). HP-HMG remained cost-saving even after key parameters in the model were varied in the probabilistic sensitivity analysis. Treatment with HP-HMG was found to be the dominant treatment strategy in IVF because of improved live birth rates and lower costs. Within a fixed healthcare budget, the cost-savings achieved using HP-HMG would allow for the delivery of additional IVF cycles.

Fasting lowers gastrin-releasing peptide and Fsh mRNA in the ovine anterior pituitary gland

USDA-ARS?s Scientific Manuscript database

Estrogen receptor beta (ER-ß), LH, and FSH are important mediators of reproduction. FSH stimulates follicle recruitment and development. During anorexia, serum concentrations of FSH and LH decrease. Gastrin-releasing peptide (GRP), neuromedin B (NMB), peroxisome proliferator-activated receptor-gamma...

Fasting lowers gastrin-releasing peptide and FSH mRNA in the ovine anterior pituitary gland

USDA-ARS?s Scientific Manuscript database

Estrogen receptor beta (ER-ß), LH, and FSH are important mediators of reproduction. FSH stimulates follicle recruitment and development. During anorexia, serum concentrations of FSH and LH decrease. Gastrin-releasing peptide (GRP), neuromedin B (NMB), peroxisome proliferator-activated receptor-gamma...

Weak evidence of bright light effects on human LH and FSH.

PubMed

Kripke, Daniel F; Elliott, Jeffrey A; Youngstedt, Shawn D; Parry, Barbara L; Hauger, Richard L; Rex, Katharine M

2010-05-11

Most mammals are seasonal breeders whose gonads grow to anticipate reproduction in the spring and summer. As day length increases, secretion increases for two gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH). This response is largely controlled by light. Light effects on gonadotropins are mediated through effects on the suprachiasmatic nucleus and responses of the circadian system. There is some evidence that seasonal breeding in humans is regulated by similar mechanisms, and that light stimulates LH secretion, but primate responses seem complex. To gain further information on effects of bright light on LH and FSH secretion in humans, we analyzed urine samples collected in three experiments conducted for other goals. First, volunteers ages 18-30 years and 60-75 commenced an ultra-short 90-min sleep-wake cycle, during which they were exposed to 3000 lux light for 3 hours at balanced times of day, repeated for 3 days. Urine samples were assayed to explore any LH phase response curve. Second, depressed participants 60-79 years of age were treated with bright light or dim placebo light for 28 days, with measurements of urinary LH and FSH before and after treatment. Third, women of ages 20-45 years with premenstrual dysphoric disorder (PMDD) were treated to one 3-hour exposure of morning light, measuring LH and FSH in urine before and after the treatments. Two of the three studies showed significant increases in LH after light treatment, and FSH also tended to increase, but there were no significant contrasts with parallel placebo treatments and no significant time-of-day treatment effects. These results gave some support for the hypothesis that bright light may augment LH secretion. Longer-duration studies may be needed to clarify the effects of light on human LH and FSH.

FSH: fast spaced seed hashing exploiting adjacent hashes.

PubMed

Girotto, Samuele; Comin, Matteo; Pizzi, Cinzia

2018-01-01

Patterns with wildcards in specified positions, namely spaced seeds , are increasingly used instead of k -mers in many bioinformatics applications that require indexing, querying and rapid similarity search, as they can provide better sensitivity. Many of these applications require to compute the hashing of each position in the input sequences with respect to the given spaced seed, or to multiple spaced seeds. While the hashing of k -mers can be rapidly computed by exploiting the large overlap between consecutive k -mers, spaced seeds hashing is usually computed from scratch for each position in the input sequence, thus resulting in slower processing. The method proposed in this paper, fast spaced-seed hashing (FSH), exploits the similarity of the hash values of spaced seeds computed at adjacent positions in the input sequence. In our experiments we compute the hash for each positions of metagenomics reads from several datasets, with respect to different spaced seeds. We also propose a generalized version of the algorithm for the simultaneous computation of multiple spaced seeds hashing. In the experiments, our algorithm can compute the hashing values of spaced seeds with a speedup, with respect to the traditional approach, between 1.6[Formula: see text] to 5.3[Formula: see text], depending on the structure of the spaced seed. Spaced seed hashing is a routine task for several bioinformatics application. FSH allows to perform this task efficiently and raise the question of whether other hashing can be exploited to further improve the speed up. This has the potential of major impact in the field, making spaced seed applications not only accurate, but also faster and more efficient. The software FSH is freely available for academic use at: https://bitbucket.org/samu661/fsh/overview.

[From theory to clinical practice: recombinant FSH in daily practice].

PubMed

Kably Ambe, A; Barrón Vallejo, J; Góngora Rodríguez, A; Carballo Mondragón, E; Anta Jaén, E

1999-08-01

The purpose of the present study is to determine the efficacy of induction ovulation with recombinant FSH in patients treated with in vitro fertilization and embryo transfer (IVF-ET) and basic assisted reproductive techniques (ART). One hundred seven cycles were analyzed. The patients were divided in two groups: Group 1, treated with IVF (n = 12) and group 2, treated with basic ART (n = 95). Only recombinant FSH was utilized for ovulation induction; human corionic gonadotropin (hCG), 10,000 IU, were administered when one or more dominant follicles with diameter > or = 18 mm were presents; oocyte retrieval was performed 34 hour, while intrauterine insemination was practiced at 36 hours after the hCG injection. The pregnancy rate per IVF cycle was 25.0%, and 16.4% for basic ART. It is concluded that ovulation induction with recombinant FSH is a good and efficient alternative for both variations of ART.

Evaluation of seminal plasma proteomics and relevance of FSH in identification of nonobstructive azoospermia: A preliminary study.

PubMed

Cui, Z; Agarwal, A; da Silva, B F; Sharma, R; Sabanegh, E

2018-06-01

Nonobstructive azoospermia (NOA) patients present with high levels of serum FSH. At the protein level, the aetiology and pathways underlying different subtypes of NOA are unclear. The aim was to evaluate quantitatively differences in proteomic profiles of NOA patients presenting with normal serum FSH and normal testicular volume and high serum FSH and small testicular volume. The study comprised of 14 nonobstructive azoospermic men (N = 4; normal FSH and normal testicular volume and N = 10; high FSH and small testicular volume) and seven normozoospermic men. Proteomic analysis was done using LC-MS. GSTM3 and PGK2 were less abundant in the normal and high FSH group compared to controls. HSPA4L and HSPA4 were exclusively present in control group whereas HSP90AB1, HSPA1B, HSP90AA1 and HSPA2 were less abundant and exclusive to the normal and high FSH group. We have identified six heat-shock proteins that may have a role in the pathology of NOA. FSH and testicular volume by itself are not good markers of NOA. The inverse association of GSTM3 and PGK2 regulation with FSH levels along with 12 proteins exclusively in NOA groups suggests further evaluation of their predictive potential in a larger cohort of patients. © 2018 Blackwell Verlag GmbH.

Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice.

PubMed

Wang, Huizhen; Larson, Melissa; Jablonka-Shariff, Albina; Pearl, Christopher A; Miller, William L; Conn, P Michael; Boime, Irving; Kumar, T Rajendra

2014-04-15

FSH and luteinizing hormone (LH) are secreted constitutively or in pulses, respectively, from pituitary gonadotropes in many vertebrates, and regulate ovarian function. The molecular basis for this evolutionarily conserved gonadotropin-specific secretion pattern is not understood. Here, we show that the carboxyterminal heptapeptide in LH is a gonadotropin-sorting determinant in vivo that directs pulsatile secretion. FSH containing this heptapeptide enters the regulated pathway in gonadotropes of transgenic mice, and is released in response to gonadotropin-releasing hormone, similar to LH. FSH released from the LH secretory pathway rescued ovarian defects in Fshb-null mice as efficiently as constitutively secreted FSH. Interestingly, the rerouted FSH enhanced ovarian follicle survival, caused a dramatic increase in number of ovulations, and prolonged female reproductive lifespan. Furthermore, the rerouted FSH vastly improved the in vivo fertilization competency of eggs, their subsequent development in vitro and when transplanted, the ability to produce offspring. Our study demonstrates the feasibility to fine-tune the target tissue responses by modifying the intracellular trafficking and secretory fate of a pituitary trophic hormone. The approach to interconvert the secretory fate of proteins in vivo has pathophysiological significance, and could explain the etiology of several hormone hyperstimulation and resistance syndromes.

Efficacy of a single intramuscular injection of porcine FSH in hyaluronan prior to ovum pick-up in Holstein cattle.

PubMed

Vieira, L M; Rodrigues, C A; Castro Netto, A; Guerreiro, B M; Silveira, C R A; Freitas, B G; Bragança, L G M; Marques, K N G; Sá Filho, M F; Bó, G A; Mapletoft, R J; Baruselli, P S

2016-03-15

Plasma FSH profiles, in vitro embryo production (IVP) after ovum pickup (OPU), and establishment of pregnancy with IVP embryos were compared in untreated Holstein oocyte donors and those superstimulated with multiple injections or a single intramuscular (IM) injection of porcine FSH (pFSH) in hyaluronan (HA). Plasma FSH profiles were determined in 23 heifers randomly allocated to one of four groups. Controls received no treatment, whereas the F200 group received 200 mg of pFSH in four doses, 12 hours apart. The F200HA and F300HA groups received 200- or 300-mg pFSH in 5 mL or 7.5 mL, respectively of a 0.5% HA solution by a single IM injection. Plasma FSH levels were determined before the first pFSH treatment and every 6 hours over 96 hours. All data were analyzed by orthogonal contrasts. Circulating FSH area under curve (AUC) in pFSH-treated animals was greater than that in the control group (P = 0.02). Although the AUC did not differ among FSH-treated groups (P = 0.56), the total period with elevated plasma FSH was greater in the F200 group than in the HA groups (P < 0.0001). However, the F300HA group had a greater AUC than the F200HA group (P = 0.006), with a similar total period with elevated plasma FSH (P = 0.17). The IVP was performed in 90 nonlactating Holstein cows randomly allocated to one of the four treatment groups as in the first experiment. A greater proportion of medium-sized (6-10 mm) follicles was observed in cows receiving pFSH, regardless of the treatment group (P < 0.0001). Also, numbers of follicles (P = 0.01), cumulus-oocyte complexes (COCs) retrieved (P = 0.01) and matured (P = 0.02), cleavage rates (P = 0.002), and blastocysts produced per OPU session (P = 0.06) were greater in cows receiving pFSH, regardless of the treatment group. Cows in the F200HA group had a greater recovery rate (P = 0.009), number of COCs cultured (P = 0.04), and blastocysts produced per OPU session (P = 0.06) than cows in the F300HA group. Similar pregnancy rates were

An FSH and TSH pituitary adenoma, presenting with precocious puberty and central hyperthyroidism

PubMed Central

Vargas, Guadalupe; Balcazar-Hernandez, Lourdes-Josefina; Melgar, Virgilio; Magriña-Mercado, Roser-Montserrat; Gonzalez, Baldomero; Baquera, Javier

2017-01-01

A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH. Learning points: Although functioning gonadotrophinomas are infrequent, they should be included in the differential diagnosis of isosexual central precocious puberty. Some functioning gonadotrophinomas are mixed adenomas, secreting other biologically active hormones besides FSH, such as TSH. Early recognition and appropriate treatment of these tumors by transsphenoidal surgery is crucial in order to avoid unnecessary therapeutic interventions that may irreversibly compromise gonadal function. PMID:28721217

An FSH and TSH pituitary adenoma, presenting with precocious puberty and central hyperthyroidism.

PubMed

Vargas, Guadalupe; Balcazar-Hernandez, Lourdes-Josefina; Melgar, Virgilio; Magriña-Mercado, Roser-Montserrat; Gonzalez, Baldomero; Baquera, Javier; Mercado, Moisés

2017-01-01

A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH. Although functioning gonadotrophinomas are infrequent, they should be included in the differential diagnosis of isosexual central precocious puberty.Some functioning gonadotrophinomas are mixed adenomas, secreting other biologically active hormones besides FSH, such as TSH.Early recognition and appropriate treatment of these tumors by transsphenoidal surgery is crucial in order to avoid unnecessary therapeutic interventions that may irreversibly compromise gonadal function.

Validation of a noninvasive diagnostic tool to verify neuter status in dogs: The urinary FSH to creatinine ratio.

PubMed

Albers-Wolthers, C H J; de Gier, J; Oei, C H Y; Schaefers-Okkens, A C; Kooistra, H S

2016-09-15

Determining the presence of functional gonadal tissue in dogs can be challenging, especially in bitches during anestrus or not known to have been ovariectomized, or in male dogs with nonscrotal testes. Furthermore, in male dogs treated with deslorelin, a slow-release GnRH agonist implant for reversible chemical castration, the verification of complete downregulation of the hypothalamic-pituitary-gonadal (HPG) axis can be difficult, especially if pretreatment parameters such as the size of the testes or prostate gland are not available. The aims of this study were to validate an immunoradiometric assay for measurement of FSH in canine urine, to determine if the urinary FSH to creatinine ratio can be used to verify the neuter status in bitches and male dogs, as an alternative to the plasma FSH concentration, and to determine if downregulation of the HPG axis is achieved in male dogs during deslorelin treatment. Recovery of added canine FSH and serial dilutions of urine reported that the immunoradiometric assay measures urinary FSH concentration accurately and with high precision. Plasma FSH concentrations (the mean of two samples, taken 40 minutes apart) and the urinary FSH to creatinine ratio were determined before gonadectomy and 140 days (median, range 121-225 days) and 206 days (median, range 158-294 days) after gonadectomy of 13 bitches and five male dogs, respectively, and in 13 male dogs before and 132 days (median, range 117-174 days) after administration of a deslorelin implant. In both bitches and male dogs, the plasma FSH concentration and the urinary FSH to creatinine ratio were significantly higher after gonadectomy, with no overlapping of their ranges. Receiver operating characteristic analysis of the urinary FSH to creatinine ratio revealed a cut-off value of 2.9 in bitches and 6.5 in males to verify the presence or absence of functional gonadal tissue. In male dogs treated with deslorelin, the plasma FSH concentrations and urinary FSH to

Mutations and polymorphisms in FSH receptor: functional implications in human reproduction.

PubMed

Desai, Swapna S; Roy, Binita Sur; Mahale, Smita D

2013-12-01

FSH brings about its physiological actions by activating a specific receptor located on target cells. Normal functioning of the FSH receptor (FSHR) is crucial for follicular development and estradiol production in females and for the regulation of Sertoli cell function and spermatogenesis in males. In the last two decades, the number of inactivating and activating mutations, single nucleotide polymorphisms, and spliced variants of FSHR gene has been identified in selected infertile cases. Information on genotype-phenotype correlation and in vitro functional characterization of the mutants has helped in understanding the possible genetic cause for female infertility in affected individuals. The information is also being used to dissect various extracellular and intracellular events involved in hormone-receptor interaction by studying the differences in the properties of the mutant receptor when compared with WT receptor. Studies on polymorphisms in the FSHR gene have shown variability in clinical outcome among women treated with FSH. These observations are being explored to develop molecular markers to predict the optimum dose of FSH required for controlled ovarian hyperstimulation. Pharmacogenetics is an emerging field in this area that aims at designing individual treatment protocols for reproductive abnormalities based on FSHR gene polymorphisms. The present review discusses the current knowledge of various genetic alterations in FSHR and their impact on receptor function in the female reproductive system.

Development and Application of a Sensitive, Second Antibody Format Enzymeimmunoassay (EIA) for Estimation of Plasma FSH in Mithun (Bos frontalis).

PubMed

Mondal, Mohan; Baruah, Kishore Kumar; Prakash, B S

2016-01-01

Mithun (Bos frontalis) is a semi-wild rare ruminant species. A simple sensitive enzymeimmunoassay suitable for assaying FSH in the blood plasma of mithun is not available which thereby limits our ability to understand this species reproductive processes. Therefore, the aim of this article was to develop a simple and sensitive enzymeimmunoassay (EIA) for estimation of FSH in mithun plasma and apply the assay to understand the estrous cycle and superovulatory process in this species. To accomplish this goal, biotinylated FSH was bridged between streptavidin-peroxidase and immobilized antiserum in a competitive assay. Forty microlitre mithun plasma was used directly in the EIA. The FSH standards were prepared in hormone free plasma and ranged from 5-1280 pg/well/40 μL. The sensitivity of EIA was 5 pg/well FSH, which corresponds to 0.125 ng/mL plasma and the 50% relative binding sensitivity was 90 pg/well/40 μL. Although the shape of the standard curve was not influenced by different plasma volumes viz. 40 and 80 μL, a slight drop in the OD450 was observed with the increasing volume of plasma. Parallelism tests conducted between the endogenous mithun FSH and bovine FSH standards showed good homology between them. Plasma FSH estimated using the developed EIA and commercially available FSH EIA kit in the same samples were correlated (r = 0.98) and showed linearity. Both the Intra- and inter-assay CV were below 6%. Recovery of known concentrations of added FSH showed linearity (r = 0.99). The developed EIA was further validated biologically by estimating FSH in cyclic cows for the entire estrous cycle, in mithun heifers administered with GnRH analogues and in mithun cows during superovulatory treatment with FSH. In conclusion, the EIA developed for FSH determination in mithun blood plasma is simple and highly sensitive for estimation of mithun FSH in all physiological conditions.

Lower sperm DNA fragmentation after r-FSH administration in functional hypogonadotropic hypogonadism.

PubMed

Ruvolo, Giovanni; Roccheri, Maria Carmela; Brucculeri, Anna Maria; Longobardi, Salvatore; Cittadini, Ettore; Bosco, Liana

2013-04-01

An observational clinical and molecular study was designed to evaluate the effects of the administration of recombinant human FSH on sperm DNA fragmentation in men with a non-classical form of hypogonadotropic hypogonadism and idiopathic oligoasthenoteratozoospermia. In the study were included 53 men with a non-classical form of hypogonadotropic hypogonadism and idiopathic oligoasthenoteratozoospermia. In all patients, sperm DNA fragmentation index (DFI), assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) in situ DNA nick end-labelling (TUNEL) assay, was evaluated before starting the treatment with 150 IU of recombinant human FSH, given three times a week for at least 3 months. Patients' semen analysis and DNA fragmentation index were re-evaluated after the 3-month treatment period. After recombinant human FSH therapy, we did not find any differences in terms of sperm count, motility and morphology. The average DNA fragmentation index was significantly reduced (21.15 vs 15.2, p<0.05), but we found a significant reduction in patients with high basal DFI values (>15 %), while no significant variation occurred in the patients with DFI values ≤ 15 %. Recombinant human FSH administration improves sperm DNA integrity in hypogonadotropic hypogonadism and idiopathic oligoasthenoteratozoospermia men with DNA fragmentation index value >15 % .

The effect of estradiol on granulosa cell responses to FSH in women with polycystic ovary syndrome.

PubMed

Homer, Michael V; Rosencrantz, Marcus A; Shayya, Rana F; Chang, R Jeffrey

2017-02-10

The influence of estradiol (E 2 ) on granulosa cell (GC) function has not been tested clinically in women with polycystic ovary syndrome (PCOS). The objective of this study is to determine if E 2 influences GC responses to FSH in women with PCOS. This is a two phase, single cohort study conducted over a 2-year period at a single academic center. Nine women with PCOS according to NIH criteria. In Phase 1, FSH stimulation of GC responses as measured by E 2 and Inhibin B (Inh B) were assessed before and at 5 and 6 weeks after GnRH agonist administration. In Phase 2, the same protocol was employed with the addition of an aromatase inhibitor (letrozole, LET) administered daily beginning at week 4 for 2 weeks. In Phase 1, recovery of FSH, E 2 and Inh B from ovarian suppression occurred at 5 and 6 weeks after GnRH agonist injection and preceded resumption of LH and androgen secretion. In Phase 2, hormone recovery after GnRH agonist was characterized by elevated FSH and suppressed E 2 levels whereas recovery of LH and androgen levels were unchanged. In Phase 1, FSH stimulated E 2 and Inh B responses were unaltered during recovery from ovarian suppression. In Phase 2, E 2 and Inh B fold changes after FSH were significantly reduced at weeks 5 (p < 0.04) and 6 (p < 0.01), respectively. In anovulatory women with PCOS, chronic, unopposed E 2 secretion may contribute, at least in part, to enhanced ovarian responsiveness to FSH. NCT02389088.

Timing of mating and ovarian response in llamas (Lama glama) treated with pFSH.

PubMed

Ratto, M H; Gatica, R; Correa, J E

1997-08-01

The effect of the timing of mating on ovarian response in llamas was evaluated using 20 adult llamas weighing 90-120 kg which had been in oestrus for 5 days and were treated with 20 mg pFSH every 12 h for the following 5 days (total dose: 200 mg of FSH-NIH-P1). They were randomly allocated to Group A (N = 10) and mated immediately at the end of pFSH treatment or to Group B (n = 10) and mated 36 h after the end of pFSH treatment. Llamas of both groups were given hCG (750 iu, i.m.) immediately after mating. A second mating was allowed 12 h later. Ova and embryos were recovered by non-surgical uterine flushing 7 days after the first mating. Ovarian response was immediately evaluated afterwards via laparoscopy. The mean ovulation rate of 4.5 corpora lutea for Group A was significantly lower (P < 0.01) than the mean of 13.8 observed for Group B. The total ovarian response (number of corpora lutea + follicles > 10 mm) was also significantly higher (P < 0.01) in Group B than in Group A. Twenty-seven ova were recovered in each group, corresponding to 60% and 20% (P < 0.01) of the corpora lutea observed in Groups A and B, respectively; however, no significant difference (P > 0.05) in fertilisation rate was observed. The results show that pFSH induces superovulation in llamas treated during oestrus and that a 36-h interval between the end of FSH treatment and mating increases ovulation rate and the total ovarian response but does not affect the number of ova/embryos recovered.

Sphingosine-1-phosphate, regulated by FSH and VEGF, stimulates granulosa cell proliferation.

PubMed

Hernández-Coronado, C G; Guzmán, A; Rodríguez, A; Mondragón, J A; Romano, M C; Gutiérrez, C G; Rosales-Torres, A M

2016-09-15

Sphingosine-1-phosphate (S1P) is a bioactive polar sphingolipid which stimulates proliferation, growth and survival in various cell types. In the ovary S1P has been shown protect the granulosa cells and oocytes from insults such as oxidative stress and radiotherapy, and S1P concentrations are greater in healthy than atretic large follicles. Hence, we postulate that S1P is fundamental in follicle development and that it is activated in ovarian granulosa cells in response to FSH and VEGF. To test this hypothesis we set out: i) to evaluate the effect of FSH and VEGF on S1P synthesis in cultured bovine granulosa cells and ii) to analyse the effect of S1P on proliferation and survival of bovine granulosa cells in vitro. Seventy five thousand bovine granulosa cells from healthy medium-sized (4-7mm) follicles were cultured in 96-well plates in McCoy's 5a medium containing 10ng/mL of insulin and 1ng/mL of LR-IGF-I at 37°C in a 5% CO2/air atmosphere at 37°C. Granulosa cell production of S1P was tested in response to treatment with FSH (0, 0.1, 1 and 10ng/mL) and VEGF (0, 0.01, 0.1, 1, 10 and 100ng/mL) and measured by HPLC. Granulosa cells produced S1P at 48 and 96h, with the maximum production observed with 1ng/mL of FSH. Likewise, 0.01ng/mL of VEGF stimulated S1P production at 48, but not 96h of culture. Further, the granulosa cell expression of sphingosine kinase-1 (SK1), responsible for S1P synthesis, was demonstrated by Western blot after 48h of culture. FSH increased the expression of phosphorylated SK1 (P<0.05) and the addition of a SK1 inhibitor reduced the constitutive and FSH-stimulated S1P synthesis (P<0.05). Sphingosine-1-phosphate had a biphasic effect on granulosa cell number after culture. At low concentration S1P (0.1μM) increased granulosa cell number after 48h of culture (P<0.05) and the proportion of cells in the G2 and M phase of the cell cycle (P<0.05), whereas higher concentrations decreased cell number (10μM; P<0.05) by an increase (P<0.05) in the

Follicle-stimulating hormone (FSH), current suicidal ideation and attempt in female patients with major depressive disorder.

PubMed

Kim, Bora; Kang, Eun-Suk; Fava, Maurizio; Mischoulon, David; Soskin, David; Yu, Bum-Hee; Lee, Dongsoo; Lee, Dong-Yun; Park, Hyung-Doo; Jeon, Hong Jin

2013-12-30

Current suicidal ideation and attempts are more commonly found in female patients with major depressive disorder (MDD) than in males. However, little is known about the relationship between activity of female reproductive hormones and suicide. The study population consisted of 490 female MDD patients of age ≥18. They were assessed by the Mini-International Neuropsychiatric Interview. At the same visit, we measured blood Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), estradiol, progesterone, Adrenocorticotropic Hormone (ACTH), cortisol, thyroid hormones, and prolactin. Blood FSH showed a significant difference among female MDD patients with suicide attempt, those with ideation, and those without within the previous month. Post-hoc analysis also showed that FSH was significantly lower in MDD patients with suicide attempt and ideation than those without, whereas other hormones showed no differences between those with and without attempt. FSH was negatively associated with current suicidality scores after adjustment for age and education years in all age groups. FSH was significantly lower in those with current suicide ideation or attempt than those without in age 45 years or under, but not in other age groups. In conclusion, blood FSH is significantly lower in female MDD patients with current suicide attempt or ideation than those without, especially in age 45 years or under. © 2013 Elsevier Ireland Ltd. All rights reserved.

High levels of testosterone inhibit ovarian follicle development by repressing the FSH signaling pathway.

PubMed

Liu, Tao; Cui, Yu-qian; Zhao, Han; Liu, Hong-bin; Zhao, Shi-dou; Gao, Yuan; Mu, Xiao-li; Gao, Fei; Chen, Zi-jiang

2015-10-01

The effect of high concentrations of testosterone on ovarian follicle development was investigated. Primary follicles and granulosa cells were cultured in vitro in media supplemented with a testosterone concentration gradient. The combined effects of testosterone and follicle-stimulating hormone (FSH) on follicular growth and granulosa cell gonadotropin receptor mRNA expression were also investigated. Follicle growth in the presence of high testosterone concentrations was promoted at early stages (days 1-7), but inhibited at later stage (days 7-14) of in vitro culture. Interestingly, testosterone-induced follicle development arrest was rescued by treatment with high concentrations of FSH (400 mIU/mL). In addition, in cultured granulosa cells, high testosterone concentrations induced cell proliferation, and increased the mRNA expression level of FSH receptor (FSHR), and luteinized hormone/choriogonadotropin receptor. It was concluded that high concentrations of testosterone inhibited follicle development, most likely through regulation of the FSH signaling pathway, although independently from FSHR downregulation. These findings are an important step in further understanding the pathogenesis of polycystic ovary syndrome.

Interactions between androgens, FSH, anti-Müllerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary.

PubMed

Dewailly, Didier; Robin, Geoffroy; Peigne, Maëliss; Decanter, Christine; Pigny, Pascal; Catteau-Jonard, Sophie

2016-11-01

Androgens, FSH, anti-Müllerian hormone (AMH) and estradiol (E2) are essential in human ovarian folliculogenesis. However, the interactions between these four players is not fully understood. The purpose of this review is to highlight the chronological sequence of the appearance and function of androgens, FSH, AMH and E2 and to discuss controversies in the relationship between FSH and AMH. A better understanding of this interaction could supplement our current knowledge about the pathophysiology of the polycystic ovary syndrome (PCOS). A literature review was performed using the following search terms: androgens, FSH, FSH receptor, anti-Mullerian hormone, AMHRII, estradiol, follicle, ovary, PCOS, aromatase, granulosa cell, oocyte. The time period searched was 1980-2015 and the databases interrogated were PubMed and Web of Science. During the pre-antral ('gonadotropin-independent') follicle growth, FSH is already active and promotes follicle growth in synergy with theca cell-derived androgens. Conversely, AMH is inhibitory by counteracting FSH. We challenge the hypothesis that AMH is regulated by androgens and propose rather an indirect effect through an androgen-dependent amplification of FSH action on granulosa cells (GCs) from small growing follicles. This hypothesis implies that FSH stimulates AMH expression. During the antral ('gonadotropin-dependent') follicle growth, E2 production results from FSH-dependent activation of aromatase. Conversely, AMH is inhibitory but the decline of its expression, amplified by E2, allows full expression of aromatase, characteristic of the large antral follicles. We propose a theoretical scheme made up of two triangles that follow each other chronologically. In PCOS, pre-antral follicle growth is excessive (triangle 1) because of intrinsic androgen excess that renders GCs hypersensitive to FSH, with consequently excessive AMH expression. Antral follicle growth and differentiation are disturbed (triangle 2) because of the

Response of prepubertal ewes primed with monensin or progesterone to administration of FSH.

PubMed

Sumbung, F P; Williamson, P; Carson, R S

1987-11-01

Prepubertal ewe lambs were treated with FSH after progesterone priming for 12 days (Group P), monensin supplementation for 14 days (Group M) or a standard diet (Group C). Serial blood samples were taken for LH and progesterone assay, and ovariectomy was performed on half of each group 38-52 h after start of treatment to assess ovarian function, follicular steroid production in vitro and the concentration of gonadotrophin binding sites in follicles. The remaining ewe lambs were ovariectomized 8 days after FSH treatment to determine whether functional corpora lutea were present. FSH treatment was followed by a preovulatory LH surge which occurred significantly later (P less than 0.05) and was better synchronized in ewes in Groups P and M than in those in Group C. At 13-15 h after the LH surge significantly more large follicles were present on ovaries from Group P and M ewes than in Group C. Follicles greater than 5 mm diameter from ewes in Groups P and M produced significantly less oestrogen and testosterone and more dihydrotestosterone, and had significantly more hCG binding sites, than did similar-sized follicles from Group C animals. Ovariectomy on Day 8 after the completion of FSH treatment showed that ewes in Groups P and M had significantly greater numbers of functional corpora lutea. These results indicate that, in prepubertal ewes, progesterone priming and monensin supplementation may delay the preovulatory LH surge, allowing follicles developing after FSH treatment more time to mature before ovulation. This may result in better luteinization of ruptured follicles in these ewes, with the formation of functional corpora lutea.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of estradiol and FSH on leptin levels in women with suppressed pituitary.

PubMed

Geber, Selmo; Brandão, Augusto H F; Sampaio, Marcos

2012-06-15

Female fertility depends on adequate nutrition and energy reserves, suggesting a correlation between the metabolic reserve and reproductive capacity. Leptin regulates body weight and energy homeostasis. The aim of this study was to investigate whether estradiol or FSH alone has a direct effect on the production of leptin. A total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction and 20 patients using estradiol valerate for endometrial preparation for oocyte donation treatment were included in the study. All patients used GnRH analogues before starting treatment to achieve pituitary suppression. Blood samples for hormonal measurements were collected before starting and after completing the respective treatments. Data were analyzed statistically by the chi-square test, Student's t-test and Pearson's correlation test. We observed an elevation of serum leptin levels secondary to the increase in estradiol, in the absence of influence of any other ovarian or pituitary hormone. The rising rate of leptin levels was higher in women treated with recombinant FSH, which also had higher levels of estradiol, than in those treated with estradiol valerate. This study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH.

[Low-dose desmopressin (DDAVP) and blood levels of FSH, LH and testosterone in men].

PubMed

García-Pascual, I J; Rozán Flores, M A

1996-03-01

The effect of desmopressin (DDAVP) administration (2.5 micrograms/12 hours) on serum concentrations of FSH, LH and testosterone was studied in six men. No significant changes were observed in serum concentrations of FSH and LH after 9 days with DDAVP therapy. Nevertheless, serum concentrations of testosterone after 12 hours of DDAVP administration were significantly higher than basal concentrations. Three hours after the administration of DDAVP, serum testosterone concentrations decreased significantly. The conclusion reached was that low doses of desmopressin do not change serum concentrations of FSH and LH, but serum concentration of testosterone is decreased within three hours after the administration, although an increase is observed 12 hours later possibly due to a "rebound effect". Desmopressin would therefore directly act upon human testicle.

Effects of FSH and 17beta-estradiol on the transactivation of estrogen-regulated promoters and cell proliferation in L cells.

PubMed

Pasapera, Ana María; Jiménez-Aguilera, María del Pilar; Chauchereau, Anne; Milgrom, Edwin; Olivares, Aleida; Uribe, Aída; Gutiérrez-Sagal, Rubén; Ulloa-Aguirre, Alfredo

2005-03-01

In the present study, we analyzed human follicle-stimulating hormone (FSH)-induced cell proliferation and transactivation of estrogen-sensitive reporter genes-in L cells stably expressing the human FSH receptor [L-(hFSHR(+)) cells]. In order to dissect the signaling pathways involved in this process, L-(hFSHR(+)) cells were transiently transfected with either the 3X-ERE-TAT-Luc or the ERE-VitA2-TK-CAT reporter genes and treated with FSH or PKA activators (cholera toxin, forskolin and 8-Br-cAMP) in the presence or absence of various kinase inhibitors. We found that FSH and all PKA activators, specifically induced transactivation of both reporter genes. Transactivation of estrogen-sensitive genes by FSH or PKA activators were blocked (approximately 90%) by H89 (PKA inhibitor) and LY294002 but not by Wortmannin (PI3-K inhibitors), 4-OH-tamoxifen, ICI182,780 or SB203580 (p38 MAPK inhibitor); PD98059 (ERK1/2 inhibitor) partially (approximately 30%) blocked the FSH-mediated effect. The combination of FSH and estradiol resulted in a synergistic effect on transactivation as well as on cell proliferation, and this enhancement was attenuated by antiestrogens. We additionally analyzed the participation of the coactivators SRC-1 and cAMP response element binding protein (CREB)-binding protein (CBP) in FSH-evoked estrogen receptor (ER)-dependent transactivation; we found that CBP but not SRC-1 potentiated FSH-induced transcriptional activation of both ER-sensitive reporters, being this effect stronger on the ERE-VitA2-TK-CAT than on the 3X-ERE-TAT-Luc reporter. Thus, in L-(hFSHR(+)) cells FSH induces transcriptional activation of estrogen-sensitive genes through an A-kinase-triggered signaling pathway, using also to a lesser extent the ERK1/2 and p38 pathways. PI3-K is not apparently involved in this FSH-mediated process since LY294002, but not Wortmannin, specifically binds ERs and completely blocks estrogen action. Presumably, CBP cooperates with the ER on genes that contain

CRTC2 and Nedd4 ligase involvement in FSH and TGFβ1 upregulation of connexin43 gap junction.

PubMed

Fang, Wei-Ling; Lai, Si-Yi; Lai, Wei-An; Lee, Ming-Ting; Liao, Ching-Fong; Ke, Ferng-Chun; Hwang, Jiuan-Jiuan

2015-12-01

The major mission of the ovarian follicle is the timely production of the mature fertilizable oocyte, and this is achieved by gonadotropin-regulated, gap junction-mediated cell-cell communication between the oocyte and surrounding nurturing granulosa cells. We have demonstrated that FSH and transforming growth factor beta 1 (TGFβ1) stimulate Gja1 gene-encoded connexin43 (Cx43) gap junction formation/function in rat ovarian granulosa cells is important for their induction of steroidogenesis; additionally, cAMP-protein kinase A (PKA)- and calcium-calcineurin-sensitive cAMP response element-binding (CREB) coactivator CRTC2 plays a crucial role during steroidogenesis. This study was to explore the potential molecular mechanism whereby FSH and TGFβ1 regulate Cx43 synthesis and degradation, particularly the involvement of CRTC2 and ubiquitin ligase Nedd4. Primary culture of granulosa cells from ovarian antral follicles of gonadotropin-primed immature rats was used. At 48 h post-treatment, FSH plus TGFβ1 increased Cx43 level and gap junction function in a PKA- and calcineurin-dependent manner, and TGFβ1 acting through its type I receptor modulated FSH action. Chromatin-immunoprecipitation analysis reveals FSH induced an early-phase (45 min) and FSH+TGFβ1 further elicited a late-phase (24 h) increase in CRTC2, CREB and CBP binding to the Gja1 promoter. Additionally, FSH+TGFβ1 increased the half-life of hyper-phosphorylated Cx43 (Cx43-P2). Also, the proteasome inhibitor MG132 prevented the brefeldin A (blocker of protein transport through Golgi)-reduced Cx43-P2 level and membrane Cx43 gap junction plaque. This is associated with FSH+TGFβ1-attenuated Cx43 interaction with Nedd4 and Cx43 ubiquitination. In all, this study uncovers that FSH and TGFβ1 upregulation of Cx43 gap junctions in ovarian granulosa cells critically involves enhancing CRTC2/CREB/CBP-mediated Cx43 expression and attenuating ubiquitin ligase Nedd4-mediated proteosomal degradation of Cx43 protein

Comparing Serum Follicle-Stimulating Hormone (FSH) Level with Vaginal PH in Women with Menopausal Symptoms.

PubMed

Vahidroodsari, Fatemeh; Ayati, Seddigheh; Yousefi, Zohreh; Saeed, Shohreh

2010-01-01

Despite the important implication for women's health and reproduction, very few studies have focused on vaginal PH for menopausal diagnosis. Recent studies have suggested vaginal PH as a simple, noninvasive and inexpensive method for this purpose. The aim of this study is to compare serum FSH level with vaginal PH in menopause. This is a cross-sectional, descriptive study, conducted on 103 women (aged 31-95 yrs) with menopausal symptoms who were referred to the Menopausal Clinic at Ghaem Hospital during 2006. Vaginal pH was measured using pH meter strips and serum FSH levels were measured using immunoassay methods. The data was analyzed using SPSS software (version 11.5) and results were evaluated statistically by the Chi-square and Kappa tests. p≤0.05 was considered statistically significant. According to this study, in the absence of vaginal infection, the average vaginal pH in these 103 menopausal women was 5.33±0.53. If the menopausal hallmark was considered as vaginal pH>4.5, and serum FSH as ≥20 mIU/ml, then the sensitivity of vaginal pH for menopausal diagnosis was 97%. The mean of FSH levels in this population was 80.79 mIU/ml. Vaginal pH is a simple, accurate, and cost effective tool that can be suggested as a suitable alternative to serum FSH measurement for the diagnosis of menopause.

The BET protein FSH functionally interacts with ASH1 to orchestrate global gene activity in Drosophila

PubMed Central

2013-01-01

Background The question of how cells re-establish gene expression states after cell division is still poorly understood. Genetic and molecular analyses have indicated that Trithorax group (TrxG) proteins are critical for the long-term maintenance of active gene expression states in many organisms. A generally accepted model suggests that TrxG proteins contribute to maintenance of transcription by protecting genes from inappropriate Polycomb group (PcG)-mediated silencing, instead of directly promoting transcription. Results and discussion Here we report a physical and functional interaction in Drosophila between two members of the TrxG, the histone methyltransferase ASH1 and the bromodomain and extraterminal family protein FSH. We investigated this interface at the genome level, uncovering a widespread co-localization of both proteins at promoters and PcG-bound intergenic elements. Our integrative analysis of chromatin maps and gene expression profiles revealed that the observed ASH1-FSH binding pattern at promoters is a hallmark of active genes. Inhibition of FSH-binding to chromatin resulted in global down-regulation of transcription. In addition, we found that genes displaying marks of robust PcG-mediated repression also have ASH1 and FSH bound to their promoters. Conclusions Our data strongly favor a global coactivator function of ASH1 and FSH during transcription, as opposed to the notion that TrxG proteins impede inappropriate PcG-mediated silencing, but are dispensable elsewhere. Instead, our results suggest that PcG repression needs to overcome the transcription-promoting function of ASH1 and FSH in order to silence genes. PMID:23442797

Effects of estradiol and FSH on leptin levels in women with suppressed pituitary

PubMed Central

2012-01-01

Background Female fertility depends on adequate nutrition and energy reserves, suggesting a correlation between the metabolic reserve and reproductive capacity. Leptin regulates body weight and energy homeostasis. The aim of this study was to investigate whether estradiol or FSH alone has a direct effect on the production of leptin. Methods A total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction and 20 patients using estradiol valerate for endometrial preparation for oocyte donation treatment were included in the study. All patients used GnRH analogues before starting treatment to achieve pituitary suppression. Blood samples for hormonal measurements were collected before starting and after completing the respective treatments. Data were analyzed statistically by the chi-square test, Student’s t-test and Pearson’s correlation test. Results We observed an elevation of serum leptin levels secondary to the increase in estradiol, in the absence of influence of any other ovarian or pituitary hormone. The rising rate of leptin levels was higher in women treated with recombinant FSH, which also had higher levels of estradiol, than in those treated with estradiol valerate. Conclusions This study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH. PMID:22703959

Patterns of LH and FSH in men during high-frequency blood sampling.

PubMed

Scheele, F; Lambalk, C B; Schoemaker, J; van Kessel, H; de Koning, J; van Dieten, J A; van Rees, G P; de Vries Robles-Korsen, T J

1987-07-01

The aim of the study was to test the hypothesis that in serial determinations of concentrations of LH and FSH involving blood samples taken every minute, the observed pulses of LH and FSH which last less than 3-4 min might not be a physiological phenomenon but part of the 'noise' of the radioimmunoassay or blood-sampling technique. Blood was sampled every minute for a period of 90 min in six men. During the first 45 min, blood was sampled by means of vacuum tubes only. During the second 45 min, sampling took place with a syringe via a rubber stopper, either using a tourniquet (n = 3) or flushing the cannula with heparinized saline. Three criteria were used to identify variations in the patterns of LH and FSH as true hormonal changes. First, a threshold was used which had to be exceeded by the difference between nadir and maximum values before a pulse could be identified. An average of approximately six pulses per 90 min was found in both the LH and FSH series. The majority of these pulses lasted less than 3-4 min. In two subjects, larger LH pulses of longer duration were measured. Secondly, differences between duplicate measurements of nadir and/or maximum values of more than one-third of the amplitude of a pulse were considered unacceptable. This involved about 75% of the pulses. Thirdly, the reproducibility of the hormone variations was estimated. In one subject, concentrations of LH were measured four times in four separate assays.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro hCG and human recombinant FSH actions on testicular steroidogenesis in the toad Bufo arenarum.

PubMed

Canosa, L F; Ceballos, N R

2002-05-01

In order to study the regulation of testicular steroidogenesis in the toad Bufo arenarum, the effect of gonadotropins (hCG and hrFSH) on steroidogenic enzymes was determined using an in vitro system. 3beta-Hydroxysteroid dehydrogenase/isomerase activity was not affected by any of the gonadotropins, at any of the concentrations used. In contrast, 5alpha-reductase activity was strongly reduced by both hCG and hrFSH. Human chorionic gonadotropin inhibited the activity of cytochrome P450 17alpha-hydroxylase-C(17-20) lyase (P450(c17)), only at the highest concentration used, while hrFSH strongly reduced P450(c17) activity at all the doses assayed. In conclusion, these data suggest that LH (hCG) and FSH regulate steroidogenic enzymes such as 5alphaRed and P450(c17). The results also suggest that FSH could be involved in the regulation of the change in steroidogenesis undergone by the testis during the breeding season. In turn, the inhibition of P450(c17) activity could result in a reduction of androgen production and an increment of C21 steroids. (c) 2002 Elsevier Science (USA).

On the synergistic action of androgen and FSH on progestin secretion of cultured rat granulosa cells. Cellular and mitochondrial cholesterol metabolism.

PubMed

Nimrod, A

1981-01-01

The effect of FSH and androgen on the conversion of cholesterol into progesterone by cultured rat granulosa cells (GC) was studied in intact cells or mitochondrial preparations. Culture of GC for immature hypophysectomized diethylstilbestrol-treated rats for 48 h in the presence of ovine FSH (5 microgram/ml) alone, or FSH + testosterone (Te; 0.5 microgram/ml) caused a slight increase in the activity of the mitochondrial marker enzyme succinic dehydrogenase, while Te had no effect. Culture with the hormones for 48 h had no significant effect on the levels of free and esterified cellular cholesterol. GC monolayers after 48 h with or without FSH and Te converted [3H]cholesterol into 4 major metabolites, 3 of which were secreted into the medium and, in thin-layer chromatographic behavior, resembled pregnenolone, progesterone and 20 alpha-dihydroprogesterone. The total amount of the 3 C-21 steroids was higher (p less than 0.01) in FSH- or Te-treated than in control cells, and combined treatment had a synergistic effect. The uptake of labeled cholesterol (4--10%) was significantly higher (p less than 0.01) in cells pretreated with FSH or Te, whereas a combined FSH and Te treatment had an additive effect. Mitochondria isolated from GC monolayers took up cholesterol in a temperature-dependent fashion, but this uptake was not affected by hormonal pretreatment. In the presence of cyanoketone, the mitochondrial fractions activity converted cholesterol into pregnenolone. This activity was enhanced by FSH or Te (p less than 0.01), and further enhancement was observed with FSH + Te; the combined effect appeared to be more than additive (p = 0.05). The results suggest that both FSH and Te enhance the activity of cholesterol side-chain cleavage, but do not affect the transport of cholesterol into the mitochondria. A possible hormonal effect on a pre-mitochondrial step is discussed.

Use of FSH in two different regimens for ovarian superstimulation prior to ovum pick up and in vitro embryo production in Holstein cows.

PubMed

da Silva, Júlio César Barboza; Ferreira, Roberta Machado; Maturana Filho, Milton; Naves, Julianne de Rezende; Santin, Thiago; Pugliesi, Guilherme; Madureira, Ed Hoffmann

2017-03-01

We aimed with the present study to evaluate the effects of FSH treatment (200 mg) split in four or six administrations on ovarian follicle stimulation and in vitro oocyte competence for embryo production in dairy cows with synchronized follicular wave emergence. On random days of the estrous cycle (Day 0), non-lactating Holstein cows received a progesterone (P4)-releasing intravaginal device and 2 mg estradiol benzoate IM. On Day 3, they received 0.530 mg sodium cloprostenol (PGF2α) IM. Control cows (n = 35) received no further treatments, whereas FSH-treated cows received 200 mg FSH split in four (FSH4 group; n = 33) or six (FSH6 group; n = 33) administration regimens. Starting on Day 4, cows in FSH4 group received 200 mg FSH split in four equivalent doses of 50 mg 12 h apart. Cows in FSH6 group received the same total FSH dose split in six equivalent doses of 33.3 mg 12 h apart, but treatments started on Day 3. On Day 7 AM (36 h of "coasting" period for FSH-treated groups), the P4 devices were removed and cows were subjected to ovum pick up (OPU). Viable oocytes were in vitro fertilized using sexed-sorted semen. Although FSH treatment did not (P > 0.1) increase the total number of follicles (Control, 53.2 ± 4.5 vs. FSH-treated, 51.4 ± 3.1), the two hormonal stimulation regimens, FSH4 and FSH6, increased the number of medium follicles (6-10 mm; 5.2 ± 0.5 vs. 18.1 ± 1.4; P < 0.0001) and reduced the number of small follicles (2-5.9 mm; 46.3 ± 5.1 vs. 31.0 ± 2.4 P < 0.0001). Also, FSH treatment or regimen did not increase (P > 0.1) the number of viable oocytes (Control, 12.6 ± 1.26 vs. FSH-treated, 12.70 ± 1.03), recovery rate (Control, 36.5% vs. FSH-treated, 36%) and the number of in vitro produced blastocyst (Control, 4.1 ± 0.52 vs. FSH-treated 4.3 ± 0.5). We concluded that FSH stimulation protocol proposed herein is effective to stimulate the growth of small antral follicle population prior to OPU, but it

FSH-FSHR3-stem cells in ovary surface epithelium: basis for adult ovarian biology, failure, aging, and cancer.

PubMed

Bhartiya, Deepa; Singh, Jarnail

2015-01-01

Despite extensive research, genetic basis of premature ovarian failure (POF) and ovarian cancer still remains elusive. It is indeed paradoxical that scientists searched for mutations in FSH receptor (FSHR) expressed on granulosa cells, whereas more than 90% of cancers arise in ovary surface epithelium (OSE). Two distinct populations of stem cells including very small embryonic-like stem cells (VSELs) and ovarian stem cells (OSCs) exist in OSE, are responsible for neo-oogenesis and primordial follicle assembly in adult life, and are modulated by FSH via its alternatively spliced receptor variant FSHR3 (growth factor type 1 receptor acting via calcium signaling and the ERK/MAPK pathway). Any defect in FSH-FSHR3-stem cell interaction in OSE may affect folliculogenesis and thus result in POF. Ovarian aging is associated with a compromised microenvironment that does not support stem cell differentiation into oocytes and further folliculogenesis. FSH exerts a mitogenic effect on OSE and elevated FSH levels associated with advanced age may provide a continuous trigger for stem cells to proliferate resulting in cancer, thus supporting gonadotropin theory for ovarian cancer. Present review is an attempt to put adult ovarian biology, POF, aging, and cancer in the perspective of FSH-FSHR3-stem cell network that functions in OSE. This hypothesis is further supported by the recent understanding that: i) cancer is a stem cell disease and OSE is the niche for ovarian cancer stem cells; ii) ovarian OCT4-positive stem cells are regulated by FSH; and iii) OCT4 along with LIN28 and BMP4 are highly expressed in ovarian cancers. © 2015 Society for Reproduction and Fertility.

Evaluation of different ranges of LH:FSH ratios in polycystic ovarian syndrome (PCOS) - Clinical based case control study.

PubMed

Malini, N A; Roy George, K

2018-05-01

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine and metabolic disorder among reproductive aged women, leading to infertility. One of the common clinical manifestations in PCOS is that there is a difference in the range of LH production in different case of PCOS and accordingly variability in LH:FSH ratio was observed. The aim of the present study was to evaluate different ranges of LH:FSH ratios in PCOS. In this cross sectional study, a consecutive series of 745 women (aged 28.11 ± 0.2) who were subjected to infertility treatment at specialist infertility clinics in central Travancore region were considered. About 50 healthy females (aged 27.58 ± 0.4) with regular menstrual cycles were regarded as control. The data were collected from hospital records using subject's written informed consent. PCOS patients were observed to have different ranges of LH:FSH ratios from < 1 range to 4.6-5.5 and subjects were classified into 7 PCO subgroups on the basis of their LH:FSH ratios. In whole PCO group, body weight, LH, FSH, LH:FSH ratio, insulin, HbA1c, estradiol, testosterone and TSH were significantly (P < .05) increased whereas progesterone and SHBG levels were significantly (P < .05) decreased in comparison to control. In various PCO subgroups as LH levels and LH:FSH ratios were increased, levels of insulin, testosterone and AMH were increased and SHBG levels were decreased accordingly. This finding suggested a dependence of insulin, LH and testosterone in initiating the hormonal imbalances in PCOS. Copyright © 2018 Elsevier Inc. All rights reserved.

Phosphoinositide 3-Kinase p110δ Mediates Estrogen- and FSH-Stimulated Ovarian Follicle Growth

PubMed Central

Li, Qian; He, Hui; Zhang, Yin-Li; Li, Xiao-Meng; Guo, Xuejiang; Huo, Ran; Bi, Ye; Li, Jing

2013-01-01

In the mammalian ovary, primordial follicles are generated early in life and remain dormant for prolonged periods. Their growth resumes via primordial follicle activation, and they continue to grow until the preovulatory stage under the regulation of hormones and growth factors, such as estrogen, FSH, and IGF-1. Both FSH and IGF-1 activate the phosphatidylinositol-3 kinase (PI3K)/Akt (acute transforming retrovirus thymoma protein kinase) signaling pathway in granulosa cells (GCs), yet it remains inconclusive whether the PI3K pathway is crucial for follicle growth. In this study, we investigated the p110δ isoform (encoded by the Pik3cd gene) of PI3K catalytic subunit expression in the mouse ovary and its function in fertility. Pik3cd-null females were subfertile, exhibited fewer growing follicles and more atretic antral follicles in the ovary, and responded poorly to exogenous gonadotropins compared with controls. Ovary transplantation showed that Pik3cd-null ovaries responded poorly to FSH stimulation in vitro; this confirmed that the follicle growth defect was intrinsically ovarian. In addition, estradiol (E2)-stimulated follicle growth and GC proliferation in preantral follicles was impaired in Pik3cd-null ovaries. FSH and E2 substantially activated the PI3K/Akt pathway in GCs of control mice but not in those of Pik3cd-null mice. However, primordial follicle activation and oocyte meiotic maturation were not affected by Pik3cd knockout. Taken together, our findings indicate that the p110δ isoform of the PI3K catalytic subunit is a key component of the PI3K pathway for both FSH and E2-stimulated follicle growth in ovarian GCs; however, it is not required for primordial follicle activation and oocyte development. PMID:23820902

Effects and interactions of tachykinins and dynorphin on FSH and LH secretion in developing and adult rats.

PubMed

Ruiz-Pino, F; Garcia-Galiano, D; Manfredi-Lozano, M; Leon, S; Sánchez-Garrido, M A; Roa, J; Pinilla, L; Navarro, V M; Tena-Sempere, M

2015-02-01

Kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which coexpress kisspeptins (Kps), neurokinin B (NKB), and dynorphin (Dyn), regulate gonadotropin secretion. The KNDy model proposes that NKB (a stimulator, through NK3R) and Dyn (an inhibitor, through κ-opioid receptor) shape Kp secretion onto GnRH neurons. However, some aspects of this paradigm remain ill defined. Here we aimed to characterize the following: 1) the effects of NKB signaling on FSH secretion and 2) the role of Dyn in gonadotropin secretion after NK3R activation; 3) additionally, we explored the roles of other tachykinin receptors, NK1R and NK2R, on gonadotropin release. Thus, the effects of the NK3R agonist, senktide, on FSH release were explored across postnatal development in male and female rats; gonadotropin responses to agonists of NK1R substance P and NK2R [neurokinin A (NKA)] were also monitored. Moreover, the effects of senktide on gonadotropin secretion were assessed after antagonizing Dyn actions by nor-binaltorphimine didydrochloride. Before puberty, rats of both sexes showed increased FSH secretion to senktide (and Kp-10). Conversely, adult female rats were irresponsive to senktide in terms of FSH, despite proven LH responses, whereas the adult males did not display FSH or LH responses to senktide, even at high doses. In turn, substance P and NKA stimulated gonadotropin secretion in prepubertal rats, whereas in adults modest gonadotropin responses to NKA were detected. By pretreatment with a Dyn antagonist, adult males became responsive to senktide in terms of LH secretion and displayed elevated basal LH and FSH levels; nor-binaltorphimine didydrochloride treatment uncovered FSH responses to senktide in adult females. Furthermore, the expression of Pdyn and Opkr1 (encoding Dyn and κ-opioid receptor, respectively) in the mediobasal hypothalamus was greater in males than in females at prepubertal ages. Overall, our data contribute to refining our understanding on how the elements of the

[Corifollitropin alfa compared to daily FSH in controlled ovarian stimulation for oocyte donors].

PubMed

Benchabane, M; Santulli, P; Maignien, C; Bourdon, M; De Ziegler, D; Chapron, C; Gayet, V

2017-02-01

To demonstrate that corifollitropin alfa is as effective as daily FSH in controlled ovarian stimulation of oocyte donors. From January 2013 to October 2015, 77 cycles controlled ovarian stimulation, derived from a continuous cohort of 77 oocyte donors, were analyzed. After synchronization by oestroprogestatif or estrogens, ovarian stimulation was started by corifollitropin alfa (Group corifollitropin alfa) or by daily FSH (Group daily FSH). In both groups, a GnRH antagonist was used for the prevention of premature surge of luteinizing hormone (LH). The induction of ovulation was induced by a GnRH agonist. The duration of treatment, estradiol rate, numbers of mature oocytes, fertilization rate, clinical and ongoing pregnancies rates were evaluated in the two groups. There is no difference for the age, the markers of ovarian reserve and the duration of treatment. The average rate of estradiol on the eighth day of the stimulation is lower for the corifollitropin alfa (845±694.5 vs 1742±1177.3, P<0.001), there is no difference in the number of mature oocytes retrieved (14.4 vs 13.4, P=0.979), with a fertilization rate significantly higher in the corifollitropin alfa group (59.8% vs 49.3%, P<0.001). The rate of ongoing pregnancies is higher but without reaching significant difference in this same group (36.6% vs 26%, P=0.277). As compared to daily FSH, corifollitropin alfa, in oocyte donors offers, advantages in terms of ease of use with identical efficiency. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Patient preference for a long-acting recombinant FSH product in ovarian hyperstimulation in IVF: a discrete choice experiment.

PubMed

van den Wijngaard, L; Rodijk, I C M; van der Veen, F; Gooskens-van Erven, M H W; Koks, C A M; Verhoeve, H R; Mol, B W J; van Wely, M; Mochtar, M H

2015-02-01

What factors or attributes of a long-acting recombinant FSH (rFSH) or daily-administrated rFSH influence women's preferences IVF? Patients' preferences for rFSH products are primary influenced by the attribute 'number of injections', but a low 'number of injections' is exchanged for a high 'number of injections' at a 6.2% decrease in 'risk of cycle cancellation due to low response' and at a 4.5% decrease in 'chance of OHSS'. Injections of long-acting rFSH have been claimed to be preferred over daily-administrated rFSH injections, but patient preference studies to underpin this assumption have not been performed. A discrete choice experiment (DCE) was created to assess women's preference for long-acting or daily-administrated rFSH under varying attributes of efficiency, safety and burden. The selected attributes were the 'total number of injections', 'chance of ovarian hyperstimulation syndrome (OHSS)' and the 'risk of cycle cancellation due to low response'. Questionnaires were handed out during information gathering sessions in one academic hospital and two teaching hospitals in The Netherlands between April 2011 and April 2012. Women at the start of their first IVF treatment were asked to participate in this patient preference study. Participation was voluntary. We analysed the data by using mixed logit models to estimate the utility of each attribute. Questionnaires (n = 125) were handed out with a response rate of 77% (97/125). Four respondents did not complete the questionnaire. Hence, there were 93 questionnaires available for analysis. All attributes significantly influenced women's preference. Overall, the lower 'number of injections' was preferred above the higher 'number of injections' (mean coefficient 1.25; P < 0.001), while an increase of 1% in 'chance of OHSS' or 5% 'risk of cycle cancellation due to low response' was non-preferred (mean coefficients -0.31 and -0.24, respectively, P < 0.01). The majority of respondents was willing to trade-off a lower

Potential role of follicle-stimulating hormone (FSH) and transforming growth factor (TGFβ1) in the regulation of ovarian angiogenesis.

PubMed

Kuo, Shih-Wei; Ke, Ferng-Chun; Chang, Geen-Dong; Lee, Ming-Ting; Hwang, Jiuan-Jiuan

2011-06-01

Angiogenesis occurs during ovarian follicle development and luteinization. Pituitary secreted FSH was reported to stimulate the expression of endothelial mitogen VEGF in granulosa cells. And, intraovarian cytokine transforming growth factor (TGF)β1 is known to facilitate FSH-induced differentiation of ovarian granulosa cells. This intrigues us to investigate the potential role of FSH and TGFβ1 regulation of granulosa cell function in relation to ovarian angiogenesis. Granulosa cells were isolated from gonadotropin-primed immature rats and treated once with FSH and/or TGFβ1 for 48 h, and the angiogenic potential of conditioned media (granulosa cell culture conditioned media; GCCM) was determined using an in vitro assay with aortic ring embedded in collagen gel and immunoblotting. FSH and TGFβ1 increased the secreted angiogenic activity in granulosa cells (FSH + TGFβ1 > FSH ≈ TGFβ1 >control) that was partly attributed to the increased secretion of pro-angiogenic factors VEGF and PDGF-B. This is further supported by the evidence that pre-treatment with inhibitor of VEGF receptor-2 (Ki8751) or PDGF receptor (AG1296) throughout or only during the first 2-day aortic ring culture period suppressed microvessel growth in GCCM-treated groups, and also inhibited the FSH + TGFβ1-GCCM-stimulated release of matrix remodeling-associated gelatinase activities. Interestingly, pre-treatment of AG1296 at late stage suppressed GCCM-induced microvessel growth and stability with demise of endothelial and mural cells. Together, we provide original findings that both FSH and TGFβ1 increased the secretion of VEGF and PDGF-B, and that in turn up-regulated the angiogenic activity in rat ovarian granulosa cells. This implicates that FSH and TGFβ1 play important roles in regulation of ovarian angiogenesis during follicle development. Copyright © 2010 Wiley-Liss, Inc.

FSH supplementation to culture medium is beneficial for activation and survival of preantral follicles enclosed in equine ovarian tissue.

PubMed

Aguiar, F L N; Lunardi, F O; Lima, L F; Rocha, R M P; Bruno, J B; Magalhães-Padilha, D M; Cibin, F W S; Nunes-Pinheiro, D C S; Gastal, M O; Rodrigues, A P R; Apgar, G A; Gastal, E L; Figueiredo, J R

2016-04-01

This study investigated the effect of adding different concentrations of bovine recombinant follicle-stimulating hormone on the IVC of equine preantral follicles enclosed in ovarian tissue fragments. Randomized ovarian fragments were fixed immediately (fresh noncultured control) or cultured for 1 or 7 days in α-MEM(+) supplemented with 0, 10, 50, and 100 ng/mL FSH and subsequently analyzed by classical histology. Culture media collected on Day 1 or Day 7 and were analyzed for steroids (estradiol and progesterone) and reactive oxygen species (ROS). After Day 1 and Day 7 of culture, 50-ng/mL FSH treatment had a greater (P < 0.05) percentage of morphologically normal follicles when compared to the other groups, except the 10-ng/mL FSH treatment at Day 1 of culture. The percentage of developing follicles (transition, primary, and secondary), and follicular and oocyte diameters were higher (P < 0.05) in the 50-ng/mL FSH treatment compared to the other groups after Day 7 of culture. Furthermore, estradiol secretion and ROS production were maintained (P > 0.05) throughout the culture in the 50-ng/mL FSH treatment. In conclusion, the addition of 50 ng/mL of FSH promoted activation of primordial follicles to developing follicles, improved survival of preantral follicles, and maintained estradiol and ROS production of equine ovarian tissue after 7 days of culture. Copyright © 2016 Elsevier Inc. All rights reserved.

Regulation of steroidogenesis in fetal bovine ovaries: differential effects of LH and FSH.

PubMed

Allen, J J; Herrick, S L; Fortune, J E

2016-11-01

In cattle, primordial follicles form before birth. Fetal ovarian capacity to produce progesterone and estradiol is high before follicle formation begins and decreases around the time follicles first appear (around 90 days of gestation). However, mechanisms that regulate steroid production during this time remain unclear. We hypothesized that LH stimulates progesterone and androgen production and that FSH stimulates aromatization of androgens to estradiol. To test this, we cultured pieces from fetal bovine ovaries for 10 days without or with exogenous hormones and then measured the accumulation of steroids in the culture medium by RIA. LH (100 ng/mL) alone increased the accumulation of progesterone, androstenedione, testosterone and estradiol. FSH (100 ng/mL) alone increased both progesterone and estradiol accumulation, but had no effect on androgens. Exogenous testosterone (0.5 µM) alone greatly increased estradiol accumulation and the combination of testosterone + FSH, but not testosterone + LH, increased estradiol relative to testosterone alone. Interestingly, exogenous testosterone and estradiol decreased progesterone accumulation in a dose-dependent manner. Because the highest dose of estradiol (0.5 µM) decreased progesterone accumulation, but increased both pregnenolone and androstenedione in the same cultures, endogenous estradiol may be a paracrine regulator of steroid synthesis. Together, these results confirm our initial hypotheses and indicate that LH stimulates androgen production in fetal bovine ovaries via the Δ 5 pathway, whereas FSH stimulates aromatization of androgens to estradiol. These results are consistent with the two-cell, two-gonadotropin model of estradiol production by bovine preovulatory follicles, which suggests that the mechanisms regulating ovarian steroid production are established during fetal life. © 2016 Society for Endocrinology.

Shortened estrous cycle length, increased FSH levels, FSH variance, oocyte spindle aberrations, and early declining fertility in aging senescence-accelerated mouse prone-8 (SAMP8) mice: concomitant characteristics of human midlife female reproductive aging.

PubMed

Bernstein, Lori R; Mackenzie, Amelia C L; Kraemer, Duane C; Morley, John E; Farr, Susan; Chaffin, Charles L; Merchenthaler, István

2014-06-01

Women experience a series of specific transitions in their reproductive function with age. Shortening of the menstrual cycle begins in the mid to late 30s and is regarded as the first sign of reproductive aging. Other early changes include elevation and increased variance of serum FSH levels, increased incidences of oocyte spindle aberrations and aneuploidy, and declining fertility. The goal of this study was to investigate whether the mouse strain senescence-accelerated mouse-prone-8 (SAMP8) is a suitable model for the study of these midlife reproductive aging characteristics. Midlife SAMP8 mice aged 6.5-7.85 months (midlife SAMP8) exhibited shortened estrous cycles compared with SAMP8 mice aged 2-3 months (young SAMP8, P = .0040). Midlife SAMP8 mice had high FSH levels compared with young SAMP8 mice, and mice with a single day of high FSH exhibited statistically elevated FSH throughout the cycle, ranging from 1.8- to 3.6-fold elevation on the days of proestrus, estrus, metestrus, and diestrus (P < .05). Midlife SAMP8 mice displayed more variance in FSH than young SAMP8 mice (P = .01). Midlife SAMP8 ovulated fewer oocytes (P = .0155). SAMP8 oocytes stained with fluorescently labeled antitubulin antibodies and scored in fluorescence microscopy exhibited increased incidence of meiotic spindle aberrations with age, from 2/126 (1.59%) in young SAMP8 to 38/139 (27.3%) in midlife SAMP8 (17.2-fold increase, P < .0001). Finally, SAMP8 exhibited declining fertility from 8.9 pups/litter in young SAMP8 to 3.5 pups/litter in midlife SAMP8 mice (P < .0001). The age at which these changes occur is younger than for most mouse strains, and their simultaneous occurrence within a single strain has not been described previously. We propose that SAMP8 mice are a model of midlife human female reproductive aging.

Supplemented base medium containing Amburana cearensis associated with FSH improves in vitro development of isolated goat preantral follicles.

PubMed

Gouveia, B B; Macedo, T J S; Santos, J M S; Barberino, R S; Menezes, V G; Müller, M C; Almeida, J R G S; Figueiredo, J R; Matos, M H T

2016-09-15

The effects of Amburana cearensis ethanolic extract, with or without addition of a mix of supplements associated or not with FSH, on in vitro morphology and development of caprine secondary follicles were evaluated. In experiment 1, isolated follicles (250 μm in diameter) were cultured for 12 days in alpha-modified minimal essential medium (α-MEM) alone (control) or in medium composed of different concentrations of A. cearensis extract (Amb 0.1; 0.2, or 0.4 mg/mL). In experiment 2, culture media were α-MEM or Amb 0.2 mg/mL (both without supplements), or these same media supplemented with BSA, insulin, transferrin, selenium, glutamine, hypoxanthine, and ascorbic acid (referred as α-MEM(+) and Amb 0.2(+), respectively), or these last groups also supplemented with sequential FSH (100 ng/mL from Day 0 to Day 6; 500 ng/mL from Day 6 to Day 12), constituting groups α-MEM(+) + FSH and Amb 0.2(+) + FSH. At the end of culture in experiment 1, control medium (α-MEM) and Amb 0.2 mg/mL had higher percentages (P < 0.05) of morphologically normal follicles and percentage of fully grown oocytes, i.e., oocyte greater than 110 μm, compared to the other A. cearensis extract concentrations. In experiment 2, all supplemented media had higher percentages (P < 0.05) of normal follicles and antrum formation than nonsupplemented media. In addition, follicles cultured in Amb 0.2(+) + FSH showed an average increase in diameter higher (P < 0.05) than the other treatments. Oocytes cultured in both treatments supplemented with FSH showed greater glutathione and active mitochondria levels than nonsupplemented media but similar to the other treatments. In conclusion, A. cearensis extract (0.2 mg/mL) added by supplements and FSH improves follicular growth. Therefore, it can be an alternative culture medium for goat preantral follicle development. Copyright © 2016 Elsevier Inc. All rights reserved.

Persistent organic pollutants as predictors of increased FSH:LH ratio in naturally cycling, reproductive age women.

PubMed

Gallo, Mia V; Ravenscroft, Julia; Carpenter, David O; Schell, Lawrence M; Akwesasne Task Force On The Environment

2018-07-01

Although several recent studies suggest endocrine disrupting compounds, such as polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p', DDE), and hexachlorobenzene (HCB), target different organs and systems in the body, their impact on female reproductive function in humans is not well characterized. We seek to determine the relationship between several known endocrine disrupting compounds and a marker of ovarian responsivity, the FSH:LH ratio (higher ratio indicates less ovarian responsivity). For this analysis, 169 naturally cycling women between 21 and 38 years of age completed interviews and had their blood drawn on day 3 of their menstrual cycle for analyses of toxicants, gonadal sex hormones (E 2 and P 4 ), and gonadotropins (FSH and LH). PCB congeners were classified into five groups based on their environmental persistence, distribution in human tissue, and toxicological action, reflecting the structure, mechanism, and known biological activity of individual PCB congeners. For every unit (ppb) increase in the level of the estrogenic PCB group, there was a 5-fold greater risk of a FSH:LH ratio ≥ 2, controlling for individual differences in age, percent body fat, cycle day 3 estradiol levels, parity, alcohol use and cigarette smoking in the past year (exp[ß] = 5; p = ≤0.01). PCB congeners identified as estrogenic were analyzed individually, and, of the 19 potentially estrogenic congeners, five were significantly, and positively related to an increased FSH:LH ratio. Four of these congeners are non-persistent, easily volatilize in the environment, and are easily metabolized, and hence, are indicative of very recent or current exposure. p,p'-DDE and HCB were not associated with FSH:LH ratio. We find a clinical indicator of ovarian responsivity, FSH:LH ratio, is associated with a specific group of estrogenic PCBs. These congeners may become airborne when they volatilize from dredged PCB-contaminated soil or from indoor PCB

HP-HMG versus rFSH in treatments combining fresh and frozen IVF cycles: success rates and economic evaluation.

PubMed

Wex-Wechowski, Jaro; Abou-Setta, Ahmed M; Kildegaard Nielsen, Sandy; Kennedy, Richard

2010-08-01

The economic implications of the choice of gonadotrophin influence decision making but their cost-effectiveness in frozen-embryo transfer cycles has not been adequately studied. An economic evaluation was performed comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) using individual patient data (n=986) from two large randomized controlled trials using a long agonist IVF protocol. The simulation model incorporated live birth data and published UK costs of IVF-related medical resources. After treatment for up-to-three cycles (one fresh and up to two subsequent fresh or frozen cycles conditional on availability of cryopreserved embryos), the cumulative live birth rate was 53.7% (95% CI 49.3-58.1%) for HP-HMG and 44.6% (40.2-49.0%) for rFSH (OR 1.44, 95% CI 1.12-1.85; P<0.005). The mean costs per IVF treatment for HP-HMG and rFSH were pound5393 ( pound5341-5449) and pound6269 ( pound6210-6324), respectively (number needed to treat to fund one additional treatment was seven; P<0.001). With maternal and neonatal costs applied, the median cost per IVF baby delivered with HP-HMG was pound11,157 ( pound11,089-11,129) and pound14,227 ( pound14,183-14,222) with rFSH (P<0.001). The cost saving using HP-HMG remained after varying model parameters in a probabilistic sensitivity analysis. 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

An economic evaluation of highly purified HMG and recombinant FSH based on a large randomized trial.

PubMed

Wechowski, Jaroslaw; Connolly, Mark; McEwan, Philip; Kennedy, Richard

2007-11-01

Public funding for IVF is increasingly being challenged by health authorities in an attempt to minimize health service costs. In light of treatment rationing, the need to consider costs in relation to outcomes is paramount. To assess the cost implications of gonadotrophin treatment options, an economic evaluation comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) has been conducted. The analysis is based on individual patient data from a large randomized controlled trial (n = 731) in a long agonist IVF protocol. The economic evaluation uses a discrete event simulation model to assess treatment costs in relation to live births for both treatments based on published UK costs. After one cycle the mean costs per IVF treatment for HP-HMG and rFSH were pound2396 (95% CI pound2383-2414) and pound2633 ( pound2615-2652), respectively. The average cost-saving of pound237 per IVF cycle using HP-HMG allows one additional cycle to be delivered for every 10 cycles. With maternal and neonatal costs applied, the median cost per IVF baby delivered with HP-HMG was pound8893 compared with pound11,741 for rFSH (P < 0.001). The cost-saving potential of HP-HMG in IVF was still apparent after varying critical cost parameters in the probabilistic sensitivity analysis.

Effectiveness of intravaginal progesterone inserts and FSH for inducing synchronized estrus and increasing lambing rate in anestrous ewes.

PubMed

Knights, M; Hoehn, T; Lewis, P E; Inskeep, E K

2001-05-01

The objectives of this study were to determine whether a new progesterone (P4)-releasing intravaginal insert would induce fertile estrus and whether FSH combined with the insert would increase prolificacy in anestrous ewes introduced to rams. Ewes of mixed breeding on six farms were assigned to four randomized treatments: control (C), n = 73; 12 d P4 (polycapralactone [PCL] insert with 0.82 g P4), (P12), n = 73; 12 d P4 plus i.m. FSH (Folltropin, 55 mg NIH-FSH-P1 equivalent) in propylene glycol, 24 h before insert removal, (P12F), n = 71; and 5 d P4 plus FSH (P5F), n = 77. Growth and ovulation of follicles were observed ultrasonographically in 20 ewes at four farms (five/treatment) at insert removal and 36, 48, 72, and 96 h later. Intact rams (1:15 ewes in multiple-sire groups) were joined at insert removal, and raddle marks were observed every 12 h for 5 d. On d 26 to 30, rams were removed; ewes were examined for pregnancy then and 20 d later. Percentage of ewes marked by rams was greater in P4-treated (66 to 79%) than in C (12%; P < 0.01) ewes and in P5F (79%) than in P12F (66%; P < 0.05). Diameters of largest follicles at insert removal were greater (P < 0.05) in P4-treated (5.5 +/- 0.2) than in C ewes (4.8 +/- 0.2). Progesterone increased numbers of follicles > 3 mm (P < 0.01) or ovulated (P < 0.05; 2.6 +/- 0.6 vs 1.3 +/- 0.6 in C ewes) and FSH increased number of follicles > 3 mm (P < 0.05). In FSH-treated ewes, ovulation rate tended to be greater after treatment with P4 for 5 than for 12 d (P = 0.09, 3.3 +/- 0.6 and 2.2 +/- 0.4, respectively). More P4-treated than C ewes lambed (P < 0.01) to the first (38 to 45 vs 0%) or both (63 to 66 vs 41%) service periods. Prolificacy (first service) did not differ between FSH-treated ewes (P12F + P5F; 1.8 +/- 0.1) and ewes treated with P4 only (P12; 1.6 +/- 0.1). However, FSH increased prolificacy to first service (1.8 +/- 0.1) over prolificacy to second service (C ewes 1.5 +/- 0.1; P < 0.05, and all ewes 1.4 +/- 0.1; P

Reanalysis of the preoptic afferents and efferents involved in the surge of LH, FSH and prolactin release in the proestrous rat.

PubMed

Kimura, F; Kawakami, M

1978-01-01

In order to elucidate neural pathways concerned with the proestrous surge of LH, FSH and prolactin (Prl) release, brain transection or lesion was made acutely under ether anesthesia between 12.00 and 14.00 h of proestrus, and electrochemical stimulation was done under anesthesia with pentobarbital sodium (31.5 mg/kg b.w.) injected at 13.45 h. Transection which interrupted the connection of septum (SEPT), diagonal band of Broca (DBB) and bed nucleus of stria terminalis (BST) with the preoptic-suprachiasmatic area interfered with ovulation and surge of release of all 3 hormones. Isolation of the basal part of the suprachiasmatic area, including the suprachiasmatic nucleus (SCH), blocked ovulation also. Bilateral lesions in the medial preoptic area (MPO) with platinium-iridium electrode blocked ovulation and the surge of LH and Prl release, but not of FSH. Lesions in the SCH blocked ovulation and the surge of LH, but not of FSH and Prl. In the rat with acute isolation of the basal part of the suprachiasmatic area and SCH, stimulation of the MPO failed to induce ovulation and LH release, but was followed by FSH release. Prl release was not inhibited as in the intact rat. When the rat had the antero-SCH cut, stimulation of the SCH induced LH release but not FSH, and the inhibition on Prl release was pronounced. These findings offer evidence that the limbic-forebrain inputs are necessary for the preoptic integration in order to stimulate the proestrous surge of LH, FSH and Prl release. Furthermore, it is possible that separate pathways from the preoptic area to the medial basal hypothalamus are concerned in the stimulation of individual hormones--a restricted route for LH which may pass through the SCH, a diffuse one for FSH which may pass through either the SCH or anterior hypothalamic area, and a relatively diffuse one for Prl which may pass outside the SCH.

Occurrence of FSH, inhibin and other hypothalamic-pituitary-intestinal hormones in normal fertility, subfertility, and tumors of human testes.

PubMed

Mehta, M K; Garde, S V; Sheth, A R

1995-01-01

To compare the distribution of peptide hormones in presumably normal human testicular tissues and specimens exhibiting any of five pathologies. Biopsies from patients having testicular malfunctions were prepared as sections and specifically immunohistochemically stained for inhibin, FSH, serotonin, AUP, and oxytocin. Immunocytochemical studies revealed the presence of various hypophysial-pituitary-intestinal hormones, viz., FSH, inhibin, arginine vasopressin (AVP), calcitonin, serotonin, oxytocin, adrenocorticotropin (ACTH), gastrin, secretin, and somatostatin in human testicular biopsies exhibiting normal spermatogenesis, Sertoli-cell-only syndrome, spermatogenic arrest, Leydig cell hyperplasia, Leydig cell tumor, and seminoma. Intensity of immunostaining for all peptides except FSH was stronger in cases of subfertile as compared to normal testis. Intensity of immunostaining with inhibin was maximum in Leydig cell tumor. These regulatory peptides may be involved in the pathophysiology of the testes.

Involvement of ERK1/2 signaling pathway in atrazine action on FSH-stimulated LHR and CYP19A1 expression in rat granulosa cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fa, Svetlana; Pogrmic-Majkic, Kristina; Samardzija, Dragana

Worldwide used herbicide atrazine is linked to reproductive dysfunction in females. In this study, we investigated the effects and the mechanism of atrazine action in the ovary using a primary culture of immature granulosa cells. In granulosa cells, follicle-stimulating hormone (FSH) activates both cyclic adenosine monophosphate (cAMP) and extracellular-regulated kinase 1/2 (ERK1/2) cascades, with cAMP pathway being more important for luteinizing hormone receptor (LHR) and aromatase (CYP19A1) mRNA expression. We report that 48 h after atrazine exposure the FSH-stimulated LHR and CYP19A1 mRNA expression and estradiol synthesis were decreased, with LHR mRNA being more sensitive to atrazine than CYP19A1 mRNA.more » Inadequate acquisition of LHR in the FSH-stimulated and atrazine-exposed granulosa cells renders human chorionic gonadotropin (hCG) ineffective to stimulate amphiregulin (Areg), epiregulin (Ereg), and progesterone receptor (Pgr) mRNA expression, suggesting anti-ovulatory effect of atrazine. To dissect the signaling cascade involved in atrazine action in granulosa cells, we used U0126, a pharmacological inhibitor of ERK1/2. U0126 prevents atrazine-induced decrease in LHR and CYP19A1 mRNA levels and estradiol production in the FSH-stimulated granulosa cells. ERK1/2 inactivation restores the ability of hCG to induce expression of the ovulatory genes in atrazine-exposed granulosa cells. Cell-based ELISA assay revealed that atrazine does not change the FSH-stimulated ERK1/2 phosphorylation in granulosa cells. The results from this study reveal that atrazine does not affect but requires ERK1/2 phosphorylation to cause decrease in the FSH-induced LHR and CYP19A1 mRNA levels and estradiol production in immature granulosa cells, thus compromising ovulation and female fertility. - Highlights: • Atrazine inhibits estradiol production in FSH-stimulated granulosa cells. • Atrazine inhibits LHR and Cyp19a1 mRNA expression in FSH-stimulated granulosa cells. �

Regulation of LH/FSH expression by secretoglobin 3A2 in the mouse pituitary gland.

PubMed

Miyano, Yuki; Tahara, Shigeyuki; Sakata, Ichiro; Sakai, Takafumi; Abe, Hiroyuki; Kimura, Shioko; Kurotani, Reiko

2014-04-01

Secretoglobin (SCGB) 3A2 was originally identified as a downstream target for the homeodomain transcription factor NKX2-1 in the lung. NKX2-1 plays a role in the genesis and expression of genes in the thyroid, lung and ventral forebrain; Nkx2-1-null mice have no thyroid and pituitary and severely hypoplastic lungs and hypothalamus. To demonstrate whether SCGB3A2 plays any role in pituitary hormone production, NKX2-1 and SCGB3A2 expression in the mouse pituitary gland was examined by immunohistochemical analysis and RT-PCR. NKX2-1 was localized in the posterior pituitary lobe, whereas SCGB3A2 was observed in both anterior and posterior lobes as shown by immunohistochemistry and RT-PCR. Expression of CCAAT-enhancer binding proteins (C/EBPs), which regulate mouse Scgb3a2 transcription, was also examined by RT-PCR. C/EBPβ, γ, δ and ζ were expressed in the adult mouse pituitary gland. SCGB3A2 was expressed in the anterior and posterior lobes from postnatal days 1 and 5, respectively and the areas where SCGB3A2 expression was found coincided with the area where FSH-secreting cells were found. Double-staining for SCGB3A2 and pituitary hormones revealed that SCGB3A2 was mainly localized in gonadotrophs in 49 % of FSH-secreting cells and 47 % of LH-secreting cells. In addition, SCGB3A2 dramatically inhibited LH and FSH mRNA expression in rat pituitary primary cell cultures. These results suggest that SCGB3A2 regulates FSH/LH production in the anterior pituitary lobe and that transcription factors other than NKX2-1 may regulate SCGB3A2 expression.

Measurement Differences Between Two Immunoassay Systems for LH and FSH: A Comparison of Roche Cobas e601 vs. Abbott Architect i2000sr.

PubMed

Yin, Lianli; Tang, Yinghua; Chen, Xiang; Sun, Yifan

2018-03-01

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) regulate the growth and reproductive activity of gonadal tissue and determine the concentration of LH is essential for the prediction of ovulation. Collectively, FSH and LH are important measurements to ascertain the causes of infertility as well as diagnosing disorders such as polycystic ovary syndrome and pituitary and gonadal dysfunction. This study compares the correlation between LH and FSH measurements during examination with two different systems, Architect i2000sr (Abbott Laboratories; Lake Bluff, IL, USA) and Cobas e601 (Roche; Geneva, Switzerland), and assesses the differences between these systems. Serum analysis was performed for 95 patients using both the Cobas e601 and Architect i2000sr systems. The method used to compare the systems was Passing-Bablok regression analysis with a Bland-Altman agreement plot. Inter-rater agreement was analyzed using a concordance correlation coefficient. Architect i2000sr and Cobas e601 have strong correlations in their LH and FSH results. However, the Bland-Altman plot shows that LH and FSH measurements in Cobas e601 are about 1.31 times and 1.26 times higher than those in Architect i2000sr, respectively. Passing-Bablok regression analysis also shows significant proportional deviation between them. The difference between the test results for LH and FSH in Cobas e601 and Architect i2000sr indicate that the results from one system cannot be directly used to evaluate the other system.

Body mass index and gonadotropin hormones (LH & FSH) associate with clinical symptoms among women with polycystic ovary syndrome.

PubMed

Esmaeilzadeh, Seddigheh; Andarieh, Maryam Ghanbari; Ghadimi, Reza; Delavar, Mouloud Agajani

2014-09-28

To evaluate the relevance of body mass index (BMI), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and LH/FSH ratio with clinical symptoms in polycystic ovary syndrome (PCOS) women. We reviewed the medical records of all women visited in the PCOS Clinic of Babol (Iran) from 2008 to 2012. A retrospective cross-sectional study was conducted on 175 PCOS women; aged 18-38 years diagnosed based on the Rotterdam criteria. Among the PCOs women, the prevalence of oligomenorrhea, acne, and hirsutism were found to be 92.0%, 31.4%, and 78.9%, respectively. Positive finding of polycystic ovaries was observed in 89.1% of PCOS women with by using sonography. A total of 69.2% overweight/obesity patients had polycystic ovary morphology on ultrasound image. Compared with non- overweight/obesity, the adjusted OR of PCOS women for sonographic view of polycystic ovaries was 4.33 (95% CI, 1.42-13.15, p=0.001), Nevertheless, the adjusted odds ratio (OR) showed no significant associations between LH, FSH, and LH/FSH ratio with clinical symptoms in these women. The findings of this study indicated that the overweight/obese women with PCOS are at an increased risk for sonographic view of polycystic ovaries. Therefore, it is suggested that successful weight loss is the most effective method of restoring ovulation, menstruation that should be used as major advice in obese PCOS patients.

The effect of Ramadan fasting on LH, FSH, oestrogen, progesterone and leptin in pregnant women.

PubMed

Khoshdel, A; Kheiri, S; Hashemi-Dehkordi, E; Nasiri, J; Shabanian-Borujeni, S; Saedi, E

2014-10-01

Many pregnant Muslim women fast during Ramadan. Leptin has an important role in the reproductive system and hormones. In this study, FSH, LH, oestrogen, progesterone and leptin were measured in the first, second and fourth week of Ramadan and the second week post-Ramadan, in 30 fasting pregnant women. Data were analysed using repeated measures ANOVA by SPSS. The weight and BMI did not change during the study. A significant change in FSH, oestrogen, progesterone and leptin was observed (p < 0.05). The lowest value of FSH was in the second week of Ramadan. Progesterone increased at the end of Ramadan and the second week after. Oestrogen increased significantly during Ramadan and decreased after Ramadan. A decreasing trend was seen in LH during the Ramadan and 2 weeks after (p < 0.1). Leptin decreased significantly 2 weeks after Ramadan. We found poor weight gain and hypoleptinaemia in pregnant fasted women during the study. Food restriction in pregnant fasted women during Ramadan may induce poor weight gain during pregnancy. These data confirm that Ramadan fasting by pregnant women may have potential risks during pregnancy. We recommend further study to evaluate long-term effects of Ramadan fasting during pregnancy in different countries with different food habits and traditions, to obtain reliable and documented data.

Whole brain-pituitary in vitro preparation of the transgenic medaka (Oryzias latipes) as a tool for analyzing the differential regulatory mechanisms of LH and FSH release.

PubMed

Karigo, Tomomi; Aikawa, Masato; Kondo, Chika; Abe, Hideki; Kanda, Shinji; Oka, Yoshitaka

2014-02-01

Two types of gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), are important pituitary hormones for sexual maturation and reproduction, and both of them are centrally regulated by gonadotropin-releasing hormone (GnRH) from the hypothalamus. In mammals, these two gonadotropins are secreted from a single type of gonadotrope. The mechanisms of differential regulation by GnRH of the release of two types of gonadotropins with different secretory profiles are still unknown. In teleosts, however, LH and FSH are secreted from separate cellular populations, unlike in mammals. This feature makes them useful for studying the regulatory mechanisms of LH and FSH secretions independently. Here, we generated transgenic medaka lines that express Ca(2+) indicator protein, inverse-pericam, specifically in the LH or FSH cells. We performed cell-type-specific Ca(2+) imaging of LH and FSH cells, respectively, using the whole brain-pituitary preparations of these transgenic fish in which all neural circuits and GnRH neuronal projection to the pituitary are kept intact. LH and FSH cells showed different Ca(2+) responses to GnRH. The results suggest differential regulation mechanisms for LH and FSH release by GnRH. Moreover, we also succeeded in detecting the effect on LH cells of endogenous GnRH peptide, which was released by electrical stimulation of the axons of GnRH1 neurons. Thus, our newly developed experimental model system using the whole brain-pituitary in vitro preparation of the transgenic medaka is a powerful tool for analyzing the differential regulatory mechanisms of the release of LH and FSH by multisynaptic neural inputs to the pituitary.

Expression of progesterone receptor protein in the ovine uterus during the estrous cycle: Effects of nutrition, arginine and FSH.

PubMed

Grazul-Bilska, Anna T; Thammasiri, Jiratti; Kraisoon, Aree; Reyaz, Arshi; Bass, Casie S; Kaminski, Samantha L; Navanukraw, Chainarong; Redmer, Dale A

2018-03-01

To evaluate expression of progesterone receptor (PGR) AB in follicle stimulating hormone (FSH)-treated or non-treated sheep administered with arginine (Arg) or saline (Sal) fed a control (C), excess (O) or restricted (U) diet, uterine tissues were collected at the early, mid and/or late luteal phases. In exp. 1, ewes from each diet were randomly assigned to one of two treatments, Arg or Sal administration three times daily from day 0 of the first estrous cycle until uterine tissue collection. In exp. 2, ewes were injected twice daily with FSH on days 13-15 of the first estrous cycle. Uterine tissues were immunostained to detect PGR followed by image analysis. PGR were detected in luminal epithelium (LE), endometrial glands (EG), endometrial stroma (ES), myometrium (Myo), and endometrial and myometrial blood vessels. The percentage of PR-positive cells and/or intensity of staining were affected by phase of the estrous cycle, plane of nutrition, and/or FSH but not by Arg. In exp. 1, percentage of PGR-positive cells in LE and EG but not in ES and Myo was greater at the early and mid than late luteal phase, was not affected by plane of nutrition, and was similar in LE and EG. Intensity of staining was affected by phase of the estrous cycle and plane of nutrition in LE, EG and Myo, and was the greatest in LE, less in EG, and least in ES and Myo. In exp. 2, percentage of PGR-positive cells in LE, EG, ES and Myo was affected by phase of the estrous cycle, but not by plane of nutrition; was greater at the early than mid luteal phase; and was greatest in LE and EG, less in luminal (superficial) ES and Myo and least in deep ES. Intensity of staining was affected by phase of the estrous cycle and plane of nutrition in all compartments but ES, and was the greatest in LE and luminal EG, less in deep EG, and least in ES and Myo. Comparison of data for FSH (superovulated) and Sal-treated (non-superovulated) ewes demonstrated that FSH affected PR expression in all evaluated

PIVET rFSH dosing algorithms for individualized controlled ovarian stimulation enables optimized pregnancy productivity rates and avoidance of ovarian hyperstimulation syndrome.

PubMed

Yovich, John L; Alsbjerg, Birgit; Conceicao, Jason L; Hinchliffe, Peter M; Keane, Kevin N

2016-01-01

The first PIVET algorithm for individualized recombinant follicle stimulating hormone (rFSH) dosing in in vitro fertilization, reported in 2012, was based on age and antral follicle count grading with adjustments for anti-Müllerian hormone level, body mass index, day-2 FSH, and smoking history. In 2007, it was enabled by the introduction of a metered rFSH pen allowing small dosage increments of ~8.3 IU per click. In 2011, a second rFSH pen was introduced allowing more precise dosages of 12.5 IU per click, and both pens with their individual algorithms have been applied continuously at our clinic. The objective of this observational study was to validate the PIVET algorithms pertaining to the two rFSH pens with the aim of collecting ≤15 oocytes and minimizing the risk of ovarian hyperstimulation syndrome. The data set included 2,822 in vitro fertilization stimulations over a 6-year period until April 2014 applying either of the two individualized dosing algorithms and corresponding pens. The main outcome measures were mean oocytes retrieved and resultant embryos designated for transfer or cryopreservation permitted calculation of oocyte and embryo utilization rates. Ensuing pregnancies were tracked until live births, and live birth productivity rates embracing fresh and frozen transfers were calculated. Overall, the results showed that mean oocyte numbers were 10.0 for all women <40 years with 24% requiring rFSH dosages <150 IU. Applying both specific algorithms in our clinic meant that the starting dose was not altered for 79.1% of patients and for 30.1% of those receiving the very lowest rFSH dosages (≤75 IU). Only 0.3% patients were diagnosed with severe ovarian hyperstimulation syndrome, all deemed avoidable due to definable breaches from the protocols. The live birth productivity rates exceeded 50% for women <35 years and was 33.2% for the group aged 35-39 years. Routine use of both algorithms led to only 11.6% of women generating >15 oocytes

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial

PubMed Central

2012-01-01

Background Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. Methods/Design Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial.

PubMed

van Tilborg, Theodora C; Eijkemans, Marinus J C; Laven, Joop S E; Koks, Carolien A M; de Bruin, Jan Peter; Scheffer, Gabrielle J; van Golde, Ron J T; Fleischer, Kathrin; Hoek, Annemieke; Nap, Annemiek W; Kuchenbecker, Walter K H; Manger, Petra A; Brinkhuis, Egbert A; van Heusden, Arne M; Sluijmer, Alexander V; Verhoeff, Arie; van Hooff, Marcel H A; Friederich, Jaap; Smeenk, Jesper M J; Kwee, Janet; Verhoeve, Harold R; Lambalk, Cornelis B; Helmerhorst, Frans M; van der Veen, Fulco; Mol, Ben Willem J; Torrance, Helen L; Broekmans, Frank J M

2012-09-18

Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the

Studies on the synergistic effect of androgen on the stimulation of progestin secretion by FSH in cultured rat granulosa cells: a search for the mechanism of action.

PubMed

Nimrod, A

1977-09-01

Cultures of granulosa cells from immature hypophysectomized DES-treated rats were unable to maintain progestin production of more than 48 h in medium without hormone supplementation or in the presence of FSH only. Production of progestin (20alpha-dihydroprogesterone, as measured by radioimmunoassay) remained unimpaired in the presence of androstenedione (Ad) and was markedly increased in the presence of both Ad and FSH. The combined treatment with FSH and Ad during the first 48 h of culture brought about persistent changes in the cultured cells, since progestin accumulation did not decline upon subsequent removal of these hormones during days 3 and 4 of culture. Dibutyryl cyclic AMP (DBC) was able to mimic the changes in steroidogenic capability induced by the combined action of FSH and Ad. The extent of [125I]-FSH binding, FSH-stimulable cAMP accumulation and cyclic 3',5'-nucleotide phosphodiesterase activity were not affected by addition of Ad to the culture medium. Ad synergized with DBC in the stimulation of progestin accumulation in granulosa cell cultures. It is suggested that androgen acts at a step in the regulation of progestin biosynthesis distal to cAMP production.

Activin Decoy Receptor ActRIIB:Fc Lowers FSH and Therapeutically Restores Oocyte Yield, Prevents Oocyte Chromosome Misalignments and Spindle Aberrations, and Increases Fertility in Midlife Female SAMP8 Mice.

PubMed

Bernstein, Lori R; Mackenzie, Amelia C L; Lee, Se-Jin; Chaffin, Charles L; Merchenthaler, István

2016-03-01

Women of advanced maternal age (AMA) (age ≥ 35) have increased rates of infertility, miscarriages, and trisomic pregnancies. Collectively these conditions are called "egg infertility." A root cause of egg infertility is increased rates of oocyte aneuploidy with age. AMA women often have elevated endogenous FSH. Female senescence-accelerated mouse-prone-8 (SAMP8) has increased rates of oocyte spindle aberrations, diminished fertility, and rising endogenous FSH with age. We hypothesize that elevated FSH during the oocyte's FSH-responsive growth period is a cause of abnormalities in the meiotic spindle. We report that eggs from SAMP8 mice treated with equine chorionic gonadotropin (eCG) for the period of oocyte growth have increased chromosome and spindle misalignments. Activin is a molecule that raises FSH, and ActRIIB:Fc is an activin decoy receptor that binds and sequesters activin. We report that ActRIIB:Fc treatment of midlife SAMP8 mice for the duration of oocyte growth lowers FSH, prevents egg chromosome and spindle misalignments, and increases litter sizes. AMA patients can also have poor responsiveness to FSH stimulation. We report that although eCG lowers yields of viable oocytes, ActRIIB:Fc increases yields of viable oocytes. ActRIIB:Fc and eCG cotreatment markedly reduces yields of viable oocytes. These data are consistent with the hypothesis that elevated FSH contributes to egg aneuploidy, declining fertility, and poor ovarian response and that ActRIIB:Fc can prevent egg aneuploidy, increase fertility, and improve ovarian response. Future studies will continue to examine whether ActRIIB:Fc works via FSH and/or other pathways and whether ActRIIB:Fc can prevent aneuploidy, increase fertility, and improve stimulation responsiveness in AMA women.

Cullen's sign and massive ovarian enlargement secondary to primary hypothyroidism in a patient with a normal FSH receptor

PubMed Central

Sultan, A; Velaga, M R; Fleet, M; Cheetham, T

2006-01-01

Ovarian hyperstimulation is a recognised complication of longstanding hypothyroidism. A 12 year old girl with atrophic thyroiditis who presented with abdominal pain and distension is reported. She was noted to have bruising in the vicinity of the umbilicus (Cullen's sign). She had pronounced ovarian enlargement on ultrasonography and it was hypothesised that this profound phenotype might reflect an abnormal FSH receptor. However sequencing of the FSH receptor was normal. The ovarian enlargement resolved with thyroxine replacement. Physicians and surgeons should consider longstanding hypothyroidism in patients presenting with Cullen's sign. PMID:16714722

Cost effectiveness of letrozole and purified urinary FSH in treating women with clomiphene citrate-resistant polycystic ovarian syndrome: a randomized controlled trial.

PubMed

Hassan, AbdelGany; Shehata, Nesreen; Wahba, Amr

2017-04-01

We aimed to compare the cost effectiveness of letrozole versus purified urinary follicle stimulating hormone (FSH) in treating patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). This was a randomized trial conducted in Cairo University and Beni-Suef University Hospitals, Egypt. A cohort of 140 eligible women was randomized to receive either letrozole 2.5 mg twice daily for five days, or FSH using a graduated regimen starting with a dose of 75 IU. Treatment was repeated for three months if pregnancy did not occur. There were no significant differences between the two treatments in the cumulative clinical pregnancy rate (30% vs. 34%; p = 0.578), cumulative ovulation rate (47% vs. 57%; p = 0.236), miscarriage rate (9% vs. 4%, p > 0.999) or multiple pregnancy rate (0% and 8%, p = 0.491) but the FSH cycles were 4.8 times more expensive. Letrozole and FSH were both effective in treating women with CC-resistant PCOS but letrozole was more cost effective.Study registration number: NCT02304107.

Effects of eCG and FSH on ovarian response, recovery rate and number and quality of oocytes obtained by ovum pick-up in Holstein cows.

PubMed

Sendag, Sait; Cetin, Yunus; Alan, Muhammet; Hadeler, Klaus-Gerd; Niemann, Heiner

2008-06-01

The goal of the present study was to compare the ovarian response, oocyte yields per animal, and the morphological quality of oocytes collected by ultrasound guided follicular aspiration from Holstein cows treated either with FSH or eCG. Twenty four normal cyclic, German Holstein cows were randomly divided into two groups. Fourteen cows received 3000 IU eCG on day-4 prior to ovum pick-up (OPU) (day 0), 2 days later (day-2), 625 microg cloprostenol was administered. On day-1 GnRH was administered i.m. and 24h later OPU (day 0) was performed. In ten cows a total dose of 500 IU follicle stimulating hormone (Pluset) was administered intramuscularly in a constant dosage for 4 days with intervals of 12h, starting on day-5. Luteolysis was induced by application of 625 microg cloprostenol on day-2. On day-1 (24h after the last FSH treatment) GnRH was administered i.m. and 24h later OPU (day 0) was performed. Ovarian follicles were visualized on the ultrasound monitor, counted and recorded. All visible antral follicles were punctured. Recovered oocytes were graded morphologically based on the cumulus investment. Average follicle number in ovaries was higher in FSH group than eCG group (p<0.05). Oocyte yields per animal did not differ between FSH and eCG groups. The proportion of grade A oocytes was higher in the FSH group in the than eCG group (p<0.05). Likewise, rate of grade C oocytes in FSH group were lower than eCG group (p<0.05). In conclusion, these results suggest that ovarian response, follicle number in ovaries and oocyte quality are affected by the type of gonadotropin and FSH is better alternative than eCG for OPU treatment.

Comparison of ovulation induction and pregnacy outcomes in IVF patients with normal ovarian reserve who underwent long protocol with recombinant-FSH and highly purified-hMG.

PubMed

Celik, Cem; Sofuoğlu, Kenan; Selçuk, Selçuk; Asoğlu, Mehmet Reşit; Abalı, Remzi; Cetingöz, Elçin; Baykal, Bahar; Uludoğan, Mehmet

2011-01-01

Gonadotropins used in controlled ovarian stimulation have been increasing in number. Beside the recombinant preparations such as rec-FSH, rec-LH and h-hMG human-derived preparations have entered the market. We decided to compare the effects of rec-FSH and HP-hMG with GnRHa on embryo quality and pregnancy outcome in women undergoing an IVF cycle. In this study, data of 87 patients who had applied to our center from 2007 to 2008 and who had met all inclusion criteria, were analyzed. The patients underwent controlled ovarian hyperstimulation with HP-hMG, rec-FSH following down-regulation with a GnRHa in a long protocol, selected according to determined criteria and acquired embryo via IVF transfer. Of the 87 patients, 44 were stimulated with rec-FSH and 43 with HP-hMG. Distribution of infertility causes was similar between the groups. Duration of gonadotropin administration (p=0.677, Student's t-test) and the total dose of gonadotropin received (p=0.392, Student's t-test) were similar between the two groups. The fertilization rate of the rec-FSH group was significantly higher than the HP-hMG group (p=0.001, Mann-Whitney U test). No significant differences were observed between the study groups in biochemical, clinical and ongoing pregnancy parameters. The higher oocyte yield with rec-FSH does not result in higher quality embryos. LH activity in combination with FSH activity positively affected the oocyte and embryo maturation. Therefore, when we consider the clinical and ongoing pregnancy rates there is no inferiority of HP-hMG in controlled ovarian stimulation.

Comparison of ovulation induction and pregnacy outcomes in IVF patients with normal ovarian reserve who underwent long protocol with recombinant-FSH and highly purified-hMG

PubMed Central

Çelik, Cem; Sofuoğlu, Kenan; Selçuk, Selçuk; Asoğlu, Mehmet Reşit; Abalı, Remzi; Çetingöz, Elçin; Baykal, Bahar; Uludoğan, Mehmet

2011-01-01

Objective Gonadotropins used in controlled ovarian stimulation have been increasing in number. Beside the recombinant preparations such as rec-FSH, rec-LH and h-hMG human-derived preparations have entered the market. We decided to compare the effects of rec-FSH and HP-hMG with GnRHa on embryo quality and pregnancy outcome in women undergoing an IVF cycle. Material and Methods In this study, data of 87 patients who had applied to our center from 2007 to 2008 and who had met all inclusion criteria, were analyzed. The patients underwent controlled ovarian hyperstimulation with HP-hMG, rec-FSH following down-regulation with a GnRHa in a long protocol, selected according to determined criteria and acquired embryo via IVF transfer. Results Of the 87 patients, 44 were stimulated with rec-FSH and 43 with HP-hMG. Distribution of infertility causes was similar between the groups. Duration of gonadotropin administration (p=0.677, Student’s t-test) and the total dose of gonadotropin received (p=0.392, Student’s t-test) were similar between the two groups. The fertilization rate of the rec-FSH group was significantly higher than the HP-hMG group (p=0.001, Mann-Whitney U test). No significant differences were observed between the study groups in biochemical, clinical and ongoing pregnancy parameters. Conclusion The higher oocyte yield with rec-FSH does not result in higher quality embryos. LH activity in combination with FSH activity positively affected the oocyte and embryo maturation. Therefore, when we consider the clinical and ongoing pregnancy rates there is no inferiority of HP-hMG in controlled ovarian stimulation. PMID:24591951

Atrazine enhances progesterone production through activation of multiple signaling pathways in FSH-stimulated rat granulosa cells: evidence for premature luteinization.

PubMed

Pogrmic-Majkic, Kristina; Samardzija, Dragana; Fa, Svetlana; Hrubik, Jelena; Glisic, Branka; Kaisarevic, Sonja; Andric, Nebojsa

2014-11-01

Premature luteinization is a possible cause of infertility in women. It is currently unknown whether environmental chemicals can induce changes associated with premature luteinization. Using rat granulosa cells (GC) in vitro, we demonstrated that exposure to atrazine (ATR), a widely used herbicide, causes GC phenotype that resembles that of human premature luteinization. At the end of the 48-h stimulation with FSH, ATR-exposed GC showed (1) higher levels of progesterone, (2) overexpression of luteal markers (Star and Cyp11a1), and (3) an increase in progesterone:estradiol ratio above 1. Mechanistic experiments were conducted to understand the signaling events engaged by ATR that lead to this phenotype. Western blot analysis revealed prolonged phosphorylation of protein kinase B (AKT) and cAMP response element-binding protein (CREB) in ATR- and FSH-exposed GC. An increased level of ERK1/2-dependent transcriptional factor CCATT/enhancer-binding protein beta (CEBPB) was observed after 4 h of ATR exposure. Inhibitors of PI3K (wortmannin) and MEK (U0126) prevented ATR-induced rise in progesterone level and expression of luteal markers in FSH-stimulated GC. Atrazine intensified AKT and CEBPB signaling and caused Star overexpression in forskolin-stimulated GC but not in epidermal growth factor (EGF)-stimulated GC. In the presence of rolipram, a specific inhibitor of phosphodiesterase 4 (PDE4), ATR was not able to further elevate AKT phosphorylation, CEBPB protein level, and Star mRNA in FSH-stimulated GC, suggesting that ATR inhibits PDE4. Overall, this study showed that ATR acts as a FSH sensitizer leading to enhanced cAMP, AKT, and CEBPB signaling and progesterone biosynthesis, which promotes premature luteinization phenotype in GC. © 2014 by the Society for the Study of Reproduction, Inc.

Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study.

PubMed

Homburg, R; Hendriks, M L; König, T E; Anderson, R A; Balen, A H; Brincat, M; Child, T; Davies, M; D'Hooghe, T; Martinez, A; Rajkhowa, M; Rueda-Saenz, R; Hompes, P; Lambalk, C B

2012-02-01

Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the hypothesis that pregnancy rate (PR) and live birth rates (LBR) are higher after OI with low-dose FSH than with CC as first-line treatment. Infertile women (<40 years old) with PCOS-related anovulation, without prior OI treatment, attending 10 centres in Europe/South America were randomized to OI with either CC (50-150 mg/day for 5 days) or FSH (starting dose 50 IU) for up to three treatment cycles. The primary outcome was clinical PR. Patients (n = 302) were randomized to OI with FSH (n = 132 women; 288 cycles) or CC (n = 123; 310 cycles). Per protocol analysis revealed that reproductive outcome was superior after OI with FSH than with CC with respect to PR per first cycle [30 versus 14.6%, respectively, 95% confidence interval (CI) 5.3-25.8, P = 0.003], PR per woman, (58 versus 44% of women, 95% CI 1.5-25.8, P = 0.03), LBR per woman (52 versus 39%, 95% CI 0.4-24.6, P = 0.04), cumulative PR (52.1 versus 41.2%, P = 0.021) and cumulative LBR (47.4 versus 36.9%, P = 0.031), within three cycles of OI. Pregnancies and live births are achieved more effectively and faster after OI with low-dose FSH than with CC. This result has to be balanced by convenience and cost in favour of CC. FSH may be an appropriate first-line treatment for some women with PCOS and anovulatory infertility, particularly older patients.

In vitro growth and maturation of isolated caprine preantral follicles: Influence of insulin and FSH concentration, culture dish, coculture, and oocyte size on meiotic resumption.

PubMed

Silva, G M; Brito, I R; Sales, A D; Aguiar, F L N; Duarte, A B G; Araújo, V R; Vieira, L A; Magalhães-Padilha, D M; Lima, L F; Alves, B G; Silveira, L B R; Lo Turco, E G; Rodrigues, A P; Campello, C C; Wheeler, M B; Figueiredo, J R

2017-03-01

The aims of this study were: (1) to evaluate the effect of different insulin concentrations, alone or in combination with either a fixed FSH concentration or increasing FSH concentrations on the in vitro culture of isolated caprine preantral follicles and (2) to analyze the efficiency of two IVM media and maturation culture systems (with or without coculture with in vivo grown oocytes) on the meiosis resumption. Secondary follicles were cultured for 18 days in a basic medium supplemented with low- or high-insulin concentration alone or with a fixed FSH concentration or with increasing FSH concentrations. Oocytes grown in vivo or in vitro were matured alone or cocultured. The high-insulin concentration associated with fixed FSH treatment had higher meiotic resumption rate (P < 0.05) and was the only treatment capable of producing oocytes in metaphase II. The rates of germinal vesicle, germinal vesicle breakdown, metaphase I, metaphase II (MII), meiotic resumption, and oocyte diameter were similar between the maturation media. In conclusion, a basic medium supplemented with 10-μg/mL insulin and 100-μg/mL FSH throughout the culture period improved meiotic resumption rate and produced MII oocytes from caprine preantral follicles cultured in vitro. The MII rate was similar between in vivo and in vitro grown oocytes ≥110 μm. Copyright © 2016 Elsevier Inc. All rights reserved.

High FSH decreases the developmental potential of mouse oocytes and resulting fertilized embryos, but does not influence offspring physiology and behavior in vitro or in vivo.

PubMed

Li, Min; Zhao, Yue; Zhao, Cui H; Yan, Jie; Yan, Ying L; Rong, Li; Liu, Ping; Feng, Huai-Liang; Yu, Yang; Qiao, Jie

2013-05-01

Do different concentrations of FSH in the assisted reproductive technology (ART) procedure in vitro or in vivo affect the developmental competence of oocytes, the embryos and the offspring conceived from these embryos? Improper FSH treatment (200 IU/l in vitro, 10 IU/ml in vivo and 200 IU/ml in vivo) impairs the development competence of oocyte and embryo, but does not influence offspring physiology and behavior. Exogenous FSH has been widely used in the field of ART. However, the effects of different concentrations of FSH on the developmental competence of oocytes, embryos and the offspring conceived from these embryos, are still unknown. In a prospective study, a total of 45 mice at 8-10 weeks of age were primed in vivo with different dosages of FSH (9 mice in the 10 IU/ml, 10 mice in the 50 IU/ml, 10 mice in the 100 IU/ml and 16 mice in the 200 IU/ml groups). Fresh MII oocytes were retrieved from ovaries: this was designated as in vivo group. Thirty six mice at 8-10 weeks of age were sacrificed by cervical dislocation to obtain ovaries without FSH treatment (9 mice in the 0 IU/l, 9 mice in the 50 IU/l, 8 mice in the 100 IU/l and 10 mice in the 200 IU/l groups), and then the immature oocytes were collected from these ovaries and cultured in vitro matured medium supplemented with 0, 50, 100 and 200 IU/l FSH: this was designated as in vitro group. Spindle assembly of matured MII oocytes was stained via an immunofluorescence method and the oocytes ratio of normal spindle was analyzed. The developmental competence of the resulting fertilized embryos in the pre- and post-implantation stages was examined in in vitro and in vivo groups. Furthermore, physiological index, including reproductive potential and body weight, of the offspring was investigated by mating experiments and behavior index, including learning, memory, probing and intelligence, was tested by Morris water maze in in vitro and in vivo groups. In the in vitro groups, the oocyte maturation competence

The long-term effects of FSH and triiodothyronine administration during the pubertal period on Connexin 43 expression and spermatogenesis efficiency in adult rats.

PubMed

Marchlewska, Katarzyna; Slowikowska-Hilczer, Jolanta; Walczak-Jedrzejowska, Renata; Oszukowska, Elzbieta; Filipiak, Eliza; Kula, Krzysztof

2015-04-01

Follicle-stimulating hormone (FSH) and triiodothyronine (T3) are known regulatory factors of spermatogenesis initiation. Hyperstimulation of both hormones evokes regressional changes in connexin 43 expression and the seminiferous epithelium in young rats during testicular maturation. However, separate treatments with T3 reduce Sertoli cell number, which seems to be closely connected with the maturation of connexin 43 gap junctions. FSH elevates Sertoli cell number and function, but this effect may take place regardless of the presence of connexin 43-dependent intercellular communication. The aim of the study was to evaluate the later effects of such treatments. Newborn, male Wistar rats were divided randomly into experimental groups receiving daily subcutaneous injections of either 7.5 IU/animal FSH, or 100 mg/kg b.w. T3, or both substances or the same volume of vehicle (control group) until day 15 of life. The animals were sacrificed on day 50. Morphometric analysis and immunohistochemical reactions were performed using antibodies against Vimentin, Proliferating Cell Nuclear Antigen and Connexin 43 in the testis. Sertoli cell count, efficiency of spermatogenesis, and hormonal pattern were examined. Disturbances in the connexin 43 expression reduced the number of Sertoli cells, the efficiency of spermatogenesis and impaired endocrine function of testes in adult rats treated with FSH and T3 during puberty. Stimulation with FSH alone increased Sertoli cell number, but was associated with a negative effect on cell-to-cell connexin 43-dependent communication, with a consequential reduction of spermatogenesis efficiency. J. Exp. Zool. 323A: 256-265, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Central hypogonadism due to a giant, "silent" FSH-secreting, atypical pituitary adenoma: effects of adenoma dissection and short-term Leydig cell stimulation by luteinizing hormone (LH) and human chorionic gonadotropin (hCG).

PubMed

Santi, Daniele; Spaggiari, Giorgia; Casarini, Livio; Fanelli, Flaminia; Mezzullo, Marco; Pagotto, Uberto; Granata, Antonio R M; Carani, Cesare; Simoni, Manuela

2017-06-01

We present a case report of an atypical giant pituitary adenoma secreting follicle-stimulating hormone (FSH). A 55-year-old patient presented for erectile dysfunction, loss of libido and fatigue. The biochemical evaluation showed very high FSH serum levels in the presence of central hypogonadism. Neither testicular enlargement nor increased sperm count was observed, thus a secretion of FSH with reduced biological activity was supposed. The histological examination after neuro-surgery showed an atypical pituitary adenoma with FSH-positive cells. Hypogonadism persisted and semen analyses impaired until azoospermia in conjunction with the reduction in FSH levels suggesting that, at least in part, this gonadotropin should be biologically active. Thus, we hypothesized a concomitant primary testicular insufficiency. The patient underwent short-term treatment trials with low doses of either recombinant luteinizing hormone (LH) or human chorionic gonadotropin (hCG) in three consecutive treatment schemes, showing an equal efficacy in stimulating testosterone (T) increase. This is the first case of atypical, giant FSH-secreting pituitary adenoma with high FSH serum levels without signs of testicular hyperstimulation, in presence of hypogonadism with plausible combined primary and secondary etiology. Hypophysectomized patients may represent a good model to assess both pharmacodynamics and effective dose of LH and hCG in the male.

Highly purified hMG versus recombinant FSH plus recombinant LH in intrauterine insemination cycles in women ≥35 years: a RCT.

PubMed

Moro, Francesca; Scarinci, Elisa; Palla, Carola; Romani, Federica; Familiari, Alessandra; Tropea, Anna; Leoncini, Emanuele; Lanzone, Antonio; Apa, Rosanna

2015-01-01

Is the treatment with recombinant FSH (rFSH) plus recombinant LH (rLH) more effective than highly purified (HP)-hMG in terms of ongoing pregnancy rate (PR) in women ≥35 years of age undergoing intrauterine insemination (IUI) cycles? The ongoing PR was not significantly different in women treated with rFSH plus rLH or with HP-hMG. Although previous studies have shown beneficial effects of the addition of LH activity to FSH, in terms of PR in patients aged over 34 years having ovulation induction, no studies have compared two different gonadotrophin preparations containing LH activity in women ≥35 years of age in IUI cycles. A single-centre RCT was performed between May 2012 and September 2013 with 579 women ≥35 years of age undergoing IUI cycles. The patients were randomly assigned to one of the two groups, rFSH in combination with rLH group or HP-hMG (Meropur) group, by giving them a code number from a computer generated randomization list, in order of enrolment. The randomization visit took place on the first day of ovarian stimulation. Five hundred and seventy-nine patients with unexplained infertility or mild male factor undergoing IUI cycles were recruited in a university hospital setting. All women were enrolled in this study only for one cycle of treatment. Five hundred and seventy-nine cycles were included in the final analysis. Two hundred and ninety patients were treated with rFSH in combination with rLH and 289 patients were treated with HP-hMG. The ovarian stimulation cycle started on the third day of the menstrual cycle and the starting gonadotrophin doses used were 150 IU/day of rFSH plus 150 IU/day of rLH or 150 IU/day of HP-hMG. The drug dose was adjusted according to the individual follicular response. A single IUI per cycle was performed 34-36 h after hCG injection. The main outcome measures were ongoing PR and number of interrupted cycles for high risk of ovarian hyperstimulation syndrome (OHSS). Ongoing pregnancy rates were 48/290 (17

Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 2: The predicted hyper responder.

PubMed

Oudshoorn, Simone C; van Tilborg, Theodora C; Eijkemans, Marinus J C; Oosterhuis, G Jur E; Friederich, Jaap; van Hooff, Marcel H A; van Santbrink, Evert J P; Brinkhuis, Egbert A; Smeenk, Jesper M J; Kwee, Janet; de Koning, Corry H; Groen, Henk; Lambalk, Cornelis B; Mol, Ben Willem J; Broekmans, Frank J M; Torrance, Helen L

2017-12-01

Does a reduced FSH dose in women with a predicted hyper response, apparent from a high antral follicle count (AFC), who are scheduled for IVF/ICSI lead to a different outcome with respect to cumulative live birth rate and safety? Although in women with a predicted hyper response (AFC > 15) undergoing IVF/ICSI a reduced FSH dose (100 IU per day) results in similar cumulative live birth rates and a lower occurrence of any grade of ovarian hyperstimulation syndrome (OHSS) as compared to a standard dose (150 IU/day), a higher first cycle cancellation rate and similar severe OHSS rate were observed. Excessive ovarian response to controlled ovarian stimulation (COS) for IVF/ICSI may result in increased rates of cycle cancellation, the occurrence of OHSS and suboptimal live birth rates. In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can be used to predict response to COS. No consensus has been reached on whether ORT-based FSH dosing improves effectiveness and safety in women with a predicted hyper response. Between May 2011 and May 2014, we performed an open-label, multicentre RCT in women with regular menstrual cycles and an AFC > 15. Women with polycystic ovary syndrome (Rotterdam criteria) were excluded. The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. Secondary outcomes included the occurrence of OHSS and cost-effectiveness. Since this RCT was embedded in a cohort study assessing over 1500 women, we expected to randomize 300 predicted hyper responders. Women with an AFC > 15 were randomized to an FSH dose of 100 IU or 150 IU/day. In both groups, dose adjustment was allowed in subsequent cycles (maximum 25 IU in the reduced and 50 IU in the standard group) based on pre-specified criteria. Both effectiveness and cost-effectiveness were evaluated from an intention-to-treat perspective. We randomized 255 women to a daily FSH dose of 100 IU and 266 women to a daily FSH dose of 150 IU. The

Pretreatment and co-administration of oral anti-diabetic agent with clomiphene citrate or rFSH for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome.

PubMed

Begum, Mosammat Rashida; Akhter, Sayeba; Ehsan, Mariya; Begum, Mosammat Shahina; Khan, Farzana

2013-05-01

The objective of this study was to explore the result of pretreatment and concomitant use of metformin with clomiphene citrate (CC) and rFSH for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome (PCOS). This randomized controlled trial was done in the Dhaka Medical College and Hospital and the Infertility Care and Research Centre, Dhaka, Bangladesh. A total of 165 infertile patients with CC-resistant PCOS who attended for treatment were the target population for this study. Patients were divided into three groups: groups A and B were given metformin and group C was the control. Along with metformin, group A received CC and group B received rFSH. Group C was treated with only rFSH. Metformin was given 1500 mg daily for 4 weeks. Afterwards CC or rFSH were added for induction of ovulation along with metformin. Six ovulatory cycles were assessed. Treatment was terminated when there was no response with maximum dose of CC and rFSH or after six ovulatory cycles without pregnancy or after achieving pregnancy. A P-value of <0.5 was considered as significant. Ovulation (89.09%) and pregnancy (54.55%) rates were higher in group B. Ovulation (74.55%) and pregnancy (29.09%) rates were also satisfactory in group C but a dose of rFSH requirement was significantly higher (P = 0.000). In group A, both ovulation and pregnancy rate were much lower than the other two groups (27.27% and 12.73%, respectively). Use of metformin increases the response of ovulation-inducing agents and can be used safely in PCOS. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

Evaluating the role of the FSH receptor gene Thr307-Ala and Asn680-Ser polymorphisms in male infertility and their association with semen quality and reproductive hormones.

PubMed

Safarinejad, Mohammad Reza; Shafiei, Nayyer; Safarinejad, Saba

2011-07-01

To determine whether Thr(307)-Asn(680) and Ala(307)-Ser(680) polymorphisms of the follicle-stimulating hormone receptor (FSH-R) gene are associated with male infertility, semen quality, and reproductive hormones. The FSH-R polymorphisms at codons 680 and 307 were analysed by restriction-fragment-length polymorphism (RFLP) in 172 infertile men and in an equal number of age-matched healthy fertile men. Genotyping of the FSH-R gene was performed using the polymerase chain reaction RFLP technique. All of the participants underwent semen analysis, and reproductive hormones were also measured. Allelic frequencies were 29.7% serine (Ser) and 70.3% asparagine (Asn) for fertile men (the control group), and 33.1% Ser and 66.9% Asn for infertile men (P > 0.05). The FSH-R genotype at position 680 was 49.4% (Asn/Asn), 41.9% (Asn/Ser), and 8.7% (Ser/Ser) in the control group and 40.1% (Asn/Asn), 46.5% (Asn/Ser), and 13.4% (Ser/Ser) in infertile men, respectively (P > 0.05, chi-squared test). Allelic frequencies were 33.1% alanine (Ala) and 66.9% threonine (Thr) for the control group, and 37.8% Ala and 62.2% Thr for the infertile men. The frequencies of genotypes at position 307 were 45.5% Thr/Thr, 43% Thr/Ala, and 11.6% Ala/Ala for the control group and 36.1% Thr/Thr, 52.3% Thr/Ala, and 11.6% Ala/Ala for infertile men. No significant association between codon 680 and codon 307 genotypes and infertility was observed (P = 0.076 and P = 0.073, respectively). The odds ratio (OR) values indicated that individuals with the Thr/Thr + Asn/Ser combined genotypes had a > 50% decreased risk for developing infertility (OR = 0.44; 95% confidence interval [CI]: 0.22-0.77; P = 0.006). The patients with heterozygous Thr/Ala + Asn/Ser combined genotype were 2.65 times more susceptible to infertility than the control group (OR = 2.65; 95% CI: 1.74-3.82; P = 0.0053). The FSH-R codon 680 and codon 307 genotypes did not result in different serum FSH levels either in men with normal spermatogenesis

A randomized controlled trial investigating the use of a predictive nomogram for the selection of the FSH starting dose in IVF/ICSI cycles.

PubMed

Allegra, Adolfo; Marino, Angelo; Volpes, Aldo; Coffaro, Francesco; Scaglione, Piero; Gullo, Salvatore; La Marca, Antonio

2017-04-01

The number of oocytes retrieved is a relevant intermediate outcome in women undergoing IVF/intracytoplasmic sperm injection (ICSI). This trial compared the efficiency of the selection of the FSH starting dose according to a nomogram based on multiple biomarkers (age, day 3 FSH, anti-Müllerian hormone) versus an age-based strategy. The primary outcome measure was the proportion of women with an optimal number of retrieved oocytes defined as 8-14. At their first IVF/ICSI cycle, 191 patients underwent a long gonadotrophin-releasing hormone agonist protocol and were randomized to receive a starting dose of recombinant (human) FSH, based on their age (150 IU if ≤35 years, 225 IU if >35 years) or based on the nomogram. Optimal response was observed in 58/92 patients (63%) in the nomogram group and in 42/99 (42%) in the control group (+21%, 95% CI = 0.07 to 0.35, P = 0.0037). No significant differences were found in the clinical pregnancy rate or the number of embryos cryopreserved per patient. The study showed that the FSH starting dose selected according to ovarian reserve is associated with an increase in the proportion of patients with an optimal response: large trials are recommended to investigate any possible effect on the live-birth rate. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

HMG versus rFSH for ovulation induction in developing countries: a cost-effectiveness analysis based on the results of a recent meta-analysis.

PubMed

Al-Inany, Hesham G; Abou-Setta, Ahmed M; Aboulghar, Mohamed A; Mansour, Ragaa T; Serour, Gamal I

2006-02-01

Both cost and effectiveness should be considered conjointly to aid judgments about drug choice. Therefore, based on the results of a recent published meta-analysis, a Markov model was developed to conduct a cost-effectiveness analysis for estimation of the cost of an ongoing pregnancy in IVF/intracytoplasmic sperm injection (ICSI) cycles. In addition, Monte Carlo micro-simulation was used to examine the potential impact of assumptions and other uncertainties represented in the model. The results of the study reveal that the estimated average cost of an ongoing pregnancy is 13,946 Egyptian pounds (EGP), and 18,721 EGP for a human menopausal gonadotrophin (HMG) and rFSH cycle respectively. On performing a sensitivity analysis on cycle costs, it was demonstrated that the rFSH price should be 0.61 EGP/IU to be as cost-effective as HMG at the price of 0.64 EGP/IU (i.e. around 60% reduction in its current price). The difference in cost between HMG and rFSH in over 100,000 cycles would result in an additional 4565 ongoing pregnancies if HMG was used. Therefore, HMG was clearly more cost-effective than rFSH. The decision to adopt a more expensive, cost-ineffective treatment could result in a lower number of cycles of IVF/ICSI treatment undertaken, especially in the case of most developing countries.

Genetic variations altering FSH action affect circulating hormone levels as well as follicle growth in healthy peripubertal girls.

PubMed

Busch, Alexander S; Hagen, Casper P; Almstrup, Kristian; Main, Katharina M; Juul, Anders

2016-04-01

Do variants of the genes encoding follicle stimulating hormone (FSH) beta subunit (B) and FSH receptor (R) impact circulating reproductive hormone levels and ovarian follicle maturation in healthy peripubertal girls? FSHB and FSHR genetic variants exert, alone or their combination, distinct effects on reproductive hormone levels as well as ovarian follicle maturation in healthy peripubertal girls. FSHB and FSHR genetic variants impact reproductive hormone levels as well as associated pathologies in women. While FSHR c. 2039A>G is known to alter gonadotrophin levels in women, FSHR c.-29G>A has not yet been shown to exert effect and there are conflicting results concerning FSHB c.-211G>T. This population-based study included 633 girls recruited as part of two cohorts, the COPENHAGEN Puberty Study (2006-2014, a cross-sectional and ongoing longitudinal study) and the Copenhagen Mother-Child Cohort (1997-2002, including transabdominal ultrasound (TAUS) of the ovaries in a subset of 91 peripubertal girls). Clinical examinations, including pubertal breast stage (Tanner's classification B1-B5) were performed. Circulating levels of FSH, luteinizing hormone (LH), estradiol, anti-Mullerian hormone (AMH) and inhibin-B were assessed by immunoassays. In a subset of the girls (n = 91), ovarian volume and the number/size of antral follicles were assessed by TAUS. Genotypes were determined by competitive PCR. FSHR c.2039A>G minor alleles were positively associated with serum FSH (β = 0.08, P = 0.004), LH (β = 0.06, P = 0.012) and estradiol (β = 0.06, P = 0.017) (adjusted for Tanner stages). In a combined model, FSHR c.-29G>A and FSHR c.2039A>G alleles were positively associated with FSH levels in early-pubertal girls (B2 + B3, n = 327, r = 0.1, P = 0.02) and in young adolescents (B4 + B5, n = 149, r = 0.2, P = 0.01). Serum AMH and inhibin B levels were not significantly influenced by the single nucleotide polymorphisms (SNPs). Single SNPs were not associated with follicles

Serum LH and FSH Responses to Synthetic LH-RH in Normal Infants, Children and Patients With Turner's Syndrome

ERIC Educational Resources Information Center

Suwa, Seizo; And Others

1974-01-01

Effects of luteinizing hormone-releasing hormone (LH-RH) on LH and follicle-stimulating hormone (FSH) release were studied in 26 normal children and six patients (from 1-to 14-years-old) with Turner's syndrome. (Author)

Studies on the synergistic effect of androgen on the stimulation of progestin secretion by FSH in cultured rat granulosa cells: progesterone metabolism and the effect of androgens.

PubMed

Nimrod, A

1977-09-01

Metabolic transformations of progesterone in cultures of granulosa cells from immature hypophysectomized rats treated with diethylstilbestrol were studied in relation to the synergistic action of exogenous androgen and FSH on progestin (progesterone and 20alpha-dihydroprogesterone) accumulation. Androstenedione (Ad; 10 ng/ml) enhanced the sensitivity of rat granulosa cells to this steroidogenic action of FSH, lowering the threshold of the response from greater than 4 ng/ml (FSH alone) to 0.8 ng/ml in the presence of Ad. A synergistic effect with FSH was also shown by various 5alpha-androstane derivatives. They were, however, less effective than the parent delta4-3 keto androstenes. Progesterone underwent extensive 5alpha-reduction during culture, leading to accumulation of endogenous 5alpha-pregnane compounds, and to transformation of labelled progesterone into 5 alpha-reduced radiometabolites. These compounds corresponded in gas-liquid and thin-layer chromatographic behaviour to 3alpha-hydroxy-5alpha-pregnan-20-one, 20alpha-hydroxy-5alpha-pregnan-3-one and 5alpha-pregnane-3alpha,20alpha-diol. The rate of 5alpha-reduction of progestins was not affected by the presence of exogenous Ad (1 microgram/ml), ruling out the possibility that the effect of androgen on progestin accumulation depends on competitive inhibition of 5alpha-reductase. An involvement of androgen of thecal origin in the enhancement of the sensitivity of the FSH-responsive mechanism in granulosa cells is suggested.

Hyperthyroidism secondary to a pituitary adenoma secreting TSH, FSH, alpha-subunit and GH.

PubMed

Patrick, A W; Atkin, S L; MacKenzie, J; Foy, P M; White, M C; MacFarlane, I A

1994-02-01

A 51-year-old man had been treated for hyperthyroidism with antithyroid drugs for 8 years. He was then found to have a large pituitary adenoma with biochemical evidence of overproduction of TSH, FSH and alpha-subunit. Subsequent immunocytochemical and tissue culture studies confirmed secretion of these hormones. In addition, the tumour stained for GH and was capable of GH production in vitro. This combination of hormones produced by a pituitary adenoma has not been previously reported.

True and sham acupuncture produced similar frequency of ovulation and improved LH to FSH ratios in women with polycystic ovary syndrome.

PubMed

Pastore, Lisa M; Williams, Christopher D; Jenkins, Jeffrey; Patrie, James T

2011-10-01

Acupuncture may represent a nonpharmaceutical treatment for women with polycystic ovary syndrome (PCOS), based on four studies. The objective of the study was to determine whether true, as compared with sham, acupuncture normalizes pituitary gonadotropin hormones and increases ovulatory frequency in women with PCOS. This was a randomized, double-blind, sham-controlled clinical trial (5 month protocol). The study was conducted in central Virginia. Eighty-four reproductive-aged women completed the intervention. Eligibility required a PCOS diagnosis and no hormonal intervention 60 d before enrollment. Intervention included 12 sessions of true or sham acupuncture (Park sham device) for 8 wk. Serum LH and FSH at baseline, after intervention, and 3 months later were measured. Ovulation was measured with weekly urine or blood samples. Both arms demonstrated a similar mean ovulation rate over the 5 months (0.37/month among n = 40 true acupuncture and 0.40/month among n = 44 sham participants, P = 0.6), similar LH to FSH ratio improvement (-0.5 and -0.8 true and sham, respectively, P < 0.04 after intervention vs. baseline) and a similar decline in LH over the 5-month protocol (P < 0.05). Neither arm experienced a change in FSH. There were seven pregnancies (no difference by intervention, P = 0.7). Lower fasting insulin and free testosterone were highly correlated with a higher ovulation rate within the true acupuncture group only (P = 0.03), controlling for prestudy menstrual frequency and body mass index. We were unable to discern a difference between the true and sham acupuncture protocols for these women with PCOS, and both groups had a similar improvement in their LH/FSH ratio.

Hormonal therapy (hCG and rhFSH) for infertile men with adult-onset idiopathic hypogonadotropic hypogonadism.

PubMed

Kobori, Yoshitomo; Suzuki, Keisuke; Iwahata, Toshiyuki; Shin, Takeshi; Sato, Ryo; Nishio, Kojiro; Yagi, Hiroshi; Arai, Gaku; Soh, Shigehiro; Okada, Hiroshi

2015-04-01

Adult-onset idiopathic male hypogonadotropic hypogonadism (IMHH) is a very rare but treatable disease. This study was conducted to examine the efficacy and safety of a combination of human chorionic gonadotropin (hCG) and recombinant human follicle-stimulating hormone (rhFSH) for inducing spermatogenesis in men with adult-onset IMHH. Seven men (34-45 years of age) with azoospermia and/or sexual dysfunction, with a low serum testosterone concentration, and apulsatile secretion of luteinizing hormone, were referred to our hospital for infertility. All had normal secondary sexual characteristics. Thorough endocrinologic examination and magnetic resonance imaging revealed no identifiable cause of hypogonadotropic hypogonadism. Adult-onset IMHH was diagnosed in all cases and treatment was started with 150 IU rhFSH and 5,000 IU hCG, both administered two times per week. Spermatogenesis was restored in five of the seven patients. During treatment one patient achieved spontaneous pregnancy with his wife, and spermatozoa recovered from the other four patients were frozen for future use in intracytoplasmic sperm injection.

The effects of levonorgestrel on FSH-stimulated primary rat granulosa cell cultures through gene expression profiling are associated to hormone and folliculogenesis processes.

PubMed

Lira-Albarrán, Saúl; Larrea-Schiavon, Marco F; González, Leticia; Durand, Marta; Rangel, Claudia; Larrea, Fernando

2017-01-05

Levonorgestrel (LNG), a synthetic progestin, is used in emergency contraception (EC). The mechanism is preventing or delaying ovulation at the level of the hypothalamic pituitary unit; however, little knowledge exists on LNG effects at the ovary. The aim of this study was to identify the effects of LNG on FSH-induced 17β-estradiol (E 2 ) production, including LNG-mediated changes on global gene expression in rat granulosa cells (GC). Isolated GC from female Wistar rats were incubated in vitro in the presence or absence of human FSH and progestins. At the end of incubations, culture media and cells were collected for E 2 and mRNA quantitation. The results showed the ability of LNG to inhibit both hFSH-induced E 2 production and aromatase gene expression. Microarray analysis revealed that LNG treatment affects GC functionality particularly that related to folliculogenesis and steroid metabolism. These results may offer additional evidence for the mechanisms of action of LNG as EC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Reproductive performance of donor mares subsequent to eFSH treatment in early vernal transition: Comparison between the first, second, and mid-season estrous cycles of the breeding season.

PubMed

Raz, Tal; Hunter, Barbara; Carley, Sylvia; Card, Claire

2009-11-01

The objective was to compare the reproductive performances associated with the first (Cycle-1), second (Cycle-2), and mid-season (MS-Cycle) ovulations of the breeding season in donor mares that were treated with equine-FSH (eFSH) in the early vernal transition. Mares (n=15) kept under ambient light were examined ultrasonographically per-rectum starting January 30. When an ovarian follicle > or =25mm in diameter was detected, twice daily eFSH treatments were initiated. The eFSH treatments ceased when a follicle > or =35mm was detected, and 36h later hCG was administered. Thereafter, mares were artificially inseminated every 48h until ovulation (Day 0). Trans-cervical embryo recovery attempts were performed on Day 8, and subsequently PGF2alpha was administered. Equine FSH was not administered in the subsequent estrous cycles. In Cycle-2 and in the MS-Cycle, hCG was administered when a follicle > or =35mm was detected; breeding, embryo recovery, and PGF2alpha administration, were similar to Cycle-1. Mares had an untreated estrous cycle (no treatment or breeding) between Cycle-2 and the MS-Cycle. All mares developed follicle(s) > or =35mm after 4.9+/-0.6 days of eFSH treatment, and subsequently ovulations occurred; mean (95% CI) interval from treatment initiation to ovulation was 7.9 (6.5-9.3) days. The number of preovulatory follicles (> or =30mm) at the time of hCG administration (Cycle-1: 2.2+/-0.3 compared with Cycle-2: 1.0+/-0 compared with MS-Cycle: 1.1+/-0.1 follicles), and the number of ovulations (2.5+/-0.4 compared with 1.0+/-0 compared with 1.1+/-0.1 ovulations) were greater (p<0.05) in Cycle-1. Nevertheless, mean embryo numbers did not differ among cycles (0.8+/-0.2 compared with 0.5+/-0.1 compared with 0.5+/-0.1 embryo/mare). On average, embryo morphology grade was less (p<0.05) in Cycle-1 as compared to non-eFSH cycles (combined Cycle-2 and MS-Cycle). This impaired embryo quality could be due to a seasonal effect, or negative effect of the eFSH treatment

Disruption of sexual function, FSH secretion, and spermiogenesis in rabbits following developmental exposure to vinclozolin, a fungicide.

PubMed

Veeramachaneni, D N R; Palmer, J S; Amann, R P; Kane, C M; Higuchi, T T; Pau, K-Y F

2006-04-01

We studied sequelae of prenatal plus infantile exposure of male rabbits to vinclozolin, because it is ingested by women and children. Female Dutch-Belted rabbits (7-10/group) were treated daily per orum from gestation day 15 through post-natal week 4 to provide 0, 7.2, or 72 mg vinclozolin/kg dam's body weight/day. Vinclozolin had no effect on maintenance of pregnancy, growth of pups, age at testicular descent or weight of organs. Concentrations of serum LH or testosterone at 6, 12, or 24 weeks of age were unaffected. However, FSH was lower (P < 0.05) in both vinclozolin groups at all three ages. Following injection of GnRH at 12 or 24 weeks, the increase in FSH was less (P < 0.05) in both vinclozolin groups, as was testosterone at 12 weeks of age. After full sexual maturity, 2 of 7 low dose rabbits were uninterested in female or male teasers and never achieved erection or ejaculation. Overall, rates of ejaculation failure were: control 0% (0/48), low dose 29% (12/42), and high dose 5% (3/60). Daily sperm production per gram of testis and total number of sperm per ejaculate in both vinclozolin groups were similar (P > 0.1) to controls. However, semen from vinclozolin rabbits contained over two times more (P < 0.05) morphologically abnormal spermatozoa, mostly nuclear and acrosomal defects, than semen from controls. Seminiferous tubules with degenerative changes were more frequent (P < 0.05) in vinclozolin rabbits than in controls. Lesions included syncytia of spherical spermatids and desquamation of germ cells. Hence, developmental exposure to vinclozolin caused presumably permanent changes in copulatory ability, secretion of FSH, and spermiogenesis.

Transient dwarfism and hypogonadism in mice lacking Otx1 reveal prepubescent stage-specific control of pituitary levels of GH, FSH and LH.

PubMed

Acampora, D; Mazan, S; Tuorto, F; Avantaggiato, V; Tremblay, J J; Lazzaro, D; di Carlo, A; Mariano, A; Macchia, P E; Corte, G; Macchia, V; Drouin, J; Brûlet, P; Simeone, A

1998-04-01

Genetic and molecular approaches have enabled the identification of regulatory genes critically involved in determining cell types in the pituitary gland and/or in the hypothalamus. Here we report that Otx1, a homeobox-containing gene of the Otx gene family, is postnatally transcribed and translated in the pituitary gland. Cell culture experiments indicate that Otx1 may activate transcription of the growth hormone (GH), follicle-stimulating hormone (betaFSH), luteinizing hormone (betaLH) and alpha-glycoprotein subunit (alphaGSU) genes. Analysis of Otx1 null mice indicates that, at the prepubescent stage, they exhibit transient dwarfism and hypogonadism due to low levels of pituitary GH, FSH and LH hormones which, in turn, dramatically affect downstream molecular and organ targets. Nevertheless, Otx1-/- mice gradually recover from most of these abnormalities, showing normal levels of pituitary hormones with restored growth and gonadal function at 4 months of age. Expression patterns of related hypothalamic and pituitary cell type restricted genes, growth hormone releasing hormone (GRH), gonadotropin releasing hormone (GnRH) and their pituitary receptors (GRHR and GnRHR) suggest that, in Otx1-/- mice, hypothalamic and pituitary cells of the somatotropic and gonadotropic lineages appear unaltered and that the ability to synthesize GH, FSH and LH, rather than the number of cells producing these hormones, is affected. Our data indicate that Otx1 is a new pituitary transcription factor involved at the prepubescent stage in the control of GH, FSH and LH hormone levels and suggest that a complex regulatory mechanism might exist to control the physiological need for pituitary hormones at specific postnatal stages.

Sexually dimorphic expression of gonadotropin subunits in the pituitary of protogynous honeycomb grouper (Epinephelus merra): evidence that follicle-stimulating hormone (FSH) induces gonadal sex change.

PubMed

Kobayashi, Yasuhisa; Alam, Mohammad Ashraful; Horiguchi, Ryo; Shimizu, Akio; Nakamura, Masaru

2010-06-01

Recent studies have suggested that the hypothalamic-pituitary-gonadal axis is involved in gonadal sex change in sex-changing teleosts. However, its underlying mechanism remains largely unknown. In this study, we focused on the distinct roles of two gonadotropins (GTHs), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), in the protogynous hermaphrodite teleost, honeycomb grouper (Epinephelus merra). First, we investigated the expression pattern of mRNAs for GTH subunits (cga, fshb, and lhb) in the pituitaries from fish at the different sexual phases. Real-time RT-PCR analyses showed that fhsb mRNA levels in the female pituitary were low. However, fshb transcripts increased dramatically in association with testis development. In contrast, levels of cga and lhb mRNAs did not significantly vary during sex change. In addition, immunohistochemical observations of Fshb- and Lhb-producing cells in the pituitary, through the use of specific antibodies for detections of teleost GTH subunits, were consistent with sexually dimorphic expression of Fshb. In order to identify the role of GTH in gonad of honeycomb grouper, we treated females with bovine FSH (50 or 500 ng/fish) or LH (500 ng/fish) in vivo. After 3 wk, FSH treatments induced female-to-male sex change and up-regulated endogenous androgen levels and fshb transcripts, whereas LH treatment had no effect on sex change. These results suggest that FSH may trigger the female-to-male sex change in honeycomb grouper.

Effects of FSH addition to an enriched medium containing insulin and EGF after long-term culture on functionality of equine ovarian biopsy tissue.

PubMed

Aguiar, F L N; Gastal, G D A; Ishak, G M; Gastal, M O; Teixeira, D I A; Feugang, J M; Figueiredo, J R; Gastal, E L

2017-09-01

The effect of FSH supplementation on an enriched cultured medium containing insulin (10 ng/mL) and EGF (50 ng/mL) was investigated on in vitro culture of equine ovarian biopsy tissue. Ovarian tissue fragments were collected from mares (n = 10) and distributed in the following treatments: noncultured control, cultured control, and cultured + FSH. Both treated groups were cultured for 7 or 15 days. The end points evaluated were: follicular morphology, estradiol levels in the culture medium, fluorescence intensity for TUNEL, EGFR and Ki-67 detection, and gene expression of GDF-9, BMP-15, and Cyclin-D2 in the ovarian tissue. After seven days of culture, medium supplemented with FSH had a similar (P > 0.05) percentage of morphologically normal follicles compared to the noncultured control group. Estradiol levels increased (P < 0.05) from Day 7 to Day 15 of culture for both treated groups. No difference (P > 0.05) was observed for TUNEL and EGFR intensity between the noncultured control group and the treated groups after 15 days of culture. Ki-67 intensity did not differ (P > 0.05) between treated groups after 15 days of culture, but decreased (P < 0.05) when compared with the noncultured control group. Similar (P > 0.05) mRNA expression for GDF-9, BMP-15, and Cyclin-D2 was observed among all treatments after 15 days of culture. In conclusion, an enriched medium supplemented or not with FSH was able to maintain the functionality of equine ovarian biopsy tissue after a long-term in vitro culture. Copyright © 2017 Elsevier Inc. All rights reserved.

USGS field activity 09FSH02 on the west Florida shelf, Gulf of Mexico, in August 2009

USGS Publications Warehouse

Robbins, Lisa L.; Knorr, Paul O.; Liu, Xuewu; Byrne, Robert H.; Raabe, Ellen A.

2009-01-01

From August 17 to 21, 2009, a cruise led by the U.S. Geological Survey (USGS) collected air and sea surface partial pressure of carbon dioxide (pCO2), pH, dissolved inorganic carbon (DIC), and total alkalinity (TA) data on the west Florida shelf. Approximately 2,000 data points were collected underway over a 1,320-kilometer (km) track line using the Multiparameter Inorganic Carbon Analyzer (MICA). The collection of data extended from Crystal River to Marco Island, Florida (~400 km), and westward up to 160 km off the Florida coast. Discrete water samples were also taken at specific localities to corroborate underway data measurements. The USGS St. Petersburg Coastal and Marine Science Center (SPCMSC) assigns a unique identifier to each cruise or field activity. For example, 09FSH02 tells us that the data were collected in 2009 for the Response of Florida Shelf (FSH) Ecosystems to Climate Change project, and the data were collected during the second field activity for that study in that calendar year.

USGS field activity 09FSH01 on the west Florida shelf, Gulf of Mexico, in February 2009

USGS Publications Warehouse

Robbins, Lisa L.; Knorr, Paul O.; Liu, Xuewu; Byrne, Robert H.; Raabe, Ellen A.

2009-01-01

From February 24 to 28, 2009, a cruise led by the U.S. Geological Survey (USGS) collected air and sea surface partial pressure of carbon dioxide (pCO2), pH, dissolved inorganic carbon (DIC), and total alkalinity (TA) data on the west Florida shelf. Approximately 1,800 data points were collected underway over a 1,300-kilometer (km) trackline using the Multiparameter Inorganic Carbon Analyzer (MICA). The collection of data extended from Crystal River to Marco Island, Florida (~400 km), and westward up to 160 km off the Florida coast. Discrete water samples were also taken at specific localities to corroborate underway data measurements. The USGS St. Petersburg Coastal and Marine Science Center (SPCMSC) assigns a unique identifier to each cruise or field activity. For example, 09FSH01 tells us that the data were collected in 2009 for the Response of Florida Shelf (FSH) Ecosystems to Climate Change project, and the data were collected during the first field activity for that study in that calendar year.

USGS field activity 08FSH01 on the west Florida shelf, Gulf of Mexico, in August 2008

USGS Publications Warehouse

Robbins, Lisa L.; Knorr, Paul O.; Liu, Xuewu; Byrne, Robert H.; Raabe, Ellen A.

2009-01-01

From August 11 to 15, 2008, a cruise led by the U.S. Geological Survey (USGS) collected air and sea surface partial pressure of carbon dioxide (pCO2), pH, dissolved inorganic carbon (DIC), and total alkalinity (TA) data on the west Florida shelf. Approximately 1,600 data points were collected underway over a 650-kilometer (km) trackline using the Multiparameter Inorganic Carbon Analyzer (MICA). The collection of data extended from Crystal River southward to Marco Island, Florida (~400 km), and westward up to 160 km off the Florida coast. Discrete water samples from approximately 40 locations were also taken at specific localities to corroborate underway data measurements. The USGS St. Petersburg Coastal and Marine Science Center (SPCMSC) assigns a unique identifier to each cruise or field activity. For example, 08FSH01 tells us the data were collected in 2008 for the Response of Florida Shelf (FSH) Ecosystems to Climate Change project, and the data were collected during the first field activity for that study in that calendar year.

Effect of addition of FSH, LH and proteasome inhibitor MG132 to in vitro maturation medium on the developmental competence of yak (Bos grunniens) oocytes.

PubMed

Xiao, Xiao; Zi, Xiang-Dong; Niu, Hui-Ran; Xiong, Xian-Rong; Zhong, Jin-Cheng; Li, Jian; Wang, Li; Wang, Yong

2014-04-22

The competence for embryonic development after IVF is low in the yak, therefore, we investigated the effects of supplementation of FSH, LH and the proteasome inhibitor MG132 in IVM media on yak oocyte competence for development after IVF. In Experiment 1, yak cumulus-oocyte complexes (COCs) were in vitro matured (IVM) in TCM-199 with 20% fetal calf serum (FCS), 1 microg/mL estradiol-17beta, and different combinations of LH (50 or 100 IU/mL) and FSH (0, 1, 5, 10 microg/mL) at 38.6 degrees C, 5% CO2 in air for 24 h. Matured oocytes were exposed to frozen-thawed, heparin-capacitated yak sperm. Presumptive zygotes were cultured in SOF medium containing 6 mg/ml BSA, 0.5 mg/mL myoinositol, 3% (v/v) essential amino acids, 1% nonessential amino acids and 100 μg/mL L-glutamine (48 h, 38.5 degrees C, 5% CO2, 5% O2, and 90% N2). In Experiment 2, cumulus cells were collected at the end of IVM to determine FSHR and LHR mRNA expression by real-time PCR. In Experiment 3 and 4, COCs were cultured in the presence or absence of the proteasomal inhibitor MG132 from either 0-6 h or 18-24 h after initiation of maturation. The optimum concentration of FSH and LH in IVM media was 5 microg/mL FSH and 50 IU/mL LH which resulted in the greatest cleavage (79.1%) and blastocyst rates (16.1%). Both FSHR and LHR mRNA were detected in yak cumulus cells after IVM. Treatment with MG132 early in maturation reduced (P<0.05) cleavage and blastocyst rates. Conversely, treatment with MG132 late in maturation improved (P<0.05) blastocyst rate. Optimal results with MG132 were achieved at a concentration of 10 microM. An optimum concentration of FSH and LH in IVM medium, and treatment with MG132 late in maturation can improve yak oocytes competence for development after IVF.

Corifollitropin alfa compared to daily rFSH or HP-HMG in GnRH antagonist controlled ovarian stimulation protocol for patients undergoing assisted reproduction.

PubMed

Souza, Priscila Morais Galvão; Carvalho, Bruno Ramalho de; Nakagawa, Hitomi Miura; Rassi, Thalita Reis Esselin; Barbosa, Antônio César Paes; Silva, Adelino Amaral

2017-06-01

This study aimed to compare the outcomes of controlled ovarian stimulation (COS) with corifollitropin alfa versus daily recombinant follicle-stimulating hormone (rRFSH) or highly purified human menopausal gonadotropin (HP-HMG) in patients undergoing in vitro fertilization (IVF) cycles based on gonadotropin-releasing hormone (GnRH) antagonist protocols. The primary endpoints were total number of oocytes and mature oocytes. This retrospective study looked into 132 controlled ovarian stimulation cycles from IVF or oocyte cryopreservation performed in a private human reproduction center between January 1 and December 31, 2014. Enrollment criteria: women aged < 40 years submitted to COS with corifollitropin alfa 100µg or 150µg (n = 26) and rFSH or HP-HMG in the first seven days of treatment with daily doses of 150-225 IU (n = 106); all subjects were on GnRH antagonist protocols. The groups had similar mean ages and duration of stimulation. The mean number ± standard deviation of total aspirated oocytes and MII oocytes was 11.9±10 and 10.3±7.9 in the corifollitropin alfa group, and 10.9±7.2 and 8.6±5.7 in the group on rFSH or HMG (p>0.05). There were no significant differences in fertilization (76.9% vs. 76.8%, p=1.0), biochemical pregnancy (66.7% vs. 47.2%, p=0.1561) or embryo implantation rates (68.7% vs. 50%, p=0.2588) between the groups using corifollitropin alfa and rFSH or HMG, respectively. Corifollitropin alfa seems to be as effective as rFSH or HP-HMG when used in the first seven days of ovulation induction for patients undergoing assisted reproduction in GnRH antagonist protocols.

Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI: a multicentre trial and cost-effectiveness analysis.

PubMed

van Tilborg, Theodora C; Oudshoorn, Simone C; Eijkemans, Marinus J C; Mochtar, Monique H; van Golde, Ron J T; Hoek, Annemieke; Kuchenbecker, Walter K H; Fleischer, Kathrin; de Bruin, Jan Peter; Groen, Henk; van Wely, Madelon; Lambalk, Cornelis B; Laven, Joop S E; Mol, Ben Willem J; Broekmans, Frank J M; Torrance, Helen L

2017-12-01

Is there a difference in live birth rate and/or cost-effectiveness between antral follicle count (AFC)-based individualized FSH dosing or standard FSH dosing in women starting IVF or ICSI treatment? In women initiating IVF/ICSI, AFC-based individualized FSH dosing does not improve live birth rates or reduce costs as compared to a standard FSH dose. In IVF or ICSI, ovarian reserve testing is often used to adjust the FSH dose in order to normalize ovarian response and optimize live birth rates. However, no robust evidence for the (cost-)effectiveness of this practice exists. Between May 2011 and May 2014 we performed a multicentre prospective cohort study with two embedded RCTs in women scheduled for IVF/ICSI. Based on the AFC, women entered into one of the two RCTs (RCT1: AFC < 11; RCT2: AFC > 15) or the cohort (AFC 11-15). The primary outcome was ongoing pregnancy achieved within 18 months after randomization resulting in a live birth (delivery of at least one live foetus after 24 weeks of gestation). Data from the cohort with weight 0.5 were combined with both RCTs in order to conduct a strategy analysis. Potential half-integer numbers were rounded up. Differences in costs and effects between the two treatment strategies were compared by bootstrapping. In both RCTs women were randomized to an individualized (RCT1:450/225 IU, RCT2:100 IU) or standard FSH dose (150 IU). Women in the cohort all received the standard dose (150 IU). Anti-Müllerian hormone (AMH) was measured to assess AMH post-hoc as a biomarker to individualize treatment. For RCT1 dose adjustment was allowed in subsequent cycles based on pre-specified criteria in the standard group only. For RCT2 dose adjustment was allowed in subsequent cycles in both groups. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. We included 1515 women, of whom 483 (31.9%) entered the cohort, 511 (33.7%) RCT1 and 521 (34.4%) RCT2. Live births occurred in 420

Effects of human chorionic gonadotropin combined with clomiphene on Serum E2, FSH, LH and PRL levels in patients with polycystic ovarian syndrome.

PubMed

Yonggang, Huang; Xiaosheng, Lu; Zhaoxia, Huang; Yilu, Chen; Jiqiang, Lv; Huina, Zhang

2017-02-01

Effects of human chorionic gonadotropin combined with clomiphene on serum E 2 , FSH, LH and PRL levels in patients with polycystic ovarian syndrome were analyzed. 90 patients with polycystic ovarian syndrome treated from January 2015 to March 2016 were randomly and evenly divided into control group and observation group. Patients in the control group were only treated with clomiphene. On the basis of the treatment in control group, human chorionic gonadotropin was added in the treatment of observation group. The changes of E 2 , FSH, LH, PRL levels were compared between two groups before and after the treatment. Clinical curative effects of patients in the two groups was evaluated. Adverse reactions during treatment in two groups were observed and recorded. The incidence of adverse reactions was calculated. Serum E 2 , FSH, LH and PRL levels in the two groups decreased significantly after treatment compared with that before treatment. The difference is statistical significant ( P  < 0.05). After the treatment, E 2 , FSH, LH and PRL levels in the observation group were lower than that in the control group and the difference is statistical significant ( P  < 0.05). Total effective rate was 64.44% in the control group and 93.33% in the observation group. There were statistically significant difference in clinical curative effects in the two groups ( P  < 0.05). Different degrees of adverse reactions were found in both groups during treatment, such as nausea, vomiting, anorexia, liver dysfunction. There were 2 cases of nausea, 2 cases of vomiting, 3 cases of anorexia and 1 case of liver dysfunction from the 45 patients in control group. The total incidence of adverse reactions was 17.78% (8/45). There were 1 case of nausea, 1 case of vomiting, 1 case of anorexia and no liver dysfunction from the 45 patients in observation group. The total incidence of adverse reactions was 6.67% (3/45). The total incidence of adverse reactions in the observation group was

Serum FSH level below 10 mIU/mL at twelve years old is an index of spontaneous and cyclical menstruation in Turner syndrome.

PubMed

Aso, Keiko; Koto, Shinobu; Higuchi, Asako; Ariyasu, Daisuke; Izawa, Masako; Miyamoto Igaki, Junko; Hasegawa, Yukihiro

2010-01-01

The gonadal function of patients with Turner syndrome (TS) is variable. Individuals with mosaicism characterized by 45,X/46,XX or 45,X/47,XXX are more likely to experience spontaneous menarche compared with other karyotypes. Prepubertal gonadotropins of TS patients with spontaneous menarche are reportedly normal or significantly lower than those of patients with induced menarche. The present study investigated an index of spontaneous and cyclical menstruation at 10-12 years old in TS. Subjects comprised 50 patients with TS, divided into three groups: Group A (n=7), with spontaneous menarche before 16 years old and regular menstruation for at least 1 year and 6 months; Group B (n=6), with irregular menstruation since menarche leading to secondary amenorrhea despite spontaneous menarche before 16 years old; and Group C (n=37), without spontaneous breast budding before 14 years old or without spontaneous menarche before 16 years old. Karyotype, LH and FSH concentrations at 10 and 12 years old were analyzed retrospectively. Spontaneous and cyclical menstruation was more frequently observed in TS with mosaicism characterized by 45,X/46,XX or 45,X/47,XXX than in TS with other karyotypes, as previously described. Spontaneous and cyclical menstruation in TS was observed when serum FSH level was <10 mIU/mL at 12 years old, suggesting this FSH level as an index of spontaneous and cyclical menstruation in TS.

A new way of setting rFSH deposit: a case of severe injection error in IVF/ICSI cycle ending with live birth.

PubMed

Mayer, Richard Bernhard; Ebner, Thomas; Shebl, Omar; Tews, Gernot

2012-01-01

a 25- year old woman with secondary infertility caused by a male factor was enrolled in our IVF/ICSI-ET program. Stimulation was performed in a long- protocol and ovarian stimulation, using rFSH follitropin beta, starting on the third day of the menstrual cycle. The rFSH dose per day was 900 IU-0 IU-0 IU-0 IU. Due to normal ovarian response and follicle growth, stimulation was continued and there was no detriment in oocyte quality and no symptoms of OHSS. Following blastocyte transfer cesarean section was unpreventable at 37+5 weeks of gestation due to an impacted transverse lie. Different stimulation protocols are needed for appropriate treatment of various patients provided that the administration of treatment was done correctly. In the case of injection errors, continuing stimulation protocol seems to be achievable in certain cases considering hormone levels and the process of follicle growth.

A new fully human recombinant FSH (follitropin epsilon): two phase I randomized placebo and comparator-controlled pharmacokinetic and pharmacodynamic trials.

PubMed

Abd-Elaziz, Khalid; Duijkers, Ingrid; Stöckl, Lars; Dietrich, Bruno; Klipping, Christine; Eckert, Kelvin; Goletz, Steffen

2017-08-01

What are the differences and similarities of pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the novel recombinant human FSH follitropin epsilon expressed in the human cell line GlycoExpress compared with a Chinese hamster ovary (CHO) derived compound and a urinary derived product? Overall follitropin epsilon, with a fully human glycosylation, shows a comparable PK profile at single-dose as well as multiple-dose administration compared to recombinant CHO-derived FSH as well as urinary derived FSH, whereas the PD properties differ from product to product with follitropin epsilon being most active in PD parameters. Recombinant FSH produced in CHO and FSH obtained from the urine of postmenopausal women show comparable PK and PD properties. However, more recently a comparative study of a recombinant FSH produced in the human cell line PerC6 and a CHO-derived FSH preparation revealed differences in PK and PD properties of the molecule. Both studies were randomized, placebo- and comparator-controlled, single-blind phase I studies in healthy pituitary-suppressed female volunteers aged 18 and 40 years. The single-dose, dose escalation study included 19 women (April 2011 to September 2011) with three ascending dose levels per subject or placebo/comparators with a 14-day washout phase between dosings. The multiple-dose study included 57 women (October 2011 to April 2012) in five cohorts with three dose levels versus placebo and two comparators. Randomization to the respective treatment was performed after successful downregulation of the pituitary gland prior to Investigational Medicinal Product dosing. In the single-dose study, 12 subjects received follitropin epsilon (25, 75, 150 and 300 IU) in three of four possible ascending doses and seven subjects received one dose of two comparators (150 IU Bravelle and 150 IU Gonal-f) and placebo in random order in each treatment period. In the multiple-dose study, 30 subjects received follitropin epsilon (75 IU or

Age, FSH dose and follicular aspiration frequency affect oocyte yield from juvenile donor lambs.

PubMed

Valasi, I; Leontides, L; Papanikolaou, Th; Amiridis, G S

2007-06-01

Experiments were conducted to determine the effects of lamb age, frequency of follicular aspirations, and hormone stimulation by fixed or variable FSH dose, on the number of collected oocytes and their maturational competence. In trial 1, the characteristics of follicular population (number and diameter of follicles) were studied in 40 lambs which were slaughtered at the age of 30 days (S1), 42 days (S2), 60 days (S3) and 5-6 months (S4), each n = 10. In trial 2, 27 lambs were divided into four groups. group MF lambs (n = 6) had follicular aspiration (OPU) in four monthly intervals commencing from the age of 8-9 weeks (sessions MF1, MF2, MF3 and MF4). In groups SF2, SF3 and SF4 (each n = 6), OPU was conducted once during the 12-13, 16-17 and 20-21 week of age, respectively. Ovarian stimulation was conducted with fixed FSH dose (3.52 mg/animal). In trial 3, 10 lambs (group MV) were treated as those of group MF apart from the FSH dose, which was administered according to the body weight in a dose of 0.27 mg/kg. The number and the size of follicles, the number and the quality of collected oocytes and the maturational competence of the oocytes were compared between and within groups. In trial 1, the total number and the number of small follicles were greater in groups S1 and S2 compared with those of S3 and S4 (p < 0.01). Similarly, the follicular population was greater in group MF1 than in group SF3 (p < 0.01). In sessions MF2, MF3, MV2, MV3 and MV4, more oocytes were collected in comparison with those from the respective once-aspirated age mates (groups SF2, SF3 and SF4). In total, more (p = 0.02) oocytes per donor were collected from group MV (15.2 +/- 5.5) than from group MF (9.0 +/- 3.2). An absolute maturational failure was observed in oocytes collected from groups SF2 and SF3. Maturational competence varied between 16.7% and 58.3% (p = 0.017) among sessions of group MF, but it was more uniform among sessions of group MV (range 12.5-42.9%, p > 0.05). Our results

The canonical WNT2 pathway and FSH interact to regulate gap junction assembly in mouse granulosa cells.

PubMed

Wang, Hong-Xing; Gillio-Meina, Carolina; Chen, Shuli; Gong, Xiang-Qun; Li, Tony Y; Bai, Donglin; Kidder, Gerald M

2013-08-01

WNTs are extracellular signaling molecules that exert their actions through receptors of the frizzled (FZD) family. Previous work indicated that WNT2 regulates cell proliferation in mouse granulosa cells acting through CTNNB1 (beta-catenin), a key component in canonical WNT signaling. In other cells, WNT signaling has been shown to regulate expression of connexin43 (CX43), a gap junction protein, as well as gap junction assembly. Since previous work demonstrated that CX43 is also essential in ovarian follicle development, the objective of this study was to determine if WNT2 regulates CX43 expression and/or gap-junctional intercellular communication (GJIC) in granulosa cells. WNT2 knockdown via siRNA markedly reduced CX43 expression and GJIC. CX43 expression, the extent of CX43-containing gap junction membrane, and GJIC were also reduced by CTNNB1 transient knockdown. CTNNB1 is mainly localized to the membranes between granulosa cells but disappeared from this location after WNT2 knockdown. Furthermore, CTNNB1 knockdown interfered with the ability of follicle-stimulating hormone (FSH) to promote the mobilization of CX43 into gap junctions. We propose that the WNT2/CTNNB1 pathway regulates CX43 expression and GJIC in granulosa cells by modulating CTNNB1 stability and localization in adherens junctions, and that this is essential for FSH stimulation of GJIC.

A new way of setting rFSH deposit: a case of severe injection error in IVF/ICSI cycle ending with live birth

PubMed Central

Mayer, Richard Bernhard; Ebner, Thomas; Shebl, Omar; Tews, Gernot

2012-01-01

We present a case with a severe injection error: a 25- year old woman with secondary infertility caused by a male factor was enrolled in our IVF/ICSI-ET program. Stimulation was performed in a long- protocol and ovarian stimulation, using rFSH follitropin beta, starting on the third day of the menstrual cycle. The rFSH dose per day was 900 IU-0 IU-0 IU-0 IU. Due to normal ovarian response and follicle growth, stimulation was continued and there was no detriment in oocyte quality and no symptoms of OHSS. Following blastocyte transfer cesarean section was unpreventable at 37+5 weeks of gestation due to an impacted transverse lie. Different stimulation protocols are needed for appropriate treatment of various patients provided that the administration of treatment was done correctly. In the case of injection errors, continuing stimulation protocol seems to be achievable in certain cases considering hormone levels and the process of follicle growth. PMID:24592042

Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 1: The predicted poor responder.

PubMed

van Tilborg, Theodora C; Torrance, Helen L; Oudshoorn, Simone C; Eijkemans, Marinus J C; Koks, Carolien A M; Verhoeve, Harold R; Nap, Annemiek W; Scheffer, Gabrielle J; Manger, A Petra; Schoot, Benedictus C; Sluijmer, Alexander V; Verhoeff, Arie; Groen, Henk; Laven, Joop S E; Mol, Ben Willem J; Broekmans, Frank J M

2017-12-01

Does an increased FSH dose result in higher cumulative live birth rates in women with a predicted poor ovarian response, apparent from a low antral follicle count (AFC), scheduled for IVF or ICSI? In women with a predicted poor ovarian response (AFC < 11) undergoing IVF/ICSI, an increased FSH dose (225/450 IU/day) does not improve cumulative live birth rates as compared to a standard dose (150 IU/day). In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can predict ovarian response to stimulation. The FSH starting dose is often adjusted based on the ORT from the belief that it will improve live birth rates. However, the existing RCTs on this topic, most of which show no benefit, are underpowered. Between May 2011 and May 2014, we performed an open-label multicentre RCT in women with an AFC < 11 (Dutch Trial Register NTR2657). The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. We needed 300 women to assess whether an increased dose strategy would increase the cumulative live birth rate from 25 to 40% (two-sided alpha-error 0.05, power 80%). Women with an AFC ≤ 7 were randomized to an FSH dose of 450 IU/day or 150 IU/day, and women with an AFC 8-10 were randomized to 225 IU or 150 IU/day. In the standard group, dose adjustment was allowed in subsequent cycles based on pre-specified criteria. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. In total, 511 women were randomized, 234 with an AFC ≤ 7 and 277 with an AFC 8-10. The cumulative live birth rate for increased versus standard dosing was 42.4% (106/250) versus 44.8% (117/261), respectively [relative risk (RR): 0.95 (95%CI, 0.78-1.15), P = 0.58]. As an increased dose strategy was more expensive [delta costs/woman: €1099 (95%CI, 562-1591)], standard FSH dosing was the dominant strategy in our economic analysis. Despite our training programme, the AFC might have

Concomitant use of FSH and low-dose recombinant hCG during the late follicular phase versus conventional controlled ovarian stimulation for intracytoplasmic sperm injection cycles.

PubMed

Iaconelli, Carla Andrade Rebello; Setti, Amanda Souza; Braga, Daniela Paes Almeida Ferreira; Maldonado, Luiz Guilherme Louzada; Iaconelli, Assumpto; Borges, Edson; Aoki, Tsutomu

2017-12-01

The objective of this study was to investigate the effects of low-dose hCG supplementation on ICSI outcomes and controlled ovarian stimulation (COS) cost. Three hundred and thirty patients undergoing ICSI were split into groups according to the COS protocol: (i) control group (n = 178), including patients undergoing conventional COS treatment; and (ii) low-dose hCG group (n = 152), including patients undergoing COS with low-dose hCG supplementation. Lower mean total doses of FSH administered and higher mean oestradiol level and mature oocyte rates were observed in the low-dose hCG group. A significantly higher fertilization rate, high-quality embryo rate and blastocyst formation rate were observed in the low-dose hCG group as compared to the control group. The miscarriage rate was significantly higher in the control group compared to the low-dose hCG group. A significantly lower incidence of OHSS was observed in the low-dose hCG group. There was also a significantly lower gonadotropin cost in the low-dose hCG group as compared to the control group ($1235.0 ± 239.0×$1763.0 ± 405.3, p < 0.001). The concomitant use of low-dose hCG and FSH results in a lower abortion rate and increased number of mature oocytes retrieved, as well as improved oocyte quality, embryo quality and blastocyst formation and reduced FSH requirements.

Radiotherapy for Rectal Cancer Is Associated With Reduced Serum Testosterone and Increased FSH and LH

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruheim, Kjersti; Svartberg, Johan; Department of Medicine, University Hospital of North Norway, Tromso

Purpose: It is known that scattered radiation to the testes during pelvic radiotherapy can affect fertility, but there is little knowledge on its effects on male sex hormones. The aim of this study was to determine whether radiotherapy for rectal cancer affects testosterone production. Methods and Materials: All male patients who had received adjuvant radiotherapy for rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Patients treated with surgery alone were randomly selected from the same registry as control subjects. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sex hormone bindingmore » globulin (SHBG) were analyzed, and free testosterone was calculated (N = 290). Information about the radiotherapy treatment was collected from the patient hospital charts. Results: Serum FSH was 3 times higher in the radiotherapy group than in the control group (median, 18.8 vs. 6.3 IU/L, p <0.001), and serum LH was 1.7 times higher (median, 7.5 vs. 4.5 IU/l, p <0.001). In the radiotherapy group, 27% of patients had testosterone levels below the reference range (8-35 nmol/L), compared with 10% of the nonirradiated patients (p <0.001). Irradiated patients had lower serum testosterone (mean, 11.1 vs. 13.4 nmol/L, p <0.001) and lower calculated free testosterone (mean, 214 vs. 235 pmol/L, p <0.05) than control subjects. Total testosterone, calculated free testosterone, and gonadotropins were related to the distance from the bony pelvic structures to the caudal field edge. Conclusions: Increased serum levels of gonadotropins and subnormal serum levels of testosterone indicate that curative radiotherapy for rectal cancer can result in permanent testicular dysfunction.« less

Nocturnal Urinary Excretion of FSH and LH in Children and Adolescents With Normal and Early Puberty.

PubMed

Kolby, Nanna; Busch, Alexander S; Aksglaede, Lise; Sørensen, Kaspar; Petersen, Jorgen Holm; Andersson, Anna-Maria; Juul, Anders

2017-10-01

Clinical use of single serum gonadotropin measurements in children is limited by the pulsatile secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, first morning voided (FMV) urine may integrate the fluctuating gonadotropin serum levels. We aimed to evaluate urinary and serum gonadotropin levels according to age, sex, and pubertal stage in healthy children and to assess the clinical use of FMV urinary gonadotropins in children with disordered puberty. Cross-sectional part of the COPENHAGEN Puberty Study and longitudinal study of patients. Population-based and outpatient clinic. Eight hundred forty-three healthy children from the COPENHAGEN Puberty Study and 25 girls evaluated for central precocious puberty (CPP). Clinical pubertal staging, including serum and urinary gonadotropin levels. Urinary gonadotropins increased with advancing age and pubertal development and were detectable in FMV urine before physical signs of puberty. FMV urinary LH correlated strongly with basal (r = 0.871, P < 0.001) and gonadotropin-releasing hormone (GnRH)-stimulated serum LH (r = 0.82, P < 0.001). Urinary LH was superior to urinary FSH in differentiating the pubertal stage. Receiver operating curve analysis revealed that a cut-off standard deviation (SD) score of 2 for urinary LH (IU/L) gave a sensitivity of 75% and a specificity of 92% in predicting a positive GnRH stimulation test (LHmax > 5 IU/L). Urinary concentrations of LH decreased after 3 months of GnRH treatment to levels below +2 SDs. Urinary gonadotropin levels increased before the onset of puberty and were elevated in girls with CPP. We suggest urinary LH as an alternative noninvasive method to improve diagnosing and therapeutic management of children with disordered puberty. Copyright © 2017 Endocrine Society

The anti-Müllerian hormone (AMH) acts as a gatekeeper of ovarian steroidogenesis inhibiting the granulosa cell response to both FSH and LH.

PubMed

Sacchi, Sandro; D'Ippolito, Giovanni; Sena, Paola; Marsella, Tiziana; Tagliasacchi, Daniela; Maggi, Elena; Argento, Cindy; Tirelli, Alessandra; Giulini, Simone; La Marca, Antonio

2016-01-01

Anti Müllerian Hormone (AMH) has a negative and inhibitory role in many functions of human granulosa-lutein cells (hGCs) including notoriously the reduction of the aromatase CYP19A1 expression induced by follicle-stimulating hormone (FSH). No data have been provided on the possible role of AMH in modulating the response to luteinizing hormone (LH) (alone or combined with FSH) as well as its effect on other enzymes involved in steroidogenesis including aromatase P450scc. The aim of this study was to investigate the role of AMH as regulator of the basal and stimulated steroids production by hGCs. Primary culture of hGCs were incubated with hormones AMH, LH, and FSH, alone or in combination. The CYP19A1 and P450scc messenger RNA (mRNA) expression, normalized by housekeeping ribosomal protein S7 (RpS7) gene, was evaluated by reverse transcriptase quantitative PCR (RT-qPCR). Each reaction was repeated in triplicate. Negative controls using corresponding amount of vehicle control for each hormone treatment were performed. AMH did not modulate the basal mRNA expression of both aromatase genes at any of the concentrations tested. Meanwhile, the strong mRNA induction of CYP19A1 and P450scc generated by a 24-h gonadotropin treatment (alone and combined) was suppressed by 20 ng/ml AMH added to culture medium. These findings contribute in clarifying the relationship between hormones regulating the early phase of steroidogenesis confirming that AMH is playing a suppressive role on CYP19A1 expression stimulated by gonadotropin in hGCs. Furthermore, a similar inhibitory effect for AMH was observed on P450scc gene expression when activated by gonadotropin treatment.

Testicular growth and spermatogenesis: new goals for pubertal hormone replacement in boys with hypogonadotropic hypogonadism? -a multicentre prospective study of hCG/rFSH treatment outcomes during adolescence.

PubMed

Rohayem, Julia; Hauffa, Berthold P; Zacharin, Margaret; Kliesch, Sabine; Zitzmann, Michael

2017-01-01

Testosterone treatment for pubertal induction in boys with hypogonadotropic hypogonadism (HH) provides virilization, but does not induce testicular growth or fertility. Larger studies evaluating the outcomes of gonadotropin replacement during adolescence have not been reported to date; whether previous testosterone substitution affects testicular responses is unresolved. We aimed to assess the effects of human chorionic gonadotropin (hCG) and recombinant FSH (rFSH) in boys and adolescents with HH with respect to a) testicular growth, b) spermatogenesis, c) quality of life (QoL) and to identify factors influencing therapeutic success. A prospective case study was conducted in 26 paediatric endocrine centres PATIENTS/INTERVENTIONS: HCG and rFSH were administered until cessation of testicular growth and plateauing of spermatogenesis to (1) prepubertal HH boys with absent or early arrested puberty (group A) and to (2) HH adolescents who had previously received full testosterone replacement (group B). Bi-testicular volumes (BTVs), sperm concentrations and QoL. Sixty (34 A/26 B) HH patients aged 14-22 years were enrolled. BTVs rose from 5 ± 5 to 34 ± 3 ml in group A vs 5 ± 3 to 32 ± 3 ml in group B, with normal final BTVs (≥24 ml) attained in 74%/70% after 25/23 months in A/B, respectively. Sperm in the ejaculate were found in 21/23(91%)/18/19(95%), with plateauing concentrations after 31/30 months of hCG and 25/25 months of combined treatment in A/B. Sperm concentrations were normal (≥15 mill/ml) in 61%/32%, with mean concentrations of 40 ± 73 vs 19 ± 38 mill/ml in A/B (n.s.). Outcomes were better in patients without bilateral cryptorchidism, with non-congenital HH causes, higher baseline BTVs, and higher baseline inhibin B and AMH levels. QoL increased in both groups. HCG/rFSH replacement during adolescence successfully induces testicular growth and spermatogenesis, irrespective of previous testosterone replacement, and enhances QoL. © 2016 John Wiley & Sons

The influence of chronic exposure to low frequency pulsating magnetic fields on concentrations of FSH, LH, prolactin, testosterone and estradiol in men with back pain.

PubMed

Woldanska-Okonska, Marta; Karasek, Michal; Czernicki, Jan

2004-06-01

There is widespread public concern that electromagnetic fields might be hazardous. However, studies on the biological effects of magnetic fields (MFs) have not always been consistent. Influence of extremely-low frequency MFs used in physiotherapy on endocrine system was rarely examined. Therefore, the aim of the present study was to investigate the concentrations of some pituitary (FSH, LH, prolactin) and sex (testosterone, estradiol) hormones in men with back pain exposed to magnetic fields applied during magnetotherapy or magnetostimulation over the period of three weeks. The study was performed on 20 men aged 28-62 years (mean+/-SEM: 46.4+/-2.0 years) suffering from chronic low back pain who underwent magnetotherapy (10 patients, mean age+/-SEM: 48.4 years, range: 28-62 years) or subjected to magnetostimulation (10 patients, mean age+/-SEM: 44.3 years, range: 34-52 years) for 15 days (daily at 10:00 h, with weekend breaks). Blood samples were collected at 08:00 before magnetic field application, one day and one month following the application. Concentrations of hormones were measured by micromethod of chemiluminescence. Both magnetotherapy and magnetostimulation lowered levels of prolactin. The levels of LH decreased significantly one month after magnetotherapy in comparison with the baseline whereas following magnetostimulation slight but insignificant increase was observed. Estradiol concentrations were significantly lower one day and one month following magnetosimulation in comparison to the baseline and did not change after magnetotherapy. No statistically significant changes were observed in levels of FSH and testosterone after either magnetotherapy or magnetosimulation at any time examined. Magnetic fields applied in physiotherapy exert no or very subtle effect on concentrations of FSH, LH, prolactin, testosterone, and estradiol in men.

Androstenedione response to recombinant human FSH is the most valid predictor of the number of selected follicles in polycystic ovarian syndrome: (a case-control study).

PubMed

Ozyurek, Eser Sefik; Yoldemir, Tevfik; Artar, Gokhan

2017-05-12

We aimed to test the hypothesis that the correlation of the changes in the blood Androstenedione (A 4 ) levels to the number of selected follicles during ovulation induction with low-dose recombinant human follicle stimulating hormone (rhFSH) is as strong as the correlation to changes in the blood Estradiol (E 2 ) levels in polycystic ovary syndrome (PCOS). Prospective Case-control study conducted from October 2014 to January 2016. 61 non-PCOS control (Group I) and 46 PCOS (Group II) patients treated with the chronic low-dose step up protocosl with rhFSH. A 4 , E 2 , progesterone blood levels and follicular growth were monitored.. Univariate and hierarchical multivariable analysis were performed for age, BMI, HOMA-IR, A 4 and E 2 (with the number of selected follicles as the dependent variable in both groups). ROC analysis was performed to define threshold values for the significant determinants of the number of selected follicles to predict cyle cancellations due to excessive ovarian response. The control group (Group I) was comprised of 61 cycles from a group of primary infertile non-PCOS patients, and the study group (Group II) of 46 cycles of PCOS patients. The analysis revealed that the strongest independent predictor of the total number of selected follicles in Group I was the E 2 (AUC) (B = 0.0006[0.0003-0.001]; P < 0.001); whereas for Group II, it was the A 4 (AUC) (B = 0.114[0.04-0.25]; P = 0.01). Optimum thresholds for the A 4 related parameters were defined to predict excessive response within Group II were 88.7%, 3.1 ng/mL and 5.4 ng*days for the percentage increase in A 4 , the maximum A 4 value and area under the curve values for A 4 , respectively. A 4 response to low-dose rhFSH in PCOS has a stronger association with the number of follicles selected than the E 2 reponse. A 4 response preceding the E 2 response is essential for progressive follicle development. Monitoring A 4 rather than E 2 may be more preemptive to define the initial

Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells.

PubMed

Park, Jong-Ju; Seong, Hun-Ki; Kim, Jeong-Soo; Munkhzaya, Byambaragchaa; Kang, Myung-Hwa; Min, Kwan-Sik

2017-06-01

Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn 56 of the α-subunit. Both the rec-eCGs were obtained from CHO-K1 cells. The agonist activation of receptors was analyzed by measuring stimulation time and concentrations of rec-eCGs. Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. The dose-dependent response was highest when 10 ng of rec-eCGβ/α was used. The deglycosylated eCGβ/αΔ56 mutant did not enhance the agonist-stimulated internalization. We concluded that the state of activation of rFSHR and rLH/CGR could be modulated through agonist-stimulated internalization. Our results suggested that the eLH/CGRs are mostly internalized within 60 min by agonist-stimulation by rec-eCG. We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR.

High Serum FSH is Associated with Brown Oocyte Formation and a Lower Pregnacy Rate in Human IVF Parctice.

PubMed

Xu, Hongyi; Deng, Kai; Luo, Qingbing; Chen, Juan; Zhang, Xin; Wang, Xiaoyan; Diao, Honglu; Zhang, Changjun

2016-01-01

To investigate whether brown zona pellucida (ZP) of oocytes affects the outcome of fertilization, embryo quality and pregnancy rate in in vitro fertilization-embryo transfer (IVF-ET). Based on the ZP color of their oocytes, a total number of 703 patients dated from 2012 to 2014 were divided into a normal egg group (group A) and a brown oocyte group (group B), with 629 and 74 cases, respectively. Clinical characteristics, gonadotropin (Gn) days, Gn dosage, serum hormone levels on the day of human chorionic gonadotropin (HCG) injection, ZP thickness (ZPT) of the eggs, fertilization rate, rescue intracytoplasmic sperm injection (rICSI) rate, good-quality embryo rate and pregnancy rate were compared between the two groups. No significant differences were found in the duration and the causes of infertility, and their basal level of endocrine hormone before IVF-ET between normal egg group and brown egg group. The level of serum hormone including estradiol, progesterone and luteinizing hormone on the day of HCG injection were again similar. Moreover, there were no differences in number of mature oocytes, oocyte fertilization rates and rICSI rates after IVF between the two groups. However, we observed that the ZPT of brown oocytes (group B) was higher than that of normal oocytes (group A). Moreover, the Gn dosage and FSH levels on the day of HCG injection were significantly higher in group B than in group A and the good-quality embryo rate and pregnancy rate in group B were lower than those in group A. Compared with normal eggs, oocytes with a brown ZP were found to have a higher ZPT, lower embryo quality and lower pregnancy rate, which might be due to a high Gn dosage injection and high serum FSH levels during IVT-ET cycles. © 2016 The Author(s) Published by S. Karger AG, Basel.

Han Chinese polycystic ovary syndrome risk variants in women of European ancestry: relationship to FSH levels and glucose tolerance.

PubMed

Saxena, R; Georgopoulos, N A; Braaten, T J; Bjonnes, A C; Koika, V; Panidis, D; Welt, C K

2015-06-01

Are PCOS risk variants identified in women of Han Chinese ethnicity also associated with risk of PCOS or the phenotypic features of PCOS in European women? One variant, rs2268361-T, in the intron of FSHR was associated with PCOS and lower FSH levels, while another variant rs705702-G near the RAB5B and SUOX genes was associated with insulin and glucose levels after oral glucose testing in women with PCOS of European ethnicity. Three of the eleven variants associated with PCOS in the Han Chinese genome-wide association studies were also associated with PCOS in at least one European population when corrected for multiple testing (DENND1A, THADA and YAP1). However, additional replication is needed to establish the importance of these variants in European women and to determine the relationship to PCOS phenotypic traits. The study was a case-control examination in a discovery cohort of women with PCOS (n = 485) and controls (n = 407) from Boston (Boston 1). Replication was performed in women from Greece (cases n = 884 and controls n = 311) and an additional cohort from Boston (Boston electronic medical record (EMR); n = 350 cases and n = 1258 controls). Women had PCOS defined by the National Institutes of Health criteria in Boston 1 and Greece (n = 783), with additional subjects fulfilling the Rotterdam criteria (hyperandrogenism, polycystic ovary morphology and regular menses) in Greece (n = 101). Controls in Boston and Greece had regular menstrual cycles and no hyperandrogenism. The second cohort from Boston was defined using the EMR and natural language processing. Allele frequencies for variants associated with PCOS in Han Chinese women were examined in PCOS cases and controls, along with the relationship to quantitative traits. A variant rs2268361-T in an intron of FSHR was associated with PCOS (0.84 [0.76-0.93], OR [95% CI]; P = 0.002). The rs2268361-T was associated with lower FSH levels (-0.15 ± 0.05; P = 0.0029). A variant rs705702-G near RAB5B and SUOX was

Corifollitropin alfa followed by highly purified HMG versus recombinant FSH in young poor ovarian responders: a multicentre randomized controlled clinical trial.

PubMed

Drakopoulos, Panagiotis; Vuong, Thi Ngoc Lan; Ho, Ngoc Anh Vu; Vaiarelli, Alberto; Ho, Manh Tuong; Blockeel, Christophe; Camus, Michel; Lam, Anh Tuan; van de Vijver, Arne; Humaidan, Peter; Tournaye, Herman; Polyzos, Nikolaos P

2017-11-01

Does administration of corifollitropin alfa followed by highly purified (hp) HMG result in higher ongoing pregnancy rates compared with daily recombinant FSH (rFSH) in young poor responders? Corifollitropin alfa followed by hp-HMG does not increase ongoing pregnancy rates compared with rFSH in young poor responders, although more supernumerary cryopreserved embryos were obtained with corifollitropin alfa and hp-HMG. Poor ovarian response remains one of the main therapeutic challenges in women undergoing ovarian stimulation, given that very low live birth rates of 6% have been reported in this particular group of infertile patients. Nevertheless, concerns have been raised that a degree of heterogeneity remains, as the prognostic effect of individual factors is still unclear, particularly for the young poor responder group. The rationale for conducting the current randomized trial was based on the results of a previous pilot study demonstrating promising results with the administration of hp-HMG following corifollitropin alpha in women younger than 40 years of age, fulfilling the 'Bologna' criteria. A multicenter, phase III, superiority, randomized trial was conducted using a parallel two-arm design. The study included 152 patients younger than 40 years old and fulfilling the 'Bologna' criteria for poor ovarian response, from one tertiary referral centre in Europe and one tertiary referral centre in Asia. Enrolment was performed from March 2013 to May 2016. Eligible patients were randomized to either administration of 150 μg corifollitropin alfa followed by 300 IU hp-HMG (Group A) or to 300 IU of daily recombinant FSH (Group B) in a fixed GnRH antagonist protocol. The randomization sequence was created using a computer generated randomization list stratified by centre, using 1:1 allocation. The primary outcome was ongoing pregnancy rate (defined as the presence of an intrauterine gestational sac with an embryonic pole demonstrating cardiac activity at 9-10 weeks of

Overexpression of hyaluronan synthase 2 and gonadotropin receptors in cumulus cells of goats subjected to one-shot eCG/FSH hormonal treatment for ovarian stimulation.

PubMed

Santos, Juliana D R; Batista, Ribrio I T P; Magalhães, Livia C; Paula, Alexandre R; Souza, Samara S; Salamone, Daniel F; Bhat, Maajid H; Teixeira, Dárcio I A; Freitas, Vicente J F; Melo, Luciana M

2016-07-01

Hormonal ovarian stimulation may affect transcripts in somatic cells of cumulus-oocyte complexes (COCs) and affect the resulting oocyte quality. Here, in parallel with morphological classification and in vitro maturation (IVM) rate analysis, we investigated the expression of hyaluronan synthase 2 (HAS2), gonadotropic receptors (FSHR and LHR) and connexin 43 (GJA1) in cumulus cells (CCs) from goat COCs after multi-dose FSH (MD) or one-shot FSH/eCG (OS) treatments, using bovine COCs as control groups. The MD treatment produced more large follicles, and the resulting COCs had a better morphology and IVM rate than were obtained with OS. The OS treatment produced COCs with increased HAS2, FSHR, LHR and GJA1 expression. This gene expression pattern was also observed in the CCs of COCs that showed poor morphological characteristics. On the other hand, the mRNA levels were more similar between groups after IVM; FSHR and LHR were the main genes that showed decreased expression. Some events that occurred in bovine CCs during IVM, such as cell expansion, increased HAS2 expression and decreased GJA1 expression, were less evident or did not occur in goat COCs. In conclusion, increasing HAS2, FSHR, LHR and GJA1 expression in goat COCs does not confer greater meiotic competence to oocytes. Instead, it may result from poor regulation of gene expression in CCs by lower quality oocytes. Finally, cumulus expansion, together with HAS2 upregulation and GJA1 downregulation, seems to be more important for bovine COCs than for goat COCs. Additional studies are needed to investigate the importance of other HAS isoforms and connexins in goat COCs. Copyright © 2016 Elsevier B.V. All rights reserved.

De Novo-Synthesized Retinoic Acid in Ovarian Antral Follicles Enhances FSH-Mediated Ovarian Follicular Cell Differentiation and Female Fertility

PubMed Central

Kawai, Tomoko; Yanaka, Noriyuki; Richards, JoAnne S.

2016-01-01

Retinoic acid (RA) is the active form of vitamin A and is synthesized from retinol by two key enzymes, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH). As the physiological precursor of RA, retinol impacts female reproductive functions and fertility. The expression of Adh1 and Adh5 as well as Aldh1a1 and Aldh1a7 are significantly increased in the ovaries of mice treated with equine chorionic gonadotropin/FSH. The RA receptor is expressed and localized in granulosa cells and is activated by endogenous RA as indicated by LacZ expression in granulosa cells of RA-responsive transgene-LacZ transgenic mice (RA reporter mice). Coinjection of the ADH inhibitor, 4-methylpyrazole, with equine chorionic gonadotropin significantly decreases the number and developmental competence of oocytes ovulated in response to human chorionic gonadotropin/LH as compared with controls. Injections of RA completely reverse the effects of the inhibitor of ovulation and oocyte development. When mice were fed a retinol-free, vitamin A-deficient diet that significantly reduced the serum levels of retinol, the expression of the LH receptor (Lhcgr) was significantly lower in the ovaries of the vitamin A-deficient mice, and injections of human chorionic gonadotropin failed to induce genes controlling ovulation. These results indicate that ovarian de novo biosynthesis of RA is required for the follicular expression of Lhcgr in granulosa cells and their ability to respond to the ovulatory LH surge. PMID:27022678

The cost-effectiveness of IVF in the UK: a comparison of three gonadotrophin treatments.

PubMed

Sykes, D; Out, H J; Palmer, S J; van Loon, J

2001-12-01

The objective of this study was to evaluate the cost-effectiveness of women undergoing IVF treatment with recombinant FSH (rFSH) in comparison with highly purified urinary FSH (uFSH-HP) and human menopausal gonadotrophins (HMG). A decision-analytic model was used to estimate cost-effectiveness ratios for 'the average cost per ongoing pregnancy' and 'incremental cost per additional pregnancy' for women entering into IVF treatment for a maximum of three cycles. The model was constructed based on a previously published large prospective randomized clinical trial comparing rFSH and uFSH-HP. Where necessary, these data were augmented with a combination of expert opinion, evidence from the literature and observational data relating to the management and cost of IVF treatment in the UK. The cost of rFSH, uFSH-HP and HMG were obtained from National Health Service list prices in the UK. The model predicted a cumulative pregnancy rate after three cycles of 57.1% for rFSH and 44.4% for both uFSH-HP and HMG. The cost of IVF treatment was 5135 pounds sterling for rFSH, 4806 pounds sterling for uFSH-HP and 4202 pounds sterling for HMG. When assessed in association with outcomes, the average cost per ongoing pregnancy was more favourable with rFSH (8992 pounds sterling) than with either uFSH-HP (10 834 pounds sterling) or HMG (9472 pounds sterling). The incremental cost per additional pregnancy was 2583 pounds sterling using rFSH instead of uFSH-HP and 7321 pounds sterling using rFSH instead of HMG. These results were robust to changes in the baseline assumptions of the model. rFSH is a cost-effective treatment strategy in ovulation induction prior to IVF.

Suppression of LH during ovarian stimulation: analysing threshold values and effects on ovarian response and the outcome of assisted reproduction in down-regulated women stimulated with recombinant FSH.

PubMed

Balasch, J; Vidal, E; Peñarrubia, J; Casamitjana, R; Carmona, F; Creus, M; Fábregues, F; Vanrell, J A

2001-08-01

It has been recently suggested that gonadotrophin-releasing hormone agonist down-regulation in some normogonadotrophic women may result in profound suppression of LH concentrations, impairing adequate oestradiol synthesis and IVF and pregnancy outcome. The aims of this study, where receiver-operating characteristic (ROC) analysis was used, were: (i) to assess the usefulness of serum LH measurement on stimulation day 7 (S7) as a predictor of ovarian response, IVF outcome, implantation, and the outcome of pregnancy in patients treated with recombinant FSH under pituitary suppression; and (ii) to define the best threshold value, if any, to discriminate between women with 'low' or 'normal' LH concentrations. A total of 144 infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment were included. Seventy-two consecutive patients having a positive pregnancy test (including 58 ongoing pregnancies and 14 early pregnancy losses) were initially selected. As a control non-pregnant group, the next non-conception IVF/ICSI cycle after each conceptual cycle in our assisted reproduction programme was used. The median and range of LH values in non-conception cycles, conception cycles, ongoing pregnancies, and early pregnancy losses, clearly overlapped. ROC analysis showed that serum LH concentration on S7 was unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.52; 95% CI: 0.44 to 0.61) or ongoing pregnancy versus early pregnancy loss groups (AUC(ROC) = 0.59; 95% CI: 0.46 to 0.70). To assess further the potential impact of suppressed concentrations of circulating LH during ovarian stimulation on the outcome of IVF/ICSI treatment, the three threshold values of mid-follicular serum LH proposed in the literature (<1, < or =0.7, <0.5 IU/l) to discriminate between women with 'low' or 'normal' LH were applied to our study population. No significant differences were found with respect to ovarian response, IVF/ICSI outcome, implantation

Prospective, randomized comparison between pulsatile GnRH therapy and combined gonadotropin (FSH+LH) treatment for ovulation induction in women with hypothalamic amenorrhea and underlying polycystic ovary syndrome.

PubMed

Dubourdieu, Sophie; Fréour, Thomas; Dessolle, Lionel; Barrière, Paul

2013-05-01

To compare the efficacy of pulsatile GnRH therapy versus combined gonadotropins for ovulation induction in women with both hypothalamic amenorrhoea and polycystic ovarian syndrome (HA/PCOS) according to their current hypothalamic status. This single-centre, prospective, randomized study was conducted in the Nantes University Hospital, France. Thirty consecutive patients were treated for ovulation induction with either pulsatile GnRH therapy or combined gonadotropins (rFSH+rLH). Frequency of adequate ovarian response (mono- or bi-follicular) and clinical pregnancy rate were then compared between both groups. Ovarian response was similar in both groups with comparable frequency of adequate ovarian response (73% vs 60%), but the clinical pregnancy rate was significantly higher in the pulsatile GnRH therapy group than in the combined gonadotropin group (46% vs 0%). HA/PCOS is a specific subgroup of infertile women. Pulsatile GnRH therapy is an effective and safe method of ovulation induction that can be used successfully in these patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Comparison of the effects of pretreatment with Veramix sponge (medroxyprogesterone acetate) or CIDR (natural progesterone) in combination with an injection of estradiol-17β on ovarian activity, endocrine profiles, and embryo yields in cyclic ewes superovulated in the multiple-dose Folltropin-V (porcine FSH) regimen.

PubMed

Bartlewski, Pawel M; Seaton, Patricia; Szpila, Patrycja; Oliveira, Maria E F; Murawski, Maciej; Schwarz, Tomasz; Kridli, Rami T; Zieba, Dorota A

2015-10-15

Follicular wave status at the beginning of exogenous FSH administration is an important contributor to variability in superovulatory responses in ruminants. Studies in ewes have shown a decrease in the number of ovulations when superovulation is initiated in the presence of ostensibly ovulatory-sized ovarian follicles. Hormonal ablation of large antral follicles with the progestin-estradiol (E2-17β) treatment significantly reduces this variability in superovulated anestrous ewes, but the effects of the treatment in cycling ewes have not yet been assessed. Sixteen Rideau Arcott × Polled Dorset ewes (November-December) received either medroxyprogesterone acetate (MAP)-releasing intravaginal sponges (60 mg) or controlled internal drug release (CIDR) devices (containing 300 mg of natural progesterone) for 14 days (Days 0-14), with a single intramuscular injection of 350 μg of E2-17β on Day 6. The superovulatory treatment consisted of six injections of porcine FSH (Folltropin-V) given twice daily, followed by a bolus GnRH injection (50 μg intramuscular) on Day 15. There were no differences (P < 0.05) in the ovulatory responses and embryo yields between the two groups of ewes. In both subsets of animals, the next follicular wave emerged ∼2.5 days after an E2-17β injection (P > 0.05). A decline in maximum follicle size after an E2-17β injection was more abrupt in CIDR- compared with MAP-treated animals, and the ewes pretreated with exogenous progesterone had significantly more 3-mm follicles at the start of the superovulatory treatment. The metabolic clearance rate of exogenous E2-17β appeared to be greater in MAP-treated ewes, but circulating concentrations of porcine FSH failed to increase significantly after each Folltropin-V injection in CIDR-treated animals. The CIDR-treated ewes exceeded (P < 0.05) their MAP-treated counterparts in serum E2-17β concentrations during superovulation. In spite of differences in antral follicle numbers and endocrine profiles

Follicular development and hormonal levels following highly purified or recombinant follicle-stimulating hormone administration in ovulatory women undergoing ovarian stimulation after pituitary suppression for in vitro fertilization: implications for implantation potential.

PubMed

Balasch, J; Fábregues, F; Creus, M; Peñarrubia, J; Vidal, E; Carmona, F; Puerto, B; Vanrell, J A

2000-01-01

The main goal in the present study was to compare follicular development and estradiol levels after ovarian stimulation in pituitary suppressed normally ovulating women undergoing IVF, using highly purified urinary follicle stimulating hormone (FSH) (u-FSH-HP) and recombinant FSH (rec-FSH). A secondary variable in our study was embryo implantation potential, which is closely related to appropriate follicular development and oocyte competence. For the main purpose of this study, 30 IVF patients (group 1) were treated during IVF consecutive cycles, using the same stimulation protocol, with u-FSH-HP in the first treatment study cycle and rec-FSH in the second one. As a control group (group 2) for implantation rates obtained in cycles treated with rec-FSH, 30 additional IVF patients were included who underwent a second IVF attempt again with u-FSH-HP. The total dose of FSH used and ovarian response obtained in terms of estradiol plasma levels and the total number of growing follicles on the day of human chronic gonadotropin (HCG) injection were similar in both treatment cycles in group 1 but better follicular dynamics and oocyte maturity were obtained with rec-FSH. The implantation rate was significantly higher in rec-FSH treated cycles in patients in group 1 than in control women (group 2). rec-FSH is more efficacious than u-FSH-HP when used in the same patient in inducing multiple follicular development in down-regulated cycles as indicated by ovarian performance and oocyte maturity. In addition, rec-FSH yields significantly higher implantation rates than u-FSH-HP when used in patients undergoing their second IVF attempt.

Investigative clinical study on prostate cancer part VI: Follicle-stimulating hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population.

PubMed

Porcaro, Antonio B; Migliorini, Filippo; Petrozziello, Aldo; Sava, Teodoro; Romano, Mario; Caruso, Beatrice; Cocco, Claudio; Ghimenton, Claudio; Zecchinini Antoniolli, Stefano; Lacola, Vincenzo; Rubilotta, Emanuele; Monaco, Carmelo; Comunale, Luigi

2012-01-01

To evaluate the physiopathology of follicle-stimulating hormone (FSH) along the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer in relation to the available clinical variables and to the subsequent cluster selection of the patient population. The study included 98 patients who were diagnosed with prostate cancer. Age, percentages of positive cores (P+) at transrectal ultrasound scan biopsy, biopsy Gleason score (bGS), luteinizing hormone (LH), FSH, total testosterone, free testosterone (FT) and prostate-specific antigen (PSA) were the continuous clinical variables. All patients had not previously received hormonal manipulations. FSH correlation and multiple linear analyses were computed in the population. The FSH/PSA ratio was computed and then ranked for clustering the population as groups A (0.13≤FSH/PSA≤0.57), B (0.57<FSH/PSA≤1.61) and C (1.61<FSH/PSA≤19.4). The model was assessed by simple linear and multiple linear regression analysis and differences between the groups were assessed by analysis of variance. In the patient population, FSH correlated to LH (p < 0.0001), FT (p = 0.007) and age (p = 0.004). FSH was independently predicted by both LH (p < 0.0001) and PSA (p = 0.04). PSA predicted FSH/PSA A (p < 0.0001), B (p < 0.0001) and C (p = 0.04). On multiple regression analysis, FSH/PSA A was predicted by PSA (p < 0.0001), P+ (p = 0.03) and bGS (p = 0.04); FSH/PSA B by LH (p = 0.002) and PSA (p < 0.0001); FSH/PSA C by LH (p < 0.0001) and PSA (p < 0.0001). Moreover, FSH/PSA A, B and C differed for mean values of FSH (p < 0.0001), LH (p < 0.0001), PSA (p < 0.0001) and PSA/FT ratio (p < 0.0001). FSH/PSA clusters showed features of decreasing aggressive disease as the FSH/PSA ratio progressed from A to C. At the diagnosis of prostate cancer and along the pituitary-testis-prostate axis in a patient population FSH significantly correlated to LH, FT and age, and FSH was independently and significantly predicted by both

[In vitro fertilization in France: economic aspects and influence of the gonadotropin choice (urinary vs. recombinant) on cost].

PubMed

de Mouzon, J; Allavena, E; Schmitt, C; Frappé, M

2004-06-01

The objective of the study was to make an economic evaluation of in vitro fertilization and to determine the impact of some factors on its cost, particularly the choice between recombinant follicle stimulating hormone (r-FSH) and urinary FSH (u-FSH) for ovarian stimulation. Costs were calculated in a Public Health view, by studying two phases: the stimulation cycle (including down-regulation) and the pregnancy (including the neonatal period). The calculation has included the side effects and the frozen embryos transfers. Economic data came from various sources: the French nomenclature on medical treatments (NGAP), the French drugs dictionary (Vidal) and the French Information system medical plan (PMSI). FSH costs were computed according to the currently marketed products, i.e., Fostimon (Laboratoires Genévrier, Sophia-Antipolis, France) for urinary FSH, and Gonal-F (Laboratoires Serono, Boulogne-Billancourt, France) and Puregon (Laboratoires Organon, Puteaux, France) for recombinant FSH. Two different ways of efficacy between u-FSH and r-FSH were considered for the calculations, those reported in Daya's meta-analysis (3.7% in favour of r-FSH for the clinical pregnancy rate per initiated cycle) and in the only double-blind study (Frydman et al., no difference). The annual cost of ART reaches approximately 130 million Euros in France, for the cycles only, and 170 million Euros when including the pregnancy costs. Urinary FSH is much cheaper than recombinant FSH. Whereas the number of administered FSH units was higher in u-FSH, this results in a mean lower cost of 500 Euros per cycle (2422 Euros for u-FSH and 2959 Euros for r-FSH). For one complete year, in France, the potential over cost of recombinant products reaches 24 million Euros when considering only the cycles (128.4 vs. 104.0 million Euros) and 24-31 million Euros when pregnancies and babies (neonatal period) are considered (171.4 vs 140.7 and 147.0 million Euros, respectively). The IVF per baby cost can be

Photonic homeostatics

NASA Astrophysics Data System (ADS)

Liu, Timon C.; Li, Fan-Hui

2010-11-01

Photonic homeostatics is a discipline to study the establishment, maintenance, decay, upgrading and representation of function-specific homoestasis (FSH) by using photonics. FSH is a negative-feedback response of a biosystem to maintain the function-specific fluctuations inside the biosystem so that the function is perfectly performed. A stress may increase sirtuin 1 (SIRT1) activities above FSH-specific SIRT1 activity to induce a function far from its FSH. On the one hand, low level laser irradiation or monochromatic light (LLL) can not modulate a function in its FSH or a stress in its stress-specific homeostasis (StSH), but modulate a function far from its FSH or a stress far from its StSH. On the other hand, the biophotons from a biosystem with its function in its FSH should be less than the one from the biosystem with its function far from its FSH. The non-resonant interaction of low intensity laser irradiation or monochromatic light (LIL) and a kind of membrane protein can be amplified by all the membrane proteins if the function is far from its FSH. This amplification might hold for biophoton emission of the membrane protein so that the photonic spectroscopy can be used to represent the function far from its FSH, which is called photonomics.

Amount of bone loss in relation to time around the final menstrual period and follicle-stimulating hormone staging of the transmenopause.

PubMed

Sowers, MaryFran R; Zheng, Huiyong; Jannausch, Mary L; McConnell, Daniel; Nan, Bin; Harlow, Sioban; Randolph, John F

2010-05-01

The objective of the study was to describe bone loss rates across the transmenopause related to FSH staging and the final menstrual period (FMP). This was a population-based cohort of 629 women (baseline age 24-44 yr) with annual data points over 15 yr. Measures were bone mineral density (BMD), FSH to define four FSH stages, and menstrual bleeding cessation to define the FMP. Bone loss rates were reported by obesity status. Annualized rates of lumbar spine bone loss began in FSH stage 3, which occurs approximately 2 yr prior to the FMP (1.67%/yr); bone loss continued into FSH stage 4 (1.21%/yr). Mean spine BMD in FSH stage 4 was 6.4% less than spine BMD value in FSH stage 1. Annualized rates of femoral neck (FN) bone loss began in FSH stage 3 (0.55%/yr) and continued into FSH stage 4 (0.72%/yr). The FN difference between mean values in FSH stage 1 and FSH stage 4 was 5%. Annualized rates of spine bone loss in the 2 yr prior to the FMP were 1.7%/yr, 3.3%/yr in the 2 yr after the FMP, and 1.1%/yr in the 2- to 7-yr period after the FMP. Nonobese women had lower BMD levels and greater bone loss rates. Spine and FN bone loss accelerates in FSH stage 3. Bone loss also began to accelerate 2 yr before the FMP with the greatest loss occurring in the 2 yr after the FMP. Bone loss rates in both spine and FN BMD were greater in nonobese women than obese women.

Immunization with FSHβ fusion protein antigen prevents bone loss in a rat ovariectomy-induced osteoporosis model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geng, Wenxin; Yan, Xingrong; Du, Huicong

Highlights: •A GST-FSH fusion protein was successfully expressed in E. coli. •Immunization with GST-FSH antigen can raise high-titer anti-FSH polyclonal sera. •Anti-FSH polyclonal sera can neutralize osteoclastogenic effect of FSH in vitro. •FSH immunization can prevent bone loss in a rat osteoporosis model. -- Abstract: Osteoporosis, a metabolic bone disease, threatens postmenopausal women globally. Hormone replacement therapy (HTR), especially estrogen replacement therapy (ERT), is used widely in the clinic because it has been generally accepted that postmenopausal osteoporosis is caused by estrogen deficiency. However, hypogonadal α and β estrogen receptor null mice were only mildly osteopenic, and mice with eithermore » receptor deleted had normal bone mass, indicating that estrogen may not be the only mediator that induces osteoporosis. Recently, follicle-stimulating hormone (FSH), the serum concentration of which increases from the very beginning of menopause, has been found to play a key role in postmenopausal osteoporosis by promoting osteoclastogenesis. In this article, we confirmed that exogenous FSH can enhance osteoclast differentiation in vitro and that this effect can be neutralized by either an anti-FSH monoclonal antibody or anti-FSH polyclonal sera raised by immunizing animals with a recombinant GST-FSHβ fusion protein antigen. Moreover, immunizing ovariectomized rats with the GST-FSHβ antigen does significantly prevent trabecular bone loss and thereby enhance the bone strength, indicating that a FSH-based vaccine may be a promising therapeutic strategy to slow down bone loss in postmenopausal women.« less

A comparison of the efficacy of two doses of letrozole alone or with continuous recombinant follicle-stimulating hormone for ovulation induction in anovulatory women.

PubMed

Wang, Hai-Yan; Zheng, Peng-Sheng

2015-01-01

To determine the efficacy of letrozole alone or with recombinant follicle-stimulating hormone (rFSH) for ovarian induction in anovulatory women. A total of 322 patients undergoing intrauterine insemination (IUI) were included in this retrospective study. Letrozole (2.5 or 5.0 mg) was administered from days 5 to 9 of menses, alone or followed with rFSH started on day 9 until the day of human chorionic gonadotropin administration. A single IUI was performed 24 h after ovulation. The number of follicles, endometrial thickness and serum estradiol levels were significantly higher in the letrozole + rFSH groups than in the letrozole-alone groups (p < 0.05), but no significant difference was found between the two doses of letrozole, whether alone or with rFSH. Women treated with 5.0 mg/day of letrozole + rFSH required a total dose of rFSH similar to women treated with 2.5 mg/day of letrozole + rFSH (230.77 ± 118.29 vs. 258.55 ± 130.13 IU, respectively; p = 0.205). There was no significant difference in pregnancy rates between the two doses of letrozole, whether alone or with rFSH. Treatment with letrozole + rFSH was more efficacious than letrozole alone for pregnancy in the IUI program; however, the effect of 5.0 mg/day of letrozole versus 2.5 mg/day of letrozole on ovulation was equivalent, regardless of whether rFSH was used. © 2014 S. Karger AG, Basel.

Follicle-Stimulating Hormone Increases the Risk of Postmenopausal Osteoporosis by Stimulating Osteoclast Differentiation

PubMed Central

Yu, Chunxiao; Zhang, Xu; Zhang, Haiqing; Guan, Qingbo; Zhao, Jiajun; Xu, Jin

2015-01-01

Objective The objectives of this study were to observe the changes in follicle-stimulating hormone (FSH) and bone mineral density (BMD) in postmenopausal women, to research the relationship between FSH and postmenopausal osteoporosis, and to observe the effects of FSH on osteoclast differentiation in RAW264.7 cells. Methods We analyzed 248 postmenopausal women with normal bone metabolism. A radioimmunoassay (RIA) was used to detect serum FSH, luteinizing hormone (LH), and estradiol (E2). Dual-energy X-ray absorptiometry was used to measure forearm BMD. Then, we analyzed the age-related changes in serum FSH, LH and E2. Additionally, FSH serum concentrations were compared between a group of postmenopausal women with osteoporosis and a control group. Osteoclasts were induced from RAW264.7 cells in vitro by receptor activator of nuclear factor kappa B ligand (RANKL), and these cells were treated with 0, 5, 10, and 20 ng/ml FSH. After the osteoclasts matured, tartrate-resistant acid phosphatase (TRAP) staining was used to identify osteoclasts, and the mRNA expression levels of genes involved in osteoclastic phenotypes and function, such as receptor activator of NF-κB (Rank), Trap, matrix metalloproteinase-9 (Mmp-9) and Cathepsin K, were detected in different groups using real-time PCR (polymerase chain reaction). Results 1. FSH serum concentrations in postmenopausal women with osteoporosis increased notably compared with the control group. 2. RANKL induced RAW264.7 cell differentiation into mature osteoclasts in vitro. 3. FSH increased mRNA expression of genes involved in osteoclastic phenotypes and function, such as Rank, Trap, Mmp-9 and Cathepsin K, in a dose-dependent manner. Conclusions The circulating concentration of FSH may play an important role in the acceleration of bone loss in postmenopausal women. FSH increases osteoclastogenesis in vitro. PMID:26241313

Multiple forms of hypogonadism of central, peripheral or combined origin in males with Prader-Willi syndrome.

PubMed

Radicioni, A F; Di Giorgio, G; Grugni, G; Cuttini, M; Losacco, V; Anzuini, A; Spera, S; Marzano, C; Lenzi, A; Cappa, M; Crinò, A

2012-01-01

Hypogonadism in Prader-Willi syndrome (PWS) is generally attributed to hypothalamic dysfunction or to primary gonadal defect, but pathophysiology is still unclear. To investigate the aetiology of hypothalamic-pituitary-gonadal axis dysfunction in PWS males. Clinical examination and blood sampling for luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, inhibin B and sexhormone-binding globulin (SHBG) were performed in 34 PWS patients, age 5·1-42·7 years, and in 125 healthy males of same age range. All participants were divided into two groups : < or ≥13·5 years. Pubertal PWS patients showed an arrest of pubertal development. Patients <13·5 years had normal LH, FSH, testosterone and 7/10 had low inhibin B. Among those ≥13·5 years, 8/24 patients had normal LH and testosterone, high FSH and low inhibin B. 5/24 had low FSH, LH, testosterone and inhibin B; one showed normal LH and FSH despite low testosterone and inhibin B; 4/24 had low testosterone and LH but normal FSH despite low inhibin B; 6/24 showed high FSH, low inhibin B and normal LH despite low testosterone. Compared with controls, patients <13·5 years had lower LH, inhibin B, similar FSH, testosterone, SHBG levels and testicular volume; those ≥13·5 years had smaller testicular volume, near-significantly lower LH, testosterone, SHBG, inhibin B and higher FSH. PWS patients display heterogeneity of hypogonadism: (i) hypogonadotropic hypogonadism of central origin for LH and/or FSH; (ii) early primary testicular dysfunction (Sertoli cells damage); and (iii) a combined hypogonadism (testicular origin for FSH-inhibin B axis and central origin for LH-T axis). © 2011 Blackwell Publishing Ltd.

Follicle-Stimulating Hormone Increases the Risk of Postmenopausal Osteoporosis by Stimulating Osteoclast Differentiation.

PubMed

Wang, Jie; Zhang, Wenwen; Yu, Chunxiao; Zhang, Xu; Zhang, Haiqing; Guan, Qingbo; Zhao, Jiajun; Xu, Jin

2015-01-01

The objectives of this study were to observe the changes in follicle-stimulating hormone (FSH) and bone mineral density (BMD) in postmenopausal women, to research the relationship between FSH and postmenopausal osteoporosis, and to observe the effects of FSH on osteoclast differentiation in RAW264.7 cells. We analyzed 248 postmenopausal women with normal bone metabolism. A radioimmunoassay (RIA) was used to detect serum FSH, luteinizing hormone (LH), and estradiol (E2). Dual-energy X-ray absorptiometry was used to measure forearm BMD. Then, we analyzed the age-related changes in serum FSH, LH and E2. Additionally, FSH serum concentrations were compared between a group of postmenopausal women with osteoporosis and a control group. Osteoclasts were induced from RAW264.7 cells in vitro by receptor activator of nuclear factor kappa B ligand (RANKL), and these cells were treated with 0, 5, 10, and 20 ng/ml FSH. After the osteoclasts matured, tartrate-resistant acid phosphatase (TRAP) staining was used to identify osteoclasts, and the mRNA expression levels of genes involved in osteoclastic phenotypes and function, such as receptor activator of NF-κB (Rank), Trap, matrix metalloproteinase-9 (Mmp-9) and Cathepsin K, were detected in different groups using real-time PCR (polymerase chain reaction). 1. FSH serum concentrations in postmenopausal women with osteoporosis increased notably compared with the control group. 2. RANKL induced RAW264.7 cell differentiation into mature osteoclasts in vitro. 3. FSH increased mRNA expression of genes involved in osteoclastic phenotypes and function, such as Rank, Trap, Mmp-9 and Cathepsin K, in a dose-dependent manner. The circulating concentration of FSH may play an important role in the acceleration of bone loss in postmenopausal women. FSH increases osteoclastogenesis in vitro.

Follicle-stimulating hormone receptor-mediated uptake of sup 45 Ca sup 2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grasso, P.; Reichert, L.E. Jr.

1990-08-01

We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+more » influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel.« less

What is the optimum maximal gonadotropin dosage used in microdose flare-up cycles in poor responders?

PubMed

Berkkanoglu, Murat; Ozgur, Kemal

2010-07-01

To find out the optimum maximal dosage of recombinant follicle stimulating hormone (rFSH) in microdose gonadotropin-releasing hormone analog (GnRH-a) flare cycles in poor responders. Prospective randomized study. Private infertility clinic. A total of 119 women were taken into the study. The study group underwent a microdose protocol with a GnRH-agonist followed by rFSH administration. On the third day of GnRH-a administration, 119 patients were randomized in three groups to receive daily fixed doses of 300 IU of rFSH (group A, n = 38), or 450 IU of rFSH (group B, n = 39), or 600 IU of rFSH (group C, n = 42). Peak E(2) levels, days of stimulation with rFSH, total rFSH dosage, total number of oocytes retrieved, M2 oocytes retrieved, total number of embryos, number of embryos transferred, number of Grade-1 embryos transferred, clinical pregnancy rate (positive fetal cardiac activity), and cancellation rates of stimulation and embryo transfer. Clinical pregnancy rates were 13.1%, 15.3%, and 16.1% for group A, group B, and group C, respectively. There were no significant differences in the age, peak serum E(2) concentration, days of stimulation with rFSH, total number of M2 oocytes retrieved, number of embryos transferred, clinical pregnancy rates, and cancellation rates of stimulation and embryo transfer between the three groups except for total rFSH dosage. There is no need to use doses above 300 IU of rFSH to increase the pregnancy rate in microdose cycles. In addition, because the duration of stimulation does not differ between the groups, the usage of 300 IU rFSH in microdose cycles results in less total amount of rFSH consumed in a cycle compared with higher dosages, and this would obviously cost less money to the patients. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Determination of porcine plasma follitropin levels during superovulation treatment in cows.

PubMed

Demoustier, M M; Beckers, J F; Van Der Zwalmen, P; Closset, J; Gillard, J L; Ectors, F

1988-08-01

Porcine follicle stimulating hormone (pFSH) and porcine luteinizing hormone (pLH), are widely used to induce superovulation in cows. An advantage of this treatment is that the LH:FSH ratio can be varied to optimize the growth of the ovarian follicles. However, due to the relatively short half-life of FSH, the superovulatory treatment requires numerous injections. A performant radioimmunoassay system (sensitivity=0.2 ng/ml plasma) was used to determine plasma pFSH levels in cows that were superovulated with 2 daily injections of 4 Armour Units (A.U.) of pFSH for 4 d. From plasma profiles, the half-life and the disappearance of pFSH were estimated at 5 h and at 10 to 12 h, respectively, confirming the necessity of using two daily injections.

Conversion of human choriogonadotropin into a follitropin by protein engineering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campbell, R.K.; Dean-Emig, D.M.; Moyle, W.R.

1991-02-01

Human reproduction is dependent upon the action of follicle-stimulating hormone (hFSH), luteinizing hormone (hLH), and chorionic gonadotropin (hCG). While the {alpha} subunits of these heterodimeric proteins can be interchanged without effect on receptor-binding specificity, their {beta} subunits differ and direct hormone binding to either LH/CG or FSH receptors. Previous studies employing chemical modifications of the hormones, monoclonal antibodies, or synthetic peptides have implicated hCG {beta}-subunit residues between Cys-38 and Cys-57 and corresponding regions of hLH{beta} and hFSH{beta} in receptor recognition and activation. Since the {beta} subunits of hCG or hLH and hFSH exhibit very little sequence similarity in this region,more » the authors postulated that these residues might contribute to hormone specificity. To test this hypothesis the authors constructed chimeric hCG/hFSH {beta} subunits, coexpressed them with the human {alpha} subunit, and examined their ability to interact with LH and FSH receptors and hormone-specific monoclonal antibodies. Surprisingly, substitution of hFSH{beta} residues 33-52 for hCG{beta} residues 39-58 had no effect on receptor binding or stimulation. However, substitution of hFSH{beta} residues 88-108 in place of the carboxyl terminus of hCG{beta} (residues 94-145) resulted in a hormone analog identical to hFSH in its ability to bind and stimulate FSH receptors. The altered binding specificity displayed by this analog is not attributable solely to the replacement of hCG{beta} residues 108-145 or substitution of residues in the determinant loop located between hCD{beta} residues 93 and 100.« less

Cadmium, follicle-stimulating hormone, and effects on bone in women age 42-60 years, NHANES III

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gallagher, Carolyn M., E-mail: 2crgallagher@optonline.net; Department of Preventive Medicine, Stony Brook University Medical Center, Stony Brook, New York; Moonga, Baljit S.

Background: Increased body burden of environmental cadmium has been associated with greater risk of decreased bone mineral density (BMD) and osteoporosis in middle-aged and older women, and an inverse relationship has been reported between follicle-stimulating hormone (FSH) and BMD in middle-aged women; however, the relationships between cadmium and FSH are uncertain, and the associations of each with bone loss have not been analyzed in a single population. Objectives: The objective of this study was to evaluate the associations between creatinine-adjusted urinary cadmium (UCd) and FSH levels, and the associations between UCd and FSH with BMD and osteoporosis, in postmenopausal andmore » perimenopausal women aged 42-60 years. Methods: Data were obtained from the Third National Health Examination and Nutrition Survey, 1988-1994 (NHANES III). Outcomes evaluated were serum FSH levels, femoral bone mineral density measured by dual energy X-ray absorptiometry, and osteoporosis indicated by femoral BMD cutoffs based on the international standard. Urinary cadmium levels were analyzed for association with these outcomes, and FSH levels analyzed for association with bone effects, using multiple regression. Subset analysis was conducted by a dichotomous measure of body mass index (BMI) to proxy higher and lower adipose-synthesized estrogen effects. Results: UCd was associated with increased serum FSH in perimenopausal women with high BMI (n=642; {beta}=0.45; p{<=}0.05; R{sup 2}=0.35) and low BMI (n=408; {beta}=0.61; p{<=}0.01; R{sup 2}=0.34). Among perimenopausal women with high BMI, BMD was inversely related to UCd ({beta}=-0.04; p{<=}0.05) and FSH ({beta}=-0.03; p{<=}0.05). In postmenopausal women with low BMI, an incremental increase in FSH was associated with 2.78 greater odds for osteoporosis (109 with and 706 without) (OR=2.78; 95% CI=1.43, 5.42; p{<=}0.01). Conclusion: Long-term cadmium exposure at environmental levels is associated with increased serum FSH, and

The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double-blind, randomized, prospective study.

PubMed

Tarlatzis, B; Tavmergen, E; Szamatowicz, M; Barash, A; Amit, A; Levitas, E; Shoham, Z

2006-01-01

The effect of recombinant human LH (r-hLH; lutropin alfa) in women undergoing controlled ovarian stimulation with recombinant human FSH (r-hFSH) prior to IVF was investigated. After down-regulation with the GnRH agonist, buserelin, 114 normo-ovulatory women (aged 18-37 years) received r-hFSH alone until the lead follicle reached a diameter of 14 mm. Patients were then randomized in a double-blind fashion to receive r-hFSH in addition to r-hLH, 75 IU s.c., or placebo daily for a maximum of 10 days prior to oocyte retrieval and IVF. The primary end-point was the number of metaphase II oocytes. There were no significant differences between treatment groups for the primary end-point. Serum estradiol concentrations on the day of HCG administration were significantly higher in the group receiving r-hLH plus r-hFSH than in the group receiving r-hFSH alone (P = 0.0001), but there were no significant differences between the groups in dose and duration of r-hFSH treatment required, oocyte maturation, fertilization rate, pregnancy rate and live birth rate. In this patient population, the addition of r-hLH during the late follicular phase of a long GnRH agonist and r-hFSH stimulation cycle provides no further benefit in terms of oocyte maturation or other end-points.

Flavonoid-enriched extract from Hippophae rhamnoides seed reduces high fat diet induced obesity, hypertriglyceridemia, and hepatic triglyceride accumulation in C57BL/6 mice.

PubMed

Yang, Xin; Wang, Qian; Pang, Zeng-Run; Pan, Meng-Ran; Zhang, Wen

2017-12-01

Flavonoid-enriched extract from Hippophae rhamnoides L. (Elaeagnaceae) seed (FSH) has shown beneficial effects in anti-hypertension and lowering cholesterol level. However, evidence for its efficacy in treating obesity is limited. We sought to determine if FSH can reduce body weight and regulate lipid metabolism disorder in high fat diet (HFD)-induced obese mouse model, and to investigate potential molecular targets involved. C57BL/6 mice were fed with HFD for 8 weeks to induce obesity. The modeled mice were divided into four groups and treated with vehicle, rosiglitazone (2 mg/kg), low (100 mg/kg) and high (300 mg/kg) dose of FSH, respectively. Normal control was also used. The treatments were administered orally for 9 weeks. We measured the effect of FSH on regulating body weight, various liver and serum parameters, and molecular targets that are key to lipid metabolism. FSH administration at 100 and 300 mg/kg significantly reduced body weight gain by 33.06 and 43.51%, respectively. Additionally, triglyceride concentration in serum and liver were decreased by 15.67 and 49.56%, individually, after FSH (300 mg/kg) treatment. Upon FSH (100 and 300 mg/kg) treatment, PPARα mRNA expression was upregulated in liver (1.24- and 1.42-fold) and in adipose tissue (1.66- and 1.72-fold). Furthermore, FSH downregulated PPARγ protein level both in liver and adipose tissue. Moreover, FSH inhibited macrophage infiltration into adipose tissues, and downregulated TNFα mRNA expression in adipose tissue (38.01-47.70%). This effect was mediated via regulation of PPARγ and PPARα gene expression, and suppression of adipose tissue inflammation.

Recombinant follicle-stimulating hormone: new biotechnology for infertility.

PubMed

Prevost, R R

1998-01-01

The frequency of infertility in developed countries is approximately 8-10%. New drugs are available for assisted reproduction techniques. Two recombinant follicle-stimulating hormone (FSH) products, follitropin-beta (Follistim in the United States, Puregon in Europe) and follitropin-alpha (Gonal-F), join compounds derived through transfecting nonhuman cell lines with genetic material capable of replicating identical amino acid sequences to human compounds. The cell line used for recombinant (r)-FSH production is the Chinese hamster ovary (CHO). Previously, the only agents that showed benefit in controlled ovulatory stimulation were derived from the urine of menopausal women. Those compounds contain additional substances, such as urinary proteins and various amounts of luteininzing hormone. The amino acid sequence of r-FSH is identical to that of human FSH, but the two recombinant products exist in many different isoforms and differ from each other and from human FSH due to varied carbohydrate side chains. Due to variation in the carbohydrate side chains, follitropin-beta in solution has a higher pH than urine-derived FSH, which enhances receptor affinity and therefore is a greater inducer of folliculogenesis. Follitropin-beta does not cause endogenous production of anti-CHO or anti-FSH antibodies, and is well tolerated.

The effectiveness of zinc supplementation in men with isolated hypogonadotropic hypogonadism.

PubMed

Liu, Yan-Ling; Zhang, Man-Na; Tong, Guo-Yu; Sun, Shou-Yue; Zhu, Yan-Hua; Cao, Ying; Zhang, Jie; Huang, Hong; Niu, Ben; Li, Hong; Guo, Qing-Hua; Gao, Yan; Zhu, Da-Long; Li, Xiao-Ying

2017-01-01

A multicenter, open-label, randomized, controlled superiority trial with 18 months of follow-up was conducted to investigate whether oral zinc supplementation could further promote spermatogenesis in males with isolated hypogonadotropic hypogonadism (IHH) receiving sequential purified urinary follicular-stimulating hormone/human chorionic gonadotropin (uFSH/hCG) replacement. Sixty-seven Chinese male IHH patients were recruited from the Departments of Endocrinology in eight tertiary hospitals and randomly allocated into the sequential uFSH/hCG group (Group A, n = 34) or the sequential uFSH plus zinc supplementation group (Group B, n = 33). In Group A, patients received sequential uFSH (75 U, three times a week every other 3 months) and hCG (2000 U, twice a week) treatments. In Group B, patients received oral zinc supplementation (40 mg day-1 ) in addition to the sequential uFSH/hCG treatment given to patients in Group A. The primary outcome was the proportion of patients with a sperm concentration ≥1.0 × 106 ml-1 during the 18 months. The comparison of efficacy between Groups A and B was analyzed. Nineteen of 34 (55.9%) patients receiving sequential uFSH/hCG and 20 of 33 (60.6%) patients receiving sequential uFSH/hCG plus zinc supplementation achieved sperm concentrations ≥1.0 × 106 ml-1 by intention to treat analyses. No differences between Group A and Group B were observed as far as the efficacy of inducing spermatogenesis (P = 0.69). We concluded that the sequential uFSH/hCG plus zinc supplementation regimen had a similar efficacy to the sequential uFSH/hCG treatment alone. The additional improvement of 40 mg day-1 oral zinc supplementation on spermatogenesis and masculinization in male IHH patients is very subtle.

Effects of recombinant gonadotropin hormones on the expression of vitellogenin, gonadotropin subunits and gonadotropin receptors in cinnamon clownfish, Amphiprion melanopus.

PubMed

Kim, Na Na; Habibi, Hamid R; Lee, Jehee; Choi, Cheol Young

2012-08-01

Gonadotropins (GTHs) are the key regulators of reproduction in vertebrates. The present study investigated autoregulatory effects of gonadotropins, using recombinant FSH (rFSH) and LH (rLH) in cinnamon clownfish (Amphiprion melanopus). Experiments were carried out to investigate the actions of cinnamon clownfish rFSH and rLH on expression of GTH subunits, GTH receptors, and vitellogenin (Vtg) mRNA in vivo and in vitro. Plasma estradiol-17β (E(2)) level was also measured in immature fish following treatments with rFSH and rLH. The results demonstrate increasing levels of GTH subunits, GTH-receptors, Vtg mRNA levels, as well as plasma E(2) levels following injection with rFSH and rLH. The findings support the hypothesis that LH and FSH stimulate reproduction, in part, by autoregulatory mechanisms leading to upregulation of GTH receptors and GTH hormone production in cinnamon clownfish. The results provide a framework for better understanding of the mechanisms of GTH-mediated control of reproduction in cinnamon clownfish and other vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.

In vitro production and cryotolerance of prepubertal and adult goat blastocysts obtained from oocytes collected by laparoscopic oocyte-pick-up (LOPU) after FSH treatment.

PubMed

Leoni, Giovanni Giuseppe; Succu, Sara; Satta, Valentina; Paolo, Mereu; Bogliolo, Luisa; Bebbere, Daniela; Spezzigu, Antonio; Madeddu, Manuela; Berlinguer, Fiammetta; Ledda, Sergio; Naitana, Salvatore

2009-01-01

This study compares the developmental capacity and cryotolerance of embryos produced from oocytes of stimulated prepubertal and adult Sarda goats. Twelve prepubertal and 13 adult goats were each given 110 and 175 IU FSH, respectively, and cumulus-oocyte complexes (COCs) were collected by laparoscopic oocyte-pick-up (LOPU). After in vitro maturation, fertilisation and culture (IVMFC), blastocysts were vitrified, warmed and blastocoel re-expansion and gene expression were evaluated. Prepubertal goats produced a higher COCs number than adults (mean +/- s.e.m., 89.67 +/- 5.74 and 26.69 +/- 3.66, respectively; P < 0.01). Lower developmental competence was demonstrated in the prepubertal oocytes as shown by a higher number of COCs discarded before IVM (21.1% and 14.7% for prepubertals and adults, respectively; P < 0.01) and IVF (23.4% v. 9.1%; P < 0.01) and by the lower cleavage (55.6% and 70.3%, respectively; P < 0.01) and blastocyst rates (24.2% and 33.9%, respectively; P < 0.05). Compared with the adult, prepubertal vitrified/warmed blastocysts showed significantly (P < 0.05) lower in vitro viability, as determined by the re-expansion rate (62.5% and 40.3%). No differences were observed in the time required for blastocoel re-expansion or in cyclin B1, E-cadherin, Na/K ATPase, HSP90beta and aquaporin 3 messenger RNA quantity. These results show that in vitro-produced embryos produced from prepubertal goat oocytes have a lower developmental rate and cryotolerance compared with their adult counterparts. However, we can assume that the quality of re-expanded embryos does not differ between the two groups.

Live birth rates after modified natural cycle compared with high-dose FSH stimulation using GnRH antagonists in poor responders.

PubMed

Lainas, Trifon G; Sfontouris, Ioannis A; Venetis, Christos A; Lainas, George T; Zorzovilis, Ioannis Z; Tarlatzis, Basil C; Kolibianakis, Efstratios M

2015-10-01

Do live birth rates differ between modified natural cycles (MNCs) and cycles using high-dose follicle stimulating hormone (HDFSH) with gonadotrophin-releasing hormone (GnRH) antagonist in poor responder patients? Live birth rates are significantly higher in MNC compared with HDFSH GnRH antagonist cycles in poor responder patients. Previous data on the efficiency of MNC in poor responders are very limited and suggest that MNC in vitro fertilization (IVF) does not offer a realistic solution for parenthood in these patients, since live birth rates are disappointingly low. To date, no studies exist comparing MNC with HDFSH stimulation protocols in poor responders. The present retrospective study included 161 MNCs (106 women in the MNC group) and 164 HDFSH antagonist cycles (136 women in the HDFSH group) performed between January 2008 and December 2013 at Eugonia Assisted Reproduction Unit. The patients included in the study had to fulfill the Bologna criteria for the definition of poor ovarian response. Irrespective of their age, poor responder patients should have a diminished ovarian reserve as shown by low antral follicle count (≤5) and increased basal FSH (>12 IU/l), and one or more previous failed IVF cycles in which ≤3 oocytes were retrieved using a high gonadotrophin dose. Analysis was performed by adjusting for the non-independence of the data. The probability of live birth was significantly higher in the MNC when compared with the HDFSH group (OR: 4.01, 95% CI: 1.14-14.09), after adjusting for basal FSH, female age and cause of infertility, variables which were shown to be associated with the probability of live birth in univariable analysis. MNCs were characterized by significantly lower total gonadotrophin dose (490.0 ± 35.2 IU versus 2826.1 ± 93.4 IU, P < 0.001), lower estradiol concentrations (237.5 ± 12.3 pg/ml versus 487.3 ± 29.8 pg/ml, P < 0.001), fewer follicles present on the day of hCG (1.9 ± 0.1 versus 3.2 ± 0.2, P < 0.001), fewer oocytes

Effect of human gonadotropins on spermiation and androgen biosynthesis in the testis of the toad Bufo arenarum (Amphibia, Anura).

PubMed

Pozzi, Andrea Gabriela; Rosemblit, Cinthia; Ceballos, Nora Raquel

2006-01-01

This paper analyzes, in the toad Bufo arenarum, the effect on spermiation and androgen secretion of two human recombinant gonadotropins, human recombinant LH (hrLH) and human recombinant FSH (hrFSH) as well as the well-known spermiation-inducing hormone, human chorionic gonadotropin (hCG). For this purpose, testes were incubated with different concentrations of hrLH (0.01-2.5 microg/ml) and hrFSH (0.05-5 microg/ml), and results were compared with those obtained with 2.5 microg/ml hCG. Spermiation was most efficiently stimulated by hrFSH, which elicited a higher response than either hrLH or hCG. Both hrFSH and hrLH produced a bell-shaped dose-response curve, with a 50% inhibition on spermiation at a concentration twice higher than that necessary to get the highest response. However, none of the gonadotropins yielded a biphasic response on androgen secretion, hrLH producing the highest response at a concentration that evoked a 70% inhibition in the spermiation test. Regarding steroidogenesis, hrLH and hrFSH were more active than hCG. Taken together, the results described in this paper suggest that, in B. arenarum, spermiation and androgen secretion are mediated by different receptors. After comparing the effects of recombinant hormones, we conclude that hrFSH has a greater effect on spermiation than hCG or hrLH.

The effects of EGF and IGF-1 on FSH-mediated in vitro maturation of domestic cat oocytes derived from follicular and luteal stages.

PubMed

Yıldırım, Koray; Vural, M Rıfat; Küplülü, Sükrü; Ozcan, Ziya; Polat, I Mert

2014-04-01

The objective of this study was to evaluate the influence of epidermal growth factor (EGF) and insulin like growth factor-I (IGF-1) on the in vitro maturation of cat oocytes recovered from follicular and luteal stage ovaries. Oocytes from follicular (n=580) and luteal (n=209) stages were harvested and divided into four groups, which were cultured in FSH-mediated maturation medium supplemented with: (1) EGF alone (25ng/mL); (2) IGF-1 alone (100ng/mL); (3) EGF+IGF-1 (25ng/mL EGF+100ng/mL IGF-I); or (4) no growth factor (control). The proportion of follicular stage oocytes reaching the metaphase II stage was significantly higher than that of oocytes obtained at the luteal stage in both control and study groups (p<0.001). The percentages of oocytes reaching the metaphase II stage during the follicular period were 62.6% in control; 70.9% in EGF; 72.8% in IGF-1, and 78.1% in EGF+IGF-1 groups, whereas the respective values for gametes collected from luteal stage ovaries were 12.5%, 17.5%, 12.5%, and 16.9%. Additionally, the differences between the study and control groups were significant in the case of follicular stage oocytes. Finally, supplementing the maturation medium with EGF and/or IGF-1 significantly enhanced the meiotic maturation of oocytes recovered from follicular stage ovaries. The present study also demonstrated that the combination of EGF and IGF-I provides an additional or synergic effect on meiotic maturation of oocytes recovered from the follicular stage. Copyright © 2014 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Superstimulation prior to the ovum pick-up to improve in vitro embryo production in lactating and non-lactating Holstein cows.

PubMed

Vieira, L M; Rodrigues, C A; Castro Netto, A; Guerreiro, B M; Silveira, C R A; Moreira, R J C; Sá Filho, M F; Bó, G A; Mapletoft, R J; Baruselli, P S

2014-07-15

The present study evaluated the efficacy of superstimulation with p-FSH (Folltropin) before the ovum pick-up (OPU) on IVP in lactating and nonlactating Holstein donors. A total of 30 Holstein cows (15 lactating and 15 nonlactating) were blocked by lactation status to one of two groups (control or p-FSH), in a cross-over design. On a random day of the estrous cycle, all cows received an intravaginal progesterone device and 2.0 mg IM of estradiol benzoate (Day 0). Cows in the control group received no further treatment, whereas cows in the p-FSH group received a total dosage of 200 mg of p-FSH on Days 4 and 5 in four decreasing doses 12 hours apart (57, 57, 43, and 43 mg). On Day 7, the progesterone device was removed, and OPU was conducted in both groups (40 hours after the last p-FSH injection in the p-FSH-treated group). There was no difference between groups (P = 0.92) in the numbers of follicles that were aspirated per OPU session (17.2 ± 1.3 vs. 17.1 ± 1.1 in control and p-FSH-treated cows, respectively); however, p-FSH-treated cows had a higher (P < 0.001) percentage of medium-sized follicles (6-10 mm) at the time of the OPU (55.1%; 285/517) than control cows (20.8%; 107/514). Although recovery rate was lower (60.0%, 310/517 vs. 69.8%, 359/514; P = 0.002), p-FSH-treated cows had a higher blastocyst production rate (34.5%, 89/258 vs. 19.8%, 55/278; P < 0.001) and more transferable embryos per OPU session were produced in the p-FSH group (3.0 ± 0.5 vs. 1.8 ± 0.4; P = 0.02). Regardless of treatment, non-lactating cows had a higher blastocyst rate (41.9%, 106/253 vs. 13.4%, 38/283; P = 0.001) and produced more transferable embryos per OPU session (3.5 ± 0.5 vs. 1.3 ± 0.3; P = 0.003) than lactating cows. Thus, superstimulation of Holstein donors with p-FSH before OPU increased the efficiency of IVP. In addition, non-lactating donors had higher percentage of in vitro blastocyst development and produced more embryos per OPU session than lactating cows

Effects of gonadotropin-releasing hormone agonist/recombinant follicle-stimulating hormone versus gonadotropin-releasing hormone antagonist/recombinant follicle-stimulating hormone on follicular fluid levels of adhesion molecules during in vitro fertilization.

PubMed

Fornaro, Felice; Cobellis, Luigi; Mele, Daniela; Tassou, Argyrò; Badolati, Barbara; Sorrentino, Simona; De Lucia, Domenico; Colacurci, Nicola

2007-01-01

To compare the effects of GnRH-agonist/recombinant rFSH versus GnRH-antagonist/recombinant FSH stimulation on follicular fluid levels of soluble intercellular adhesion molecule (sICAM)-1 and vascular cell adhesion molecule-1 (sVCAM-1) during in vitro fertilization (IVF). Prospective, randomized study. University hospital. Seventy-three women underwent IVF. GnRH-agonist/rFSH or GnRH-antagonist/rFSH administration and collection of follicular fluid from 3 small (11-14 mm in diameter) and 3 large (18-21 mm in diameter) follicles on the day of oocyte retrieval. Follicular fluid levels of sICAM-1 and sVCAM-1 and intrafollicular estradiol and progesterone were also measured. Women who underwent GnRH-agonist/rFSH showed higher concentrations of sICAM-1 in both small and large follicles were compared with patients who received GnRH-antagonist/rFSH treatment; follicular fluid levels of sVCAM-1 were similar between the 2 stimulation protocols. Content of sICAM-1 in small and large follicles positively correlated with the number of follicles of > or =15 mm and the number of oocytes that were retrieved in both study groups. Concentrations of follicular fluid sVCAM-1 and progesterone were higher in large than in small follicles and were correlated positively to each other in both follicular classes. In IVF, GnRH-agonist/rFSH is associated with higher follicular fluid levels of sICAM-1 compared with GnRH-antagonist/rFSH regimen. Intrafollicular sICAM-1 content may predict ovarian response, and sVCAM-1 appears as an indicator of the degree of follicular luteinization.

High frequency of discordance between antimüllerian hormone and follicle-stimulating hormone levels in serum from estradiol-confirmed days 2 to 4 of the menstrual cycle from 5,354 women in U.S. fertility centers.

PubMed

Leader, Benjamin; Hegde, Aparna; Baca, Quentin; Stone, Kimberly; Lannon, Benjamin; Seifer, David B; Broekmans, Frank; Baker, Valerie L

2012-10-01

To determine the frequency of clinical discordance between antimüllerian hormone (AMH, ng/mL) and follicle-stimulating hormone (FSH, IU/L) by use of cut points defined by response to controlled ovarian stimulation in the same serum samples drawn on estradiol-confirmed, menstrual cycle days 2 to 4. Retrospective analysis. Fertility centers in 30 U.S. states and a single reference laboratory with uniform testing protocols. 5,354 women, 20 to 45 years of age. None. Frequency of discordance between serum AMH and FSH values. Of the 5,354 women tested, 1 in 5 had discordant AMH and FSH values defined as AMH <0.8 (concerning) with FSH <10 (reassuring) or AMH ≥ 0.8 (reassuring) with FSH ≥ 10 (concerning). Of the women with reassuring FSH values (n = 4,469), the concerning AMH values were found in 1 in 5 women in a highly age-dependent fashion, ranging from 1 in 11 women under 35 years of age to 1 in 3 women above 40 years of age. On the other hand, of the women with reassuring AMH values (n = 3,742), 1 in 18 had concerning FSH values, a frequency that did not vary in a statistically significant fashion by age. Clinical discordance in serum AMH and FSH values was frequent and age dependent using common clinical cut points, a large patient population, one reference laboratory, and uniform testing methodology. This conclusion is generalizable to women undergoing fertility evaluation, although AMH testing has not been standardized among laboratories, and the cut points presented are specific to the laboratory in this study. Copyright © 2012. Published by Elsevier Inc.

GnRH-agonist implantation of prepubertal male cats affects their reproductive performance and testicular LH receptor and FSH receptor expression.

PubMed

Mehl, N S; Khalid, M; Srisuwatanasagul, S; Swangchan-Uthai, T; Sirivaidyapong, S

2016-03-15

This study was conducted to investigate the effect of GnRH-agonist implantation in prepubertal tomcats on sexual behavior, reproductive performance, and expression of testicular LH receptor (LHR) and FSH receptor (FSHR) and also to compare the testicular characteristics, LHR and FSHR expression between prepubertal and adult tomcats. In experiment 1, 3-month-old tomcats (n = 6/group) were either treated with or left without 4.7 mg deslorelin implants. Semen collection and evaluation were performed just before castration at 48 weeks after treatment; removed testes were analyzed for mRNA and protein expression of LHR and FSHR. We were able to collect semen from six non-treated cats, whereas in treated cats, semen was uncollectable. The results revealed that sexual behavior was absent in the implanted cats throughout the study period. Testicular volume was found to decrease from 30 weeks after treatment onward in the implanted cats compared to the controls (P < 0.05). Semen production was found only in non-implanted cats. Testicular tissue score, seminiferous tubule diameter, and LHR protein expression were found lower in the implanted cats (P < 0.05), but no differences were observed in mRNA expression of LHR and protein expression of FSHR between groups. The mRNA expression of FSHR was higher in the implanted (P < 0.05) compared to control cats. In experiment 2, testes from prepubertal (n = 6) and adult (n = 6) male cats were collected after castration and analyzed for mRNA and protein expression of LHR and FSHR. No differences were observed in the protein expression of LHR and FSHR between the two groups, whereas mRNA expression of FSHR was higher in prepubertal cats (P < 0.05). Testicular and epididymal weight, diameter of seminiferous tubules, and the testicular grade were higher in the adult compared to prepubertal cats (P < 0.05). In conclusion, deslorelin implants suppressed protein expression of LHR and enhanced mRNA expression of FSHR along with suppression

Efficacy and safety of follitropin alfa/lutropin alfa in ART: a randomized controlled trial in poor ovarian responders.

PubMed

Humaidan, P; Chin, W; Rogoff, D; D'Hooghe, T; Longobardi, S; Hubbard, J; Schertz, J

2017-03-01

How does the efficacy and safety of a fixed-ratio combination of recombinant human FSH plus recombinant human LH (follitropin alfa plus lutropin alfa; r-hFSH/r-hLH) compare with that of r-hFSH monotherapy for controlled ovarian stimulation (COS) in patients with poor ovarian response (POR)? The primary and secondary efficacy endpoints were comparable between treatment groups and the safety profile of both treatment regimens was favourable. Although meta-analyses of clinical trials have suggested some beneficial effect on reproductive outcomes with r-hLH supplementation in patients with POR, the definitions of POR were heterogeneous and limit the comparability across studies. Phase III, single-blind, active-comparator, randomized, parallel-group clinical trial. Patients were followed for a single ART cycle. A total of 939 women were randomized (1:1) to receive either r-hFSH/r-hLH or r-hFSH. Randomization, stratified by study site and participant age, was conducted via an interactive voice response system. Women classified as having POR, based on criteria incorporating the ESHRE Bologna criteria, were down-regulated with a long GnRH agonist protocol and following successful down-regulation were randomized (1:1) to COS with r-hFSH/r-hLH or r-hFSH alone. The primary efficacy endpoint was the number of oocytes retrieved following COS. Safety endpoints included the incidence of adverse events, including ovarian hyperstimulation syndrome (OHSS). Post hoc analyses investigated safety outcomes and correlations between live birth and baseline characteristics (age and number of oocytes retrieved in previous ART treatment cycles or serum anti-Müllerian hormone (AMH)). The significance of the treatment effect was tested by generalized linear models (Poisson regression for counts and logistic regression for binary endpoints) adjusting for age and country. Of 949 subjects achieving down-regulation, 939 were randomized to r-hFSH/r-hLH (n = 477) or r-hFSH (n = 462) and received

Plurihormonal cells of normal anterior pituitary: Facts and conclusions

PubMed Central

Mitrofanova, Lubov B.; Konovalov, Petr V.; Krylova, Julia S.; Polyakova, Victoria O.; Kvetnoy, Igor M.

2017-01-01

Introduction plurihormonality of pituitary adenomas is an ability of adenoma cells to produce more than one hormone. After the immunohistochemical analysis had become a routine part of the morphological study, a great number of adenomas appeared to be multihormonal in actual practice. We hypothesize that the same cells of a normal pituitary gland releases several hormones simultaneously. Objective To analyse a possible co-expression of hormones by the cells of the normal anterior pituitary of adult humans in autopsy material. Materials and methods We studied 10 pituitary glands of 4 women and 6 men with cardiovascular and oncological diseases. Double staining immunohistochemistry using 11 hormone combinations was performed in all the cases. These combinations were: prolactin/thyroid-stimulating hormone (TSH), prolactin/luteinizing hormone (LH), prolactin/follicle-stimulating hormone (FSH), prolactin/adrenocorticotropic hormone (ACTH), growth hormone (GH)/TSH, GH/LH, GH/FSH, GH/ACTH, TSH/LH, TSH/FSH, TSH/ACTH. Laser Confocal Scanning Microscopy with a mixture of primary antibodies was performed in 2 cases. These mixtures were ACTH/prolactin, FSH/prolactin, TSH/prolactin, ACTH/GH, and FSH/GH. Results We found that the same cells of the normal adenohypophysis can co-express prolactin with ACTH, TSH, FSH, LH; GH with ACTH, TSH, FSH, LH, and TSH with ACTH, FSH, LH. The comparison of the average co-expression coefficients of prolactin, GH and TSH with other hormones showed that the TSH co-expression coefficient was significantly the least (9,5±6,9%; 9,6±7,8%; 1,0±1,3% correspondingly). Conclusion Plurihormonality of normal adenohypophysis is an actually existing phenomenon. Identification of different hormones in pituitary adenomas enables to find new ways to improve both diagnostic process and targeted treatment. PMID:28418929

Prevention of microbial hazard on fresh-cut lettuce through adoption of food safety and hygienic practices by lettuce farmers.

PubMed

Oyinlola, Lateefah A; Obadina, Adewale O; Omemu, Adebukunola M; Oyewole, Olusola B

2017-01-01

Lettuce is consumed raw in salads and is susceptible to microbial contamination through environment, agricultural practices, and its morphology, thus, a potential vehicle for food-borne illness. This study investigated the effect of adoption of food safety and hygienic practices by lettuce farmers on the microbial safety of field sourced lettuce in Lagos State, Nigeria. Ten structured questionnaires were administered randomly to 10 lettuce farmers to assess food safety and hygienic practices (FSH). Two farmers who practice FSH and two farmers who do not practice NFSH were finally used for this study. Samples of ready-to-harvest lettuce, manure applied, and irrigation water were obtained for a period of five months (August - December 2013) and analyzed for total plate count (TPC), total coliform count (TCC), Escherichia coli, Listeria spp., Salmonella spp., and Shigella spp . counts. Result of microbial analyses of lettuce samples was compared with international microbiological specification for ready-to-eat foods. Results showed that the range of TPC on lettuce was 6.00 to 8.11 LogCFU/g from FSH farms and TPC of lettuce samples from NFSH farms ranged from 6.66 to 13.64 LogCFU/g. 1.49 to 4.85LogCFU/g were TCC ranges from lettuce samples obtained from FSH farms while NFSH farms had TCC ranging between 3.95 and 10.86 LogCFU/g, respectively. The range of isolated pathogen count on lettuce from FSH and NFSH farms exceeded the international safety standard; there was a significant difference in the microbial count of lettuce from FSH farms and NFSH farms. This study concludes that the lettuce samples obtained did not pass the international microbial safety standards. FSH compliance is a major determinant of the microbial safety of lettuce. Hence, the institution of FSH on farm to improve microbial safety of lettuce produced for public consumption is emphasized.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Hui; Lin, Lu; Haq, Ihtesham Ul

The transcription factor nuclear factor-κB (NF-κB) plays an important role in diverse processes, including cell proliferation and differentiation, apoptosis and inflammation. However, the role of NF-κB in porcine follicle development is not clearly elucidated. In this study, we demonstrated that follicle stimulating hormone (FSH) increased the level of inhibitor of NF-κB (IκB) protein and promoted the cytoplasmic localization of p65, indicating that FSH inhibits the activation of NF-κB in porcine granulosa cells. Moreover, inhibition of NF-κB by FSH or another specific inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), could activate JNK signaling and enhance autophagic activity in porcine granulosa cells. Knockdownmore » of RelA (p65) Subunit of NF-κB by RNA interference abrogated the activation of JNK signaling pathway and the increase of autophagic protein expression by FSH. Meanwhile, the functional significance of FSH or PDTC-mediated autophagy were further investigated. Our results demonstrated that the increased autophagy promoted progesterone secretion in porcine granulosa cells. Blockage of autophagy by chloroquine obviated the FSH or PDTC-induced progesterone production. Taken together, these results indicate that inhibition of NF-κB increased autophagy via JNK signaling, and promote steroidogenesis in porcine granulosa cells. Our results provide new insights into the regulation and function of autophagy in mammalian follicle development. - Highlights: • FSH inhibits the activation of NF-κB in porcine primary granulosa cells. • Inhibition of NF-κB by FSH promotes autophagy via JNK signaling in granulosa cells. • Increased autophagy contributes to progesterone production in granulosa cells. • This is the first report against beclin1 regulation in porcine granulosa cells.« less

Economic evaluation of highly purified human menopausal gonadotropin versus recombinant human follicle-stimulating hormone in fresh and frozen in vitro fertilization/intracytoplasmic sperm-injection cycles in Sweden

PubMed Central

Wex, Jaro; Abou-Setta, Ahmed M

2013-01-01

Gonadotropin-releasing hormone-analog type, fertilization method, and number of embryos available for cryopreservation should be incorporated into economic evaluations of highly purified human menopausal gonadotropin (HP-hMG) and recombinant human follicle-stimulating hormone (r-hFSH), as they may affect treatment costs. We searched for randomized trials and meta-analyses comparing HP-hMG and r-hFSH. Meta-analysis showed no significant difference in live births (odds ratio 0.82, 95% confidence interval [CI] 0.66–1.01), but a greater number of oocytes with r-hFSH (mean difference [MD] 1.96, 95% CI 1.02–2.90). Using a cost-minimization model for Sweden, accounting for embryo availability, survival following thawing, and patient dropout, we simulated patients individually for up to three cycles. R-hFSH was found to be cost-saving, at 2,767 kr (95% CI 1,580–4,057) per patient (€315 or $411); baseline savings were 6.43% of the total HP-hMG cost. In fresh cycles only, the savings for r-hFSH were 1,752 kr (95% CI 48–3,658) per patient (€200 or $260). In univariate sensitivity analyses, savings were obtained until the price of r-hFSH increased by 30% or the dosage of HP-hMG decreased by 38%–62% of baseline value. In probabilistic sensitivity analysis, r-hFSH was cost-saving in 100% of the simulated cohort per patient and in 85% per live birth; the respective percentages for fresh cycles only were 97.3% and 73.1%. In conclusion, a greater number of oocytes with r-hFSH allows for more frozen embryo transfers, thereby reducing overall treatment cost. PMID:23966798

Luteinizing hormone-follicle stimulating hormone ratio as biological predictor of post-partum depression.

PubMed

Ramachandran Pillai, R; Sharon, Leena; Premkumar, Nancy R; Kattimani, Shivanand; Sagili, Haritha; Rajendiran, Soundravally

2017-01-01

Post-partum depression (PPD) is the common adverse outcome of child bearing which affects the wellbeing of both mother and newborn and has long-term effects. Hence, reliable potential biological tests for early detection of PPD are essential. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were associated with depressive disorders and the present study estimated the levels of serum FSH, LH in postpartum depression and explored them as predictive biomarkers in the development of PPD. In this nested case control study done at a tertiary care hospital in South India, 450 postpartum women were screened at 6th week post-delivery for PPD. Socio-demographic and clinical data were recorded and depressive symptoms were assessed using Edinburgh Postnatal Depression Scale (EPDS). Out of 450 subjects screened, 100 women with depressive symptoms were categorized as cases and 100 controls were selected from the remaining subjects matching for age and BMI with cases. Serum levels of FSH and LH were measured using direct competitive immunoassay by chemiluminescene technology. Serum LH/FSH ratio was found to be significantly (p=0.02) low in PPD women when compared to normal postpartum subjects. We also found a significant negative correlation between LH/FSH ratio and EPDS scores. Based on the receiver operating characteristic curve, the optimal cut-off value for serum of LH/FSH levels in predicting postpartum depression was estimated to be 0.22mlU/mL with an AUC of 0.598 (95%CI, 0.291-0.859). Our study demonstrated that low LH/FSH ratio after delivery was associated with increased risk for the development of PPD. Low LH/FSH ratio at six-week post delivery can be used as a robust biochemical predictor of post-partum depression. Copyright © 2016 Elsevier Inc. All rights reserved.

Large, comparative, randomized double-blind trial confirming noninferiority of pregnancy rates for corifollitropin alfa compared with recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist controlled ovarian stimulation protocol in older patients undergoing in vitro fertilization.

PubMed

Boostanfar, Robert; Shapiro, Bruce; Levy, Michael; Rosenwaks, Zev; Witjes, Han; Stegmann, Barbara J; Elbers, Jolanda; Gordon, Keith; Mannaerts, Bernadette

2015-07-01

To compare corifollitropin alfa with recombinant FSH treatment in terms of the vital pregnancy rate in older patients undergoing IVF. Phase 3 randomized, double-blind, noninferiority trial. Multicenter trial. A total of 1,390 women aged 35-42 years. A single injection of 150 μg of corifollitropin alfa or daily 300 IU of recombinant FSH for the first 7 days then daily recombinant FSH until three follicles reach ≥17 mm in size. Ganirelix was started on stimulation day 5 up to and including the day of recombinant hCG administration. If available, two good quality embryos were transferred on day 3. Vital pregnancy rate (PR), number of oocytes, and live birth rate. Vital PRs per started cycle were 23.9% in the corifollitropin alfa group and 26.9% in the recombinant FSH group, with an estimated difference (95% confidence interval) of -3.0% (-7.4 to 1.4). The mean (SD) number of recovered oocytes per started cycle was 10.7 (7.2) and 10.3 (6.8) in the corifollitropin alfa and the recombinant FSH groups, respectively, with an estimated difference of 0.5 (-0.2 to 1.2). The live birth rates per started cycle were 21.3% in the corifollitropin alfa group and 23.4% in the recombinant FSH group, with an estimated difference (95% confidence interval) -2.3% (-6.5 to 1.9). The incidence of serious adverse events was 0.4% versus 2.7% in the corifollitropin alfa and recombinant FSH groups, respectively, and of ovarian hyperstimulation syndrome (OHSS; all grades) was 1.7% in both groups. Treatment with corifollitropin alfa was proven noninferior to daily recombinant FSH with respect to vital PRs, number of oocytes retrieved, and live birth rates, and was generally well tolerated. NCT01144416. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The combined effect of age and basal follicle-stimulating hormone on the cost of a live birth at assisted reproductive technology.

PubMed

Henne, Melinda B; Stegmann, Barbara J; Neithardt, Adrienne B; Catherino, William H; Armstrong, Alicia Y; Kao, Tzu-Cheg; Segars, James H

2008-01-01

To predict the cost of a delivery following assisted reproductive technologies (ART). Cost analysis based on retrospective chart analysis. University-based ART program. Women aged >or=26 and FSH levels FSH was used to estimate the probability of a live birth. Cost analysis was applied to the resulting prediction. The predicted probability of a live birth following ART based on a woman's age and FSH and the associated cost of a live birth. Analysis of 1,238 first ART cycles produced a prediction model for live birth rates following ART incorporating both age and FSH. A cost analysis based upon combination of age and FSH revealed the cost of a live birth exceeded $100,000 when the probability of a live birth fell below 15% and the cost rose exponentially at lower probabilities of live birth. Based upon a woman's age and FSH and expected cost for a live birth using ART may be calculated. At live birth rates <5%, the cost of ART is high and greatly exceeds the cost of donor cycles. This information is vital for patient counseling.

Serum androgen and gonadotropin levels decline after progestogen-induced withdrawal bleeding in oligomenorrheic women with or without polycystic ovaries.

PubMed

Anttila, L; Koskinen, P; Kaihola, H L; Erkkola, R; Irjala, K; Ruutiainen, K

1992-10-01

To examine the effect of short-term progestogen treatment on androgen, gonadotropin, and sex hormone-binding globulin (SHBG) levels in oligomenorrheic women. Comparative study of changes in hormonal parameters in patients with or without ultrasonographically diagnosed polycystic ovarian disease (PCOD). Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. Seventy-five oligomenorrheic women with (n = 51) or without (n = 24) PCOD. Serum concentrations of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG. The levels of T, A, LH, and the LH:FSH ratios decreased significantly after oral treatment with medroxyprogesterone acetate (10 mg/d for 10 days) in non-PCOD women and in women with PCOD decreasing the frequencies of pathological laboratory findings, in particular elevated levels of LH:FSH ratio and A in PCOD women and of LH:FSH ratio in non-PCOD women. The levels of T, A, and LH as well as the LH:FSH ratio were significantly higher in women with PCOD. Obesity was associated with high free androgen indices, low LH:FSH ratios, and low concentrations of LH, A, and SHBG. The serum samples for hormonal analyses used as an aid in diagnosing PCOD should be obtained without pretreatment with progestogen because it masks the biochemical findings of PCOD.

Effect of psychological stress on fertility hormones and seminal quality in male partners of infertile couples.

PubMed

Bhongade, M B; Prasad, S; Jiloha, R C; Ray, P C; Mohapatra, S; Koner, B C

2015-04-01

The present study evaluated the effect of psychological stress on male fertility hormones and seminal quality in male partner of infertile couples. Seventy male partners of infertile couples were evaluated for level of psychological stress using Hospital Anxiety and Depression Score (HADS) questionnaire, serum total testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) by electrochemiluminescence assay and serum GnRH by ELISA. Seminal analysis was performed as per WHO guideline. Nineteen (27%) of them had HADS anxiety and depression score ≥8 (abnormal HADS score). The persons having abnormal HADS had lower serum total testosterone, higher serum FSH and LH than those of persons having normal HADS. Serum total testosterone correlated negatively with HADS, but LH and FSH correlated positively. There was no change in GnRH with the change in stress or testosterone levels. Sperm count, motility and morphologically normal spermatozoa were lower in persons having abnormal HADS. Sperm count correlated positively with total testosterone and negatively with FSH and LH. Abnormal sperm motility and morphology were related to lower testosterone and higher LH and FSH levels. Psychological stress primarily lowers serum total testosterone level with secondary rise in serum LH and FSH levels altering seminal quality. Stress management is warranted for male infertility cases. © 2014 Blackwell Verlag GmbH.

Weight loss increases follicle stimulating hormone in overweight postmenopausal women [corrected].

PubMed

Kim, Catherine; Randolph, John F; Golden, Sherita H; Labrie, Fernand; Kong, Shengchun; Nan, Bin; Barrett-Connor, Elizabeth

2015-01-01

To examine the impact of a weight loss intervention upon follicle stimulating hormone (FSH) levels in postmenopause. Participants were postmenopausal, overweight, glucose-intolerant women not using exogenous estrogen (n = 382) in the Diabetes Prevention Program. Women were randomized to intensive lifestyle change (ILS) with the goals of weight reduction of at least 7% of initial weight and 150 min per week of moderate-intensity exercise, metformin 850 mg twice a day, or placebo administered twice a day. Randomization to ILS led to small increases in FSH between baseline and 1-year follow-up vs. placebo (2.3 IU/l vs. -0.81 IU/l, P < 0.01). Increases in FSH were correlated with decreases in weight (r = -0.165, P < 0.01) and estradiol (E2) (r = -0.464, P < 0.0001) after adjustment for age, race/ethnicity, and randomization arm. Changes in FSH were still significantly associated with changes in weight even after adjustment for E2 levels. Metformin users had reductions in weight but non-significant changes in FSH and E2 levels vs. placebo. Weight loss leads to small increases in FSH among overweight, postmenopausal women, potentially through pathways mediated by endogenous estrogen as well as other pathways. © 2014 The Obesity Society.

Recombinant luteinizing hormone priming in multiple follicular stimulation for in-vitro fertilization in downregulated patients.

PubMed

Lisi, F; Caserta, D; Montanino, M; Berlinghieri, V; Bielli, W; Carfagna, P; Carra, M C; Costantino, A; Lisi, R; Poverini, R; Ciardo, F; Rago, R; Marci, R; Moscarini, M

2012-09-01

Follicle development is controlled amongst other factors by pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) that act in synergy in completing follicle maturation. Exogenous gonadotropins, combined with gonadotropin-releasing hormone agonists, have been successfully used in patients with ovulatory disorders undergoing assisted reproduction. There is some evidence of a beneficial role of androgens or LH administration before FSH stimulation. This study was designed to verify whether the addition of LH in the early follicular phase, in downregulated patients undergoing follicular stimulation for assisted reproduction, would add benefits in terms of general outcomes and pregnancy rates. We compared two groups of patients one of which was treated with recombinant FSH (rFSH) alone and the other with rFSH plus recombinant LH (rLH), in the early follicular phase only. The number of eggs recovered was higher in the group treated with FSH only; however, the number of embryos available at transfer was similar in the two groups and, more importantly, the number of Grades I and II embryos was higher in the group pretreated with LH. Similarly, although biochemical pregnancy rate and clinical pregnancy rates were similar in both groups, a beneficial role of LH priming was demonstrated by the higher implantation rate achieved in these patients.

Gene expression analysis of pig cumulus-oocyte complexes stimulated in vitro with follicle stimulating hormone or epidermal growth factor-like peptides.

PubMed

Blaha, Milan; Nemcova, Lucie; Kepkova, Katerina Vodickova; Vodicka, Petr; Prochazka, Radek

2015-10-06

The gonadotropin-induced resumption of oocyte meiosis in preovulatory follicles is preceded by expression of epidermal growth factor (EGF)-like peptides, amphiregulin (AREG) and epiregulin (EREG), in mural granulosa and cumulus cells. Both the gonadotropins and the EGF-like peptides possess the capacity to stimulate resumption of oocyte meiosis in vitro via activation of a broad signaling network in cumulus cells. To better understand the rapid genomic actions of gonadotropins (FSH) and EGF-like peptides, we analyzed transcriptomes of cumulus cells at 3 h after their stimulation. We hybridized aRNA from cumulus cells to a pig oligonucleotide microarray and compared the transcriptomes of FSH- and AREG/EREG-stimulated cumulus cells with untreated control cells and vice versa. The identified over- and underexpressed genes were subjected to functional genomic analysis according to their molecular and cellular functions. The expression pattern of 50 selected genes with a known or potential function in ovarian development was verified by real-time qRT-PCR. Both FSH and AREG/EREG increased the expression of genes associated with regulation of cell proliferation, cell migration, blood coagulation and extracellular matrix remodeling. FSH alone induced the expression of genes involved in inflammatory response and in the response to reactive oxygen species. Moreover, FSH stimulated the expression of genes closely related to some ovulatory events either exclusively or significantly more than AREG/EREG (AREG, ADAMTS1, HAS2, TNFAIP6, PLAUR, PLAT, and HSD17B7). In contrast to AREG/EREG, FSH also increased the expression of genes coding for key transcription factors (CEBPB, FOS, ID1/3, and NR5A2), which may contribute to the differing expression profiles of FSH- and AREG/EREG-treated cumulus cells. The impact of FSH on cumulus cell gene transcription was higher than the impact of EGF-like factors in terms of the number of cell functions affected as well as the number of over- and

Assessment LOPU-IVF in Japanese sika deer (Cervus nippon nippon) and application to Vietnamese sika deer (Cervus nippon pseudaxis) a related subspecies threatened with extinction.

PubMed

Locatelli, Y; Hendriks, A; Vallet, J-C; Baril, G; Duffard, N; Bon, N; Ortiz, K; Scala, C; Maurel, M-C; Mermillod, P; Legendre, X

2012-12-01

In mammals, recovery of oocytes by laparoscopic ovum pick-up (LOPU) coupled with in vitro production (IVP) of embryos represents a promising strategy for both amplification and genetic management of sparse animals from captive endangered wild species. As integrated technique developed mainly for domestic livestock, LOPU-IVP requires several studies to set up protocols for follicular stimulation or optimization of IVP before envisaging successful transposition to wild species. In deer, many endangered subspecies would be potentially concerned by applying such an approach using common subspecies for protocols optimization. The aim of the present study was to assess efficiency of follicle stimulation using ovine FSH (oFSH) for recovery of oocytes by LOPU in common sika deer (Cervus nippon nippon) before transposition of an optimized methodology for IVP of embryos from endangered Vietnamese sika deer hinds (Cervus nippon pseudaxis). In common sika deer, two doses of oFSH (0.25 and 0.5 U) and two frequencies of administration (12 and 24 h) were compared by monitoring of subsequent ovarian response, quality of oocytes recovered by LOPU, and in vitro developmental competence. In a first experiment, the dose of oFSH administered did not significantly affect the total number of follicles aspirated per hind per session (8.6 ± 1.0 vs. 8.2 ± 1.6 with 0.5 vs. 0.25 U oFSH, respectively; not significant). In a second experiment, frequency of 0.25 U oFSH administration did not affect ovarian response. Efficiency of IVP determined on blastocysts rates after in vitro maturation, fertilization, and development in oviduct epithelial cells coculture was increased when FSH was administered at 12-h intervals. Immune response after several follicular stimulations was detected against exogenous oFSH in plasma from the majority of sika deer hinds but was not associated with decreased ovarian response. When 0.25 U oFSH was administered at 12-h intervals to Vietnamese sika deer (N = 4

FOLLITROPIN RECEPTORS CONTAIN CRYPTIC LIGAND BINDING SITES1

PubMed Central

Lin, Win; Bernard, Michael P.; Cao, Donghui; Myers, Rebecca V.; Kerrigan, John E.; Moyle, William R.

2007-01-01

Human choriogonadotropin (hCG) and follitropin (hFSH) have been shown to contact different regions of the extracellular domains of G-protein coupled lutropin (LHR) and follitropin (FSHR) receptors. We report here that hCG and hFSH analogs interact with an FSHR/LHR chimera having only two unique LHR residues similar to the manners in which they dock with LHR and FSHR, respectively. This shows that although the FSHR does not normally bind hCG, it contains a cryptic lutropin binding site that has the potential to recognize hCG in a manner similar to the LHR. The presence of this cryptic site may explain why equine lutropins bind many mammalian FSHR and why mutations in the transmembrane domain distant from the extracellular domain enable the FSHR to bind hCG. The leucine-rich repeat domain (LRD) of the FSHR also appears to contain a cryptic FSH binding site that is obscured by other parts of the extracellular domain. This will explain why contacts seen in crystals of hFSH complexed with an LRD fragment of the human FSHR are hard to reconcile with the abilities of FSH analogs to interact with membrane G-protein coupled FSHR. We speculate that cryptic lutropin binding sites in the FSHR, which are also likely to be present in thyrotropin receptors (TSHR), permit the physiological regulation of ligand binding specificity. Cryptic FSH binding sites in the LRD may enable alternate spliced forms of the FSHR to interact with FSH. PMID:17059863

Corifollitropin alfa versus recombinant follicle-stimulating hormone: an individual patient data meta-analysis.

PubMed

Griesinger, Georg; Boostanfar, Robert; Gordon, Keith; Gates, Davis; McCrary Sisk, Christine; Stegmann, Barbara J

2016-07-01

A meta-analysis was conducted of individual patient data (n = 3292) from three randomized controlled trials of corifollitropin alfa versus rFSH: Engage (150 µg corifollitropin alfa n = 756; 200 IU rFSH n = 750), Ensure (100 µg corifollitropin alfa n = 268; 150 IU rFSH n = 128), and Pursue (150 µg corifollitropin alfa n = 694; 300 IU rFSH n = 696). Women with regular menstrual cycles aged 18-36 and body weight >60 kg (Engage) or ≤60 kg (Ensure), or women aged 35-42 years and body weight ≥50 kg (Pursue), received a single injection (100 µg or 150 µg) of corifollitropin alfa (based on body weight and age) or daily rFSH. The difference (corifollitropin alfa minus rFSH) in the number of oocytes retrieved was +1.0 (95% CI: 0.5-1.5); vital pregnancy rate: -2.2% (95% CI: -5.3%-0.9%); ongoing pregnancy rate: -1.7% (95% CI: -4.7%-1.4%); and live birth rate: -2.0% (95% CI: -5.0%-1.1%). The odds ratio for overall OHSS was 1.15 (95% CI: 0.82-1.61), and for moderate-to-severe OHSS: 1.29 (95% CI: 0.81-2.05). A single dose of corifollitropin alfa for the first 7 days of ovarian stimulation is a generally well-tolerated and similarly effective treatment compared with daily rFSH. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Bone Mineral Density in Adolescent Girls with Hypogonadotropic and Hypergonadotropic Hypogonadism.

PubMed

Özbek, Mehmet Nuri; Demirbilek, Hüseyin; Baran, Rıza Taner; Baran, Ahmet

2016-06-05

Deficiency of sex steroids has a negative impact on bone mineral content. In studies conducted on postmenopausal women and animal studies, elevated follicle-stimulating hormone (FSH) levels were found to be correlated with a decrease in bone mineralization and osteoporosis. The aim of the present study was to evaluate bone mineral density (BMD) in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism and also to investigate the correlation between FSH level and BMD. The study group included 33 adolescent girls with hypogonadism (14 with hypogonadotropic hypogonadism and 19 with hypergonadotropic hypogonadism). FSH, luteinizing hormone, estradiol levels, and BMD (using dual energy x-ray absorptiometry) were measured. There were no statistically significant differences between the chronological age and bone age of the two patient groups, namely, with hypogonadotropic and hypergonadotropic hypogonadism. There was also no significant difference between BMD z-score values obtained from measurements from the spine and the femur neck of patients in the two groups (p-values were 0.841 and 0.281, respectively). In the hypergonadotropic group, a moderately negative correlation was detected between FSH level and BMD z-score measured from the femur neck (ρ=-0.69, p=0.001), whilst no correlation was observed between FSH levels and height adjusted BMD-z scores measured from the spine (ρ=0.17, p=0.493). FSH level was not found to be an independent variable affecting BMD z-score. BMD z-scores were detected to be similar in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism, and FSH levels were not found to have a clinically relevant impact on BMD.

Factors affecting the outcome of "endometrial scratch" in women with recurrent implantation failure.

PubMed

Coughlan, Carol; Yuan, Xi; Demirol, Aygul; Ledger, William; Li, Tin Chiu

2014-01-01

To examine factors affecting the outcome of the endometrial scratch in women with recurrent implantation failure. A total of 57 eligible patients with a history of recurrent implantation failure underwent an endometrial biopsy in the luteal phase of the menstrual cycle in the month immediately preceding the embryo transfer cycle. The comparative group consisted of a retrospective cohort of 66 women with recurrent implantation failure but without endometrial biopsy. There were no significant differences between the intervention and control groups in terms of age, follicle-stimulating hormone (FSH), free androgen index, anti-Müllerian hormone, body mass index, the number of embryos transferred, and the number of embryo transfer cycles. The clinical pregnancy rate in the intervention group (53%) was significantly (p < 0.001) higher than that of the control group (15%). The only predictive factor was FSH. Women with FSH < or =10 IU/L had a pregnancy rate of 57.8%, significantly (p < 0.05) higher than that (20%) of women with FSH >10 IU/L. Women with a normal FSH are more likely to derive benefit from endometrial scratch.

Follicle-stimulating hormone levels in male workers exposed to urban chemical, physical, and psychosocial stressors.

PubMed

Tomei, G; Tomao, E; Ciarrocca, M; Rosati, M V; Caciari, T; Gamberale, D; Palermo, P; De Sio, S; Tria, M; Panfili, A; Tomei, F

2009-07-01

The aim of this study is to evaluate whether occupational exposure to urban stressors could cause alterations in the follicle-stimulating hormone (FSH) levels in traffic policemen compared to a control group. After excluding the subjects with main confounding factors, traffic policemen and male controls were matched by age, working life, body mass index (BMI), drinking habit, cigarette smoking history, and daily consumption of Italian coffee, 166 traffic policemen and 166 controls were included into the study. FSH levels were significantly higher in traffic policemen compared to male controls (P < 0.05). The distribution of FSH values in traffic policemen and controls was significant (P < 0.05). Our results suggest that occupational exposure to low doses of chemical and psychosocial stressors may alter plasma levels of FSH in traffic policemen more than in the control group. If the results obtained are confirmed by further research, the plasma levels of FSH may be used as early biological markers, valuable for the group, used in occupational set even before the appearance of disorders of male fertility.

Constitutively active follicle-stimulating hormone receptor enables androgen-independent spermatogenesis.

PubMed

Oduwole, Olayiwola O; Peltoketo, Hellevi; Poliandri, Ariel; Vengadabady, Laura; Chrusciel, Marcin; Doroszko, Milena; Samanta, Luna; Owen, Laura; Keevil, Brian; Rahman, Nafis A; Huhtaniemi, Ilpo T

2018-05-01

Spermatogenesis is regulated by the 2 pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This process is considered impossible without the absolute requirement of LH-stimulated testicular testosterone (T) production. The role of FSH remains unclear because men and mice with inactivating FSH receptor (FSHR) mutations are fertile. We revisited the role of FSH in spermatogenesis using transgenic mice expressing a constitutively strongly active FSHR mutant in a LH receptor-null (LHR-null) background. The mutant FSHR reversed the azoospermia and partially restored fertility of Lhr-/- mice. The finding was initially ascribed to the residual Leydig cell T production. However, when T action was completely blocked with the potent antiandrogen flutamide, spermatogenesis persisted. Hence, completely T-independent spermatogenesis is possible through strong FSHR activation, and the dogma of T being a sine qua non for spermatogenesis may need modification. The mechanism for the finding appeared to be that FSHR activation maintained the expression of Sertoli cell genes considered androgen dependent. The translational message of our findings is the possibility of developing a new strategy of high-dose FSH treatment for spermatogenic failure. Our findings also provide an explanation of molecular pathogenesis for Pasqualini syndrome (fertile eunuchs; LH/T deficiency with persistent spermatogenesis) and explain how the hormonal regulation of spermatogenesis has shifted from FSH to T dominance during evolution.

Evaluation of the effect of follicular stimulating hormone on the in vitro bovine spermatogonial stem cells self-renewal: An experimental study

PubMed Central

Jabarpour, Masoome; Tajik, Parviz

2017-01-01

Background: Spermatogonial stem cells (SSCs) are undifferentiated cells which are highly reproducible and expandable. Several studies have been conducted to reproduce these cells in culture. They used growth factors, hormones and different feeder cells to improve survival and proliferation of SSCs. Objective: This study was conducted to evaluate the effects of follicular stimulating hormone (FSH) on gene expression of fibroblast growth factor (FGF2) and glial cell-derived neurotrophic factor (GDNF) in Sertoli cells. Materials and Methods: Sertoli cells and SSCs were isolated from 3-5 month-old calves. Bovine testicular cells were cultured for 15 days with or without FSH. Identification of these cells was confirmed by immunocytochemistry analysis. Colony formation of SSCs was evaluated using an inverted microscope. The gene expression of FGF2 and GDNF and the gene markers bcl6b, thy-1, and C-kit were evaluated using the quantitative RT-PCR technique. Results: The results indicated that FSH increased colonization of SSCs. the expression of GDNF, FGF2, and markers of undifferentiated spermatogonia was increased following culture in control and FSH groups (p<0.05), this increase was more in FSH group. Conversely, the expression of C-kit was decreased in both groups (p<0.05). Conclusion: The results showed that FSH can increase the self-renewal of SSCs in vitro via upregulation of GDNF and FGF2 expression in Sertoli cells. PMID:29492477

The Increased Expression of Connexin and VEGF in Mouse Ovarian Tissue Vitrification by Follicle Stimulating Hormone

PubMed Central

Yang, Yanzhou; Chen, Jie; Wu, Hao; Pei, Xiuying; Chang, Qing; Ma, Wenzhi; Ma, Huiming; Hei, Changchun; Zheng, Xiaomin; Cai, Yufang; Zhao, Chengjun; Yu, Jia; Wang, Yanrong

2015-01-01

Ovarian follicular damages were caused by cryoinjury during the process of ovarian vitrification and ischemia/reperfusion during the process of ovarian transplantation. And appropriate FSH plays an important role in antiapoptosis during ovarian follicle development. Therefore, in this study, 0.3 IU/mL FSH was administered into medium during mouse ovarian cryopreservation by vitrification to ascertain the function of FSH on ovarian vitrification and avascular transplantation. The results suggested that the expressions of Cx37, Cx43, apoptotic molecular caspase-3, and angiogenesis molecular VEGF were confirmed using immunohistochemistry, western blotting, and real-time PCR, and the results suggested that the treatment with FSH remarkably increased the number of morphologically normal follicles in vitrified/warmed ovaries by upregulating the expression of Cx37, Cx43, VEGF, and VEGF receptor 2, but downregulating the expression of caspase-3. In addition, the vitrified/warmed ovaries were transplanted, and the related fertility was analyzed, and the results suggested that the fertility, neoangiogenesis, and follicle reserve were remarkably increased in the FSH administrated group. Taken together, administration of 0.3 IU/mL FSH during ovarian cryopreservation by vitrification can maintain ovarian survival during ovarian vitrification and increases the blood supply with avascular transplantation via upregulation of Cx43, Cx37, and VEGF/VEGFR2, as well as through its antiapoptotic effects. PMID:26539488

Use of letrozole in assisted reproduction: a systematic review and meta-analysis

PubMed Central

Requena, Antonio; Herrero, Julio; Landeras, José; Navarro, Esperanza; Neyro, José L.; Salvador, Cristina; Tur, Rosa; Callejo, Justo; Checa, Miguel A.; Farré, Magí; Espinós, Juan J.; Fábregues, Francesc; Graña-Barcia, María

2008-01-01

BACKGROUND Letrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis. METHODS A systematic search of the literature was performed for both prospective and retrospective studies. Meta-analyses of randomized clinical trials (RCTs) were performed for three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in IVF. In the absence of RCTs, non-randomized studies were pooled. RESULTS Nine studies were included in the meta-analysis. Four RCTs compared the overall effect of letrozole with CC in patients with polycystic ovary syndrome. The pooled result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66–2.09), or for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73–2.96) or for pregnancy rate per patient (OR = 1.37; 95% CI 0.70–2.71). In three retrospective studies which compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15 (95% CI 0.78−1.71). A final meta-analysis included one RCT and one cohort study that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI 0.67–2.91). CONCLUSIONS Letrozole is as effective as other methods of ovulation induction. Further randomized-controlled studies are warranted to define more clearly the efficacy and safety of letrozole in human reproduction. PMID:18812422

Follicle-stimulating hormone is independently associated with lean mass but not BMD in younger postmenopausal women

PubMed Central

Gourlay, Margaret L.; Specker, Bonny L.; Li, Chenxi; Hammett-Stabler, Catherine A.; Renner, Jordan B.; Rubin, Janet E.

2011-01-01

Purpose Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated. Methods We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the distal radius using peripheral quantitative computed tomography (pQCT). Results: FSH was inversely correlated with lean and fat mass, bioavailable estradiol, spine and hip aBMD, and vBMD at the ultradistal radius. In the multivariable analysis, FSH was independently associated with lean mass (β= −0.099, p=0.005) after adjustment for age, race, years since menopause, bioavailable estradiol, bioavailable testosterone, LH, PTH, SHBG and urine N-telopeptide. FSH showed no statistically significant association with aBMD at any site or pQCT measures at the distal radius in adjusted models. Race was independently associated with aBMD, and race and urine N-telopeptide were independently associated with bone area and vBMD. Conclusions After adjustment for hormonal measures and osteoporosis risk factors, higher concentrations of FSH were independently associated with lower lean mass, but not with BMD. Previously reported correlations between FSH and BMD might have been due to indirect associations via lean mass or weight. PMID:22086136

Bone Mineral Density in Adolescent Girls with Hypogonadotropic and Hypergonadotropic Hypogonadism

PubMed Central

Özbek, Mehmet Nuri; Demirbilek, Hüseyin; Baran, Rıza Taner; Baran, Ahmet

2016-01-01

Objective: Deficiency of sex steroids has a negative impact on bone mineral content. In studies conducted on postmenopausal women and animal studies, elevated follicle-stimulating hormone (FSH) levels were found to be correlated with a decrease in bone mineralization and osteoporosis. The aim of the present study was to evaluate bone mineral density (BMD) in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism and also to investigate the correlation between FSH level and BMD. Methods: The study group included 33 adolescent girls with hypogonadism (14 with hypogonadotropic hypogonadism and 19 with hypergonadotropic hypogonadism). FSH, luteinizing hormone, estradiol levels, and BMD (using dual energy x-ray absorptiometry) were measured. Results: There were no statistically significant differences between the chronological age and bone age of the two patient groups, namely, with hypogonadotropic and hypergonadotropic hypogonadism. There was also no significant difference between BMD z-score values obtained from measurements from the spine and the femur neck of patients in the two groups (p-values were 0.841 and 0.281, respectively). In the hypergonadotropic group, a moderately negative correlation was detected between FSH level and BMD z-score measured from the femur neck (ρ=-0.69, p=0.001), whilst no correlation was observed between FSH levels and height adjusted BMD-z scores measured from the spine (ρ=0.17, p=0.493). FSH level was not found to be an independent variable affecting BMD z-score. Conclusion: BMD z-scores were detected to be similar in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism, and FSH levels were not found to have a clinically relevant impact on BMD. PMID:27087454

Testicular function in patients with differentiated thyroid carcinoma treated with radioiodine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pacini, F.; Gasperi, M.; Fugazzola, L.

1994-09-01

The aim of the present study was to assess whether {sup 131}I therapy for differentiated thyroid carcinoma (DTC) can affect endocrine testicular function. Serum follicle-stimulating hormone (FSH) and testosterone (T) concentrations were measured in 103 patients periodically submitted for radioiodine therapy for residual or metastatic disease. Mean follow-up was 93.7{+-}54 mo (range 10-243 mo). Mean FSH values in {sup 131}I-treated patients tested after their last treatment were 15.3{+-}9.9 mU/ml, significantly higher than those of 19 untreated patients (6.5{+-}3.1 mU/ml). Considering the mean +3 s.d. FSH of untreated subjects as the upper limit of normal range, 36.8% of the patients hadmore » an abnormal increase in serum FSH. Longitudinal analysis performed in 21 patients showed that the behavior of FSH in response to {sup 131}I therapy was not universal. Six patients had no change or a slight increase in serum FSH after {sup 131}I administration; eleven patients had a transient increase above normal values 6-12 mo after {sup 131}I treatment, with return to normal levels in subsequent months. The administration of a second dose was followed by a similar increase in FSH levels. Finally, four patients, followed for a long period of time and treated with several {sup 131}I doses, showed a progressive increase in serum FSH, which eventually became permanent. Semen analysis, performed in a small subgroup of patients, showed a consistent reduction in the number of normokinetic sperm. No change was found in serum T levels between treated and untreated patients. The results indicate that {sup 131}I therapy for thyroid carcinoma is associated with transient impairment of testicular germinal cell function. The damage may become permanent for high-radiation activities delivered year after year and might pose a significant risk of infertility. 14 refs., 8 figs., 1 tab.« less

The time course of follicle-stimulating hormone suppression by recombinant human inhibin A in the adult male rhesus monkey (Macaca mulatta).

PubMed

Ramaswamy, S; Pohl, C R; McNeilly, A S; Winters, S J; Plant, T M

1998-08-01

In higher primates, FSH secretion appears to be regulated by a control system consistent with that described by the classical inhibin hypothesis. The purpose of the present experiment was to examine the time course of inhibin's action to suppress FSH secretion in the intact adult male rhesus monkey. To this end, five adult males implanted with indwelling venous catheters and exhibiting typical episodic patterns of LH and testosterone (T) secretion received a 4-day i.v. infusion of recombinant human (rh) inhibin A (832 ng/h x kg) followed, after a 4-week interval, by vehicle infusion of similar duration. Changes in circulating FSH concentrations during the inhibin and vehicle infusions were determined using a sensitive homologous macaque RIA, whereas enzyme-linked immunosorbent assays were employed to track inhibin A, inhibin B, and inhibin pro-alpha-C levels during the experiment. Normal pulsatile activity in the hypothalamic-pituitary-Leydig cell axis was confirmed by monitoring changes in circulating concentrations of LH and T in 12-h windows of sequential blood collection (1200-2400 h; every 20 min) before, during, and after the rh inhibin A and vehicle infusions. Although infusion of rh inhibin A, which led to a 12 ng/ml square wave increment in circulating levels of this inhibin dimer, produced a marked decline in circulating FSH concentrations, significant suppression of the secretion of this gonadotropin was not manifest until 54 h after initiation of the infusion. Despite the marked decline in FSH secretion during the last 24 h of the 4-day infusion of recombinant hormone, circulating inhibin B and pro-alpha-C concentrations were maintained at preinfusion control levels (1 ng/ml). The finding that imposition of an exaggerated circulating inhibin signal led to suppression of FSH secretion in the male monkey only after 2 days of exposure to the hormone indicates that in this species the feedback action of testicular inhibin on FSH secretion is heavily lagged

The carriers of the A/G-G/G allelic combination of the c.2039 A>G and c.-29 G>A FSH receptor polymorphisms retrieve the highest number of oocytes in IVF/ICSI cycles.

PubMed

Allegra, Adolfo; Marino, Angelo; Raimondo, Stefania; Maiorana, Antonio; Gullo, Salvatore; Scaglione, Piero; Volpes, Aldo; Alessandro, Riccardo

2017-02-01

The objective of this study was the elucidation of the possible role of the single-nucleotide polymorphisms (SNP) at position -29 and 2039 of the FSH receptor gene (FSHR) as independent predictive markers of ovarian response. Indeed, the tailoring of reproductive treatments is crucial for both maximizing the success of IVF patients and obtaining a reduction in hypo- or hyper-response rates. This prospective, observational study analyzed the association of -29 and 2039 FSHR polymorphisms with the number of retrieved oocytes in 140 patients attending an IVF/ICSI cycle for severe male factors (≤5,000,000 spermatozoa/mL) or tubal factors at the ANDROS Day Surgery Clinic, Palermo, Italy. The results of this study demonstrate that the genetic combination of A/G for polymorphism c.2039 A>G with G/G for polymorphism c.-29 G>A is significantly associated with the highest number of collected oocytes (p = 0.03). This association was significant even after controlling for the effect of other clinical variables. The A/G-G/G allelic variant, identified as an independent variable, if confirmed in a larger number of patients, could be considered as a new genetic biomarker, which could increase the efficacy of prediction models for ovarian stimulation.

Plasma inhibin A in heifers: relationship with follicle dynamics, gonadotropins, and steroids during the estrous cycle and after treatment with bovine follicular fluid.

PubMed

Bleach, E C; Glencross, R G; Feist, S A; Groome, N P; Knight, P G

2001-03-01

The relationship between follicle growth and plasma inhibin A, FSH, LH, estradiol (E), and progesterone was investigated during the normal bovine estrous cycle and after treatment with steroid-free bovine follicular fluid (bFF) to arrest follicle development. In the first study, four heifers were monitored over three prostaglandin (PG)-synchronized cycles. Blood was collected every 2-8 h, and ovaries were examined daily by ultrasonography. Inhibin A was measured using a modified enzyme-linked immunosorbent assay that employed a new monoclonal antibody against the alpha subunit of bovine inhibin. Plasma inhibin A ( approximately 50 pg/ml before luteolysis) rose steadily during the induced follicular phase (P < 0.05) to a peak ( approximately 125 pg/ml) coincident with the preovulatory E/LH/FSH surge. After ovulation, inhibin A fell sharply (P < 0.05) to a nadir ( approximately 55 pg/ml) coincident with the secondary FSH rise. During the next 3 days, inhibin A increased to approximately 90 pg/ml in association with growth of the new dominant follicle (DF). Plasma E also rose twofold during this period, whereas FSH fell by approximately 50%. Inhibin A was negatively correlated with FSH (r = -0.37, P < 0.001) and positively correlated with E (r = 0.49, P < 0.0001). Observations on eight cycles (two cycles/heifer), in which growth of the ovulatory DF was monitored from emergence to ovulation, showed that the first-wave DF (DF1) ovulated in three cycles and the second-wave DF (DF2) in five cycles. After PG, plasma inhibin A and E increased similarly in both groups, with concomitant falls in FSH. In the former group, the restricted ability of DF1 to secrete both inhibin A and E was restored after luteolysis. Results indicate that dynamic changes in the secretion of both E and inhibin A from the DF contribute to the fall in FSH during the follicular phase and to the generation and termination of the secondary FSH surge, both of which play a key role in follicle selection

Follicle-Stimulating Hormone Regulates igfbp Gene Expression Directly or via Downstream Effectors to Modulate Igf3 Effects on Zebrafish Spermatogenesis

PubMed Central

Safian, Diego; van der Kant, Henk J. G.; Crespo, Diego; Bogerd, Jan; Schulz, Rüdiger W.

2017-01-01

Previous work showed that pharmacological inactivation of Igf-binding proteins (Igfbps), modulators of Igf activity, resulted in an excessive differentiation of type A undifferentiated (Aund) spermatogonia in zebrafish testis in tissue culture when Fsh was present in the incubation medium. Using this testis tissue culture system, we studied here the regulation of igfbp transcript levels by Fsh and two of its downstream effectors, Igf3 and 11-ketotestosterone (11-KT). We also explored how Fsh-modulated igfbp expression affected spermatogonial proliferation by adding or removing the Igfbp inhibitor NBI-31772 at different times. Fsh (100 ng/mL) decreased the transcript levels of igfbp1a, -3, and -6a after 1 or 3 days, while increasing igfbp2a and -5b expression, but only after 5 days of incubation. Igf3 down-regulated the same igfbp transcripts as Fsh but with a delay of at least 4 days. 11-KT increased the transcripts (igfbp2a and 5b) that were elevated by Fsh and decreased those of igfbp6a, as did Fsh, while 11-KT did not change igfbp1a or -3 transcript levels. To evaluate Igfbps effects on spermatogenesis, we quantified under different conditions the mitotic indices and relative section areas occupied by the different spermatogonial generations (type Aund, type A differentiating (Adiff), or type B (B) spermatogonia). Igf3 (100 ng/mL) increased the area occupied by Adiff and B while decreasing the one for Aund. Interestingly, a concentration of Igf3 that was inactive by itself (25 ng/mL) became active in the presence of the Igfbp inhibitor NBI-31772 and mimicked the effect of 100 ng/mL Igf3 on spermatogonia. Studies exploiting the different dynamics of igfbp expression in response to Fsh and adding or removing NBI-31772 at different times showed that the quick downregulation of three igfbp as well as the delayed upregulated of two igfbps all support Igf3 bioactivity, namely the stimulation of spermatogonial differentiation. We conclude that Fsh

New radioimmunoassay for follicle-stimulating hormone in macaques: ovulatory menstrual cycles. [/sup 125/I tracer technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hodgen, G.D.; Wilks, J.W.; Vaitukaitis, J.L.

A sensitive and specific radioimmunoassay system for macaque follicle-stimulating hormone (mFSH) was developed utilizing an antiserum (H-31) prepared in a rabbit against purified ovine FSH as the immunogen. Sera from castrated female, adult male, and juvenile rhesus monkeys, as well as urinary extracts from castrated rhesus and bonnet monkeys, were used to demonstrate parallelism with a standard of partially purified monkey pituitary gonadotropins (LER-M-907-D). An extract of baboon pituitary tissue also showed parallelism with the reference standard. A highly purified pituitary extract (WP-X-105-28), containing approximately 75 percent macaque luteinizing hormone (mLH) and 1 percent mFSH, was used to demonstrate themore » specificity of this mFSH assay system. Sera and urinary extracts obtained from hypophysectomized monkeys did not show cross-reactivity in the assay. Macaque chorionic gonadotropin (mCG) did not produce an inhibition curve in the assay, as determined from serum samples and urinary extracts collected from pregnant monkeys at the time of peak mCG secretion. Serum concentrations of mFSH were suppressed in ovariectomized monkeys by the administration of ethinyl estradiol for 3 days, but returned to near pretreatment values by 96 h after the last estradiol administration. The determination of serum mFSH concentrations in daily blood samples obtained from 20 rhesus monkeys throughout ovulatory menstrual cycles revealed a pattern similar to that previously reported for the rhesus monkey and the woman. The peak value of serum mFSH during the menstrual cycle coincided with the midcycle surge of mLH in each case. The gonadotropin peaks were preceded by increasing serum concentrations of estradiol and followed by rises in the serum concentrations of progesterone.« less

Long-acting follicle-stimulating hormone analogs containing N-linked glycosylation exhibited increased bioactivity compared with o-linked analogs in female rats.

PubMed

Weenen, C; Peña, J E; Pollak, S V; Klein, J; Lobel, L; Trousdale, R K; Palmer, S; Lustbader, E G; Ogden, R T; Lustbader, J W

2004-10-01

The effects of altering the number and type of additional carbohydrate moieties on the pharmacokinetic and pharmacodynamic properties of FSH were examined in this report. A series of single-chain follitropins, containing variable numbers of additional N- (or O-) linked carbohydrates, were designed and expressed in Chinese hamster ovary cells. Proper folding, efficient receptor binding, and signal transduction were confirmed by in vitro assays. Pharmacokinetic and pharmacodynamic parameters were evaluated in immature female Sprague Dawley rats. Increasing the number of glycosylation sites with either N- (or O-) linked moieties extended the elimination half-life as much as 2-fold compared with recombinant human FSH (rhFSH). However, there was a maximum elimination half-life such that further glycosylation provided no additional lengthening of the half-life. Conversely, biopotency, as assessed by inhibin A levels 74 h post injection, and follicle production were significantly higher for the N-linked analogs. Rats stimulated with the longest acting analogs (either N- or O-linked) showed significantly higher ovarian weights than rats receiving a single injection of rhFSH. The analog containing four additional N-linked sites (rhFSH-N4) had the greatest number of large, preovulatory follicles. Although the half-life of rhFSH-N4 displayed no further enhancement beyond the other longest acting analogs, this analog exhibited significantly increased biopotency in rats. This work provides the basis for the generation of a series of reagents potentially useful for therapeutic applications.

[Health economic consequences of the choice of follicle stimulating hormone alternatives in IVF treatment].

PubMed

Poulsen, Peter Bo; Højgaard, Astrid; Quartarolo, Jens Piero

2007-04-02

There is a choice between two types of hormones for stimulation of the follicles in IVF treatment - recombinant FSH and the urine-derived menotrophin. A literature review by NICE (2004) in the United Kingdom documented that the two types of hormones were equally effective and safe, which is why it was recommended to use the cheaper urine-derived hormone. Based on the EISG study (European and Israeli Study Group), the aim was to analyse the health economic consequences of the choice between the two types of hormone in IVF treatment in Denmark. In a prospective cost-effectiveness analysis (health care sector perspective), menotrophin and recombinant FSH (Gonal-F) were compared. Differences in costs were compared with differences in effects of the two alternatives. The total costs for the average patient are lower when using menotrophin compared with recombinant FSH. Furthermore, the cost per clinical pregnancy was lower with menotrophin compared with recombinant FSH hormone. Menotrophin is therefore less expensive both for the patient as well as for the health care sector. The use of menotrophin instead of recombinant FSH can result in savings of up to DKK 16 million on the drug budget--savings that could finance 1,400 additional IVF cycles. The analysis shows that urine-derived menotrophin is a cost-effective alternative to recombinant FSH with a potential for considerable savings for patients as well as the public drug budget.

Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

PubMed Central

Rinaldi, Leonardo; Selman, Helmy

2016-01-01

A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH) and recombinant LH (rLH) has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I). In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood. PMID:27307766

Differential responsiveness of luteinized human granulosa cells to gonadotropins and insulin-like growth factor I for induction of aromatase activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christman, G.M.; Randolph, J.F. Jr.; Peegel, H.

1991-06-01

The objective of this study was to examine the in vitro responsiveness of cultured luteinized human granulosa cells over time to insulin-like growth factor 1 (IGF-1), human follicle-stimulating hormone (FSH), and human chorionic gonadotropin (hCG) for the induction of aromatase activity. Granulosa cells were retrieved from preovulatory follicles in patients undergoing in vitro fertilization. Cells were cultured for a period of 72 hours or 10 days. The ability of hCG, human FSH, and/or IGF-I to induce aromatase activity was assayed by the stereospecific release of tritium from (1B-3H)androstenedione. Short-term cultures (72 hours) demonstrated a marked rise in aromatase activity inmore » response to human FSH and IGF-I, whereas a smaller response to hCG was observed. In contrast, 10-day cultures demonstrated responsiveness predominantly to hCG rather than human FSH for the induction of aromatase activity with no remarkable effect of IGF-I. Luteinized human granulosa cells undergo a transformation from an initial human FSH and IGF-I responsive state to an hCG responsive state in long-term cultures.« less

Two proximal activating protein-1-binding sites are sufficient to stimulate transcription of the ovine follicle-stimulating hormone-beta gene

EPA Science Inventory

FSH is an important regulator of mammalian gametogenesis and the female reproductive cycle. Although little is known about the transcriptional regulation of the beta-subunit (the rate-limiting subunit of FSH synthesis), sequence analysis of the ovine FSHbeta promoter has revealed...

The utility of the gonadotrophin releasing hormone (GnRH) test in the diagnosis of polycystic ovary syndrome (PCOS).

PubMed

Lewandowski, Krzysztof C; Cajdler-Łuba, Agata; Salata, Ireneusz; Bieńkiewicz, Małgorzata; Lewiński, Andrzej

2011-01-01

Polycystic ovary syndrome (PCOS) is characterised by increased frequency of hypothalamic GnRH pulses leading to a relative increase in LH synthesis by the pituitary. As GnRH stimulation can reveal a relative LH excess, we have endeavoured to assess whether GnRH test might be useful in the diagnosis of PCOS. The study involved 185 subjects: a PCOS group, n = 151, all with oligo- or amenorrhoea, aged (mean ± SD) 24.8 ± ± 5.4 years, BMI 24.5 ± 6.0 kg/m²; and regularly menstruating controls, n = 34, aged 26.6 ± 5.0 years, BMI 24.6 ± 5.5 kg/m². In 121 subjects with PCOS and in 32 controls, serum LH and FSH were measured before (0 minutes) and 30 and 60 minutes after GnRH stimulation (100 μg i.v.). Insulin resistance was assessed by HOMA and Insulin Resistance Index derived from glucose and insulin concentrations during 75 gram oral glucose tolerance test. Women with PCOS had higher testosterone (p = 0.0002), androstendione (p = 0.0021), 17OH-progesterone (p < 0.0001) and were more insulin resistant. Raised concentrations of at least one androgen were, however, found only in 58.1% of women with PCOS. Baseline and stimulated LH concentrations were higher in PCOS (9.09 ± 5.56 vs 4.83 ± 1.71 IU/L, 35.48 ± 31.4 vs 16.30 ± 6.68 IU/L, 33.86 ± 31.8 vs 13.45 ± 5.2 IU/L, at 0, 30 and 60 mins post GnRH, respectively, p < 0.0001). There was no difference in baseline or stimulated FSH concentrations between groups. Relative increases of LH or FSH in comparison to respective baseline values were similar in both groups. There was, however, a marked increase in LH/FSH ratio in PCOS in comparison to controls (LH0 min/FSH(₀ min) 1.59 ± 0.95 vs 0.76 ± 0.2, LH(₃₀ min) /FSH(₃₀ min) 4.07 ± 3.0 vs 1.89 ± 0.79, LH(₆₀ min)/FSH(₆₀ min) 3.56 ± 2.58 vs 1.55 ± 0.63, p < 0.0001 at all time points). Further analysis revealed that LH30 min/FSH(₃₀ min) > 2.11 or LH(₆₀ min)/FSH(₆₀ min) > 1.72 had 78.3% and 87.5% sensitivity and 81.7% and 81

Follicle-stimulating hormone levels in female workers exposed to urban pollutants.

PubMed

Ciarrocca, Manuela; Caciari, Tiziana; Ponticiello, Barnaba Giuseppina; Gioffrè, Pier Agostino; Tomei, Gianfranco; Sancini, Angela; Schifano, Maria Pia; Palermo, Paola; Nardone, Nadia; Scimitto, Lara; Fiaschetti, Maria; Tomei, Francesco

2011-12-01

The aim of this study was to evaluate if there were alterations in FSH plasma levels in female outdoor workers (traffic policewomen and drivers) exposed to chemical urban stressors vs. control group. After excluding subjects with main confounding factors, traffic policewomen, drivers and indoor workers were matched by age, working life, socioeconomic status, marital status, menstrual cycle day, age of menarche, habitual consumption of Italian coffee and soy. A total of 129 female subjects were included in the study: some 63 workers studied during proliferative phase and 66 during secretory phase of menstrual cycle. Proliferative phase of menstrual cycle: FSH mean values were significantly higher in traffic policewomen compared to controls (p < 0.05). Results suggest that in outdoor workers exposed to urban chemical stressors there are alterations in FSH levels; therefore FSH may be used as an early biological marker, valuable for the group, used in occupational set.

FSH (Follicle-Stimulating Hormone) Test

MedlinePlus

... Time and International Normalized Ratio (PT/INR) PSEN1 Quantitative Immunoglobulins Red Blood Cell (RBC) Antibody Identification Red ... National Institutes of Health Office of Rare Diseases Research. Klinefelter Syndrome. Available online at http://rarediseases.info. ...

3',5'-cyclic adenosine monophosphate response element binding protein up-regulated cytochrome P450 lanosterol 14alpha-demethylase expression involved in follicle-stimulating hormone-induced mouse oocyte maturation.

PubMed

Ning, Gang; Ouyang, Hong; Wang, Songbo; Chen, Xiufen; Xu, Baoshan; Yang, Jiange; Zhang, Hua; Zhang, Meijia; Xia, Guoliang

2008-07-01

Cytochrome P450 lanosterol 14alpha-demethylase (CYP51) is a key enzyme in sterols and steroids biosynthesis that can induce meiotic resumption in mouse oocytes. The present study investigated the expression mechanism and function of CYP51 during FSH-induced mouse cumulus oocyte complexes (COCs) meiotic resumption. FSH increased cAMP-dependent protein kinase (PKA) RIIbeta level and induced cAMP response element-binding protein (CREB) phosphorylation and CYP51 expression in cumulus cells before oocyte meiotic resumption. Moreover, CYP51 and epidermal growth factor (EGF)-like factor [amphiregulin (AR)] expression were blocked by (2)-naphthol-AS-Ephosphate (KG-501) (a drug interrupting the formation of CREB functional complex). KG-501 and RS21607 (a specific inhibitor of CYP51 activity) inhibited oocyte meiotic resumption, which can be partially rescued by progesterone. These two inhibitors also inhibited FSH-induced MAPK phosphorylation. EGF could rescue the suppression by KG-501 but not RS21607. Furthermore, type II PKA analog pairs, N(6)-monobutyryl-cAMP plus 8-bromo-cAMP, increased PKA RIIbeta level and mimicked the action of FSH, including CREB phosphorylation, AR and CYP51 expression, MAPK activation, and oocyte maturation. All these data suggest that CYP51 plays a critical role in FSH-induced meiotic resumption of mouse oocytes. CYP51 and AR gene expression in cumulus cells are triggered by FSH via a type II PKA/CREB-dependent signal pathway. Our study also implicates that CYP51 activity in cumulus cells participates in EGF receptor signaling-regulated oocyte meiotic resumption.

Increased androgen response to follicle-stimulating hormone administration in women with polycystic ovary syndrome.

PubMed

Wachs, Deborah S; Coffler, Mickey S; Malcom, Pamela J; Shimasaki, Shunichi; Chang, R Jeffrey

2008-05-01

In women with polycystic ovary syndrome (PCOS), excess ovarian androgen production is driven by increased LH secretion. Studies conducted in animals suggest that the granulosa cell may influence LH-stimulated theca cell androgen production. The objective of this study was to determine whether FSH enhances androgen production in women with PCOS compared with that of normal women. A prospective study was conducted to compare androgen production in response to FSH in two groups of women. The study was conducted in a General Clinical Research Center in a tertiary academic medical center. Women with PCOS, 18-35 yr (n = 20), and normal ovulatory controls, 18-35 yr (n = 10), were recruited for study. Serial blood samples were obtained over a 24-h period after an iv injection of recombinant human FSH (150 IU). The main outcome measures were serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), dehydroepiandrosterone (DHEA), testosterone (T), and inhibin B (Inh B) responses after FSH administration. Basal serum 17-OHP, A, and T levels were markedly increased in women with PCOS compared with that observed in normal women. Basal DHEA and Inh B levels were similar to those of normal controls. After FSH injection, PCOS women demonstrated enhanced production of 17-OHP, A, DHEA, and Inh B, whereas in normal women no increases were observed. T levels declined slightly in both groups. These findings provide evidence that, in PCOS women, theca cell androgen production is enhanced by FSH administration and suggest a granulosa-theca cell paracrine mechanism.

Disruption of Zebrafish Follicle-Stimulating Hormone Receptor (fshr) But Not Luteinizing Hormone Receptor (lhcgr) Gene by TALEN Leads to Failed Follicle Activation in Females Followed by Sexual Reversal to Males.

PubMed

Zhang, Zhiwei; Lau, Shuk-Wa; Zhang, Lingling; Ge, Wei

2015-10-01

Gonadotropins are primary hormones that control vertebrate reproduction. In a recent study, we analyzed the impacts of FSH and LH on zebrafish reproduction by disrupting FSH and LH-β genes (fshb and lhb) using transcription activator-like effector nuclease (TALEN) technology. Using the same approach, we successfully deleted FSH and LH receptor genes (fshr and lhcgr) in the present study. In contrast to the deficiency of its cognate ligand FSH, the fshr-deficient females showed a complete failure of follicle activation with all ovarian follicles arrested at the primary growth-previtellogenic transition, which is the marker for puberty onset in females. Interestingly, after blockade at the primary growth stage for varying times, all females reversed to males, and all these males were fertile. In fshr-deficient males, spermatogenesis was normal in adults, but the initiation of spermatogenesis in juveniles was retarded. In contrast to fshr, the deletion of the lhcgr gene alone caused no obvious phenotypes in both males and females; however, double mutation of fshr and lhcgr resulted in infertile males. In summary, our results in the present study showed that Fshr was indispensable to folliculogenesis and the disruption of the fshr gene resulted in a complete failure of follicle activation followed by masculinization into males. In contrast, lhcgr does not seem to be essential to zebrafish reproduction in both males and females. Neither Fshr nor Lhcgr deficiency could phenocopy the deficiency of their cognate ligands FSH and LH, which is likely due to the fact that Fshr can be activated by both FSH and LH in the zebrafish.

Extended high dose letrozole regimen versus short low dose letrozole regimen as an adjuvant to gonadotropin releasing hormone antagonist protocol in poor responders undergoing IVF-ET.

PubMed

Fouda, Usama M; Sayed, Ahmed M

2011-12-01

To compare the efficacy and cost-effectiveness of extended high dose letrozole regimen/HPuFSH-gonadotropin releasing hormone antagonist (GnRHant) protocol with short low dose letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET. In this randomized controlled trial, 136 women who responded poorly to GnRH agonist long protocol in their first IVF cycle were randomized into two equal groups using computer generated list and were treated in the second IVF cycle by either extended letrozole regimen (5 mg/day during the first 5 days of cycle and 2.5 mg/day during the subsequent 3 days) combined with HPuFSH-GnRHant protocol or short letrozole regimen (2.5 mg/day from cycle day 3-7) combined with HPuFSH-GnRHant protocol. There were no significant differences between both groups with regard to number of oocytes retrieved and clinical pregnancy rate (5.39 ± 2.08 vs. 5.20 ± 1.88 and 22.06% vs. 16.18%, respectively).The total gonadotropins dose and medications cost per cycle were significantly lower in extended letrozole group (44.87 ± 9.16 vs. 59.97 ± 14.91 ampoules and 616.52 ± 94.97 vs. 746.84 ± 149.21 US Dollars ($), respectively).The cost-effectiveness ratio was 2794 $ in extended letrozole group and 4616 $ in short letrozole group. Extended letrozole regimen/HPuFSH-GnRHant protocol was more cost-effective than short letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET.

[The lh-rh-test in men with fertility disorders (author's transl)].

PubMed

Krause, W; Höbel, W

1976-11-01

89 mal patients with fertility disorders underwent a test with 50 mug synthetic LH-RH. The basal levels of FSH and LH are elevated in patients with azoospermia, with testicular atrophy, varicocele and Klinefelters syndrome. They increase with age. After stimulation with LH-RH the highest relative peaks (maximal value divided by control value) of LH are seen younger patients, in those with varicocele, and oligozoospermia. The FSH-values do not differ significantly between these groups. Low relative peaks of LH are seen in older patients. In Klinefelter's syndrome the relative peaks of FSH and LH are significantly lowered.

Laser homeostatics on delayed onset muscle soreness

NASA Astrophysics Data System (ADS)

Liu, T. C. Y.; Fu, D. R.; Liu, X. G.; Tian, Z. X.

2011-01-01

Delayed onset muscle soreness (DOMS) and its photobiomodulation were reviewed from the viewpoint of function-specific homeostasis (FSH) in this paper. FSH is a negative-feedback response of a biosystem to maintain the function-specific fluctuations inside the biosystem so that the function is perfectly performed. A stressor may destroy a FSH. A stress is a response of a biosystem to a stressor and may also be in stress-specific homeostasis (StSH). A low level light (LLL) is so defined that it has no effects on a function in its FSH or a stress in its StSH, but it modulate a function far from its FSH or a stress far from its StSH. For DOMS recovery, protein metabolism in the Z-line streaming muscular cell is the essential process, but the inflammation, pain and soreness are non-essential processes. For many DOMS phenomena, protein metabolism in the Z-line streaming muscular cell is in protein metabolism-specific homeostasis (PmSH) so that there are no effects of LLL although the inflammation can be inhibited and the pain can be relieved. An athlete or animal in the dysfunctional conditions such as blood flow restriction and exercise exhaustion is far from PmSH and the protein metabolism can be improved with LLL.

Ovulation disorders: part I anovulation associated with estrogen deficiency.

PubMed

Check, J H

2007-01-01

To describe the diagnosis and treatment of anovulatory disorders associated with estrogen deficiency. Anovulation with estrogen deficiency was divided into two types: association with low vs. high serum gonadotropin levels. Treatments included bromocriptine or cabergoline for hyperprolactinemia and gonadotropins for normal prolactin levels. When gonadotropins were low, lowering the elevated serum FSH to restore down-regulated FSH receptors in the few remaining follicles with either ethinyl estradiol or GnRH agonists or antagonists was used. High serum FSH was followed by either close observation for spontaneous follicular maturation or low dose gonadotropin stimulation. Progesterone supplementation, especially by vaginal use, was given in the luteal phase. Though success in ovulation induction and pregnancies was greater in women with low FSH than high FSH, pregnancies following ovulation induction were nevertheless achieved even in women in apparent menopause. The use of ethinyl estradiol as opposed to other estrogen drugs has the advantage of not being able to be measured by most serum assays for estradiol allowing the physician to detect endogenous follicular development and thus determining when follicular maturation has been achieved. Even in the presence of marked diminished ovarian egg reserve, eggs from chronically younger women are superior in quality to women aged > or = 45.

Patients with 47, XXX karyotype who experienced premature ovarian failure (POF): two case reports.

PubMed

Sugawara, Nobuo; Maeda, Machiko; Manome, Tomomi; Nagai, Rie; Araki, Yasuhisa

2013-10-01

Pubertal onset and sexual development are usually normal in 47, XXX individuals; however, we report two cases of premature ovarian failure (POF) in infertile women with trisomy X. Chromosome analysis was conducted with G-banding and fluorescence in situ hybridization using X- and Y-bearing probe. Hormonal administration was primarily Kaufmann's treatment or long-term estradiol treatment, followed by withdrawal bleeding from estrogen and progesterone. Two patients with trisomy X, aged 31 (patient 1) and 27 years (patient 2), were diagnosed with POF due to hypergonadotropic hypogonadism. Their ovaries were small. Patient 1 had a FSH level of 44.6 mIU/ml and patient 2 had a FSH level of 74.6 mIU/ml. In patient 1, with Kaufmann's treatment, the FSH decreased to 13.5 mIU/ml; however, follicle growth did not occur following HMG stimulation. In patient 2, FSH did not decrease despite Kaufmann's treatment; therefore, she was given a GnRH agonist and her FSH level decreased to 7.1 mIU/ml. However, her ovaries never responded to HMG stimulation. We report on two patients with a 47, XXX karyotype who became infertile due to POF. We recommend that when a patient is diagnosed with trisomy X, the possibility of POF must be strongly considered.

78 FR 13316 - National Forest System Land Management Planning Directives

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-27

... responsibilities. It should be used in conjunction with the FSH. FSH 1909.12--Land Management Planning Handbook... management planning. Forest Service Handbook 1909.15, section 31.12 (57 FR 43208; September 18, 1992... DEPARTMENT OF AGRICULTURE Forest Service RIN 0596-AD06 National Forest System Land Management...

[Does a short-term hemodialysis treatment influence function of the pituitary-testicular axis in patients with chronic renal failure?].

PubMed

Starzyk, J; Grzeszczak, W

1993-01-01

Abnormal function of the pituitary-gonadal axis is a well documented endocrine abnormality in chronic renal failure (CRF). The purpose of the work was to assess the influence of the short-term haemodialysis treatment on LH, FSH and testosterone secretion. In 17 men dialyzed up to 50 months and 10 non-dialyzed male patients with advanced CRF the test of stimulation with LHRH was done. Results obtained in patients were compared with those assessed in healthy subjects. Significantly higher concentration of LH and FSH and lower concentration of testosterone in serum under basal conditions were found in patients as compared to controls. Basal concentrations of LH, FSH and testosterone in dialyzed patients and in non dialyzed men were similar. The area under the curve of LH, FSH and testosterone in both groups of patients was similar. These results suggest that in men dialyzed shorter than 50 months haemodialysis treatment does not change significantly the function of the pituitary-testicular axis as compared to men with advanced CRF.

Altered ovarian function affects skeletal homeostasis independent of the action of follicle-stimulating hormone.

PubMed

Gao, Jianjun; Tiwari-Pandey, Rashmi; Samadfam, Rana; Yang, Yinzhi; Miao, Dengshun; Karaplis, Andrew C; Sairam, M Ram; Goltzman, David

2007-06-01

Osteoporosis is a leading public health problem. Although a major cause in women is thought to be a decline in estrogen, it has recently been proposed that FSH or follitropin is required for osteoporotic bone loss. We examined the FSH receptor null mouse (FORKO mouse) to determine whether altered ovarian function could induce bone loss independent of FSH action. By 3 months of age, FORKO mice developed age-dependent declines in bone mineral density and trabecular bone volume of the lumbar spine and femur, which could be partly reversed by ovarian transplantation. Bilateral ovariectomy reduced elevated circulating testosterone levels in FORKO mice and decreased bone mass to levels indistinguishable from those in ovariectomized wild-type controls. Androgen receptor blockade and especially aromatase inhibition each produced bone volume reductions in the FORKO mouse. The results indicate that ovarian secretory products, notably estrogen, and peripheral conversion of ovarian androgen to estrogen can alter bone homeostasis independent of any bone resorptive action of FSH.

Recombinant or urinary follicle-stimulating hormone? A cost-effectiveness analysis derived by particularizing the number needed to treat from a published meta-analysis.

PubMed

Ola, B; Papaioannou, S; Afnan, M A; Hammadieh, N; Gimba, S

2001-06-01

To demonstrate that particularizing pooled results of a meta-analysis can derive incremental cost effectiveness of superovulation with recombinant follicle-stimulating hormones (rFSH) vs. the highly purified urinary form (uFSH) for assisted conception. A retrospective study. An assisted conception unit in the United Kingdom. One hundred forty-five fresh in vitro fertilization (IVF) and 58 fresh intracytoplasmic sperm injection (ICSI) cycles. rFSH vs. uFSH. Incremental cost-effectiveness (i.e., cost needed to treat, or CNT) and budget-impact analyses of rFSH vs. uFSH. In women less than 30 years old, the clinical pregnancy rate was 37.7% (95% CI 24.8%-52.1%), the particularized number needed to treat (pNNT) was -19, and the cost needed to treat was 5070.51 pounds sterling (3660.53 pounds sterling to 7619.32 pounds sterling). For the 30- to 35-year-old age group, the clinical pregnancy rate was 29.9% (95% CI 20.0%--41.4%), the particularized number needed to treat was -24, and CNT was 7335.59 pounds stering (5284.11 pounds sterling to 10,941.22 pounds sterling). For the 36- to 40-year-old age group, the clinical pregnancy rate was 30.6.0% (95% CI 19.6%--43.7%), the particularized number needed to treat was -23.0, and the CNT was 8569.67 pounds sterling (5998.70 pounds sterling to 13,413.24 pounds sterling). The CNT and thus the budget impact analyses (the extra number of cycles that can be funded by the CNT) both increase directly with age of the patient, and inversely with the clinical pregnancy rate.

In Vitro Growth and Steroidogenesis of Dog Follicles as Influenced by the Physical and Hormonal Microenvironment

PubMed Central

Songsasen, N; Woodruff, TK; Wildt, DE

2011-01-01

The present study examined the influences of physical and hormonal microenvironment on in vitro growth and steroidogenesis of dog follicles. Follicles were enzymatically-isolated and individually-encapsulated in 0.5% (w/v; n = 17) or 1.5% (n = 10) alginate and cultured with 0.5 IU/ml equine chorionic gonadotropin for 192 h. In a separate experiment, follicles were encapsulated in 0.5% alginate and cultured with 0 (n = 22), 1 (n= 23), 10 (n = 20) or 100 (n = 21) µg/ml FSH for 240 h. Follicle diameter and steroid production were assessed every 48 h in both studies. Follicles encapsulated in the 0.5% alginate grew faster (P < 0.05) than those cultured in the 1.5% concentration. Oestradiol (E2) and progesterone (P4) increased consistently (P < 0.05) over time, and follicles in the 1.5% alginate produced more (P < 0.05) P4 than those in the 0.5% solution. Follicles cultured in the highest FSH concentration (100 µg/ml) increased 100% in size after 240 h compared to 50 to 70% in lower dosages. E2 concentration remained unchanged over time (P > 0.05) across FSH dosages. However, P4 increased (P < 0.05) as culture progressed and with increasing FSH concentration. Results demonstrate that dog follicles cultured in alginate retain structural integrity, grow in size and are hormonally active. Lower alginate and increasing FSH concentrations promote in vitro follicle growth. However, the absence of an E2 rise in follicles cultured in FSH alone suggests the need for luteinizing hormone supplementation to support thecal cell differentiation and granulosa cell function. PMID:21502334

Development of male contraceptive vaccine--a perspective.

PubMed

Moudgal, N R; Jeyakumar, M; Krishnamurthy, H N; Sridhar, S; Krishnamurthy, H; Martin, F

1997-01-01

This paper reviews the recent advances that have occurred in the area of development of a male contraceptive vaccine. The vaccine candidates considered for review are hormone/hormone receptor-based proteins including luteinizing hormone-releasing hormone (LHRH)/LH, follicle stimulating hormone (FSH), as well as LH and FSH receptor proteins. The review also highlights the advances in our basic understanding of gonadotrophin action which have led to development of these vaccines. Focus is mainly on studies in the non-human primate which may be directly relevant to projected studies in the human. The data indicate that the vaccines are well tolerated by the primate (including the human based on limited data) and do not give rise to any known toxic symptoms or immediate health hazards. The response to the immunogen has been uniform and it may be possible to increase antibody titres as well as prolong the immune response by adding acceptable immune stimulators to the adjuvant cocktail and developing better immunization schedules or immunogen delivery systems. Contraceptive vaccines for the male are a feasible proposition and attention should now be focussed on evaluating carefully the bioefficacy of antibodies raised to recombinant ovine FSHbeta or FSH receptor protein fragments in both human and non-human primates. The advantage of the FSH/FSH receptor over the LHRH/LH-based vaccine lies in the fact that the former does not require an exogenous testosterone supplement to maintain accessory gland function, libido etc. The LHRH/LH-based vaccine results in azoospermia, while the FSH vaccine causes the production of low numbers of poor quality spermatozoa which are incapable of impregnating cycling females.

Sexual dimorphism in postnatal gonadotrophin levels in infancy reflects diverse maturation of the ovarian and testicular hormone synthesis.

PubMed

Kuiri-Hänninen, Tanja; Dunkel, Leo; Sankilampi, Ulla

2018-04-18

The postnatal gonadotrophin surge is sexually dimorphic: FSH levels predominate in girls and LH levels in boys. However, in preterm (PT) girls, both gonadotrophin levels are higher than in PT boys. To evaluate how gonadal maturation contributes to the sex differences in FSH and LH. Monthly follow-up of 58 full-term (FT, 29 boys) and 67 PT (33 boys) infants from 1 week (D7) to 6 months of age (M1-M6). Analyses were also carried out according to postmenstrual (PM) age in PT infants. Urinary LH, FSH, oestradiol (E2), testosterone (T) and serum inhibin B (InhB) levels. High gonadotrophin levels in PT girls abruptly decreased (P < .001) by M2, corresponding to a PM age of 38-42 weeks, and LH levels fell below the levels found in boys. This decrease was parallel to a steep increase in E2 levels (P < .001), and, from M4 to M6, LH and E2 correlated positively in PT girls (P < .01). T levels in PT boys increased earlier than E2 levels in PT girls. In addition, InhB levels were high in PT boys already at D7, in contrast to low InhB in PT girls. InhB and FSH correlated negatively in the whole group (P < .001). Ovarian hormone synthesis is immature and incapable of responding to gonadotrophin stimulus before 38-42 PM weeks in PT girls, which may explain their highly elevated FSH and LH levels. The higher InhB levels in boys compared to girls may explain sexual dimorphism in FSH levels. © 2018 John Wiley & Sons Ltd.

Effects of cetrorelix, a GnRH-receptor antagonist, on gonadal axis in women with functional hypothalamic amenorrhea.

PubMed

Berardelli, Rita; Gianotti, Laura; Karamouzis, Ioannis; Picu, Andreea; Giordano, Roberta; D'Angelo, Valentina; Zinnà, Domenico; Lanfranco, Fabio; Ghigo, Ezio; Arvat, Emanuela

2011-10-01

Gonadotropin Releasing Hormone (GnRH) antagonists (GnRHa) suppress gonadotropin and sex-steroid secretion. In normal women, acute GnRHa administration induces inhibitory effect on pituitary-gonadal axis, followed by Luteinizing Hormone (LH) rebound. Functional hypothalamic amenorrhea (HA) is characterised by impaired gonadotropin secretion and hypogonadism secondary to blunted GnRH pulsatility. We studied the effects of a GnRHa, cetrorelix (CTX 3.0 mg), in six women with HA (age 30.7 ± 3.2 years; BMI 21.5 ± 1.7 kg/m(2)) and six control subjects (CS, 28.2 ± 0.6 years; 22.6 ± 0.9 kg/m(2)) on LH, Follicle-Stimulating Hormone (FSH) and oestradiol levels over 4 h (08.00-12.00 am) before, +24 h and +96 h after CTX; LH, FSH, and oestradiol were also evaluated at +6, +8, +12, +48, +72 h after CTX. CS: CTX reduced (p < 0.05) LH, FSH, and oestradiol (nadir at +12 h, +24 h, and +24 h); LH rebounded at +96 h, FSH and oestradiol recovered at +48 h and +72 h. The 4-h evaluation showed LH and FSH reduction (p < 0.05) at +24 h, with LH rebound at +96 h. HA: CTX reduced (p < 0.05) LH, FSH, and oestradiol, (nadir at +24 h, +48 h, and +48 h, recovery at +48 h, +72 h, and +96 h). The 4-h evaluation showed gonadotropin reduction (p < 0.05) 24 h after CTX, without any rebound effect. One single CTX dose still modulates gonadotropin secretion in HA. Its 'paradoxical' stimulatory effect on gonadotropins needs to be verified after prolonged administration.

Anti-Müllerian hormone, follicle stimulating hormone, antral follicle count, and risk of menopause within 5 years.

PubMed

Kim, Catherine; Slaughter, James C; Wang, Erica T; Appiah, Duke; Schreiner, Pamela; Leader, Benjamin; Calderon-Margalit, Ronit; Sternfeld, Barbara; Siscovick, David; Wellons, Melissa

2017-08-01

To evaluate the ability of concentration of anti-Müllerian hormone (AMH), antral follicle count (AFC), and concentration of follicle stimulating hormone (FSH) to predict the onset of menopause. The Coronary Artery Risk Development in Young Adults Study (CARDIA) Women's Study was an ancillary study to CARDIA, a population-based study of adults aged 18-30 years followed for 3 decades. For this report, participants were women (n=426) who had attended the CARDIA year 15-16 (2000-2001) examination, had at least one ovary, were not pregnant, and underwent serum AMH and FSH measurement and transvaginal ultrasonography in 2002-2003. The probability of menopause in 5 years based upon AMH, FSH, and AFC. The mean age of the women at the time of AMH, FSH, and AFC assessment was 43 years. The cumulative incidence of menopause at 25 years (or follow-up) was 27% (n=426), and the incidence within 5 years was 13% (n=55). Among women aged 45-49 years, undetectable AMH concentrations were associated with a greater than 60% probability of menopause within 5 years, whereas approximately 1/3 of women with no or just one antral follicle experienced menopause within 5 years. Both low and high concentrations of FSH were associated with greater odds of menopause than intermediate concentrations. Models with multiple markers did not improve the prediction of menopause over that afforded by models with single markers. The ability to predict onset of menopause was improved with any of the three menopausal markers in addition to age. AMH concentrations were more closely associated with menopause than AFC or FSH. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessing The Impact Of Cancer Therapies On Ovarian Reserve

PubMed Central

Gracia, Clarisa R.; Sammel, Mary D.; Freeman, Ellen; Prewitt, Maureen; Carlson, Claire; Ray, Anushree; Vance, Ashley; Ginsberg, Jill P.

2013-01-01

Objective To determine whether measures of ovarian reserve differ between females exposed to cancer therapies in a dose-dependent manner as compared to healthy controls of similar age and late-reproductive age. Design Cross-sectional analysis of data from a prospective cohort study Setting University Medical Center Patients 71 cancer survivors age 15-39; 67 healthy, similarly aged unexposed subjects; 69 regularly menstruating women of late-reproductive age (40-52 years). Interventions: None Main Outcome measures Early follicular phase hormones (FSH, Estradiol, Inhibin B, AMH) and ovarian ultrasound measurements (ovarian volume and Antral Follicle Counts) were compared using multivariable linear regression. Results In adjusted models, FSH, AMH and AFC differed between exposed vs. unexposed (FSH 11.12mIU/ml vs. 7.25mIU/ml, p=0.001; AMH 0.81ng/ml vs. 2.85ng/ml, p<0.001; AFC: 14.55 vs. 27.20, p<0.001. In participants with an FSH<10, survivors had lower levels of AMH and AFC compared to controls. Alkylating agent dose score was associated with increased levels of FSH (p= 0.016) and decreased levels of AMH (p=0.003). Exposure to pelvic radiation was associated with impairment in FSH, AMH, AFC and ovarian volume. AMH was similar in women previously exposed to high-dose cancer therapy and 40-42 year old controls. Conclusions Measures of ovarian reserve are impaired in a dose-dependent manner among cancer survivors compared to unexposed females of similar age. Reproductive hormone levels in menstruating survivors exposed to high-dose therapy are similar to late-reproductive women. The predictive value of measures for pregnancy and menopause must be studied. PMID:22137491

Genetic and clinical predictors of ovarian response in assisted reproductive technology

NASA Astrophysics Data System (ADS)

Wiweko, B.; Damayanti, I.; Suryandari, D.; Natadisastra, M.; Pratama, G.; Sumapraja, K.; Meutia, K.; Iffanolia, P.; Harzief, A. K.; Hestiantoro, A.

2017-08-01

Several factors are known to influence ovarian response to rFSH stimulation such as age, antral follicle count (AFC), and basal FSH level, Mutation of allele Ser680Asn in FSHR gene was responsible to ovarian resistance toward exogenous FSH. The aim of this study is to develop a prediction model of ovarian response to COS in IVF. This study was a prospective cohort study. One hundred and thirteen women undergoing their first cycle of IVF in Yasmin IVF Clinic Jakarta were recruited to this study. Clinical datas included were age, BMI, and AFC. Basal FSH and E2 as well as serum AMH was measured from peripheral blood taken at second day of cycle. Bsr-1 enzyme is used to identify the polymorphism in exon 10 position 680 with RFLP technique. Three genotype polymorphism, Asn/Asn (255 bp ribbon), Asn/Ser (97 bp and 158 bp), and Ser/Ser (97 bp, 158 bp, and 255 bp). AFC has the highest predictor for ovarian response with AUC 0.922 (CI 95% 0.833-1.000). AMH also showed high predicting value (AUC 0.843 CI 95% 0.663-1.000). The multivariate analysis revealed combination of AFC, AMH, age, and basal FSH is a good model for ovarian response prediction (AUC=0.97). No significant relation between Asn/Asn, Asn/Ser, or Ser/Ser genotype FSHR polymorphism with ovarian response (p = 0.866) and total dose of rRSH (p = 0.08). This study showed that model combination of AFC, AMH, patient’s age and basal FSH are very good to predict number of mature oocytes.

Follicle-stimulating hormone encapsulation in the cholesterol-modified chitosan nanoparticles via molecular dynamics simulations and binding free energy calculations.

PubMed

Yahyaei, Mohammad; Mehrnejad, Faramarz; Naderi-Manesh, Hossein; Rezayan, Ali Hossein

2017-09-30

Follicle-stimulating hormone (FSH) is widely applied in the modern ovarian stimulation techniques. However, it must be administered daily because of its short half-life. Recently, the cholesterol (CS) modified chitosan (CTS) nanogels have attracted significant interest as promising controlled release protein delivery because of their ability to minimize the aggregation and irreversible denaturation of proteins. Herein, we report a molecular dynamics (MD) simulation investigation on the molecular mechanisms of FSH encapsulation in the CS-CTS nanogels. The MD simulations have been performed using the GROMACS software for up to 200ns simulation time. Furthermore, the binding free energy has been calculated by the molecular mechanics [MM] with Poisson-Boltzmann [PB] and surface area solvation (MM/PBSA) method by using the g_mmpbsa tool. Our findings suggest that the main driving force of the formation of the CS-CTS nanogels is the hydrophobic interactions between the CS-CS moieties in water. The results have also indicated that the CS-CTS nanogel formation can occur through the hydrogen bonding in addition to the hydrophobic interactions. The obtained data demonstrate that the FSH encapsulation into the CS-CTS nanogels is a gradual process driven by the hydrophobic interactions between the hydrophobic patch of FSH and the hydrophobic nanodomains of the nanogel. Our results also reveal that except in the hydrophobic patch region, the flexibility of FSH was reduced in the presence of the nanogel. This study provides the elucidation of the nanogel-FSH interactions at the molecular level and presents new perspective for the ideal design and applications of the CS-CTS nanogel in protein delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Control of follicle-stimulating hormone by estradiol and the inhibins: critical role of estradiol at the hypothalamus during the luteal-follicular transition.

PubMed

Welt, Corrine K; Pagan, Yanira L; Smith, Patricia C; Rado, Kimberly B; Hall, Janet E

2003-04-01

To test the hypothesis that estradiol, inhibin A, and inhibin B contribute differentially to FSH negative feedback in specific phases of the menstrual cycle, daily blood samples were obtained across a control cycle and after selective estrogen blockade with tamoxifen. To examine the site of estradiol-negative feedback in control and tamoxifen treatment cycles, early follicular phase GnRH (free alpha-subunit) pulse frequency was assessed in normal women, and FSH levels were examined in GnRH-deficient women in whom hypothalamic output was fixed with GnRH administration. FSH was higher in the early follicular phase in the presence of estrogen receptor blockade (15.7 +/- 3.1 vs. 13.2 +/- 1.9 IU/liter; P < 0.05) but was not increased in the late follicular phase. In the luteal phase, FSH was elevated (10.1 +/- 0.7 vs. 7.3 +/- 0.6 IU/liter; P < 0.01). In normal women, free alpha-subunit pulse frequency increased (7.3 +/- 0.4 vs. 4.8 +/- 0.4 pulses per 8 h; P < 0.003), but in GnRH-deficient women, there was no FSH increase (11.1 +/- 1.6 vs. 12.5 +/- 3.6 IU/liter) in the early follicular phase in the presence of estrogen blockade. In conclusion, estradiol exerts a greater role over inhibin in FSH-negative feedback regulation during the luteal phase and the luteal-follicular transition. In contrast, inhibin A and/or B plays a more critical role as the follicular phase progresses. In addition, these studies support a primary if not exclusive hypothalamic site of estrogen-negative feedback in the early follicular phase.

Seasonally and experimentally induced changes in testicular function of the Australian bush rat (Rattus fuscipes).

PubMed

Irby, D C; Kerr, J B; Risbridger, G P; de Kretser, D M

1984-03-01

Serum concentrations of LH, FSH and testosterone were measured monthly throughout the year in male bush rats. Testicular size and ultrastructure, LH/hCG, FSH and oestradiol receptors and the response of the pituitary to LHRH were also recorded. LH and FSH rose in parallel with an increase in testicular size after the winter solstice with peak gonadotrophin levels in the spring (September). The subsequent fall in LH and FSH levels was associated with a rise in serum testosterone which reached peak levels during summer (December and January). In February serum testosterone levels and testicular size declined in parallel, while the pituitary response to an LHRH injection was maximal during late summer. The number of LH/hCG, FSH and oestradiol receptors per testis were all greatly reduced in the regressed testes when compared to active testes. In a controlled environment of decreased lighting (shortened photoperiod), temperature and food quality, the testes of sexually active adult males regressed at any time of the year, the resultant testicular morphology and endocrine status being identical to that of wild rats in the non-breeding season. Full testicular regression was achieved only when the photoperiod, temperature and food quality were changed: experiments in which only one or two of these factors were altered failed to produce complete sexual regression.

Alterations in gonadotropin secretion and ovarian function in prepubertal gilts by elevated environmental temperature.

PubMed

Flowers, B; Day, B N

1990-03-01

The effect of chronic exposure to elevated environmental temperature on gonadotropin secretion and ovarian function was studied in prepubertal gilts. Gilts were maintained under control (15.6 degrees C) or elevated temperature (33.3 degrees C) conditions from 150 to 180 days of age. Endocrine and ovarian responses to bilateral (BLO), unilateral (ULO), and sham ovariectomy were evaluated between 175 and 180 days of age. During the 96-h sampling period after BLO, plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were suppressed in heat-stressed females. Similarly, elevated temperatures abolished the transient rise in FSH and subsequent follicular growth normally associated with ULO. In contrast, environmental treatment had no effect on the secretion of FSH and LH after sham ovariectomy, yet the number of small follicles was lower in gilts exposed to elevated temperatures than in females maintained under control conditions. These results indicate that a chronic exposure to elevated environmental temperature during pubertal development diminished the ability of the hypothalamo-hypophyseal axis to secrete FSH and LH, which had physiological consequences on follicular growth. When provided an appropriate stimulus (ULO), an acute period of FSH secretion and subsequent development of follicles failed to occur in females exposed to elevated temperatures. Consequently, we propose that delayed puberty in gilts during periods of elevated environmental temperatures is due, in part, to a diminished capacity for gonadotropin secretion.

Assessment of ovarian reserve in euthyroid adolescents with Hashimoto thyroiditis.

PubMed

Pirgon, Ozgur; Sivrice, Cigdem; Demirtas, Hakan; Dundar, Bumin

2016-01-01

We aimed to investigate the ovarian function and reserve in euthyroid adolescents (TSH < 2.5 mIU/L) diagnosed with Hashimoto thyroiditis (HT). This case-control study included 30 adolescent girls (mean age 15.1 ± 1.4 years) newly diagnosed as HT with presence of high thyroid antibodies with gland heterogeneity in ultrasound and age-matched 30 healthy female subjects. Anti-ovarian antibody (AOAb), LH/FSH ratio, estradiol, anti-mullerian hormone (AMH), inhibin-B, total testosterone, antral follicle count, ovarian volumes and uterine length were measured. The clinical, laboratory, and ultrasound data of the HT and control groups were compared. There were no significant differences between the girls with HT and healthy controls in relation to LH/FSH ratio, estradiol and inhibin-B levels. AOAb (p = 0.02), AMH (p = 0.007) and total testosterone levels were higher in HT group than the control group (p = 0.03). AOAb level was found to be positively correlated with LH/FSH ratio (p = 0.03), AMH (p = 0.01) and inhibin-B (p < 0.001) in HT group. This study demonstrated that the adolescent girls diagnosed with autoimmune thyroiditis had normal ovarian reserve based on measurements of AMH, inhibin B, FSH, LH/FSH ratio, estradiol and antral follicle counts.

Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin: distributions of sulfated and sialylated oligosaccharides on bovine, ovine, and human pituitary glycoprotein hormones

DOE Office of Scientific and Technical Information (OSTI.GOV)

Green, E.D.; Baenziger, J.U.

1988-01-05

The asparagine-linked oligosaccharides on the pituitary glycoprotein hormones lutropin (LH), follitropin (FSH), and thyrotropin (TSH) consist of a heterogeneous array of neutral, sulfated, sialylated, and sulfated/sialylated structures. In this study, the authors determined the relative quantities of the various asparagine-linked oligosaccharides on LH, FSH, and TSH from these three animal species. The proportions of sulfated versus sialylated oligosaccharides varied markedly among the different hormones. Both hormone- and animal species-specific differences in the types and distributions of sulfated, sialylated, and sulfated/sialylated structures were evident. In particular, LH and FSH, which are synthesized in the same pituitary cell and bear ..cap alpha..-subunitsmore » with the identical amino acid sequence, contained significantly different distributions of sulfated and sialylated oligosaccharides. For all three animal species, the ratio of sialylated to sulfated oligosaccharides differed by >10-fold for LH and FSH, with sulfated structures dominating on LH and sialylated structures on FSH. Sialylated oligosaccharides were also heterogeneous with respect to sialic acid linkage (..cap alpha..2,3 versus ..cap alpha..2,6). The differences in oligosaccharide structures among the various pituitary glycoprotein hormones as well as among the various glycosylation sites within a single hormone support the hypothesis that glycosylation may serve important functional roles in the expression and/or regulation of hormone bioactivity.« less

Cost-saving treatment strategies in in vitro fertilization: a combined economic evaluation of two large randomized clinical trials comparing highly purified human menopausal gonadotropin and recombinant follicle-stimulating hormone alpha.

PubMed

Wechowski, Jaroslaw; Connolly, Mark; Schneider, Dirk; McEwan, Philip; Kennedy, Richard

2009-04-01

To assess the cost-effectiveness of two gonadotropin treatments that are available in the United Kingdom in light of limited public funding and the fundamental role of costs in IVF treatment decisions. An economic evaluation based on two large randomized clinical trials in IVF patients using a simulation model. Fifty-three fertility clinics in 13 European countries and Israel. Women indicated for treatment with IVF (N = 986), aged 18-38, participating in double-blind, randomized controlled trials. Highly purified menotropin (HP-hMG, Menopur) or recombinant follitropin alpha (rFSH, Gonal-F). Cost per IVF cycle and cost per live birth for HP-hMG and rFSH alpha. HP-hMG was more effective and less costly versus rFSH for both IVF cost per live birth and for IVF cost per baby (incremental cost-effectiveness ratio was negative). The mean costs per IVF treatment for HP-hMG and rFSH were 2408 pounds (95% confidence interval [CI], 2392 pounds, 2421 pounds) and 2660 pounds (95% CI 2644 pounds, 2678 pounds), respectively. The mean cost saving of 253 pounds per cycle using HP-hMG allows one additional cycle to be delivered for every 9.5 cycles. Treatment with HP-hMG was dominant compared with rFSH in the United Kingdom. Gonadotropin costs should be considered alongside live-birth rates to optimize outcomes using scarce health-care resources.

Effects of exemestane and tamoxifen on hormone levels within the Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial: results of a German substudy.

PubMed

Hadji, P; Kauka, A; Bauer, T; Tams, J; Hasenburg, A; Kieback, D G

2012-10-01

The aim of this study was to compare the effects of exemestane and tamoxifen on hormone levels in postmenopausal patients with hormone receptor-positive breast cancer within a Germany substudy of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Within the TEAM trial, patients were randomized to receive adjuvant treatment with exemestane for 5 years or tamoxifen for 2.5-3 years followed by exemestane for 2-2.5 years. Serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH) and parathyroid hormone (PTH)-intact were measured at screening and after 3, 6 and 12 months of treatment. Data on hormone levels were available from 63 patients in the tamoxifen arm and 68 patients in the exemestane arm. Treatment with exemestane resulted in decreases from baseline in SHBG and PTH-intact levels, and increases from baseline in testosterone, DHEAS and FSH levels. Tamoxifen treatment resulted in increases from baseline in SHBG and PTH-intact, whereas levels of testosterone and FSH decreased and DHEAS levels did not change. At all time points assessed, the absolute change from baseline was significantly different between tamoxifen and exemestane for testosterone, SHBG, FSH and PTH-intact (all p < 0.0001). Exemestane and tamoxifen had statistically significantly different effects on hormone levels, including testosterone, SHBG, FSH and PTH-intact.

36 CFR 215.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... cumulatively have a significant effect on the human environment and for which neither an environmental impact statement (EIS) nor an environmental assessment (EA) is required (40 CFR 1508.4; FSH 1909.15, Chapter 30... environmental assessment and a Finding of No Significant Impact (FONSI) (40 CFR 1508.13; FSH 1909.15, Chapter 40...

A comparison of menotropin, highly-purified menotropin and follitropin alfa in cycles of intracytoplasmic sperm injection

PubMed Central

Esteves, Sandro C; Schertz, Joan C; Verza, Sidney; Schneider, Danielle T; Zabaglia, Silval FC

2009-01-01

Background Over the last several decades, as a result of an evolution in manufacturing processes, a marked development has been made in the field of gonadotropins for ovarian stimulation. Initially, therapeutic gonadotropins were produced from a simple process of urine extraction and purification; now they are produced via a complex system involving recombinant technology, which yields gonadotropins with high levels of purity, quality, and consistency. Methods A retrospective analysis of 865 consecutive intracytoplasmic sperm injection (ICSI) cycles of controlled ovarian hyperstimulation (COH) compared the clinical efficacy of three gonadotropins (menotropin [hMG; n = 299], highly-purified hMG [HP-hMG; n = 330] and follitropin alfa [r-hFSH; n = 236]) for ovarian stimulation after pituitary down-regulation. The endpoints were live birth rates and total doses of gonadotropin per cycle and per pregnancy. Results Laboratory and clinical protocols remained unchanged over time, except for the type of gonadotropin used, which was introduced sequentially (hMG, then HP-hMG, and finally r-hFSH). Live birth rates were not significantly different for hMG (24.4%), HP-hMG (32.4%) and r-hFSH (30.1%; p = 0.09) groups. Total dose of gonadotropin per cycle was significantly higher in the hMG (2685 +/- 720 IU) and HP-hMG (2903 +/- 867 IU) groups compared with the r-hFSH-group (2268 +/- 747 IU; p < 0.001). Total dose of gonadotropin required to achieve clinical pregnancy was 15.7% and 11.0% higher for the hMG and HP-hMG groups, respectively, compared with the r-hFSH group, and for live births, the differences observed were 45.3% and 19.8%, respectively. Conclusion Although similar live birth rates were achieved, markedly lower doses of r-hFSH were required compared with hMG or HP-hMG. PMID:19828024

Ovarian response to recombinant human follicle-stimulating hormone in luteinizing hormone-depleted women: examination of the two cell, two gonadotropin theory.

PubMed

Ben-Chetrit, A; Gotlieb, L; Wong, P Y; Casper, R F

1996-04-01

To evaluate the relative contribution of FSH to ovarian estrogen production. Nonrandomized, prospective study. University of Toronto teaching hospital reproductive biology unit. Five women who had been treated with depot GnRH agonist with hormonal add-back for 4 to 48 months and who were confirmed to be gonadotropin depleted by both bioassay and RIA. Subjects received 75 IU SC recombinant human FSH daily for 7 days followed by 150 IU daily for 7 days and 225 IU daily for the third week. Serum steroid determination and vaginal sonography for follicle size and endometrial thickness were performed serially and follicular fluid hormone levels were measured in two subjects. Bioactive LH and FSH activity were less than the detection limit of the assay (0.1 mIU/mL; conversion factor to SI units, 1.00 for LH and FSH) before recombinant FSH treatment in all five women. In all subjects, at least one preovulatory follicle developed by the end of two to three weeks. Endometrial thickness increased to between 7 and 9 mm in four women. Mean serum E2 in the five subjects increased from 17 pg/mL (range: 5 to 33 pg/mL; conversion factor to SI unit, 3.671) at baseline to 230 pg/mL (range: 37 to 489 pg/mL) at the end of the study. Follicular fluid E2 concentrations ranged from 44,296 to 69,367 pg/mL in the four follicles aspirated. Our results indicate that LH is not necessary for ovarian E2 production. We speculate that the granulosa cells, in the absence of detectable LH bioactivity, can use circulating adrenal androgens or constitutive or FSH-stimulated thecal androgens, to produce intrafollicular E2.

Follicle-stimulating hormone and bioavailable estradiol are less important than weight and race in determining bone density in younger postmenopausal women

PubMed Central

Preisser, J. S.; Hammett-Stabler, C. A.; Renner, J. B.; Rubin, J.

2011-01-01

Summary The association between follicle-stimulating hormone (FSH) and bone density was tested in 111 postmenopausal women aged 50–64 years. In the multivariable analysis, weight and race were important determinants of bone mineral density. FSH, bioavailable estradiol, and other hormonal variables did not show statistically significant associations with bone density at any site. Introduction FSH has been associated with bone density loss in animal models and longitudinal studies of women. Most of these analyses have not considered the effect of weight or race. Methods We tested the association between FSH and bone density in younger postmenopausal women, adjusting for patient-related factors. In 111 postmenopausal women aged 50–64 years, areal bone mineral density (BMD) was measured at the lumbar spine, femoral neck, total hip, and distal radius using dual-energy X-ray absorptiometry, and volumetric BMD was measured at the distal radius using peripheral quantitative computed tomography (pQCT). Height, weight, osteoporosis risk factors, and serum hormonal factors were assessed. Results FSH inversely correlated with weight, bioavailable estradiol, areal BMD at the lumbar spine and hip, and volumetric BMD at the ultradistal radius. In the multivariable analysis, no hormonal variable showed a statistically significant association with areal BMD at any site. Weight was independently associated with BMD at all central sites (p<0.001), but not with BMD or pQCT measures at the distal radius. Race was independently associated with areal BMD at all sites (p≤0.008) and with cortical area at the 33% distal radius (p=0.004). Conclusions Correlations between FSH and bioavailable estradiol and BMD did not persist after adjustment for weight and race in younger postmenopausal women. Weight and race were more important determinants of bone density and should be included in analyses of hormonal influences on bone. PMID:21125395

Predominant Suppression of FSHβ-immunoreactivity after Long-Term Treatment of Intact and Castrate Adult Male Rats with the GnRH Agonist Deslorelin

PubMed Central

Smith, Arik W.; Asa, Cheryl S.; Edwards, Brian S.; Murdoch, William J.; Skinner, Donal C.

2017-01-01

GnRH agonists are used to treat gonadal steroid-dependent disorders in humans and contracept animals. These agonists are thought to work by desensitizing gonadotropes to GnRH, thereby suppressing FSH and LH secretion. It is not known whether changes occur in the cellular composition of the pituitary gland following chronic GnRH agonist exposure. Adult male Sprague-Dawley rats were treated with a sham, deslorelin, or deslorelin plus testosterone implant for 41.0±0.6 days. In a second experiment, rats were castrated and treated with deslorelin and/or testosterone. Pituitary sections were labeled immunocytochemically for FSHβ and LHβ, or αGSU. Deslorelin suppressed testis weight by two thirds and reduced plasma FSH and LH in intact rats. Deslorelin decreased the percentage of gonadotropes but the effect was specific to the FSHβ-ir cells. Testosterone did not reverse the deslorelin-induced reduction in the overall gonadotrope population. However, in the presence of testosterone, the proportion of gonadotropes that was FSHβ-ir increased in the remaining gonadotropes. There was no effect of treatment on the total LHβ-ir cell population although the loss of FSHβ in bi-hormonal cells increased the proportion of mono-hormonal LHβ-ir gonadotropes. The castration-induced plasma LH and FSH increases were suppressed by deslorelin, testosterone or both. Castration increased both LH-ir and FSH-ir without increasing the overall gonadotrope population; thus increasing the proportion of bi-hormonal cells. Deslorelin suppressed these increases. Testosterone increased FSH-ir in deslorelin-treated castrate rats. Deslorelin did not affect αGSU immunoreactivity, suggesting that the gonadotrope population per se is not eliminated by deslorelin but the ability of gonadotropes to synthesize FSHβ is compromised. We hypothesize that the FSH dominant suppression may be central to the long-term contraceptive efficacy of deslorelin in the male. PMID:22172059

DOE Office of Scientific and Technical Information (OSTI.GOV)

Myllymaeki, S.A.; Karjalainen, M.; Haavisto, T.E.

Phenolic compounds, such as 4-tert-octylphenol (OP), have been shown to interfere with rat ovarian steroidogenesis. However, little is known about steroidogenic effects of infantile OP exposure on immature ovary. The aim of the present study was to investigate the effects of infantile OP exposure on plasma FSH, LH, estradiol, and progesterone levels in 14-day-old female rats. The effect on ovarian steroidogenic acute regulatory protein (StAR) and FSH receptor (FSHr) expression was analyzed by Western blotting. Ex vivo analysis was carried out for follicular estradiol, progesterone, testosterone, and cAMP production. Sprague-Dawley rats were given OP (0, 10, 50, or 100 mg/kg)more » subcutaneously on postnatal days 6, 8, 10, and 12. On postnatal day 14, plasma FSH was decreased and progesterone increased significantly at a dose of 100 mg OP/kg. In addition, the highest OP dose advanced the time of vaginal opening in puberty. OP had no effect on infantile LH and estradiol levels or ovarian FSHr content. Ovarian StAR protein content and ex vivo hormone and cAMP production were decreased at all OP doses compared to controls. However, hormone levels recovered independent on FSH and even increased above the control level during a prolonged culture. On postnatal day 35, no statistically significant differences were seen between control and OP-exposed animals in plasma FSH, LH, estradiol, and progesterone levels, or in ovarian StAR protein content. The results indicate that the effect of OP on the infantile ovary is reversible, while more permanent effects in the hypothalamus and pituitary, as described earlier, are involved in the reduction of circulating FSH levels and premature vaginal opening.« less

Is ovarian reserve associated with body mass index and obesity in reproductive aged women? A meta-analysis.

PubMed

Moslehi, Nazanin; Shab-Bidar, Sakineh; Ramezani Tehrani, Fahimeh; Mirmiran, Parvin; Azizi, Fereidoun

2018-05-07

The associations of body mass index (BMI) and obesity with ovarian reserve are controversial. This systematic review and meta-analysis was conducted to investigate the associations in reproductive-aged women. PubMed and Scopus were searched up to December, 2016. Original studies on the association of BMI with ovarian reserve markers, anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), inhibin β, and antral follicle count (AFC), either according to BMI categories or a continuous variable, were selected. Analyses were stratified into three groups based on polycystic ovary syndrome (PCOS) and fertility status of women. Of 4,055 records identified, 45 studies were eligible for inclusion. Comparing the obese with nonobese, the pooled mean differences (MDs) and 95% confidence intervals (CIs) were -1.08 (95% CIs -1.52, -0.63) ng/mL for AMH, -0.22 (95% CIs -0.39, -0.06) mIU/mL for FSH, -0.09 (95% CIs -0.60, 0.42) for AFC, and -21.06 (95% CIs -41.18, -0.85) pg/mL for inhibin β in overall populations. The MDs were significant for AMH in fertile non-PCOS and PCOS women, and for FSH only in PCOS women. Fisher's Z showed significant correlations of BMI with AMH in the overall populations (-0.15 [95% CIs -0.20, -0.11]) and in all subgroups, and with FSH in the fertile non-PCOS women (-0.16 [95% CIs -0.28, -0.04]). Ovarian reserve markers of AMH and FSH are significantly lower in obese than in nonobese women, and BMI is negatively correlated with AMH in all study populations, and with FSH in fertile non-PCOS subgroups. PCOS and fertility status do not appear to affect the associations.

Sulfation of LH Does Not Affect Intracellular Trafficking

PubMed Central

Pearl, Christopher A.; Boime, Irving

2009-01-01

LH and FSH are produced by the same gonadotrope cells of the anterior pituitary but differ in their mode of secretion. LH secretion is primarily episodic, or regulated, while FSH secretion is primarily basal, or constitutive. The asparagine (N)-linked oligosaccharides of LH and FSH terminate with sulfate and sialic acid, respectively. TSH also contains sulfated N-linked oligosaccharides and is secreted through the regulated pathway. It has been hypothesized that sulfate plays a role in segregating LH to the regulated pathway. Using a mouse pituitary model, we tested this hypothesis by examining the secretory fate of LH from pituitaries treated with sodium chlorate, a known inhibitor of sulfation. Here we show that mouse LH is sulfated and secreted through the regulated pathway, while FSH is secreted constitutively. LH secretion from chlorate treated pituitaries, which showed complete inhibition of sulfation, was similar to untreated pituitaries. These data suggest that the metabolic role for sulfated N-linked oligosaccharides is not for intracellular trafficking but for the extracellular bioactivity of LH. PMID:19647136

[Specifics of hormonal and energy balance in patients with hyperplasia and endometrial neoplasia with metabolic syndrome in the background].

PubMed

Chernyshova, A L; Kolomiets, L A; Bochkarëva, N V; Kondakova, I V

2013-01-01

We conducted a comparative investigation of the hormonal status (LH, FSH, estradiol, progesterone, testosterone, prolactin, SHBG), energy status (leptin, ghrelin, insulin), and carbohydrate and lipid metabolism in patients with endometrial hyperplasia and neoplasia (168 patients) with or without metabolic syndrome in the background. Patients with metabolic syndrome had a high frequency of elevated estrogen (72%), testosterone (65%), insulin (81%), leptin (68%). There was a marked increase in the basal level of luteinizing hormone, prolactin, index, LH/FSH, but decrease in FSH and progesterone. There were significant changes in carbohydrate and lipid metabolism. The possible mechanisms for the contribution of the investigated factors to the development of the pathological processes in the endometrium are presented.

Long-term outcomes in women with polycystic ovary syndrome initially randomized to receive laparoscopic electrocautery of the ovaries or ovulation induction with gonadotrophins.

PubMed

Nahuis, M J; Kose, N; Bayram, N; van Dessel, H J H M; Braat, D D M; Hamilton, C J C M; Hompes, P G A; Bossuyt, P M; Mol, B W J; van der Veen, F; van Wely, M

2011-07-01

Long-term effects of laparoscopic electrocautery of the ovaries are unknown. To study the long-term effects of laparoscopic electrocautery of the ovaries and gonadotrophins, we followed women with clomiphene-resistant polycystic ovary syndrome (PCOS) randomly allocated to one of these treatments until 8-12 years after their initial treatment. Between February 1998 and October 2001 168 women with clomiphene citrate-resistant PCOS were included in a randomized controlled trial comparing an electrocautery strategy to a strategy starting with rFSH. In 2009 these women were contacted about their reproductive outcome and menstrual cycle regularity. Analysis was by intention-to-treat. We compared time to conception resulting in live birth, subsequent pregnancies, ectopic and multiple pregnancies, menopause, as well as minimal and maximal menstrual cycle length. After 8-12 years, the cumulative proportion of women with a first child was 86% in women who had been allocated to electrocautery versus 81% in women who had been allocated to immediate rFSH [relative ratio (RR): 1.1; 95% confidence interval (CI): 0.92-1.2]. Treatment with electrocautery resulted in a significantly lower need for stimulated cycles to reach a live birth; 53% after electrocautery versus 76% after rFSH (RR: 0.69; 95% CI: 0.55-0.88).The cumulative proportion of women with a second child was 61% after electrocautery versus 46% after immediate rFSH (RR: 1.4; 95% CI: 1.00-1.9). Overall, there were 7 twins out of 134 deliveries (5%) after electrocautery versus 10 twins out of 124 deliveries (8%) in the rFSH group (RR: 0.65; 95% CI: 0.25-1.6). Fifty-four per cent of the women allocated to electrocautery had a regular menstrual cycle 8-12 years after randomization versus 36% in those allocated to rFSH (RR: 1.5; 95% CI: 0.87-2.6). In women with clomiphene-resistant PCOS, laparoscopic electrocautery of the ovaries is as effective as ovulation induction with FSH treatment in terms of live births, but reduces

Follicle-stimulating hormone synthesis and fertility are intact in mice lacking SMAD3 DNA binding activity and SMAD2 in gonadotrope cells

PubMed Central

Fortin, Jérôme; Boehm, Ulrich; Weinstein, Michael B.; Graff, Jonathan M.; Bernard, Daniel J.

2014-01-01

The activin/inhibin system regulates follicle-stimulating hormone (FSH) synthesis and release by pituitary gonadotrope cells in mammals. In vitro cell line data suggest that activins stimulate FSH β-subunit (Fshb) transcription via complexes containing the receptor-regulated SMAD proteins SMAD2 and SMAD3. Here, we used a Cre-loxP approach to determine the necessity for SMAD2 and/or SMAD3 in FSH synthesis in vivo. Surprisingly, mice with conditional mutations in both Smad2 and Smad3 specifically in gonadotrope cells are fertile and produce FSH at quantitatively normal levels. Notably, however, we discovered that the recombined Smad3 allele produces a transcript that encodes the entirety of the SMAD3 C-terminal Mad homology 2 (MH2) domain. This protein behaves similarly to full-length SMAD3 in Fshb transcriptional assays. As the truncated protein lacks the N-terminal Mad homology 1 (MH1) domain, these results show that SMAD3 DNA-binding activity as well as SMAD2 are dispensable for normal FSH synthesis in vivo. Furthermore, the observation that deletion of proximal exons does not remove all SMAD3 function may facilitate interpretation of divergent phenotypes previously described in different Smad3 knockout mouse lines.—Fortin, J., Boehm, U., Weinstein, M. B., Graff, J. M., Bernard, D. J. Follicle-stimulating hormone synthesis and fertility are intact in mice lacking SMAD3 DNA binding activity and SMAD2 in gonadotrope cells. PMID:24308975

[Male hormonal profile in workers exposed to toluene in an industrial packaging plant].

PubMed

Miranda-Figueroa, Genezareth; Paz-Román, María del Pilar; Aguilar-Madrid, Guadalupe; Juárez-Pérez, Cuauhtémoc Arturo; Basurto-Acevedo, Lourdes; Haro-García, Luis

2013-01-01

to identify changes in the male hormonal profile (MHP), consisting of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone, in workers exposed to toluene. cross-sectional study that included 42 workers, formed in two groups: with high and low exposure to toluene (HET and LET, respectively); the hippuric acid in urine, and the serum concentration in FSH, LH, and testosterone were measured. hippuric acid in subjects with LET was 2.53 ± 1.20 g/g creatinine, and with HET: 6.31 ± 3.83 g/g creatinine (p = 0.02). Seric FSH concentration was 5.12 ± 0.77 and 3.55 ± 0.3 mU/mL (p = 0.02) in LET and HET, respectively; LH: 2.66 ± 0.45 and 2.77 ± 0.21 (p = 0.81), and testosterone 3.91 ± 0.34 and 4.86 ± 0.23 ng/mL (p = 0.04). By regression analysis, the correlation coefficient of FSH with hippuric acid was r = -0.33 (p = 0.031), with coefficient of determination of 11 %; the LH correlation coefficient was r = -0.037 (p = 0.88) and 0.05 %, respectively; and the one for testosterone was r = 0.61 (p = 0.0001) and 34 %. in HET group, FSH and LH serum levels diminished; testosterone shows an opposite response, perhaps explained by a different sensitivity of the male gonads exposed to toluene.

[Effects of ginger-separated moxibustion at Baliao points combined with Bushen Huoxue formula on patients with decreased ovarian reserve function].

PubMed

Jiang, Duosheng; Zhang, Yingchun; Wu, Xiaolan; Wang, Yanming; Fan, Qiangfang; Wu, Song

2017-10-12

To compare the efficacy differences between ginger-separated moxibustion at Baliao points combined with Bushen Huoxue formula and Bushen Huoxue formula alone on patients with decreased ovarian reserve function. Fifty patients of decreased ovarian reserve function were randomly divided into an observation group and a control group, 25 cases in each one. The patients in the observation group were treated with ginger-separated moxibustion at Baliao points combined with Bushen Huoxue formula; the moxibustion was given for 1.5 h, once every seven days, and no treatment was given during menstrual period. The patients in the control group were treated with Bushen Huoxue formula. One-month treatment was taken as one treatment course, and totally three courses were given. The change of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E 2 ), anti-mullerian hormone (AMH), antral follicle count (AFC), peak systolic velocity (PSV), resistance index (RI) were observed before and after treatment in the two groups. After treatment, the FSH, FSH/LH and RI were significantly lowered, but the E 2 , AFC, PSV were significantly increased in the two groups (all P <0.05); the FSH, FSH/LH and E 2 in the observation group were lower and AFC was higher than those in the control group (all P <0.05). The ginger-separated moxibustion at Baliao points combined with Bushen Huoxue formula are superior to Bushen Huoxue formula alone in improving ovarian reserve function.

Developmental programming: impact of prenatal testosterone excess on pre- and postnatal gonadotropin regulation in sheep.

PubMed

Manikkam, Mohan; Thompson, Robert C; Herkimer, Carol; Welch, Kathleen B; Flak, Jonathan; Karsch, Fred J; Padmanabhan, Vasantha

2008-04-01

The goal of this study was to explore mechanisms that mediate hypersecretion of LH and progressive loss of cyclicity in female sheep exposed during fetal life to excess testosterone. Our working hypothesis was that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH (but not FSH) secretion and, thus, hypersecretion of LH in adulthood, and that this results from altered developmental gene expression of GnRH and estradiol (E2) receptors, gonadotropin subunits, and paracrine factors that differentially regulate LH and FSH synthesis. We observed that, relative to controls, females exposed during fetal life to excess testosterone, as well as the nor-aromatizable androgen dihydrotestosterone, exhibited enhanced LH but not FSH responses to intermittent delivery of GnRH boluses under conditions in which endogenous LH (GnRH) pulses were suppressed. Luteinizing hormone hypersecretion was more evident in adults than in prepubertal females, and it was associated with development of acyclicity. Measurement of pituitary mRNA concentrations revealed that prenatal testosterone excess induced developmental changes in gene expression of pituitary GnRH and E2 receptors and paracrine modulators of LH and FSH synthesis in a manner consistent with subsequent amplification of LH release. Together, this series of studies suggests that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH response, leading to LH hypersecretion and acyclicity in adulthood, and that this programming involves developmental changes in expression of pituitary genes involved in LH and FSH release.

Comparison of fall prediction by the Hessisch Oldendorf Fall Risk Scale and the Fall Risk Scale by Huhn in neurological rehabilitation: an observational study.

PubMed

Hermann, Olena; Schmidt, Simone B; Boltzmann, Melanie; Rollnik, Jens D

2018-05-01

To calculate scale performance of the newly developed Hessisch Oldendorf Fall Risk Scale (HOSS) for classifying fallers and non-fallers in comparison with the Risk of Falling Scale by Huhn (FSH), a frequently used assessment tool. A prospective observational trail was conducted. The study was performed in a large specialized neurological rehabilitation facility. The study population ( n = 690) included neurological and neurosurgery patients during neurological rehabilitation with varying levels of disability. Around the half of the study patients were independent and dependent in the activities of daily living (ADL), respectively. Fall risk of each patient was assessed by HOSS and FSH within the first seven days after admission. Event of fall during rehabilitation was compared with HOSS and FSH scores as well as the according fall risk. Scale performance including sensitivity and specificity was calculated for both scales. A total of 107 (15.5%) patients experienced at least one fall. In general, fallers were characterized by an older age, a prolonged length of stay, and a lower Barthel Index (higher dependence in the ADL) on admission than non-fallers. The verification of fall prediction for both scales showed a sensitivity of 83% and a specificity of 64% for the HOSS scale, and a sensitivity of 98% with a specificity of 12% for the FSH scale, respectively. The HOSS shows an adequate sensitivity, a higher specificity and therefore a better scale performance than the FSH. Thus, the HOSS might be superior to existing assessments.

Interval of gonadotropin administration for in vitro embryo production from oocytes collected from Holstein calves between 2 and 6 months of age by repeated laparoscopy.

PubMed

Baldassarre, Hernan; Currin, Luke; Michalovic, Laura; Bellefleur, Anne-Marie; Gutierrez, Karina; Mondadori, Rafael G; Glanzner, Werner G; Schuermann, Yasmin; Bohrer, Rodrigo C; Dicks, Naomi; Lopez, Rosalba; Grand, François-Xavier; Vigneault, Christian; Blondin, Patrick; Gourdon, Jim; Bordignon, Vilceu

2018-08-01

Laparoscopic Ovum Pick-Up (LOPU) in calves followed by in vitro embryo production (IVEP) and transfer (ET) into adult recipients has great potential for accelerated genetic gain through shortening of the generation interval. In this study, 11 Holstein calves were subjected to up to six LOPU procedures between the ages of 2-6 months at 2-3 weeks interval. In all cases, the animals received a CIDR 5 days prior to LOPU and were gonadotropin-stimulated starting at 72 h before LOPU using one of three protocols that were rotated twice among the animals during the study. Calves were injected with FSH every 12 h (FSH12h), or every 8 h (FSH8h) or every 8 h until -36 h from LOPU at which point the FSH was replaced with a single dose of 400 IU eCG (FSH8h-eCG). No statistical differences were observed among the 3 treatments in terms of mean follicles available for aspiration (35.7 ± 16 vs. 38.5 ± 25 vs. 31.1 ± 22), mean oocytes recovered (26.5 ± 14 vs. 21.6 ± 10 vs. 19.4 ± 14) and cleavage rate (66.0 ± 14 vs. 61.1 ± 11 vs. 72.2 ± 8), for FSH12h, FSH8h and FSH8h-eCG, respectively. However, FSH8h-eCG resulted in a significantly higher rate of transferable embryos (17.5 ± 8%) compared with FSH12h (8.9 ± 5%, P < 0.05). Oocytes from follicles of ≥5 mm in diameter yielded a higher rate (P < 0.05) of development to the blastocyst stage (13.8%) than those collected from <5 mm follicles (6.8%). Animal age, by comparing animals at <100, 101 to 130 and > 130 days of age, did not affect the mean number of follicles (34.2 ± 15 vs. 39.3 ± 26 vs. 31.6 ± 25), the mean number of oocytes recovered (21.2 ± 10 vs. 24.5 ± 15 vs. 22.6 ± 17), and the cleavage rate (68.6 ± 11 vs. 61.7 ± 12 vs. 70.7 ± 10%), respectively. However, animals in the older age range had significantly higher development to the blastocyst stage (19.9 ± 6 vs. 9.5 ± 8%, P < 0

Targeting of follicle stimulating hormone peptide-conjugated dendrimers to ovarian cancer cells

NASA Astrophysics Data System (ADS)

Modi, Dimple A.; Sunoqrot, Suhair; Bugno, Jason; Lantvit, Daniel D.; Hong, Seungpyo; Burdette, Joanna E.

2014-02-01

Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side effects. To address these issues, we have designed poly(amidoamine) (PAMAM) dendrimers to selectively target the follicle stimulating hormone receptor (FSHR), which is overexpressed by tumorigenic ovarian cancer cells but not by immature primordial follicles and other non-tumorigenic cells. Fluorescein-labeled generation 5 (G5) PAMAM dendrimers were conjugated with the binding peptide domain of FSH (FSH33) that has a high affinity to FSHR. The targeted dendrimers exhibited high receptor selectivity to FSHR-expressing OVCAR-3 cells, resulting in significant uptake and downregulation of an anti-apoptotic protein survivin, while showing minimal interactions with SKOV-3 cells that do not express FSHR. The selectivity of the FSH33-targeted dendrimers was further validated in 3D organ cultures of normal mouse ovaries. Immunostaining of the conjugates revealed their selective binding and uptake by ovarian surface epithelium (OSE) cells that express FSHR, while sparing the immature primordial follicles. In addition, an in vivo study monitoring tissue accumulation following a single intraperitoneal (i.p.) injection of the conjugates showed significantly higher accumulation of FSH33-targeted dendrimers in the ovary and oviduct compared to the non-targeted conjugates. These proof-of-concept findings highlight the potential of these FSH33-targeted dendrimers to serve as a delivery platform for anti-ovarian cancer drugs, while reducing their systemic side effects by preventing nonspecific uptake by the primordial follicles.Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side

DOE Office of Scientific and Technical Information (OSTI.GOV)

Potashnik, G.; Yanai-Inbar, I.

The current study summarizes an 8-year reassessment of testicular function and reproductive performance in 15 workers with dibromochloropropane (DBCP)-induced azoospermia and oligozoospermia. Recovery of spermatogenesis was observed in four oligozoospermic and three azoospermic men whose plasma follicle-stimulating hormone (FSH) concentration was normal during the whole period. A marked increase in FSH and luteinizing hormone concentrations above the upper limit of normal was found in the azoospermic workers who did not recover. No significant changes in FSH concentrations were detected in both recovered and nonrecovered oligozoospermic men. Testosterone levels of all patients were normal at all times. Paternal exposure to DBCPmore » was not associated with increased risk of fetal malformations or spontaneous abortion.« less

Treatment preferences and outcome in male hypogonadotropic hypogonadism: an Indian perspective.

PubMed

Sanyal, D; Chatterjee, S

2016-06-01

This retrospective study assessed treatment preferences and outcome with testosterone or HCG / HCG-FSH combination in Indian male idiopathic hypogonadotropic hypogonadism (IHH) subjects (n = 31) above 18 years of age. 38.7% of IHH study subjects had no fertility plans and chose 3 monthly intramuscular testosterone undecanoate. 73.7% of subjects with fertility plans chose human chorionic gonadotropin (HCG) alone due to cost considerations. Spermatogenesis occurred in 21.4% on HCG alone and 60% of subjects on HCG with follicle-stimulating hormone (FSH) combination. Treatment failure is higher than published Western rates. FSH and HCG combination regimen is costly but superior to HCG alone. However, treatment failure still persists, suggesting unknown testicular defect in IHH. © 2015 Blackwell Verlag GmbH.

Testicular growth and development in puberty.

PubMed

Koskenniemi, Jaakko J; Virtanen, Helena E; Toppari, Jorma

2017-06-01

To describe pubertal testicular growth in humans, changes in testicular cell populations that result in testicular growth, and the role of testosterone and gonadotrophins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in testicular growth. When human data were not available, studies in nonhuman primates and/or rodents were used as surrogates. Testicular growth in puberty follows a sigmoidal growth curve, with a large variation in timing of testicular growth and adult testicular volume. Testicular growth early in puberty is due to increase in Sertoli cell number and length of seminiferous tubules, whereas the largest and fastest growth results from the increase in the diameter of the seminiferous tubules first due to spermatogonial proliferation and then due to the expansion of meiotic and haploid germ cells. FSH stimulates Sertoli cell and spermatogonial proliferation, whereas LH/testosterone is mandatory to complete spermatogenesis. However, FSH and LH/testosterone work in synergy and are both needed for normal spermatogenesis. Testicular growth during puberty is rapid, and mostly due to germ cell expansion and growth in seminiferous tubule diameter triggered by androgens. Pre-treatment with FSH before the induction of puberty may improve the treatment of hypogonadotropic hypogonadism, but remains to be proven.

Mucuna pruriens improves male fertility by its action on the hypothalamus-pituitary-gonadal axis.

PubMed

Shukla, Kamla Kant; Mahdi, Abbas Ali; Ahmad, Mohammad Kaleem; Shankhwar, Satya Narain; Rajender, Singh; Jaiswar, Shyam Pyari

2009-12-01

To understand the mechanism of action of Mucuna pruriens in the treatment of male infertility. Prospective study. Departments of Biochemistry, Urology, and Obstetrics and Gynecology, C.S.M. Medical University, Lucknow, India. Seventy-five normal healthy fertile men (controls) and 75 men undergoing infertility screening. High-performance liquid chromatography assay for quantitation of dopa, adrenaline, and noradrenaline in seminal plasma and blood. Estimation by RIA of hormonal parameters in blood plasma, namely T, LH, FSH, and PRL. Before and after treatment, serum T, LH, FSH, PRL, dopamine, adrenaline, and noradrenaline in seminal and blood plasma were measured. Decreased sperm count and motility were seen in infertile subjects. Serum T and LH levels, as well as seminal plasma and blood levels of dopamine, adrenaline, and noradrenaline were also decreased in all groups of infertile men. This was accompanied by significantly increased serum FSH and PRL levels in oligozoospermic subjects. Treatment with M. pruriens significantly improved T, LH, dopamine, adrenaline, and noradrenaline levels in infertile men and reduced levels of FSH and PRL. Sperm count and motility were significantly recovered in infertile men after treatment. Treatment with M. pruriens regulates steroidogenesis and improves semen quality in infertile men.

Follicle-stimulating hormone (FSH) blood test

MedlinePlus

... 4 IU/L) Female: Before puberty - 0 to 4.0 mIU/mL (0 to 4.0 IU/L) During puberty - 0.3 to 10. ... Fellow American College of Obstetricians and Gynecologists, Group Health Cooperative, Bellevue, WA. Also reviewed by David Zieve, ...

Direct antigonadal activity of cannabinoids: suppression of rat granulosa cell functions.

PubMed

Adashi, E Y; Jones, P B; Hsueh, A J

1983-02-01

The direct effects of delta 9-tetrahydrocannabinol (THC) and related cannabinoids on ovarian granulosa cells were studied in vitro. Granulosa cells from immature, hypophysectomized, estrogen-treated rats were cultured for 2 days in an androstenedione-supplemented medium in the presence or absence of follicle-stimulating hormone (FSH) (10 ng/ml) with or without cannabinoids. FSH treatment increased progesterone and estrogen biosynthesis, whereas concomitant treatment with THC led to a dose-dependent inhibition of the FSH-stimulated accumulation of progesterone and estrogen with ED50 values of 3.5 +/- 0.3 X 10(-7) and 1.8 +/- 0.2 X 10(-6) M, respectively. Treatment with related but nonpsychoactive cannabinoids (cannabidiol, cannabinol, cannabigerol, or cannabichromene) was equally effective. The THC-induced inhibition of progesterone production was reversible and was associated with an inhibition of pregnenolone biosynthesis and a decrease of 3 beta-hydroxysteroid dehydrogenase activity. In addition, treatment with THC brought about a dose-dependent inhibition of the FSH-induced increase in luteinizing hormone (LH) receptors. The inhibitory effects of THC were not associated with changes in cell number, protein content, or cell viability. Thus, THC exerts direct inhibitory effects on FSH-dependent functions related to steroidogenesis and the acquisition of LH receptors, all of which are essential to follicular maturation. Because plasma concentrations of THC similar to those used in this study have been reported in human beings, repeated exposure of female users to THC may lead to ovarian dysfunction, due in part, to the direct antigonadal activity to THC.

Serum gonadotropins and gonadal steroids associated with ovulation and egg production in sea turtles.

PubMed

Wibbels, T; Owens, D W; Licht, P; Limpus, C; Reed, P C; Amoss, M S

1992-07-01

Changes in serum concentrations of gonadotropins and gonadal steroids during the periovulatory period were monitored in green, Chelonia mydas, and loggerhead, Caretta caretta, sea turtles. Turtles were from natural populations that nest on a coral island on the Great Barrier Reef. After nesting, each turtle was transferred to a holding tank and held for a maximum of 8 days. A time series of blood samples was obtained from each of five sea turtles (three C. mydas and two C. caretta) starting immediately after nesting and then at approximately 12-hr intervals until the time of release. Prior to release back into the ocean, each turtle was examined by laparoscopy to verify that ovulation had occurred. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (PRO), and testosterone (T) in both species exhibited significant changes during this period. Surges of FSH, LH, and PRO were evident within approximately 20 to 50 hr after each turtle had nested. The significant change in FSH concentration during the periovulatory period is the first such report for a reptile. Coincident with maximal concentrations of FSH, LH, and PRO was a decline in T concentrations in both species. Estradiol-17 beta concentrations were near or below assay sensitivity in the C. mydas, whereas those in the C. caretta were detectable but exhibited no significant changes. The dynamic changes in FSH, LH, PRO, and T concentrations are consistent with the hypothesis that these hormones facilitate specific physiological events during ovulation and egg production.

Circulating basal anti-Müllerian hormone levels as predictor of ovarian response in women undergoing ovarian stimulation for in vitro fertilization.

PubMed

Nardo, Luciano G; Gelbaya, Tarek A; Wilkinson, Hannah; Roberts, Stephen A; Yates, Allen; Pemberton, Phil; Laing, Ian

2009-11-01

To evaluate the clinical value of basal anti-Müllerian hormone (AMH) measurements compared with other available determinants, apart from chronologic age, in the prediction of ovarian response to gonadotrophin stimulation. Prospective cohort study. Tertiary referral center for reproductive medicine and an IVF unit. Women undergoing their first cycle of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Basal levels of FSH and AMH as well as antral follicle count (AFC) were measured in 165 subjects. All patients were followed prospectively and their cycle outcomes recorded. Predictive value of FSH, AMH, and AFC for extremes of ovarian response to stimulation. Out of the 165 women, 134 were defined as normal responders, 15 as poor responders, and 16 as high responders. Subjects in the poor response group were significantly older then those in the other two groups. Anti-Müllerian hormone levels and AFC were markedly raised in the high responders and decreased in the poor responders. Compared with FSH and AFC, AMH performed better in the prediction of excessive response to ovarian stimulation-AMH area under receiver operating characteristic curve (ROC(AUC)) 0.81, FSH ROC(AUC) 0.66, AFC ROC(AUC) 0.69. For poor response, AMH (ROC(AUC) 0.88) was a significantly better predictor than FSH (ROC(AUC) 0.63) but not AFC (ROC(AUC) 0.81). AMH prediction of ovarian response was independent of age and PCOS. Anti-Müllerian hormone cutoffs of >3.75 ng/mL and <1.0 ng/mL would have modest sensitivity and specificity in predicting the extremes of response. Circulating AMH has the ability to predict excessive and poor response to stimulation with exogenous gonadotrophins. Overall, this biomarker is superior to basal FSH and AFC, and has the potential to be incorporated in to work-up protocols to predict patient's ovarian response to treatment and to individualize strategies aiming at reducing the cancellation rate and the iatrogenic complications of COH.

Women with oligo-/amenorrhoea and polycystic ovaries have identical responses to GnRH stimulation regardless of their androgen status: comparison of the Rotterdam and Androgen Excess Society diagnostic criteria.

PubMed

Lewandowski, Krzysztof C; Cajdler-Luba, Agata; Bieńkiewicz, Małgorzata; Lewiński, Andrzej

2011-01-01

As increased frequency of gonadotrophin-releasing hormone (GnRH) pulses is characteristic for polycystic ovary syndrome (PCOS), we assessed gonadotrophin response to GnRH in women with PCOS with normal and raised androgens and in regularly menstruating controls. The study involved 155 subjects: PCOS, n=121, age (mean±SD) 24.8±5.4 yrs, BMI 24.5±6.0 kg/m2, all with oligo-/amenorrhoea and PCO morphology, and 34 controls. Gonadotrophins were measured in early follicular phase after GnRH stimulation (0, 30 and 60 minutes). Fifty four (41.9%) women with PCOS had androgens (testosterone, androstendione, dihydroepiandrosterone sulphate) within the reference range, and would fulfil the "Rotterdam", but not the Androgen Excess Society PCOS criteria. Baseline and stimulated LH concentrations were higher in PCOS (9.09±5.56 vs 4.83±1.71 IU/l, 35.48±31.4 vs 16.30±6.68 IU/l, 33.86±31.8 vs 13.45±5.2 IU/l, at 0, 30 and 60 min post GnRH, respectively, p<0.0001). An LH/FSH ratio in PCOS increased further after GnRH stimulation. ROC analysis revealed that LH30min/FSH30min >2.11 or LH60min/FSH60min >1.72 had 78.3% and 87.5% sensitivity and 81.7% and 81.3% specificity for diagnosis of PCOS. Both baseline and GnRH-stimulated LH and FSH concentrations were similar in women with PCOS and raised androgens and with androgens within the reference range (p=0.71 and p=0.20 for LH and FSH, respectively). Regardless of their androgen status, women with PCO morphology and oligo-/amenorrhoea have higher baseline and GnRH-stimulated LH concentrations and higher GnRH-stimulated LH/FSH ratio than controls, suggestive of similar underlying mechanism accounting for menstrual irregularities. These observations support validity of PCOS diagnostic criteria based on the Rotterdam consensus.

A patient with thyrotropinoma cosecreting growth hormone and follicle-stimulating hormone with low alpha-glycoprotein: a new subentity?

PubMed

Elhadd, Tarik A; Ghosh, Sujoy; Teoh, Wei Leng; Trevethick, Katy Ann; Hanzely, Zoltan; Dunn, Laurence T; Malik, Iqbal A; Collier, Andrew

2009-08-01

Thyrotropinomas are rare pituitary tumors. In 25 percent of cases there is autonomous secretion of a second pituitary hormone, adding to the clinical complexity. We report a patient with thyrotropin (TSH)-dependant hyperthyroidism along with growth hormone (GH) and follicle-stimulating hormone (FSH) hypersecretion but low alpha-glycoprotein (alpha-subunit) concentrations, a hitherto unique constellation of findings. A 67-year-old Scottish lady presented with longstanding ankle edema, paroxysmal atrial fibrillation, uncontrolled hypertension, fine tremors, warm peripheries, and agitation. Initial findings were a small goiter, elevated serum TSH of 7.37 mU/L (normal range, 0.30-6.0 mU/L), a free-thyroxine concentration of 34.9 pmol/L (normal range, 9.0-24.0 pmol/L), a flat TSH response to TSH-releasing hormone, and serum alpha-subunit of 3.1 IU/L (normal, <3.0 IU/L). There was no evidence of an abnormal thyroid hormone beta receptor by genotyping. Serum FSH was 56.8 U/L, but the luteinizing hormone (LH) was 23.6 U/L (postmenopausal FSH and LH reference ranges both >30 U/L) Basal insulin-like growth factor I was elevated to 487 microg/L with the concomitant serum GH being 14.1 mU/L, and subsequent serum GH values 30 minutes after 75 g oral glucose being 19.1 mU/L and 150 minutes later being 13.7 mU/L. An magnetic resonance imaging pituitary revealed a macroadenoma. Pituitary adenomectomy was performed with the histology confirming a pituitary adenoma, and the immunohistochemistry staining showed positive reactivity for FSH with scattered cells staining for GH and TSH. Staining for other anterior pituitary hormones was negative. After pituitary surgery she became clinically and biochemically euthyroid, the serum IFG-1 became normal, but the pattern of serum FSH and LH did not change. This case of plurihormonal thyrotropinoma is unique in having hypersecretion of TSH, GH, and FSH with low alpha-subunit. Such a combination may represent a new subentity of TSHomas.

Inhibition of follicle-stimulating hormone-induced preovulatory follicles in rats treated with a nonsteroidal negative allosteric modulator of follicle-stimulating hormone receptor.

PubMed

Dias, James A; Campo, Brice; Weaver, Barbara A; Watts, Julie; Kluetzman, Kerri; Thomas, Richard M; Bonnet, Béatrice; Mutel, Vincent; Poli, Sonia M

2014-01-01

We previously described a negative allosteric modulator (NAM) of FSHR (ADX61623) that blocked FSH-induced cAMP and progesterone production but did not block estradiol production. That FSHR NAM did not affect FSH-induced preovulatory follicle development as evidenced by the lack of an effect on the number of FSH-dependent oocytes found in the ampullae following ovulation with hCG. A goal is the development of a nonsteroidal contraceptive. Toward this end, a high-throughput screen using human FSHR identified an additional nonsteroidal small molecule (ADX68692). Although ADX68692 behaved like ADX61623 in inhibiting production of cAMP and progesterone, it also inhibited FSH-induced estradiol in an in vitro rat granulosa primary cell culture bioassay. When immature, noncycling female rats were injected subcutaneously or by oral dosing prior to exogenous FSH administration, it was found that ADX68692 decreased the number of oocytes recovered from the ampullae. The estrous cycles of mature female rats were disrupted by administration by oral gavage of 25 mg/kg and 10 mg/kg ADX68692. In the highest dose tested (25 mg/kg), 55% of animals cohabited with mature males had implantation sites compared to 33% in the 10 mg/kg group and 77% in the control group. A surprising finding was that a structural analog ADX68693, while effectively blocking progesterone production with similar efficacy as ADX68692, did not block estrogen production and despite better oral availability did not decrease the number of oocytes found in the ampullae even when used at 100 mg/kg. These data demonstrate that because of biased antagonism of the FSHR, nonsteroidal contraception requires that both arms of the FSHR steroidogenic pathway must be effectively blocked, particularly estrogen biosynthesis. Thus, a corollary to these findings is that it seems reasonable to propose that the estrogen-dependent diseases such as endometriosis may benefit from inhibition of FSH action at the ovary using the FSHR

Regulation of follitropin-sensitive adenylate cyclase by stimulatory and inhibitory forms of the guanine nucleotide regulatory protein in immature rat Sertoli cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, G.P.

1987-01-01

Studies have been designed to examine the role of guanine nucleotides in mediating FSH-sensitive adenylate cyclase activity in Sertoli cell plasma membranes. Analysis of ({sup 3}H)GDP binding to plasma membranes suggested a single high affinity site with a K{sub d} = 0.24 uM. Competition studies indicated that GTP{sub {gamma}}S was 7-fold more potent than GDP{sub {beta}}S. Bound GDP could be released by FSH in the presence of GTP{sub {gamma}}S, but not by FSH alone. Adenylate cyclase activity was enhanced 5-fold by FSH in the presence of GTP. Addition of GDP{sub {beta}}S to the activated enzyme (FSH plus GTP) resulted inmore » a time-dependent decay to basal activity within 20 sec. GDP{sub {beta}}S competitively inhibited GTP{sub {gamma}}S-stimulated adenylate cyclase activity with a K{sub i} = 0.18 uM. Adenylate cyclase activity was also demonstrated to be sensitive to the nucleotide bound state. In the presence of FSH, only the GTP{sub {gamma}}S-bound form persisted even if GDP{sub {beta}}S previously occupied all available binding sites. Two membrane proteins, M{sub r} = 43,000 and 48,000, were ADP{centered dot}ribosylated using cholera toxin and labeling was enhanced 2 to 4-fold by GTP{sub {gamma}}S but not by GDP{sub {beta}}S. The M{sub r} = 43,000 and 48,000 proteins represented variant forms of G{sub S}. A single protein of M{sub r} = 40,000 (G{sub i}) was ADP-ribosylated by pertussis toxin in vitro. GTP inhibited forskolin-stimulated adenylate cyclase activity with an IC{sub 50} = 0.1 uM. The adenosine analog, N{sup 6}{centered dot}phenylisopropyl adenosine enhanced GTP inhibition of forskolin-stimulated adenylate cyclase activity by an additional 15%. GTP-dependent inhibition of forskolin-sensitive adenylate cyclase activity was abolished in membranes prepared from Sertoli cells treated in culture with pertussis toxin.« less

Ovarian response markers lead to appropriate and effective use of corifollitropin alpha in assisted reproduction.

PubMed

La Marca, Antonio; D'Ippolito, Giovanni

2014-02-01

Corifollitropin alpha is a highly effective gonadotrophin, which maintains multifollicular growth for a week. The advantages of its administration include ease of use of the drug, making the treatment more patient friendly, resulting in a lower level of distress for the patient. At the same time, the pregnancy rate resulting from its use in IVF/intracytoplasmic sperm injection cycles is similar to that found when daily recombinant FSH is administered. The ovarian response to corifollitropin alpha is dependent on clinically established predictors such as baseline FSH, antral follicle count (AFC) and age. There is a general trend towards a higher ovarian response with an increasing AFC and the number of oocytes per attempt decreased with increasing baseline FSH and age. Even if the risk of ovarian hyperstimulation syndrome following corifollitropin alpha is very similar to the rate reported in literature for young women undergoing IVF, the risk of overstimulation may be reduced by avoiding maximal ovarian stimulation in women anticipated to be hyperresponders. High basal anti-Müllerian hormone and/or AFC can identify women with enhanced functional ovarian reserve at risk of overstimulation, and the risk is even higher if maximally stimulated with corifollitropin alpha or high dose of daily recombinant FSH. Corifollitropin alpha is a highly effective gonadotrophin which maintains multifollicular growth for a week. The ovarian response to corifollitropin was demonstrated to be dependent on clinically established predictors such as baseline FSH, antral follicle count (AFC) and age. There was a general trend toward a higher ovarian response with an increasing AFC and the mean number of oocytes per attempt decreased with increasing baseline FSH and age. Even if the risk of ovarian hyperstimulation syndrome (OHSS) following corifollitropin alpha is very similar to the rate of OHSS reported in literature for young women undergoing IVF, the risk of overstimulation may be

Effect of altering the intervals between consecutive superovulatory doses of porcine follicle-stimulating hormone on ovarian responses and embryo yields in anestrous ewes.

PubMed

Bartlewski, P M; Murawski, M; Schwarz, T; Oliveira, M E F

2017-05-01

The effect of varying intervals between successive gonadotropin injections on the superovulatory outcomes in anestrous Rideau Arcott ewes superstimulated for ovarian follicular development with multiple doses of porcine FSH (pFSH) was evaluated in a single study. Twenty-five animals received six (1×2.5ml and 5×1.25ml) injections of Folltropin ® -V given at 0800 and 1600h or at 0800 and 2000h in Group 1 (n=9) or Group 2 (n=16), respectively. An i.m. injection of 500 IU of equine chorionic gonadotropin (eCG; Folligon ® ) was given concurrently with the first pFSH dose. Time of estrus was synchronized among ewes with intravaginal sponges containing 60mg of medroxyprogesterone acetate (Veramix ® ) that were left in place for 14days; sponges were removed at the time of the 5th pFSH injection. Six days after insertion of MAP sponges, all ewes received an i.m. injection of estradiol-17β dissolved in 1ml of sesame oil (350μg/ewe) to synchronize follicular wave emergence. Following the last pFSH dose, all animals were given a single i.m. injection of 50μg of gonadotropin-releasing hormone (GnRH; Cystorelin ® ) to induce ovulations before placing in a pen with four fertile rams for 36h. The ovarian responses were assessed and embryos recovered surgically 7days after GnRH injections. The mean number of corpora lutea was greater (P<0.05) in Group 1 compared with Group 2 ewes (21.0±2.9 compared with 10.4±1.6, respectively; mean±SEM) but there was no difference (P>0.05) in the number of transferable embryos (5.4±2.4 compared with 5.4±1.3/ewe, respectively), and Group 1 animals had significantly more degenerated embryos than Group 2 ewes (2.6±1.2 compared with 0.6±0.3/ewe, respectively). A superovulatory protocol wherein pFSH injections were given at 0800 and 1600h was more effective in terms of inducing multiple ovulations than the protocol with 12-h intervals between consecutive pFSH doses, but it was not associated with an increased production of transferable

[Effects of autologous blood injection at Zusanli (ST 36) on ovarian function in patients with primary ovarian insufficiency].

PubMed

Jiang, Renjian; Zou, Yu

2017-11-12

To observe the effects of autologous blood injection and 0.9% NaCl at Zusanli (ST 36) on ovarian function in patients with primary ovarian insufficiency. Sixty patients with primary ovarian insufficiency were randomly divided into an observation group and a control group, 30 cases in each one. The patients in the observation group were treated with injection of autologous blood at Zusanli (ST 36); the patients in the control group were treated with 0.9% NaCl with identical volume at Zusanli (ST 36). Both the treatments were given once a week for 3 months. The ovarian function, including follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E 2 ) were tested before treatment, 1 month, 2 months and 3 months after first acupoint injection; the endometrial thickness before and after treatment and clinical efficacy were compared in the two groups. Compared before treatment, FSH was lowered in the observation group after 1-month treatment ( P <0.05), while FSH and LH were lowered and E 2 was increased after 2-month treatment and 3-month treatment (all P <0.05). Compared with 1-month treatment, FSH and LH were lowered and E 2 was increased in the observation group after 2-month treatment and 3-month treatment (all P <0.05). Compared with 2-month treatment, FSH was lowered and E 2 was increased in the observation group after 3-month treatment (both P <0.05). The differences of all serum tests before and after treatment were insignificant in the control group (all P >0.05). The FSH after 1-month treatment, and FSH, LH and E 2 after 2-month treatment and 3-month treatment in the observation group were significantly different from those in the control group (all P <0.05). The endometrial thickness after treatment in the observation group was higher than that before treatment ( P <0.05), while the endometrial thickness after treatment in the control group was similar to that before treatment ( P >0.05); the difference of endometrial thickness before and

Impact of gonadotropin type on progesterone elevation during ovarian stimulation in GnRH antagonist cycles.

PubMed

Lawrenz, B; Beligotti, F; Engelmann, N; Gates, D; Fatemi, H M

2016-11-01

Does hormonal stimulation with corifollitropin alpha (CFA) only, mimicking a step down protocol, result in lower incidence of progesterone elevation on the day of hCGtrigger as compared to sustained stimulation with recombinant FSH (rFSH)? The current findings support the concept that sustained FSH stimulus contributes to premature progesterone elevation in stimulated IVF cycles. Serum progesterone rise during the follicular phase of ovarian stimulation for IVF treatment seems to be related to a poorer reproductive outcome. However, the mechanism by which the rise in progesterone is caused is not yet fully understood. This study was a post hoc analysis of data from two multi-center, randomized, double-blind, double-dummy, active-controlled, non-inferiority trials, ENGAGE and PURSUE, conducted from June 2006 to January 2008 and from July 2010 to October 2012 respectively. In the ENGAGE-study, 1506 women, aged 18-36 years, were allocated to either a single injection of 150 mg CFA or daily injections of 200 IU rFSH in the first week of stimulation, using a standard GnRH antagonist protocol. In the PURSUE-study, a total of 1390 women, aged 35-42 years, were allocated to either a single injection of 150 mg of CFA or daily 300 IU of rFSH for the first week, again using a standard GnRH antagonist protocol. In both trials, daily rFSH was continued until three follicles reached >17 mm in size. All women had a body weight of between 50 and 90 kg, regular menstrual cycles and an indication for ovarian stimulation before IVF. The incidence of progesterone elevation on day of hCG-trigger in patients with CFA only or rFSH stimulation, and triggered on Day 8 of stimulation, was analyzed. Of patients with CFA only stimulation, 5.4% (13/239 patients) showed a progesterone elevation above 1.5 ng/ml on day of hCG-trigger, whereas patients with rFSH stimulation had a significant higher incidence of progesterone elevation (18.3%; 62/339 patients) (P < 0.001). Post hoc analysis of

Ultra-low Doses of Follicle Stimulating Hormone and Progesterone Attenuate the Severity of Polycystic Ovary Syndrome Features in a Hyperandrogenized Mouse Model

PubMed Central

Tessaro, Irene; Modina, Silvia; Lodde, Valentina; Sivelli, Giulia; Franciosi, Federica; Terzaghi, Laura; Luchini, Patrizia; Rumio, Cristiano; Luciano, Alberto Maria

2017-01-01

Background: Polycystic-ovary syndrome (PCOS) is a reproductive illness characterized by hyperandrogenism and anovulation. Using hyperandrogenized mice, it was demonstrated that the oral administration of incremental dose of follicle stimulating hormone (FSH) attenuated some of PCOS characteristics. This work aimed to study the effect of ultra-low doses of combined FSH and progesterone orally administered on PCOS murine model. Moreover, the effect of sequential kinetic activation of administered hormones was tested. Methods: Thirty-two female mice were used as animal model (four groups of eight animals each). Mice were hyperandrogenized by injection of dehyidroepiandrosterone diluted in sesame oil. Control group received only oil. Simultaneously, each animal daily received per os an activated or a not-activated combination of FSH (0.44 pg) plus progesterone (0.44 pg) or saline solution as control. Serum testosterone, estradiol, progesterone and luteinizing hormone were analyzed as endocrine markers and a morphological study of antral follicle was conducted. Data were analyzed by one-way ANOVA, followed by multiple comparison test. The p<0.05 was considered significant. Results: Dehyidroepiandrosterone treatment increased both estradiol and progesterone serum levels, besides testosterone, while reduced luteinizing hormone (p<0.05); histological examination revealed an increase of cystic follicles (p<0.05). Irrespective of activation, the combined FSH and progesterone treatments restored estradiol level (p>0.05 vs. control group) and reduced cystic signs in the follicles (p<0.05 vs. dehyidroepiandrosterone treatment). Conclusion: This study indicate that ultra-low doses of FSH and progesterone orally administrated can reduce the sternness of PCOS in the mouse model and open a route for the study of innovative approaches for PCOS treatment. PMID:29062793

Induction of puberty with human chorionic gonadotropin and follicle-stimulating hormone in adolescent males with hypogonadotropic hypogonadism.

PubMed

Barrio, R; de Luis, D; Alonso, M; Lamas, A; Moreno, J C

1999-02-01

To evaluate the clinical and hormonal responses of adolescent males with hypogonadotropic hypogonadism (HH) in response to gonadotropin replacement with the use of long-term combined hCG and FSH therapy. Prospective clinical study. Clinical pediatric department providing tertiary care. Seven prepubertal males with isolated HH with a mean (+/-SD) age of 15.44+/-1.97 years and seven prepubertal males with panhypopituitarism-associated HH with a mean (+/-SD) age of 18.1+/-3.24 years were studied. Human chorionic gonadotropin (1,000-1,500 IU IM) and FSH (75-100 IU SC) were administered every alternate day of the week until the total induction of puberty and spermatogenesis was achieved. Serum testosterone levels, testicular volume, penis length, and sperm count were evaluated after the administration of hCG and FSH. All patients achieved normal sexual maturation and normal or nearly normal adult male levels of testosterone. The increase in testicular size was significant in both groups. Positive sperm production was assessed in four of five patients with isolated HH and in three of three patients with panhypopituitarism-associated HH. Long-term combined hCG and FSH therapy is effective in inducing puberty, increasing testicular volume, and stimulating spermatogenesis in adolescent males with isolated HH and panhypopituitarism-associated HH.

Social dominance in tilapia is associated with gonadotroph hyperplasia.

PubMed

Golan, Matan; Levavi-Sivan, Berta

2013-10-01

Tilapias are emerging as one of the most important fish in worldwide aquaculture and are also widely used as model fish in the study of reproduction and behavior. During the reproductive season, male tilapia are highly territorial and form spawning pits in which the dominant males court and spawn with available females. Non-territorial males stand a much lower chance of reproducing. Using transgenic tilapia in which follicle stimulating hormone (FSH) gonadotrophs were fluorescently labeled with enhanced green fluorescent protein (EGFP), we studied the effect of social dominance on the hormonal profile and pituitary cell populations in dominant and non-dominant males. Immunofluorescence studies showed that FSH-EGFP-transgenic fish reliably express EGFP in FSH-secreting cells. EGFP expression pattern differed from that of luteinizing hormone. Dominant males had larger gonads as well as higher levels of androgens and gonadotropins in the plasma. Pituitaries of dominant males exhibited higher gonadotropin content and gene expression. Flow cytometry revealed pituitary hyperplasia as well as FSH cell hyperplasia and increased granulation. Taken together, these findings suggest that gonadotroph hyperplasia as well as increased production by individual cells underlie the increased reproductive activity of dominant tilapia males. Copyright © 2013 Elsevier Inc. All rights reserved.

New perspectives in the diagnosis of pediatric male hypogonadism: the importance of AMH as a Sertoli cell marker.

PubMed

Grinspon, Romina P; Rey, Rodolfo A

2011-11-01

Sertoli cells are the most active cell population in the testis during infancy and childhood. In these periods of life, hypogonadism can only be evidenced without stimulation tests, if Sertoli cell function is assessed. AMH is a useful marker of prepubertal Sertoli cell activity and number. Serum AMH is high from fetal life until mid-puberty. Testicular AMH production increases in response to FSH and is potently inhibited by androgens. Serum AMH is undetectable in anorchidic patients. In primary or central hypogonadism affecting the whole gonad and established in fetal life or childhood, serum AMH is low. Conversely, when hypogonadism affects only Leydig cells (e.g. LHβ mutations, LH/CG receptor or steroidogenic enzyme defects), serum AMH is normal or high. In pubertal males with central hypogonadism, AMH is low for Tanner stage (reflecting lack of FSH stimulus), but high for the age (indicating lack of testosterone inhibitory effect). Treatment with FSH provokes an increase in serum AMH, whereas hCG administration increases testosterone levels, which downregulate AMH. In conclusion, assessment of serum AMH is helpful to evaluate gonadal function, without the need for stimulation tests, and guides etiological diagnosis of pediatric male hypogonadism. Furthermore, serum AMH is an excellent marker of FSH and androgen action on the testis.

Determination of the content of follicle-stimulating hormone in the blood plasma of children, healthy men, and women during menopause with the aid of a radioimmunological technique (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chemodanov, V.I.; Sel'verova, N.B.

1973-01-01

A method of radioimmunological determination of FSH in the blood plasma with the use of /sup 131/I and the technique of double antibodies is described. Forty eight children under puberty, 36 men, and 34 women during the menopause were examined. Biological and the described methods were applied to the study of various gonadotropin preparations. A conclusion was drawn that this method was sufficiently sensitive and specific and gave reproducible results, although they depended on the FSH/LH ratio. An attempt was made to use kaolin-acetone precipitates of the urine for determination of FSH in them with the aid of the systemmore » described. A low yield of the hormone that was explained by inadequate specificity and poor purification of the extracts was obtained. The role of urinary and hypophyseal standards is discussed. (auth)« less

Use of progestagen-gonadotrophin treatments in estrus synchronization of sheep.

PubMed

Boscos, C M; Samartzi, F C; Dellis, S; Rogge, A; Stefanakis, A; Krambovitis, E

2002-10-15

The main objective of this study was to investigate the effectiveness of certain progestagen-gonadotrophin treatments on synchronization of estrus in sheep. In Experiment I, 30 Chios ewes were treated at the beginning of the breeding season with medroxyprogesterone acetate (MAP) intravaginal sponges for 12 days and a single i.m. treatment of either FSH (Group 1,10 IU, n = 8; Group 2, 5 IU, n = 8; Group 3, 2.5 IU, n = 8) or eCG (Group 4, 400 IU, n = 6) at the time of sponge removal. Ten days after sponge removal laparotomy was performed to record ovarian response. Clinical estrus was observed in more (though not at a significant level) FSH treated than eCG treated sheep (62.5% versus 33.3%). Administration of 400 IU eCG resulted in the highest mean number of CL perewe ovulating (2.8 +/- 0.2), with administration of 10 IU FSH producing the next best results (2.1 +/- 0.3). Statistically significant differences in the mean number of CL per ewe ovulating were found only between ewes in Group 3 (1.7 +/- 0.4) and Group 4 (2.8 +/- 0.2) (P < 0.05). In Experiment II, 53 Chios and 30 Berrichon ewes were treated during the mid-breeding season with MAP intravaginal sponges for 12 days and a single i.m. treatment of either 10 IU FSH (27 Chios and 16 Berrichon ewes) or 400 IU eCG (26 Chios and 14 Berrichon ewes), at the time of sponge removal. Ewes that were in estrus on Days 2-4 and 19-23 after sponge removal were mated to fertile rams. No significant differences were recorded between treatment or breed groups in the proportions of ewes observed in estrus after treatment. In the Berrichon breed, FSH administration resulted in higher lambing rates (93.8% versus 57.1%, P < 0.05) and higher mean number of lambs born per ewe exposed to rams (1.4 +/- 0.2 versus 0.8 +/- 0.2, P < 0.05) than that of eCG. After treatment with eCG, the mean number of lambs born per ewe exposed to rams was higher in the Chios than the Berrichon breed (1.4 +/- 0.2 versus 0.8 +/- 0.2, P < 0.05). After

Dose-Effect Relationship of Alkylating Agents on Testicular Function in Male Survivors of Childhood Lymphoma.

PubMed

Servitzoglou, Marina; De Vathaire, Florent; Oberlin, Odile; Patte, Catherine; Thomas-Teinturier, Cécile

2015-01-01

The purpose of our study was to assess the gonadal function in male survivors of childhood lymphoma. We studied 171 male survivors of childhood lymphoma (83 with B-cell non-Hodgkin lymphoma [B-NHL], 32 with T-cell non-Hodgkin lymphoma [T-NHL], 50 with Hodgkin lymphoma [HL], and 6 with anaplastic large-cell lymphoma [ALCL]), measuring follicle-stimulating hormone [FSH] and luteinizing hormone [LH] levels at a median age of 21.1 (17-30.4) years after a median delay of 9.3 (2-22.4) years from treatment. FSH levels were above normal range (≥10 IU/L) in 42.1% and LH levels ≥8 IU/L in only 8.9% of survivors. In multivariate analysis, only the following chemotherapeutic agents were associated with higher FSH or LH levels: cyclophosphamide (P < .0001, .04), lomustine (CCNU; P = .002, 0.04), and procarbazine (P < .0001, .07). No significant correlation was found between FSH or LH levels and age or pubertal status at diagnosis. Mean FSH level was significantly lower in NHL survivors treated more recently: 6 ± 5.1 IU/L in B-NHL survivors treated since 1986 versus 12.3 ± 5.4 IU/L for those treated before 1981 (P = .0001), and 6.8 ± 9.6 IU/L in T-NHL survivors treated since 1989 versus 9.4 ± 5.7 IU/L for those treated before 1989 (P = .035). In HL, mean FSH level was 12.4 ± 9.9 IU/L following procarbazine containing chemotherapy versus 3.4 ± 1.9 IU/L in the absence of procarbazine and increased significantly with the number of MOPP/OPPA (mechlorethamine, Oncovin [vincristine], procarbazine, and prednisone/Oncovin, procarbazine, and prednisone, and Adriamycin [doxorubicin]) courses received, from 6.8 ± 5.7 IU/L for 1-2 MOPP/OPPA to 12.6 ± 7.5 for 3-4 MOPP/OPPA and 19.6 ± 13.3 for more than 4 MOPP/OPPA (P for trend = .006). Testicular toxicity of alkylating agents on childhood lymphoma survivors is dose dependent and not correlated to diagnosis, age, or pubertal status at diagnosis.

Women with clomiphene citrate resistant polycystic ovarian disease: predictors of spontaneous ovulation after laparoscopic ovarian drilling.

PubMed

Abuelghar, Wessam M; Bayoumy, Hassan A; Ellaithy, Mohamed I; Khalil, Marian S

2014-04-01

To evaluate the role of different clinical, biochemical and sonographic factors as predictors of spontaneous ovulation after laparoscopic ovarian drilling (LOD) in women with clomiphene citrate resistant polycystic ovarian disease (CCR-PCOD). This prospective study recruited 251 infertile women with CCR-PCOD. Several clinical, biochemical and sonographic criteria were tested as possible predictors of spontaneous ovulation after LOD using multivariate analysis. Women with higher preoperative levels of LH, FSH and/or androstenedione had significantly higher rates of spontaneous ovulation within the first eight weeks after LOD, but only FSH and androstenedione were found to be independent predictors. Other factors including age, BMI, type of infertility, duration of infertility, menstrual pattern, testosterone level, ovarian volume and SHBG were insignificant predictors. Receiver-operating characteristic (ROC) curves derived from FSH, LH, androstenedione, and a logistic regression model showed that the best cut-off values were 4.1IU/l, 7.8IU/l, 1.2ng/ml, and 0.4897, respectively, with sensitivity of 91.18%, 100%, 73.53%, and 88.24% and specificity of 69.57%, 69.57%, 65.22%, and 73.91% for FSH, LH, androstenedione, and logistic regression model respectively. An extended follow up (9 months after LOD) was conducted for the anovulatory and the non-pregnant ovulatory women, who were treated individually according to their clinical situation. Of these women, 53.5% (69/129) got pregnant, resulting in a cumulative pregnancy rate of 48% (82/171). Of these pregnancies, 16/82 (19.5%) were spontaneous while 35.4% (29/82) and 45.1% (37/82) occurred after ovulation induction by CC and gonadotropins, respectively. This study supports the use of androstenedione, LH and FSH as a simple reliable tool in triaging patients with CCR-PCOD to select the ideal candidates for LOD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Reciprocal Cross Talk between Gonadotropin-Releasing Hormone (GnRH) and Prostaglandin Receptors Regulates GnRH Receptor Expression and Differential Gonadotropin Secretion

PubMed Central

Naor, Zvi; Jabbour, Henry N.; Naidich, Michal; Pawson, Adam J.; Morgan, Kevin; Battersby, Sharon; Millar, Michael R.; Brown, Pamela; Millar, Robert P.

2007-01-01

The asynchronous secretion of gonadotrope LH and FSH under the control of GnRH is crucial for ovarian cyclicity but the underlying mechanism is not fully resolved. Because prostaglandins (PG) are autocrine regulators in many tissues, we determined whether they have this role in gonadotropes. We first demonstrated that GnRH stimulates PG synthesis by induction of cyclooxygenase-2, via the protein kinase C/c-Src/phosphatidylinositol 3′-kinase/MAPK pathway in the LβT2 gonadotrope cell line. We then demonstrated that PGF2α and PGI2, but not PGE2 inhibited GnRH receptor expression by inhibition of phosphoinositide turnover. PGF2α, but not PGI2 or PGE2, reduced GnRH-induction of LHβ gene expression, but not the α-gonadotropin subunit or the FSHβ subunit genes. The prostanoid receptors EP1, EP2, FP, and IP were expressed in rat gonadotropes. Incubations of rat pituitaries with PGF2α, but not PGI2 or PGE2, inhibited GnRH-induced LH secretion, whereas the cyclooxygenase inhibitor, indomethacin, stimulated GnRH-induced LH secretion. None of these treatments had any effect on GnRH-induced FSH secretion. The findings have thus elaborated a novel GnRH signaling pathway mediated by PGF2α-FP and PGI2-IP, which acts through an autocrine/paracrine modality to limit autoregulation of the GnRH receptor and differentially inhibit LH and FSH release. These findings provide a mechanism for asynchronous LH and FSH secretions and suggest the use of combination therapies of GnRH and prostanoid analogs to treat infertility, diseases with unbalanced LH and FSH secretion and in hormone-dependent diseases such as prostatic cancer. PMID:17138645

Differential regulation of luteinizing hormone and follicle-stimulating hormone expression during ovarian development and under sexual steroid feedback in the European eel.

PubMed

Schmitz, Monika; Aroua, Salima; Vidal, Bernadette; Le Belle, Nadine; Elie, Pierre; Dufour, Sylvie

2005-01-01

Pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are, in teleosts as in mammals, under the control of hypothalamic factors and steroid feedbacks. In teleosts, feedback regulations largely vary depending on species and physiological stage. In the present study the regulation of FSH and LH expression was investigated in the European eel, a fish of biological and phylogenetical interest as a representative of an early group of teleosts. The eel FSHbeta subunit was cloned, sequenced and together with earlier isolated eel LHbeta and glycoprotein hormone alpha (GPalpha) subunits used to study the differential regulation of LH and FSH. In situ hybridization indicated that FSHbeta and LHbeta are expressed by separate cells of the proximal pars distalis of the adenohypophysis, differently from the situation in mammals. The profiles of LHbeta and FSHbeta subunit expression were compared during experimental ovarian maturation, using dot-blot assays. Expression levels for LHbeta and GPalpha increased throughout ovarian development with a positive correlation between these two subunits. Conversely, FSHbeta mRNA levels decreased. To understand the role of sex steroids in these opposite variations, immature eels were treated with estradiol (E2)and testosterone (T), both steroids being produced in eel ovaries during gonadal development. E2 treatment induced increases in both LHbeta and GPalpha mRNA levels, without any significant effect on FSHbeta. In contrast, T treatment induced a decrease in FSHbeta mRNA levels, without any significant effect on the other subunits. These data demonstrate that steroids exert a differential feedback on eel gonadotropin expression, with an E2-specific positive feedback on LH and a T-specific negative feedback on FSH, leading to an opposite regulation of LH and FSH during ovarian development. Copyright 2005 S. Karger AG, Basel

Anti-Muellerian hormone, inhibin A, gonadotropins, and gonadotropin receptors in bull calves after partial scrotal resection, orchidectomy, and Burdizzo castration.

PubMed

Scarlet, Dragos; Aurich, Christine; Ille, Natascha; Walter, Ingrid; Weber, Corinna; Pieler, Dagmar; Peinhopf, Walter; Wohlsein, Peter; Aurich, Jörg

2017-01-01

Eight-week-old calves were either castrated by partial scrotal resection (SR) without removing the testes (n = 10), Burdizzo (BZ) clamp (n = 10), orchidectomy (OR; n = 10), or were left gonad intact as controls (CO; n = 10). Concentrations of anti-Muellerian hormone (AMH), inhibin A, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in plasma were determined from 16 to 48 weeks of age. At 18 months, testes of SR, BZ, and CO bulls were obtained and the immunolocalization of LH and FSH receptors and AMH analyzed. Concentration of AMH in plasma of CO and SR bulls decreased with increasing age (P < 0.001). A similar AMH profile in CO and SR indicates that SR did not induce a true cryptorchid state. In groups OR and BZ, AMH was undetectable. Plasma inhibin concentration was higher in groups CO and SR than BZ and OR (P < 0.001). Plasma LH and FSH concentrations decreased over time (P < 0.001) and were higher in groups BZ and OR than SR and CO (P < 0.001). In the testes, immunolabeling for AMH existed in Sertoli cells of CO and SR but not BZ bulls. FSH receptors were localized in Sertoli cells, Leydig cells, spermatocytes, and the epididymis of CO and SR animals, whereas LH receptors were restricted to Leydig cells. In BZ animals, FSH and LH receptors and AMH were absent, indicating complete testicular degeneration. In conclusion, AMH is a more reliable marker for the presence of testicular tissue in bulls than inhibin. Scrotal resection did not induce a true inguinal cryptorchid state but affected testicular responsiveness to gonadotropic stimulation. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of RU486 and indomethacin on meiotic maturation, formation of extracellular matrix, and progesterone production by porcine oocyte-cumulus complexes.

PubMed

Nagyova, E; Scsukova, S; Kalous, J; Mlynarcikova, A

2014-07-01

This study was designed to determine whether inhibition of either cyclooxygenase-2 (COX-2) by indomethacin or progesterone receptor (PR) by PR antagonist, RU486, affects oocyte maturation, progesterone production, and covalent binding between hyaluronan (HA) and heavy chains of inter-α trypsin inhibitor, as well as expression of cumulus expansion-associated proteins (HA-binding protein, tumor necrosis factor α-induced protein 6, pentraxin 3) in oocyte-cumulus complexes (OCCs). The experiments were based on freshly isolated porcine OCC cultures in which the consequences of PR and COX-2 inhibition on the final processes of oocyte maturation were determined. Granulosa cells (GCs) and OCCs were cultured in medium supplemented with FSH/LH (both 100 ng/mL) in the presence/absence of RU486 or indomethacin. Western blot analysis, (3)H-glucosamine hydrochloride assay, immunofluorescence, and radioimmunoassay were performed. Only treatment with RU486 (25 μM) caused a decrease in the number of oocytes that reached germinal vesicle breakdown and metaphase II stage compared with indomethacin (100 μM) or FSH/LH treatment alone after 44 h. All treated OCCs synthesized an almost equal amount of HA. Heavy chains (of inter-α trypsin inhibitor)-HA covalent complexes were formed during in vitro FSH/LH-stimulated expansion in RU486- or indomethacin-treated OCCs. Follicle-stimulating hormone/LH-induced progesterone production by OCCs was increased in the presence of RU486 after 44 h. In contrast, a decrease of FSH/LH-stimulated progesterone production by GCs was detected in the presence of either RU486 or indomethacin after 72 h. We suggest that the PR-dependent pathway may be involved in the regulation of oocyte maturation. Both PR and COX-2 regulate FSH/LH-stimulated progesterone production by OCCs and GCs. Copyright © 2014 Elsevier Inc. All rights reserved.

Can anti-Mullerian hormone (AMH) predict the outcome of intrauterine insemination with controlled ovarian stimulation?

PubMed

Bakas, Panagiotis; Boutas, Ioannis; Creatsa, Maria; Vlahos, Nicos; Gregoriou, Odysseas; Creatsas, George; Hassiakos, Dimitrios

2015-10-01

To assess whether the levels of anti-Mullerian hormone (AMH) are related to outcome of intrauterine insemination (IUI) in patients treated with gonadotropins. A total of 195 patients underwent controlled ovarian stimulation (COS) with recombinant follicle stimulating hormone (rFSH) (50-150 IU/d). All patients were submitted upto three cycles of IUI. Primary outcome was the ability of AMH levels to predict clinical pregnancy at first attempt and the cumulative clinical pregnancy probability of upto three IUI cycles. Secondary outcomes were the relation of AMH, LH, FSH, BMI, age, parity and basic estradiol levels with each other and the outcome of IUI. The area under the receiver operating characteristic (ROC) curve in predicting clinical pregnancy for AMH at first attempt was 0.53 and for cumulative clinical pregnancy was 0.76. AMH levels were positively correlated with clinical pregnancy rate at first attempt and with cumulative clinical pregnancy rate, but negatively correlated with patient's age and FSH levels. Patient's FSH, LH levels were negatively correlated with cumulative clinical pregnancy rate. AMH levels seem to have a positive correlation and patient's age and LH levels had a negative correlation with the outcome of IUI and COS with gonadotropins. AMH concentration was significantly higher and LH was significantly lower in patients with a clinical pregnancy after three cycles of IUI treatment compared with those who did not achieve pregnancy.

Early effects of cranial irradiation on hypothalamic-pituitary function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lam, K.S.; Tse, V.K.; Wang, C.

1987-03-01

Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordantmore » changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.« less

Hot flushes and reproductive hormone levels during the menopausal transition.

PubMed

Dhanoya, Tanveer; Sievert, Lynnette Leidy; Muttukrishna, Shanthi; Begum, Khurshida; Sharmeen, Taniya; Kasim, Adetayo; Chowdhury, Osul; Bentley, Gillian R

2016-07-01

Evidence suggests that hot flushes are associated with fluctuating levels of oestradiol (E2) during menopause, as well as changes in the levels of follicle-stimulating hormone (FSH) and inhibin B. The relationship between hot flushes and anti-Müllerian hormone (AMH) is unknown. To examine specific hormone levels and ethnic differences in relation to hot flushes. Data were drawn from 108 women aged 40-59 years. There were three groups of participants: European women in London, UK; Bangladeshi women in Sylhet, Bangladesh; and Bangladeshi women who had migrated to London as adults. Symptom information was collected via questionnaires. Serum blood samples were collected to detect inhibin B, AMH, FSH, and E2. AMH and FSH were significantly associated with the experience of hot flushes in the past 2 weeks. Inhibin B and E2 were not associated with hot flushes. Body mass index (BMI), ethnicity, and education level were associated with both the occurrence and the frequency hot flushes. Menopausal status was also associated with the frequency of hot flushes. Relationships between AMH, FSH and symptoms are indicative of women's progress through the menopausal transition. The influence of BMI and education suggest that lifestyle changes may contribute to the management of symptoms. This merits further research. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Changes of endocrine and ultrasound markers as ovarian aging in modifying the Stages of Reproductive Aging Workshop (STRAW) staging system with subclassification of mid reproductive age stage.

PubMed

Ding, Ting; Luo, Aiyue; Jiang, Jingjing; Du, Xiaofang; Yang, Shuhong; Lai, Zhiwen; Shen, Wei; Lu, Yunping; Ma, Ding; Wang, Shixuan

2013-01-01

To demonstrate the changes of ovarian aging markers across the Stages of Reproductive Aging Workshop (STRAW) stages and modify it with subclassification of mid reproductive age stage (MR). Healthy females were classified according to the STRAW system. Serum basal FSH, LH, E2, and anti-Müllerian hormone (AMH) were detected, FSH/LH ratio calculated, and antral follicle counts (AFCs) determined in follicular phase. Progression through the whole STRAW stages under MR stage subdivided is associated with elevations in FSH, LH, FSH/LH ratio and decreases in E2, AMH and AFCs (p < 0.001). Both serum AMH and AFCs decreased early (after 25 years) and significantly (p < 0.01) with chronological age in MR stage. 0.982 ng/ml AMH and 3 antral follicles (low level of MR 25-30 years) were set as cutoffs to distinguish MR stage into early mid reproductive age (EMR) and late mid reproductive age (LMR) stages. The women in EMR stage compared with LMR could retrieve more oocytes in IVF treatment (p < 0.05) and has a higher pregnancy chance (57.9%) though not significant. The early and marked fall in serum AMH levels and AFCs suggest fine markers to further categorize and define the MR stage, demonstrating disparate reproductive aging period with reduced ovarian reserve in young age across the STRAW stages.

Anti-müllerian hormone and sertoli cell function in paediatric male hypogonadism.

PubMed

Grinspon, Romina P; Rey, Rodolfo A

2010-01-01

In the prepubertal male, Sertoli cells are the most active testicular cell population. Without stimulation tests, prepubertal hypogonadism can only be evidenced if Sertoli cell function is assessed. Anti-müllerian hormone (AMH) is a distinctive marker of the prepubertal Sertoli cell. Serum AMH is high from fetal life until puberty. In postnatal life, AMH testicular production is stimulated by FSH and potently inhibited by androgens. In anorchid patients, AMH is undetectable. In prepubertal males with fetal- or childhood-onset primary or central hypogonadism affecting the whole gonad, serum AMH is low. Conversely, when hypogonadism only affects Leydig cells (i.e., LH/human chorionic gonadotrophin receptor or steroidogenic enzyme defects), serum AMH is normal/high. AMH is also normal/high in patients with androgen insensitivity. In patients of pubertal age with central hypogonadism, AMH is low for Tanner stage - reflecting lack of FSH stimulus, - but high for age - reflecting lack of testosterone inhibitory effect. FSH treatment results in serum AMH rise, whereas human chorionic gonadotrophin treatment increases testosterone levels which inhibit AMH production. In conclusion, AMH determination is helpful in assessing gonadal function, without need for stimulation tests, and orientates the aetiological diagnosis of paediatric male hypogonadism. Furthermore, serum AMH is an excellent marker of FSH and androgen action in the testis. Copyright 2010 S. Karger AG, Basel.

Investigation of a thiazolidinone derivative as an allosteric modulator of follicle stimulating hormone receptor: evidence for its ability to support follicular development and ovulation.

PubMed

Sriraman, Venkataraman; Denis, Deborah; de Matos, Daniel; Yu, Henry; Palmer, Stephen; Nataraja, Selva

2014-05-15

FSH signalling through its cognate receptor is critical for follicular development and ovulation. An earlier study had documented thiazolidinone derivatives to activate FSH receptor expressed in CHO cells and rat granulosa cells; however development of this compound for clinical use was halted for unobvious reasons. The objective of the current study is to extend the previous investigations in detail on the ability of thiazolidinone derivative (henceforth referred to as Compound 5) to activate FSH signalling and learn the barriers that preclude development of this derivative for clinical purposes. Our results demonstrate that the Compound 5 in a dose-dependent manner stimulated cAMP production, activated AKT and ERK signalling pathways and induced estradiol production in cultured rat granulosa cells. Compound 5 also caused dose-dependent increase in estradiol production from human granulosa cells. In increasingly more complex in vitro systems, Compound 5 was able to induce the expansion of mouse cumulus-oocyte-complex and support in vitro development of mouse preantral follicle to preovulatory stage and release of oocyte from the follicle. In vivo, the compound stimulated preovulatory follicular development and ovulation in immature rats. Pharmacokinetic and safety investigations reveal poor oral availability and genotoxicity. Together, our results document Compound 5 to act as a FSHR allosteric modulator but have poor pharmacological properties for development of an oral FSH receptor modulator. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of ethanolic extract of Lepidium meyenii Walp on serum hormone levels in ovariectomized rats.

PubMed

Zhang, Yongzhong; Yu, Longjiang; Jin, Wenwen; Ao, Mingzhang

2014-01-01

To evaluate the effect of long-term ethanol extract of Lepidium meyenii (Maca) on serum hormone levels in ovariectomized (OVX) rats and compare them with the effect of diethylstilbestrol. Fifty female Sprague-Dawley rats were ovariectomized or sham operated. Both sham and OVX control groups (n = 10, respectively) received the vehicle. The remaining OVX rats were oral administrated with ethanol extract of Maca (0.096, or 0.24g/kg; n = 10, respectively) and diethylstilbestrol (0.05 mg/kg; n = 10). The treatment continued for 28 weeks. At week 12 and week 28, the blood of rats was collected and serum hormone levels, including estradiol (E2), testosterone (T) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay. At week 12, the levels of serum E2 were slightly higher in Maca groups than that in OVX group; T levels were significantly decreased; and FSH levels were advanced slightly in Maca groups than that in sham group. After 28 weeks administration, serum E2 levels in Maca-treated animals did not differ significantly from sham control, the low dose of Maca increased serum E2 levels, and Maca prevented increase in serum FSH levels compared with OVX group. Long-term Maca supply modulates endocrine hormone balance in OVX rats, especially it decreases enhanced FSH levels. It is proposed that Maca may become a potential choice for postmenopausal women.

The use of recombinant luteinizing hormone in patients undergoing assisted reproductive techniques with advanced reproductive age: a systematic review and meta-analysis.

PubMed

Hill, Micah J; Levens, Eric D; Levy, Gary; Ryan, Mary E; Csokmay, John M; DeCherney, Alan H; Whitcomb, Brian W

2012-05-01

To evaluate the effect of recombinant LH in assisted reproduction technology (ART) cycles in patients of advanced reproductive age. A systematic review and meta-analysis. Published randomized controlled clinical trials comparing recombinant LH plus recombinant FSH versus recombinant FSH only in patients of advanced reproductive age. Patients 35 years and older undergoing assisted reproduction. Recombinant LH plus recombinant FSH controlled ovarian hyperstimulation (COH) versus recombinant FSH stimulation only in assisted reproduction cycles. Implantation and clinical pregnancy. Seven trials were identified that met inclusion criteria and comprised 902 assisted reproduction technology cycles. No differences in serum E(2) on the day of hCG administration were reported in any trials. Two trials reported lower oocyte yield and one trial reported lower metaphase II oocyte yield in the recombinant LH-supplemented group. One trial reported higher fertilization rates in the recombinant LH-supplemented group. In a fixed effect model, implantation was higher in the recombinant LH-supplemented group (odds ratio 1.36, 95% confidence interval 1.05-1.78). Similarly, clinical pregnancy was increased in the recombinant LH-supplemented group (odds ratio 1.37, 95% confidence interval 1.03-1.83). The addition of recombinant LH to ART cycles may improve implantation and clinical pregnancy in patients of advanced reproductive age. Copyright © 2012 American Society for Reproductive Medicine. All rights reserved.

Comparison of the effects of laparoscopic bipolar electrocoagulation and intracorporeal suture application to ovarian reserve in benign ovarian cysts.

PubMed

Özgönen, Hakan; Erdemoglu, Evrim; Günyeli, Ilker; Güney, Mehmet; Mungan, Tamer

2013-04-01

Aim of the present study is to determine the effects of bipolar electrocoagulation and intracorporeal suture on the ovarian reserve after ovarian cystectomy. Sixty patients aged 18-42 years old and with a persistent adnexal mass were recruited to the study. Patients were randomized into suture hemostasis group or bipolar hemostasis group. Laparoscopic ovarian cystectomy was performed to all patients. Hemostasis was obtained by bipolar coagulation in 30 patients and by intracorporeal sutures in 30 patients. Serum levels of FSH, LH, estradiol, inhibin B and ultrasonographic measurements (antral follicle count and ovarian volume) were analyzed and recorded at day 3 of menstrual cycle, 1 and 3 months after the surgery. Basal FSH level measurement at the postoperative third month was significantly increased to 6.96 ± 1.86 mIU/ml (p < 0.05) in the bipolar electrocoagulation group. However, the decreased ovarian volume and antral follicle count was restored at the postoperative third month in the bipolar electrocoagulation group. Preoperative and postoperative FSH, LH, estradiol and inhibin B levels and ultrasonographic measurements were similar in the intracorporeal suture group. The unwanted effect of bipolar electrocoagulation on ovarian reserve is probably transient and causes minimal damage to ovary. FSH levels may be slightly elevated. Gentle use of bipolar electrocoagulation or intracorporeal are not found to effect ovarian reserve.

Purification and identification of 25-hydroxycholesterol in a reptile: Seasonal variation and hormonal regulation.

PubMed

Singh, Varsha; Priyam, Manisha; Tripathy, Mamta; Rai, Umesh

2017-06-01

The present in vitro study, for the first time, demonstrates the production of 25-hydroxycholestrol (25-HC) by testicular macrophages of a non-mammalian vertebrate. The ether extracts of testicular macrophage-conditioned medium (TMCM) were fractionated on a C18 reversed phase high-performance liquid chromatography (HPLC) column using methanol as the mobile phase. The mass spectrometry (MS) fragmentation pattern of HPLC-purified 25-HC was found to be identical to that of authentic 25-HC. Further, a significant seasonal variation in 25-HC concentration was observed with maximal level in regressed and minimal during breeding phase. To understand the hormonal control of 25-HC production, testicular macrophages from regressed phase testes were incubated with 0.5μg/ml of ovine follicle stimulating hormone (FSH) and 0.1, 1 and 10μg/ml of testosterone (T). FSH considerably enhanced 25-HC production by testicular macrophages. In contrast, T markedly inhibited 25-HC production in a dose-dependent manner. In addition, T significantly inhibited FSH-induced 25-HC production, though pre-treatment with T was more effective as compared to post-treatment with T to FSH. Our findings on production, seasonal variation and hormonal control of 25-HC suggest the functional significance of 25-HC in the testis of reptiles. Copyright © 2017 Elsevier Inc. All rights reserved.

Elderly Onset of Weakness in Facioscapulohumeral Muscular Dystrophy

PubMed Central

Fee, Dominic B.

2012-01-01

A 77-year-old male is presented. He had onset of proximal weakness 10 years earlier. His course was slowly progressive. Despite having phenotypic features of facioscapulohumeral muscular dystrophy (FSH), genetic testing for this was delayed because of his age of onset, lack of family history, and benign appearing muscle biopsy. This case is one of the oldest onset of weakness in genetically confirmed FSH and highlights the recognized expansion in phenotype that has occurred since the advent of genetic testing. PMID:23024867

Elderly onset of weakness in facioscapulohumeral muscular dystrophy.

PubMed

Fee, Dominic B

2012-01-01

A 77-year-old male is presented. He had onset of proximal weakness 10 years earlier. His course was slowly progressive. Despite having phenotypic features of facioscapulohumeral muscular dystrophy (FSH), genetic testing for this was delayed because of his age of onset, lack of family history, and benign appearing muscle biopsy. This case is one of the oldest onset of weakness in genetically confirmed FSH and highlights the recognized expansion in phenotype that has occurred since the advent of genetic testing.

Short-term estriol administration modulates hypothalamo-pituitary function in patients with functional hypothalamic amenorrhea (FHA).

PubMed

Genazzani, Alessandro D; Podfigurna-Stopa, Agnieszka; Czyzyk, Adam; Katulski, Krzysztof; Prati, Alessia; Despini, Giulia; Angioni, Stefano; Simoncini, Tommaso; Meczekalski, Blazej

2016-01-01

To evaluate the influence of short-term estriol administration (10 d) on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study on patients with FHA (n = 12) in a clinical research environment. Hormonal determinations and gonadotropin (luteinizing hormone [LH] and FSH) response to a gonadotropin-releasing hormone (GnRH) bolus (10 μg) at baseline condition and after 10 d of therapy with 2 mg/d of estriol per os. Measurements of plasma LH, FSH, prolactin, estradiol, androstenedione, 17α-hydroxyprogesterone, insulin, cortisol, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine. After treatment, the FHA patients showed a statistically significant increase of both LH and FSH plasma levels and the significant increase of their responses to the GnRH bolus. Estriol short-term therapy modulates within 10 d of administration the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of both gonadotropins synthesis and secretion in hypogonadotropic patients with FHA.

Hormonal Changes After Laparoscopic Ovarian Diathermy in Patients with Polycystic Ovarian Syndrome.

PubMed

Elnaggar, Elsayed A; Elwan, Youssef Abo; Ibrahim, Safaa A; Abdalla, Mena M

2016-10-01

To assess the changes in hormonal profile (serum FSH, LH, prolactin and total testosterone) following laparoscopic ovarian drilling (LOD) in patients with polycystic ovarian syndrome. Fifty patients with PCOS have been included in this study. Serum prolactin, total testosterone, follicular-stimulating hormone (FSH) and luteinizing hormone (LH) levels have been used as biochemical markers, before and after procedures. Laparoscopic ovarian drilling was successfully employed without any surgical complications and on an average follow-up time of 24 weeks after the procedure. During the follow-up serum values for prolactin, total testosterone and LH have decreased significantly and FSH levels remained unchanged after the procedure. The LOD in patients with PCOS may avoid or reduce the risk of OHSS and the multiple pregnancy rate induced by gonadotropin therapy. The high pregnancy rate and the economic aspect of the procedure offer an attractive management for patients with PCOS. However, LOD can be considered as second-line treatment after clomiphene citrate treatment failure and/or resistance.

Naturally occurring menopause in cynomolgus monkeys: changes in hormone, lipid, and carbohydrate measures with hormonal status.

PubMed

Kavanagh, Kylie; Koudy Williams, J; Wagner, Janice D

2005-08-01

Naturally occurring post-menopausal (PM) female cynomolgus monkeys (Macaca fascicularis) were identified. Their sex hormone profile was characterized and compared with younger pre-menopausal females before and after ovariectomy (OVX). PM females had lower estrogens and increased follicle-stimulating hormone (FSH) concentrations. Two PM females had diabetes mellitus and elevated androgens (androstenodione and dihydroepiandrosterone sulfate). Non-diabetic PM females were given parenteral E(2) which normalized FSH, and caused improvements in body weight, plasma lipids and lipoprotein cholesterol. Androgens remained lower with E(2) treatment. OVX induced comparable increases in FSH seen with the PM monkeys, however they had lower body weights, and had higher estrone and androstenodione concentrations. Natural menopause occurs in cynomolgus monkeys and hormone changes with OVX are similar however, differences in sex hormones that can relate to body mass and age may be important. E(2) treatment restored estrogen levels and induced improvements in the lipid profile of PM females.

Effect of caricapryl-99 seed alkaloid extract on the serum levels of sex hormones and pituitary gonadotrophins in male albino rats.

PubMed

Udoh, P B; Udoh, F V; Umoren, E B; James, U W; Okeke, C P; Agwu, B

2009-06-01

Activity of alkaloid extract of caricapryl-99 seeds [Carica papaya Linn seeds] on the serum levels of steroid hormones was studied in adult male albino rats. Three tolerated doses obtained from the graph of percentage toxicity [10, 50 and 150 mg/kg] were separately administered orally, daily for three days to three groups of male rats [n=5] while group four of 5 rats received the vehicle [corn oil] as control. The results showed that 10 mg/kg/d caused increase serum levels of FSH and estrogen but decrease in the serum levels of LH and testosterone compared to control; 50 mg/kg/d elevated the serum levels of FSH, estrogen but inhibited testosterone; while 150 mg/kg/d pretreatments caused a significant decrease [p<0.01] in the serum levels of FSH, LH and testosterone. The results suggest that caricapryl-99 treatment inhibited the serum level of the androgen, testosterone which might result in a male infertility.

Hyperestrogenemia and presence of estrogen receptors associated with an epithelial ovarian tumor of low malignant potential.

PubMed

Ben-Hur, H; Dgani, R; Insler, V; Lifschitz-Mercer, B; Blickstein, I; Mor, G; Kohen, F; Shani, A; Biran, H

1996-01-01

An 80-year-old woman presented with breast congestion, tenderness and pain. Mammography was normal. Circulating estradiol was markedly elevated, while LH and FSH were low. Pelvic examination and imaging revealed an ovarian mass which was extirpated during total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histopathology revealed an ovarian mucinous cystadenocarcinoma of low malignant potential, stage 1. The tumor was positively stained for estrogen receptors. Estradiol levels returned to normal post-operatively, with a corresponding adjustment of LH/FSH. Possible autocrine steroid production is discussed.

Interferon-γ acts as a regulator in the trade-off between phagocytosis and production performance in dwarf chickens.

PubMed

Yuan, Yitong; Liu, Shunqi; Zhao, Yue; Lian, Ling; Lian, Zhengxing

2018-01-01

Interferon-γ (IFN-γ) is critical for innate and adaptive immunity against viral and bacterial infections. IFN-γ reportedly affects the phagocytic ability of monocytes and macrophages as well as regulates pituitary function in humans and mice. The present study analyzed the impact of IFN-γ on monocyte and macrophage phagocytosis, production performance, and pituitary function in vivo and in vitro (in dwarf chickens). IFN-γ was injected into dwarf chickens through a vein, and then, the laying rate, average egg weight, and levels of follicle-stimulating hormone (FSH) and IFN-γ were measured in treatment and control groups. For the in vitro experiment, the pituitary tissues were supplemented with IFN-γ, and the mRNA expression levels of follicle-stimulating hormone beta subunit ( FSH-β ), interferon gamma receptor 1 ( IFNGR 1), and interferon gamma receptor 2 ( IFNGR 2) in the pituitary were assessed. Monocyte and macrophage phagocytosis product (PP) was decreased by IFN-γ treatment in a dose-dependent manner in vitro. In the in vivo experiment, the level of IFN-γ in the treatment group was higher than that in the control group at 7 d ( P  < 0.05), 14 d ( P  < 0.01), and 21 d ( P  < 0.01) post-injection. Compared with the control group, monocyte and macrophage PP was lower in the treatment group after injection ( P  < 0.01). The laying rate was higher in the treatment group than in the control group at 2 and 3 wk post-injection ( P  < 0.05). There was a significant difference between the treatment and control groups in the levels of FSH at 1, 3, 7, and 14 d post-injection ( P  < 0.01). In the in vitro experiment, increased mRNA expression levels of FSH-β , IFNGR 1, and IFNGR 2 were observed in the treatment group after stimulation with 100 U/mL IFN-γ for 24 h compared to those in the control group ( P  < 0.05). IFN-γ inhibited the phagocytosis of monocytes and macrophages; up-regulated the mRNA expression levels of the FSH

A prospective evaluation of antral follicle function in women with 46,XX spontaneous primary ovarian insufficiency

PubMed Central

Hubayter, Ziad R; Popat, Vaishali; Vanderhoof, Vien H; Ndubizu, Obioma; Johnson, Diane; Mao, Edie; Calis, Karim A; Troendle, James F.; Nelson, Lawrence M.

2010-01-01

Objective To assess ovarian follicle function in women with 46,XX spontaneous primary ovarian insufficiency Design Case-control with nested prospective cohort Setting Clinical Research Center, National Institutes of Health Patients Women with primary ovarian insufficiency without estrogen replacement for two weeks (N=97) and regularly menstruating control women (N=42) Interventions Single injection of 300 IU hrFSH Main outcome measures Change in serum estradiol at 24 hours Results Antral follicles ≥ 3 mm were detected in 73% (69/95) of patients; both serum estradiol and progesterone levels correlated significantly with maximum follicle diameter in these women. Patients with a maximum follicle diameter ≥ 8 mm had significantly higher serum estradiol and progesterone levels and significantly lower FSH and LH levels as compared to patients without such follicles. In controls estradiol levels increased significantly after FSH administration but in patients this was not the case despite the presence of an antral follicle ≥ 8 mm. Conclusion Most women with 46,XX spontaneous primary ovarian insufficiency have antral follicles detectable by ultrasound, suggesting that down-regulation of FSH receptors is not the predominant mechanism of follicle dysfunction. Evidence of progesterone secretion by antral follicles ≥ 8 mm in these patients is consistent with prior histologic evidence that follicle luteinization is the predominant mechanism of follicle dysfunction in this condition. Prospective controlled investigation designed to improve ovulatory function and fertility in these women is indicated. PMID:19939372

Associations between andrological measures, hormones and semen quality in fertile Australian men: inverse relationship between obesity and sperm output.

PubMed

Stewart, T M; Liu, D Y; Garrett, C; Jørgensen, N; Brown, E H; Baker, H W G

2009-07-01

The World Health Organization developed a time to pregnancy (TTP) study (number of menstrual cycles taken to conceive) to determine whether the average TTP is increasing and semen quality decreasing with time. The present study describes clinical, semen and hormone characteristics obtained from male partners of pregnant women in Melbourne, Australia, and examines the associations between these characteristics. Male partners (n = 225) of pregnant women (16-32 weeks) who conceived naturally had physical examination, health and lifestyle questionnaires, semen and hormone (FSH, LH, sex hormone-binding globulin, testosterone and Inhibin B) analyses. Previously known associations between semen, hormone and clinical variables were confirmed as significant: sperm numbers (concentration and total sperm count) correlated positively with Inhibin B and inversely with FSH and left varicocele, while total testicular volume correlated positively with sperm numbers and Inhibin B and inversely with FSH. However, only abstinence, total testicular volume, varicocele grade and obesity (BMI > 30 kg/m2) were independently significantly related to total sperm count. Compared with those with BMI < 30 (n = 188), obese subjects (n = 35) had significantly lower total sperm count (mean 324 versus 231 million, P = 0.013) and Inhibin B (187 versus 140 pg/ml, P < 0.001) but not FSH (3.4 versus 4.0 IU/l, P = 0.6). Obese fertile men appear to have reduced testicular function. Whether this is cause or effect, i.e. adiposity impairing spermatogenesis or reduced testicular function promoting fat deposition, remains to be determined.

Effects of environmental lead pollution on blood lead and sex hormone levels among occupationally exposed group in an E-waste dismantling area.

PubMed

Yang, Yan; Lu, Xiao Song; Li, Ding Long; Yu, Yun Jiang

2013-06-01

To study the effects of environmental multi-media lead pollution on blood lead and sex hormone levels among lead exposed males engaged in E-waste dismantling, and the correlation between confounding factors and sex hormone levels. An E-waste dismantling area in Taizhou of Zhejiang Province was selected as the research site. One hundred and fifty two samples were collected from the groundwater, soil, rice, corn, chicken, and pork in the dismantling area. The effects of the multi-media lead pollution on the male blood lead and sex hormone levels of FSH, LH, and T, as well as the correlation with confounding factors, were studied. The blood lead concentrations in the males aged under 31, from 31 to 45 and from 46 to 60 were 98.55, 100.23, and 101.45 μg/L, respectively. Of all the environmental media lead exposures, the groundwater, rice and soil were main contributing factors to the lead accumulation in humans. FSH and LH levels increased with the age while the T levels decreased with the age instead. There was a significant correlation between the FSH and LH levels and wearing masks. There was correlation between the FSH, LH, and T levels, and the mean values of lead concentrations in environmental media, and the sex hormone levels were correlated with the confounding factor of wearing masks. Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

BAC mediated transgenic Large White boars with FSHα/β genes from Chinese Erhualian pigs.

PubMed

Xu, Pan; Li, Qiuyan; Jiang, Kai; Yang, Qiang; Bi, Mingjun; Jiang, Chao; Wang, Xiaopeng; Wang, Chengbin; Li, Longyun; Qiao, Chuanmin; Gong, Huanfa; Xing, Yuyun; Ren, Jun

2016-10-01

Follicle-stimulating hormone (FSH) is a critical hormone regulating reproduction in mammals. Transgenic mice show that overexpression of FSH can improve female fecundity. Using a bacterial artificial chromosome (BAC) system and somatic cell nuclear transfer, we herein generated 67 Large White transgenic (TG) boars harboring FSHα/β genes from Chinese Erhualian pigs, the most prolific breed in the world. We selected two F0 TG boars for further breeding and conducted molecular characterization and biosafety assessment for F1 boars. We showed that 8-9 copies of exogenous FSHα and 5-6 copies of exogenous FSHβ were integrated into the genome of transgenic pigs. The inheritance of exogenous genes conforms to the Mendel's law of segregation. TG boars had higher levels of serum FSH, FSHα mRNA in multiple tissues, FSHβ protein in pituitary and more germ cells per seminiferous tubule compared with their wild-type half sibs without any reproductive defects. Analysis of growth curve, hematological and biochemical parameters and histopathology illustrated that TG boars grew healthily and normally. By applying 16S rRNA gene sequencing, we demonstrated that exogenous genes had no impact on the bacterial community structures of pig guts. Moreover, foreign gene drift did not occur as verified by horizontal gene transfer. Our findings indicate that overexpression of FSH could improve spermatogenesis ability of boars. This work provides insight into the effect of FSHα/β genes on male reproductive performance on pigs by a BAC-mediated transgenic approach.

Effect of ethanolic extract of Lepidium meyenii Walp on serum hormone levels in ovariectomized rats

PubMed Central

Zhang, Yongzhong; Yu, Longjiang; Jin, Wenwen; Ao, Mingzhang

2014-01-01

Objective: To evaluate the effect of long-term ethanol extract of Lepidium meyenii (Maca) on serum hormone levels in ovariectomized (OVX) rats and compare them with the effect of diethylstilbestrol. Materials and Methods: Fifty female Sprague-Dawley rats were ovariectomized or sham operated. Both sham and OVX control groups (n = 10, respectively) received the vehicle. The remaining OVX rats were oral administrated with ethanol extract of Maca (0.096, or 0.24g/kg; n = 10, respectively) and diethylstilbestrol (0.05 mg/kg; n = 10). The treatment continued for 28 weeks. At week 12 and week 28, the blood of rats was collected and serum hormone levels, including estradiol (E2), testosterone (T) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay. Results: At week 12, the levels of serum E2 were slightly higher in Maca groups than that in OVX group; T levels were significantly decreased; and FSH levels were advanced slightly in Maca groups than that in sham group. After 28 weeks administration, serum E2 levels in Maca-treated animals did not differ significantly from sham control, the low dose of Maca increased serum E2 levels, and Maca prevented increase in serum FSH levels compared with OVX group. Conclusions: Long-term Maca supply modulates endocrine hormone balance in OVX rats, especially it decreases enhanced FSH levels. It is proposed that Maca may become a potential choice for postmenopausal women. PMID:25097281

Individualized cost-effective conventional ovulation induction treatment in normogonadotrophic anovulatory infertility (WHO group 2).

PubMed

Eijkemans, Marinus J C; Polinder, Suzanne; Mulders, Annemarie G M G J; Laven, Joop S E; Habbema, J Dik F; Fauser, Bart C J M

2005-10-01

Conventional treatment in normogonadotrophic anovulatory infertility (WHO 2) consists of clomiphene citrate (CC), followed by exogenous gonadotrophins (FSH) and IVF. Response to these treatments may be predicted on the basis of individual patient characteristics. We aimed to devise a patient-tailored, cost-effective treatment algorithm involving the above-mentioned treatment modalities, based on individual patient characteristics. Sixteen prognostic groups are defined, according to the presence or absence of: age >30 years, amenorrhea, elevated androgen levels and obesity. The chances of response with each of the three treatments were calculated using prediction models. Treatment costs were based on the data of 240 patients visiting a specialist academic fertility unit. Outcome was an ongoing pregnancy within 12 months after initiation of treatment. The costs per pregnancy of three different strategies were compared, with a threshold for cost-effectiveness of 10 000. The strategy CC + FSH + IVF compared with FSH + IVF generated more pregnancies against lower costs. Compared with CC + IVF, it also produced more pregnancies, but at higher costs. For <30 years of age with normal androgen levels, costs per pregnancy were less than 10 000. For women >30 years old, costs per pregnancy were 25 000 and over 200 000, when presenting with normal or elevated androgen levels, respectively. The conventional treatment protocol is efficient for women aged <30 years with normal androgen levels. For women >30 years old with elevated androgen levels, FSH may be skipped.

Adrenal-pituitary-gonadal relationships and ejaculate characteristics in captive leopards (Panthera pardus kotiya) isolated on the island of Sri Lanka.

PubMed

Brown, J L; Wildt, D E; Phillips, L G; Seidensticker, J; Fernando, S B; Miththapala, S; Goodrowe, K L

1989-03-01

In Study 1, semen was collected using a standardized electroejaculation procedure. Males (N = 8) produced ejaculates with a high incidence of sperm abnormalities (77 +/- 3.3%). After electroejaculation under anaesthesia, serum cortisol concentrations increased (P less than 0.05), while testosterone concentrations decreased (P less than 0.05) and LH and FSH concentrations were unchanged (P less than 0.05) over a 2-h bleeding period. In Study 2, male and female leopards were bled at 5-min intervals for 3 h and given (i.v.): (1) saline (N = 2/sex); (2) GnRH (1 microgram/kg body weight) 30 min after the onset of sampling (N = 5/sex); or (3) ACTH (250 micrograms) at 30 min followed by GnRH 1 h later (N = 5/sex). Basal concentrations of serum LH, FSH and cortisol were comparable (P greater than 0.05) between male and female leopards. After GnRH, peak LH concentrations were 2-fold greater (P less than 0.05) in males than females while FSH responses were similar. In males, testosterone concentrations increased 2-3-fold following GnRH. After ACTH, serum cortisol concentrations doubled within 15 min in both sexes. Administration of ACTH 1 h before GnRH did not affect GnRH-induced LH or FSH release (P greater than 0.05); however, testosterone secretion was only 30% of that observed after GnRH alone (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term follow-up of laparoscopic electrocautery of the ovaries versus ovulation induction with recombinant FSH in clomiphene citrate-resistant women with polycystic ovary syndrome: an economic evaluation.

PubMed

Nahuis, M J; Oude Lohuis, E; Kose, N; Bayram, N; Hompes, P; Oosterhuis, G J E; Kaaijk, E M; Cohlen, B J; Bossuyt, P P M; van der Veen, F; Mol, B W; van Wely, M

2012-12-01

-€12 549) for the electrocautery group and €14 423 (95% CI: €12 239-€16 606) for the recombinant FSH group, resulting in significantly lower costs (P < 0.05) per first live birth for women allocated to the electrocautery group (mean difference €3247; 95% CI: €650-€5814). In women with clomiphene-resistant PCOS, laparoscopic electrocautery of the ovaries results in significantly lower costs per live birth than ovulation induction with gonadotrophins for an at least equal effectiveness.

Serum bioactive and immunoreactive luteinizing hormone and follicle-stimulating hormone levels in women with cycle abnormalities, with or without polycystic ovarian disease.

PubMed

Fauser, B C; Pache, T D; Lamberts, S W; Hop, W C; de Jong, F H; Dahl, K D

1991-10-01

Serum steroid, gonadotropin, and alpha-subunit levels were assessed in 35 women with cycle abnormalities [11 with and 24 without polycystic ovarian disease (PCOD) according to strict clinical and biochemical criteria] and 8 regularly cycling women in the early (cycle day 3 or 4) and mid (cycle day 7 or 8) follicular phase. LH and FSH levels were estimated using two immunological techniques [RIA and immunoradiometric assay (IRMA)] and in vitro bioassays (BIO), using mouse Leydig cells and rat granulosa cells, respectively. In PCOD patients mean alpha-subunit, free androgen index [FAI; testosterone x 100/sex hormone-binding globulin (SHBG)], androstenedione, estrone, and estradiol (E2) were significantly elevated compared to levels in the early follicular phase of control cycles and non-PCOD patients. In addition, in PCOD patients mean IRMA-LH and RIA-LH levels were distinctly increased (2.8- to 3.6 fold, respectively; both comparisons, P less than 0.001) compared to control values, but in the same order of magnitude (1.3- to 1.4-fold increments) as that in non-PCOD patients. However, the median BIO-LH level in PCOD patients was 5.9-fold higher than that in non-PCOD patients and 4.0-fold higher than the BIO-LH in the early follicular phase of control women. Consequently, the median BIO/IRMA-LH ratio was 4.8-fold higher in PCOD patients compared to non-PCOD patients. In women with cycle abnormalities, individual BIO/IRMA-LH ratios correlated with BIO-LH (rs = 0.48), FAI (rs = 0.39), free estrogens (E2/SHBG ratios; rs = 0 0.47), and dehydroepiandrosterone sulfate (rs = 0.60) concentrations. Mean IRMA-, RIA-, and BIO-FSH levels and BIO/IRMA-FSH ratios were not significantly different when various groups were compared. Although RIA- and IRMA-LH levels showed good correlation (rs = 0.88), RIA-LH levels were consistently higher, resulting in distinctly higher RIA-LH/FSH ratios (mean, 4.5) compared to IRMA-LH/FSH ratios (median, 1.8) in PCOD patients.(ABSTRACT TRUNCATED AT

Insulin Receptor Substrate 1, the Hub Linking Follicle-stimulating Hormone to Phosphatidylinositol 3-Kinase Activation.

PubMed

Law, Nathan C; Hunzicker-Dunn, Mary E

2016-02-26

The ubiquitous phosphatidylinositol 3-kinase (PI3K) signaling pathway regulates many cellular functions. However, the mechanism by which G protein-coupled receptors (GPCRs) signal to activate PI3K is poorly understood. We have used ovarian granulosa cells as a model to investigate this pathway, based on evidence that the GPCR agonist follicle-stimulating hormone (FSH) promotes the protein kinase A (PKA)-dependent phosphorylation of insulin receptor substrate 1 (IRS1) on tyrosine residues that activate PI3K. We report that in the absence of FSH, granulosa cells secrete a subthreshold concentration of insulin-like growth factor-1 (IGF-1) that primes the IGF-1 receptor (IGF-1R) but fails to promote tyrosine phosphorylation of IRS1. FSH via PKA acts to sensitize IRS1 to the tyrosine kinase activity of the IGF-1R by activating protein phosphatase 1 (PP1) to promote dephosphorylation of inhibitory Ser/Thr residues on IRS1, including Ser(789). Knockdown of PP1β blocks the ability of FSH to activate PI3K in the presence of endogenous IGF-1. Activation of PI3K thus requires both PKA-mediated relief of IRS1 inhibition and IGF-1R-dependent tyrosine phosphorylation of IRS1. Treatment with FSH and increasing concentrations of exogenous IGF-1 triggers synergistic IRS1 tyrosine phosphorylation at PI3K-activating residues that persists downstream through protein kinase B (AKT) and FOXO1 (forkhead box protein O1) to drive synergistic expression of genes that underlies follicle maturation. Based on the ability of GPCR agonists to synergize with IGFs to enhance gene expression in other cell types, PP1 activation to relieve IRS1 inhibition may be a more general mechanism by which GPCRs act with the IGF-1R to activate PI3K/AKT. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The effect of active immunization against vasoactive intestinal peptide (VIP) and inhibin on reproductive performance of aging White Leghorn roosters.

PubMed

Avital-Cohen, N; Heiblum, R; Argov, N; Rosenstrauch, A; Chaiseha, Y; Mobarkey, N; Rozenboim, I

2012-01-01

Decreasing fertility in aging domestic roosters is a well-known phenomenon. Aging is manifested by a decrease in plasma testosterone level, testis function, and spermatogenesis, resulting in a low level of fertility. The roles of vasoactive intestinal peptide (VIP) and testicular inhibin in this aging process are not clear. The effects of active immunization against VIP, inhibin, or the combination of both hormones on the reproduction of aging White Leghorn (WL) roosters were assayed. In experiment 1a, 60 White Leghorn roosters (67 wk of age) were divided into 4 groups (n = 15/group). The first group was actively immunized against VIP, the second against inhibin, the third against VIP and inhibin, and the fourth served as a control. Active immunization against VIP decreased semen quality parameters, plasma steroid levels, and gene expression of gonadotropin-releasing hormone-I (GnRH-I), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH receptor, VIP, and prolactin (Prl). Immunization against inhibin increased some of the semen quality parameters and FSH mRNA gene expression but decreased inhibin gene expression. In experiment 1b, at 94 wk of age, we took the actively immunized against VIP group and the control group and divided them into 2 subgroups (n = 7 or 8): the first group was injected with 1 mg of ovine Prl (oPrl) daily for 7 d, and the second group served as a control. Administration of oPrl to previously VIP-immunized birds significantly elevated semen quality parameters. We suggest that VIP, Prl, and inhibin have an important effect on the reproductive axis in aging roosters. Active immunization against VIP-depressed reproductive activity and Prl administration restored their reproduction, indicating that both VIP and Prl are essential for reproduction in aging roosters. Immunization against inhibin improved FSH mRNA gene expression, suggesting a negative role of inhibin on FSH secretion in aging roosters. Not all semen quality parameters

Assessment of the biopotency of follitropin alfa and lutropin alfa combined in one injection: a comparative trial in Sprague-Dawley rats

PubMed Central

Alper, Michael; Meyer, Randal; Dekkers, Chris; Ezcurra, Diego; Schertz, Joan; Kelly, Eduardo

2008-01-01

Background The current study was designed to determine if follitropin alfa (recombinant human follicle-stimulating hormone; r-hFSH) and lutropin alfa (recombinant human luteinizing hormone; r-hLH) biopotencies were unchanged by reconstituting in sterile water for injection and mixing prior to injection. Methods The biopotencies of r-hFSH and r-hLH were determined following injection of female Sprague-Dawley rats with a mixture of follitropin alfa revised formulation female (RFF) and lutropin alfa (1:1, r-hFSH:r-hLH). Biopotencies of follitropin alfa RFF and lutropin alfa were measured using ovarian weight and ascorbic acid depletion assays, respectively, and compared with a reference standard. Stock mixtures of follitropin alfa RFF and lutropin alfa (1:1) were prepared within 1 h prior to each respective assay's injection and stored at 6 +/- 2°C. Separate low dose (follitropin alfa RFF 1.5 IU/rat, lutropin alfa 2 IU/rat) and high dose (follitropin alfa RFF 3 IU/rat, lutropin alfa 8 IU/rat) treatments were prepared from stock mixtures or individual solutions by diluting with 0.22% bovine serum albumin saline solution and injected within 1 h of preparation. The main outcome measures were ovarian weight and ovarian ascorbic acid depletion. Results FSH bioactivities were similar (p > 0.10) between the individual follitropin alfa RFF test solution (84.2 IU) and follitropin alfa RFF/lutropin alfa (87.6 IU) mixtures prepared within 1 h of injection and stored at 6 +/- 2°C. LH bioactivities were similar (p > 0.10) between lutropin alfa (94.7 IU) test solution and lutropin alfa/follitropin alfa RFF (85.3 IU) mixtures prepared within 1 h of injection and stored at 6 +/- 2°C for not more than 1 h prior to injection. Conclusion Mixing follitropin alfa RFF and lutropin alfa did not alter the bioactivity of either FSH or LH. PMID:18647398

[Diagnostic value of baseline serum luteinizing hormone level for central precocious puberty in girls].

PubMed

Ou-Yang, Li-Xue; Yang, Fan

2017-07-01

To evaluate the diagnostic value of baseline serum luteinizing hormone (LH) level for central precocious puberty (CPP) in girls. A total of 279 girls with precocious puberty were subjected to assessment of growth and development, bone age determination, baseline LH test, and follicle-stimulating hormone (FSH) test, gonadotropin-releasing hormone stimulation test, and other related examinations. Of the 279 patients, 175 were diagnosed with CPP and 104 with premature thelarche (PT). The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of baseline LH and FSH levels and their peak levels for CPP, and the correlation between the baseline LH level and the peak LH level was analyzed. The CPP group had significantly higher bone age, baseline LH and FSH levels, peak LH and FSH levels, and ratio of peak LH level to peak FSH level than the PT group (P<0.01). The ROC curve proved that baseline LH level and peak LH level had good diagnostic values for CPP. Among the three bone age subgroups in the CPP group (7.0-9.0 years, 9.0-11.0 years, and >11.0 years), baseline LH level showed the best diagnostic value in the >11.0 years subgroup, with the largest area under the ROC curve. At a baseline LH level of 0.45 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 66.7% and 80% respectively, for the diagnosis of CPP. At a peak LH level of 9.935 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 74.8% and 100% respectively, for the diagnosis of CPP. The baseline LH level was positively correlated with the peak LH level (r=0.440, P<0.01). Baseline LH level can be used as an primary screening index for the diagnosis of CPP. It has a certain diagnostic value for CPP at different bone ages, and may be used as a monitoring index during the treatment and follow-uP.

Influence of solid-liquid separation strategy on biogas yield from a stratified swine production system.

PubMed

Cestonaro do Amaral, André; Kunz, Airton; Radis Steinmetz, Ricardo Luis; Scussiato, Lucas Antunes; Tápparo, Deisi Cristina; Gaspareto, Taís Carla

2016-03-01

As the fourth largest swine producer and exporter, Brazil has increased its participation in the global swine production market. Generally, these units concentrate a large number of animals and generate effluents that must be correctly managed to prevent environmental impacts, being anaerobic digestion is an interesting alternative for treating these effluents. The low-volatile solid concentration in the manure suggests the need for solid-liquid separation as a tool to improve the biogas generation capacity. This study aimed to determine the influence of simplified and inexpensive solid-liquid separation strategies (screening and settling) and the different manures produced during each swine production phase (gestating and farrowing sow houses, nursery houses and finishing houses) on biogas and methane yield. We collected samples in two gestating sow houses (GSH-a and GSH-b), two farrowing sow houses (FSH-a and FSH-b), a nursery house (NH) and a finishing house (FH). Biochemical methane potential (BMP) tests were performed according to international standard procedures. The settled sludge fraction comprised 20-30% of the raw manure volume, which comprises 40-60% of the total methane yield. The methane potential of the settled sludge fraction was approximately two times higher than the methane potential of the supernatant fraction. The biogas yield differed among the raw manures from different swine production phases (GSH-a 326.4 and GSH-b 577.1; FSH-a 860.1 and FSH-b 479.2; NH -970.2; FH 474.5 NmLbiogas.gVS(-1)). The differences were relative to the production phase (feed type and feeding techniques) and the management of the effluent inside the facilities (water management). Brazilian swine production has increased his participation in the global market, been the fourth producer and the fourth exporter. The segregation of swine production in multiple sites has increased its importance, due to the possibilities to have more specialized units. Generally, these units

Honey Attenuates the Detrimental Effects of Nicotine on Testicular Functions in Nicotine Treated Wistar Rats.

PubMed

Kolawole, T A; Oyeyemi, W A; Adigwe, C; Leko, B; Udeh, C; Dapper, D V

2015-12-20

Effect of honey on reproductive functions of male rats exposed to nicotine was examined in this study. Thirty-two adult male wistar rats (n=8/Group) were grouped as Control (distilled water), Nicotine (1.0mg/kg bwt), Honey (100mg/kg bwt) and Nicotine with Honey. The animals were orally treated for 35 days consecutively. Epididymis sperm motility, viability, morphology and counts were estimated, serum Follicle Stimulating Hormone (FSH), Leutinizing Hormone (LH) and Testosterone were assayed using ELISA method and testicular histology were also assessed. Significant reduction in percentage sperm motility, viability, morphology and counts were observed in nicotine group compared to control. Serum FSH, LH and testosterone levels were significantly reduced in nicotine group when compared with the control. There was significant improvement in sperm motility, viability, morphology, counts, FSH, LH and Testosterone in group co-treated with nicotine and honey  relative to nicotine group. Also, the degenerative seminiferous tubule architecture due to nicotine was improved by honey. In conclusion, honey may suppress nicotine toxic effect on reproductive functions in male Wistar rats.

Immunization against exon 1 decapeptides from the lutropin/choriogonadotropin receptor or the follitropin receptor as potential male contraceptive.

PubMed

Remy, J J; Couture, L; Rabesona, H; Haertle, T; Salesse, R

1996-11-01

Pituitary gonadotropin hormones lutropin (LH) and follitropin (FSH) control steroidogenesis and gametogenesis in male and female gonads through interaction with G protein-coupled receptors, LHR and FSHR. In the male, LH acts on leydig cells and is mostly responsible for the acquisition of puberty and the production of androgens while FSH, together with androgens, regulates spermatogenesis within Sertoli cells. We have engineered filamentous phages displaying mouse LHR and human FSHR decapeptides chosen in hormone binding regions. Peptides from both receptors displayed on phages belong either to the receptor specific exon 1 (amino acids 18-27) or to the homologous exon 4 (amino acids 98-107). Vaccination of prepubertal BALB/c male mice with hybrid phages using sub-cutaneous or intraperitoneal injections induced immunity against receptors. Anti-receptor immunization produced agonist or antagonist effects depending only on the circulating levels of the antibodies. Both anti-LHR and anti-FSHR vaccines induced efficient as well as reversible male contraception, through different mechanisms: targeting LH receptors inhibited or hyperstimulated Leydig cell testosterone production while targeting FSH receptors did not affect testosterone levels.

Understanding the interactions of human follicle stimulating hormone with single-walled carbon nanotubes by molecular dynamics simulation and free energy analysis.

PubMed

Mahmoodi, Yasaman; Mehrnejad, Faramarz; Khalifeh, Khosrow

2018-01-01

Interactions of carbon nanotubes (CNTs) and blood proteins are of interest for nanotoxicology and nanomedicine. It is believed that the interactions of blood proteins and glycoproteins with CNTs may have important biological effects. In spite of many experimental studies of single-walled carbon nanotubes (SWCNT) and glycoproteins with different methods, little is known about the atomistic details of their association process or of structural alterations occurring in adsorbed glycoproteins. In this study, we have applied molecular dynamics simulation to investigate the interaction of follicle stimulating hormone (hFSH) with SWCNT. The aim of this work is to investigate possible mechanisms of nanotoxicity at a molecular level. We present details of the molecular dynamics, structure, and free energy of binding of hFSH on the surface of SWCNT. We find that hFSH in aqueous solution strongly adsorbs onto SWCNT via their concave surface as evidenced by high binding free energies for residues in both protein subunits. It was found that hydrophobic, π-cation, and π-π stacking interactions are the main driving forces for the adsorption of the protein at the nanotube surface.

How to personalize ovarian stimulation in clinical practice.

PubMed

Sighinolfi, Giovanna; Grisendi, Valentina; La Marca, Antonio

2017-09-01

Controlled ovarian stimulation (COS) in in vitro fertilization (IVF) cycles is the starting point from which couple's prognosis depends. Individualization in follicle-stimulating hormone (FSH) starting dose and protocol used is based on ovarian response prediction, which depends on ovarian reserve. Anti-Müllerian hormone levels and the antral follicle count are considered the most accurate and reliable markers of ovarian reserve. A literature search was performed for studies that addressed the ability of ovarian reserve markers to predict poor and high ovarian response in assisted reproductive technology cycles. According to the predicted response to ovarian stimulation (poor- normal- or high- response), it is possible to counsel couples before treatment about the prognosis, and also to individualize ovarian stimulation protocols, choosing among GnRH-agonists or antagonists for endogenous FSH suppression, and the FSH starting dose in order to decrease the risk of cycle cancellation and ovarian hyperstimulation syndrome. In this review we discuss how to choose the best COS therapy, based on ovarian reserve markers, in order to enhance chances in IVF.

Does the Pituitary Gland Volume Change in Polycystic Ovary Syndrome?

PubMed

Bozkurt Koseoglu, Sezen; Dinc Elibol, Funda

2018-05-15

Polycystic ovary syndrome (PCOS) is the commonest cause of menstrual irregularity and hirsutism during reproductive age. We hypothesized in the alterations in the pituitary gland in PCOS. We measured the volume of the pituitary gland in 39 PCOS patients and 42 age-matched healthy controls using 0.35 mm thick T1-weighted sagittal cranial images. Serum levels of estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured on days 3-5 of the menstrual cycle of the participants. There was a significant difference in terms of LH, FSH, and LH/FSH ratio (p < 0.05) between groups. Mean pituitary gland volume (PGV) was 4.1 ± 1.36 mm3 for the study group and 3.4 ± 0.77 mm3 for the control group. PGV was statistically significantly higher in PCOS group than the control group (p < 0.05). There was no correlation between hormone levels and PGVs in groups. Enlarged pituitary volume in PCOS may be due to excessive LH release. © 2018 S. Karger AG, Basel.

A novel model for development, organization, and function of gonadotropes in fish pituitary.

PubMed

Golan, Matan; Biran, Jakob; Levavi-Sivan, Berta

2014-01-01

The gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are key regulators of the reproductive axis in vertebrates. Despite the high popularity of zebrafish as a model organism for studying reproductive functions, to date no transgenic zebrafish with labeled gonadotropes have been introduced. Using gonadotropin regulatory elements from tilapia, we generated two transgenic zebrafish lines with labeled gonadotropes. The tilapia and zebrafish regulatory sequences were highly divergent but several conserved elements allowed the tilapia promoters to correctly drive the transgenes in zebrafish pituitaries. FSH cells reacted to stimulation with gonadotropin releasing hormone by proliferating and showing increased transgene fluorescence, whereas estrogen exposure caused a decrease in cell number and transgene fluorescence. Transgene fluorescence reflected the expression pattern of the endogenous fshb gene. Ontogenetic expression of the transgenes followed typical patterns, with FSH cells appearing early in development, and LH cells appearing later and increasing dramatically in number with the onset of puberty. Our transgenic lines provide a powerful tool for investigating the development, anatomy, and function of the reproductive axis in lower vertebrates.

Effects of gonadectomy and hormonal replacement on rat hearts.

PubMed

Scheuer, J; Malhotra, A; Schaible, T F; Capasso, J

1987-07-01

To evaluate the effects of sex hormones on heart function and biochemistry, gonadectomy (GX) was performed in postpubertal male (M) and female (F) rats and compared with sham-operated controls (SH). The groups were MSH; MGX; MGX replaced with testosterone 3 mg/day s.c. (MGX + T), FSH, and FGX replaced with estrogen 2 mg/day (FGX + E), progesterone 0.4 mg/day (FGX + P), estrogen and progesterone (FGX + EP), or testosterone 2 mg/day (FGX + T). Body weight was decreased in MGX and was decreased further in MGX + T. Heart weight was decreased in both MGX and MGX + T. Body weights were increased in FGX and FTX + P and were increased further in FGX + T but were normal in FGX + E and FGX + EP. Heart weights were unchanged in F groups except in FGX + T, where it was increased. Cardiac performance in perfused hearts, as measured by stroke work, ejection fraction, fractional shortening and mean velocity of circumferential fiber shortening, was decreased in MGX but was slightly increased in MGX + T. Papillary muscle studies showed increases in time to peak tension and one-half relaxation in MGX, but these were decreased in MGX + T. Isotonic shortening studies showed decreased velocity of shortening in MGX and increased velocity in MGX + T. Heart function was significantly decreased in FGX and FGX + P compared with FSH but was similar to FSH in FGX + E and FGX + EP. FGX + T had greater stroke work and ejection fraction than FSH and FGX.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian sensitivity index is strongly related to circulating AMH and may be used to predict ovarian response to exogenous gonadotropins in IVF

PubMed Central

2011-01-01

Background Serum anti-Mullerian hormone (AMH) is currently considered the best marker of ovarian reserve and of ovarian responsiveness to gonadotropins in in-vitro fertilization (IVF). AMH assay, however, is not available in all IVF Units and is quite expensive, a reason that limits its use in developing countries. The aim of this study is to assess whether the "ovarian sensitivity index" precisely reflects AMH so that this index may be used as a surrogate for AMH in prediction of ovarian response during an IVF cycle. Methods AMH serum levels were measured in 61 patients undergoing IVF with a "long" stimulation protocol including the GnRH agonist buserelin and recombinant follicle-stimulating hormone (rFSH). Patients were divided into four subgroups according to the percentile of serum AMH and their ovarian stimulation was prospectively followed. Ovarian sensitivity index (OSI) was calculated dividing the total administered FSH dose by the number of retrieved oocytes. Results AMH and OSI show a highly significant negative correlation (r = -0.67; p = 0.0001) that is stronger than the one between AMH and the total number of retrieved oocytes and than the one between AMH and the total FSH dose. Conclusions OSI reflects quite satisfactory the AMH level and may be proposed as a surrogate of AMH assay in predicting ovarian responsiveness to FSH in IVF. Being very easy to calculate and costless, its use could be proposed where AMH measurement is not available or in developing countries where limiting costs is of primary importance. PMID:21824441

Hormonal control of spermatogenesis in men: therapeutic aspects in hypogonadotropic hypogonadism.

PubMed

Pitteloud, Nelly; Dwyer, Andrew

2014-05-01

During the first two trimesters of intrauterine life, fetal sex steroid production is driven by maternal human chorionic gonadotropin (hCG). The HPG axis is activated around the third trimester and remains active for the first 6-months of neonatal life. This so-called mini-puberty is a developmental window that has profound effects on future potential for fertility. In early puberty, GnRH secretion is reactivated first at night and then night and day. Pulsatile GnRH stimulates both LH and FSH, which induce maturation of the seminiferous tubules and Leydig cells. Congenital hypogonadotropic hypogonadism (CHH) results from GnRH deficiency. Men with CHH lack the mini-pubertal and pubertal periods of Sertoli Cell proliferation and thus present with prepubertal testes (<4mL) and low inhibin serum levels --reflecting diminished SC numbers. To induce full maturation of the testes, GnRH-deficient patients can be treated with either pulsatile GnRH, hCG or combined gonadotropin therapy (FSH+hCG). Fertility outcomes with each of these regimens are highly variable. Recently, a randomized, open label treatment study (n=13) addressed the question of whether a sequential treatment with FSH alone prior to LH and FSH (via GnRH pump) could enhance fertility outcomes. All men receiving the sequential treatment developed sperm in the ejaculate, whereas 2/6 men in the other group remained azoospermic. A large, multicenter clinical trial is needed to definitively prove the optimal treatment approach for severe CHH. Copyright © 2014. Published by Elsevier Masson SAS.

Architecture of GnRH-Gonadotrope-Vasculature Reveals a Dual Mode of Gonadotropin Regulation in Fish.

PubMed

Golan, Matan; Zelinger, Einat; Zohar, Yonathan; Levavi-Sivan, Berta

2015-11-01

The function and components of the hypothalamic-pituitary axis are conserved among vertebrates; however, in fish, a neuroglandular mode of delivery (direct contact between axons and endocrine cells) was considered dominant, whereas in tetrapods hypothalamic signals are relayed to their targets via the hypophysial portal blood system (neurovascular delivery mode). By using a transgenic zebrafish model we studied the functional and anatomical aspects of gonadotrope regulation thus revisiting the existing model. FSH cells were found to be situated close to the vasculature whereas the compact organization of LH cells prevented direct contact of all cells with the circulation. GnRH3 fibers formed multiple boutons upon reaching the pituitary, but most of these structures were located in the neurohypophysis rather than adjacent to gonadotropes. A close association was observed between FSH cells and GnRH3 boutons, but only a fifth of the LH cells were in direct contact with GnRH3 axons, suggesting that FSH cells are more directly regulated than LH cells. GnRH3 fibers closely followed the vasculature in the neurohypophysis and formed numerous boutons along these tracts. These vessels were found to be permeable to relatively large molecules, suggesting the uptake of GnRH3 peptides. Our findings have important implications regarding the differential regulation of LH and FSH and contradict the accepted notion that fish pituitary cells are mostly regulated directly by hypothalamic fibers. Instead, we provide evidence that zebrafish apply a dual mode of gonadotrope regulation by GnRH3 that combines both neuroglandular and neurovascular components.

Procedure for maximizing oocyte harvest for in vitro embryo production in small ruminants.

PubMed

Gibbons, A; Pereyra Bonnet, F; Cueto, M I; Catala, M; Salamone, D F; Gonzalez-Bulnes, A

2007-08-01

Possible effects of repeated hormonal treatments and laparoscopic ovum pick-up (LOPU) on the efficiency of oocyte recovery rate and quality were determined in sheep and goats. In six adult Merino sheep and five Criolla goats, ovarian status was synchronized by a prostaglandin F(2 alpha) analogue and the insertion of an intravaginal sponge 48 h later. Follicle development was stimulated by a single dose of FSH (60 mg NIH-FSH-P1) plus a single dose of equine chorionic gonadotrophin (eCG; 300 UI). The first FSH/eCG doses were administered 48 h after the sponge insertion, being repeated every 4 days to complete a total of four treatments in sheep and three in goats. Follicles in both ovaries were categorized according to their diameter and follicular fluid was aspirated under laparoscopic observation without a vacuum pump. In sheep, during a 12-day-period, a total of 347 follicles were aspirated with a recovery rate of 46.9%. In goats, during an 8-day-period, 219 follicles were aspirated with a recovery rate of 45.6%. In both species, there were no significant differences in the number of aspirated follicles, oocyte recovery rate and good quality oocyte recovery rate. However, in sheep the oocyte recovery rate was higher for large follicles, whereas in goats no such effect was detected. In summary, current results indicate that retrieval of oocytes can be maximized, without affecting oocyte quality, by repeating 'oneshot' FSH/eCG regimes and LOPUs at intervals as short as 4 days.

Cost-effectiveness comparison between pituitary down-regulation with a gonadotropin-releasing hormone agonist short regimen on alternate days and an antagonist protocol for assisted fertilization treatments.

PubMed

Maldonado, Luiz Guilherme Louzada; Franco, José Gonçalves; Setti, Amanda Souza; Iaconelli, Assumpto; Borges, Edson

2013-05-01

To compare cost-effectiveness between pituitary down-regulation with a GnRH agonist (GnRHa) short regimen on alternate days and GnRH antagonist (GnRHant) multidose protocol on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcome. Prospective, randomized. A private center. Patients were randomized into GnRHa (n = 48) and GnRHant (n = 48) groups. GnRHa stimulation protocol: administration of triptorelin on alternate days starting on the first day of the cycle, recombinant FSH (rFSH), and recombinant hCG (rhCG) microdose. GnRHant protocol: administration of a daily dose of rFSH, cetrorelix, and rhCG microdose. ICSI outcomes and treatment costs. A significantly lower number of patients underwent embryo transfer in the GnRHa group. Clinical pregnancy rate was significantly lower and miscarriage rate was significantly higher in the GnRHa group. It was observed a significant lower cost per cycle in the GnRHa group compared with the GnRHant group ($5,327.80 ± 387.30 vs. $5,900.40 ± 472.50). However, mean cost per pregnancy in the GnRHa was higher than in the GnRHant group ($19,671.80 ± 1,430.00 vs. $11,328.70 ± 907.20). Although the short controlled ovarian stimulation protocol with GnRHa on alternate days, rFSH, and rhCG microdose may lower the cost of an individual IVF cycle, it requires more cycles to achieve pregnancy. NCT01468441. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Prospective follow-up of 838 fetuses conceived after ovarian stimulation with corifollitropin alfa: comparative and overall neonatal outcome.

PubMed

Bonduelle, Maryse; Mannaerts, Bernadette; Leader, Arthur; Bergh, Christina; Passier, Dorrie; Devroey, Paul

2012-07-01

Is treatment with corifollitropin alfa, a new recombinant gonadotrophin with sustained follicle-stimulating activity, safe in terms of perinatal complications and birth defects in infants conceived following corifollitropin alfa treatment for contolled ovarian stimulation (COS)? In terms of neonatal outcome and risk of malformations, treatment with a single dose of corifollitropin alfa during COS is as safe as treatment with daily recombinant FSH (rFSH). This is the first pooled analysis of individual safety data in terms of neonatal outcome and major and minor congenital malformations collected following intervention trials of corifollitropin alfa. Pregnancy and follow-up studies were conducted prospectively and data were collected from all Phase II and III trials with corifollitropin alfa intervention, including two comparative randomized controlled trials (RCTs) in which patients received either a single dose of corifollitropin alfa or daily rFSH for the first 7 days of COS. Patients with ongoing pregnancies at 10 weeks after embryo transfer were followed up to labour and the health of the offspring was assessed up to 4-12 weeks after birth. Following corifollitropin alfa treatment prior to IVF or ICSI, the health of 677 pregnant women, 838 fetuses and 806 live born infants was evaluated. Among 440 fetuses in the corifollitropin alfa arm and 381 fetuses in the rFSH arm of the two RCTs, there were 424 (96.4%) and 370 (98.7%) live births, respectively. Neonatal characteristics, the frequency of premature births and the incidence of infant adverse events were similar in both treatment arms. The overall incidence of any congenital malformations in live born infants was 16.3 and 17.0%, with major malformation rates of 4.0 and 5.4% in the corifollitropin alfa and rFSH groups, respectively [odds ratio (OR) for major malformations, 0.71; 95% confidence interval, 0.36-1.38]. From 838 fetuses assessed in all corifollitropin alfa intervention trials, there were 806 (96

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

PubMed

Lensen, Sarah F; Wilkinson, Jack; Leijdekkers, Jori A; La Marca, Antonio; Mol, Ben Willem J; Marjoribanks, Jane; Torrance, Helen; Broekmans, Frank J

2018-02-01

During a cycle of in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI), women receive daily doses of gonadotropin follicle-stimulating hormone (FSH) to induce multifollicular development in the ovaries. Generally, the dose of FSH is associated with the number of eggs retrieved. A normal response to stimulation is often considered desirable, for example the retrieval of 5 to 15 oocytes. Both poor and hyper-response are associated with increased chance of cycle cancellation. Hyper-response is also associated with increased risk of ovarian hyperstimulation syndrome (OHSS). Clinicians often individualise the FSH dose using patient characteristics predictive of ovarian response such as age. More recently, clinicians have begun using ovarian reserve tests (ORTs) to predict ovarian response based on the measurement of various biomarkers, including basal FSH (bFSH), antral follicle count (AFC), and anti-Müllerian hormone (AMH). It is unclear whether individualising FSH dose based on these markers improves clinical outcomes. To assess the effects of individualised gonadotropin dose selection using markers of ovarian reserve in women undergoing IVF/ICSI. We searched the Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Studies Online, MEDLINE, Embase, CINAHL, LILACS, DARE, ISI Web of Knowledge, ClinicalTrials.gov, and the World Health Organisation International Trials Registry Platform search portal from inception to 27th July 2017. We checked the reference lists of relevant reviews and included studies. We included trials that compared different doses of FSH in women with a defined ORT profile (i.e. predicted low, normal or high responders based on AMH, AFC, and/or bFSH) and trials that compared an individualised dosing strategy (based on at least one ORT measure) versus uniform dosing or a different individualised dosing algorithm. We used standard methodological procedures recommended by Cochrane. Primary

Biological markers of fertility (inhibin-B) in HIV-infected men: influence of HIV infection and antiretroviral therapy.

PubMed

Moreno-Pérez, O; Boix, V; Merino, E; Picó, A; Reus, S; Alfayate, R; Giner, L; Mirete, R; Sánchez-Payá, J; Portilla, J

2016-06-01

Inhibin B (IB) levels and the IB: follicle-stimulating hormone (FSH) ratio (IFR), biomarkers of global Sertoli cell function, show a strong relationship with male fertility. The aim of the study was to examine the prevalence of impaired fertility potential in HIV-infected men and the influence of antiretroviral therapy (ART) on fertility biomarkers. A cross-sectional study with sequential sampling was carried out. A total of 169 clinically stable patients in a cohort of HIV-infected men undergoing regular ambulatory assessment in a tertiary hospital were included. The mean [± standard deviation (SD)] age of the patients was 42.6 ± 8.1 years, all were clinically stable, 61.5% had disease classified as Centers for Disease Control and Prevention (CDC) stage A, and were na?ve to ART or had not had any changes to ART for 6 months (91.1%). Morning baseline IB and FSH concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) and an electrochemiluminescent immunoassay (ECLIA), respectively. A multivariate logistic regression model was used to identify factors associated with impaired fertility, defined as IB < 119 pg/mL or IFR < 23.5. The mean (± SD) IB level was 250 ± 103 pg/mL, the median [interquartile range (IQR)] FSH concentration was 5.1 (3.3-7.8) UI/L and the median (IQR) IFR was 46.1 (26.3-83.7). The prevalence of impaired fertility was 21.9% [95% confidence interval (CI) 16.3-20.7%]. Negative correlations of body mass index and waist: hip ratio with FSH and IB levels were observed (P < 0.01), while a sedentary lifestyle and previous nevirapine exposure were associated with a decreased risk of IB levels ≤ 25th percentile in multivariate analysis. Only older age, as a risk factor, and sedentary lifestyle, with a protective effect, were independently associated with impaired fertility in multivariate analysis. Global testicular Sertoli cell function and fertility potential, assessed indirectly through serum IB levels and IB: FSH ratio

Fetal programming: testosterone exposure of the female sheep during midgestation disrupts the dynamics of its adult gonadotropin secretion during the periovulatory period.

PubMed

Savabieasfahani, Mozhgan; Lee, James S; Herkimer, Carol; Sharma, Tejinder P; Foster, Douglas L; Padmanabhan, Vasantha

2005-01-01

Prenatal exposure of the female sheep to excess testosterone (T) leads to hypergonadotropism, multifollicular ovaries, and progressive loss of reproductive cycles. We have determined that prenatal T treatment delays the latency of the estradiol (E2)-induced LH surge. To extend this finding into a natural physiological context, the present study was conducted to determine if the malprogrammed surge mechanism alters the reproductive cycle. Specifically, we wished to determine if prenatal T treatment 1) delays the onset of the preovulatory gonadotropin surge during the natural follicular phase rise in E2, 2) alters pulsatile LH secretion and the dynamics of the secondary FSH surge, and 3) compromises the ensuing luteal function. Females prenatally T-treated from Day 60 to Day 90 of gestation (147 days is term) and control females were studied when they were approximately 2.5 yr of age. Reproductive cycles of control and prenatally T-treated females were synchronized with PGF2alpha, and peripheral blood samples were collected every 2 h for 120 h to characterize cyclic changes in E2, LH, and FSH and then daily for 14 days to monitor changes in luteal progesterone. To assess LH pulse patterns, blood samples were also collected frequently (each 5 min for 6 h) during the follicular and luteal phases of the cycle. The results revealed that, in prenatally T-treated females, 1) the preovulatory increase in E2 was normal; 2) the latencies between the preovulatory increase in E2 and the peaks of the primary LH and FSH surges were longer, but the magnitudes similar; 3) follicular-phase LH pulse frequency was increased; 4) the interval between the primary and secondary FSH surges was reduced but there was a tendency for an increase in duration of the secondary FSH surge; but 5) luteal progesterone patterns were in general unaltered. Thus, exposure of the female to excess T before birth produces perturbances and maltiming in periovulatory gonadotropin secretory dynamics, but these

Stimulation of ovarian stem cells by follicle stimulating hormone and basic fibroblast growth factor during cortical tissue culture.

PubMed

Parte, Seema; Bhartiya, Deepa; Manjramkar, Dhananjay D; Chauhan, Anahita; Joshi, Amita

2013-04-01

Cryopreserved ovarian cortical tissue acts as a source of primordial follicles (PF) which can either be auto-transplanted or cultured in vitro to obtain mature oocytes. This offers a good opportunity to attain biological parenthood to individuals with gonadal insufficiency including cancer survivors. However, role of various intra- and extra-ovarian factors during PF growth initiation still remain poorly understood. Ovarian biology has assumed a different dimension due to emerging data on presence of pluripotent very small embryonic-like stem cells (VSELs) and ovarian germ stem cells (OGSCs) in ovary surface epithelium (OSE) and the concept of postnatal oogenesis. The present study was undertaken to decipher effect of follicle stimulating hormone (FSH) and basic fibroblast growth factor (bFGF) on the growth initiation of PF during organ culture with a focus on ovarian stem cells. Serum-free cultures of marmoset (n=3) and human (young and peri-menopausal) ovarian cortical tissue pieces were established. Cortical tissue pieces stimulated with FSH (0.5 IU/ml) or bFGF (100 ng/ml) were collected on Day 3 for histological and molecular studies. Gene transcripts specific for pluripotency (Oct-4A, Nanog), early germ cells (Oct-4, c-Kit, Vasa) and to reflect PF growth initiation (oocyte-specific Gdf-9 and Lhx8, and granulosa cells specific Amh) were studied by q-RTPCR. A prominent proliferation of OSE (which harbors stem cells) and transition of PF to primary follicles was observed after FSH and bFGF treatment. Ovarian stem cells were found to be released on the culture inserts and retained the potential to spontaneously differentiate into oocyte-like structures in extended cultures. q-RTPCR analysis revealed an increased expression of gene transcripts specific for VSELs, OGSCs and early germ cells suggestive of follicular transition. The present study shows that both FSH and bFGF stimulate stem cells present in OSE and also lead to PF growth initiation. Thus besides being

Effects of hormones on cognition in schizophrenic male patients--preliminary results.

PubMed

Bratek, Agnieszka; Koźmin-Burzyńska, Agnieszka; Krysta, Krzysztof; Cierpka-Wiszniewska, Katarzyna; Krupka-Matuszczyk, Irena

2015-09-01

Schizophrenia is a prevalent neurodevelopmental disorder of an unknown etiology and a variable phenotypic expression. In the recent years, the impact of hormones on the course of schizophrenia has been investigated. This study is aimed at assessing the level of correlating serum levels of hormones in schizophrenic male patients with their cognitive functioning measured with neuropsychological tests. In the index group there were 15 medicated male schizophrenic patients. In the control group there were 15 age and education matched healthy men. All subjects underwent analysis of serum hormones level (TSH, testosterone, estradiol, FSH, LH, progesterone and prolactin) and a battery of tests (Trail Making Test A and B, Stroop Test, Verbal and Semantic Fluency Test). The mean serum levels of the following hormones were higher in the index group than in the control group: TSH (1.76 mIU/L vs 1.58 mIU/L; p=0.66), progesterone (0.85 ng/ml vs 0.69 ng/ml; p=0.22) and prolactin (558.71 uIU/ml vs 181 uIU/ml; p=0.025). The mean levels of estradiol (24.36 pg/ml vs 25.40 ng/ml; p=0.64), FSH (3.17 mIU/ml vs 5.72 mIU/ml; p=0.019), LH (3.85 mIU/ml vs 5.77 mIU/ml; p=0.056) and testosterone (2.90 ng/ml vs 5.38 ng/ml; p=0.003) were higher in the control group. In the index group there were significant negative correlations between FSH and semantic fluency (ρ=-0.678606), progesterone and: TMT B (ρ=-0.586763), Stroop 1 (ρ=-0.701880) and Stroop 2 (ρ=-0.601074) and prolactin and TMT A (ρ=-0.579607). The preliminary results of our study show that serum levels of FSH and testosterone are significantly lower, whereas the level of prolactin is markedly higher, in schizophrenic male patients than in healthy men. There is an inverse correlation between serum levels of progesterone, FSH and prolactin and the results of certain cognitive functioning tests in schizophrenic men.

The aryl hydrocarbon receptor is required for normal gonadotropin responsiveness in the mouse ovary.

PubMed

Barnett, Kimberly R; Tomic, Dragana; Gupta, Rupesh K; Babus, Janice K; Roby, Katherine F; Terranova, Paul F; Flaws, Jodi A

2007-08-15

The aryl hydrocarbon receptor (AHR) mediates the toxicity of a variety of environmental chemicals. Although little is known about the physiological role of the AHR, studies suggest that it plays an important role in regulating ovulation because Ahr deficient (AhRKO) mice have a reduced number of ovulations compared to wild-type (WT) mice. The reasons for the reduced ability of AhRKO mice to ovulate are unknown. Normal ovulation, however, requires estrous cyclicity, appropriate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and LH and FSH responsiveness. Thus, the purpose of this study was to test the hypothesis that Ahr deletion regulates ovulation by altering cyclicity, FSH and LH levels, follicle-stimulating hormone receptor (Fshr) and luteinizing hormone receptor (Lhcgr) levels and/or gonadotropin responsiveness. The data indicate that AhRKO and WT mice have similar levels of FSH and LH, but AhRKO mice have reduced Fshr and Lhcgr mRNA levels compared to WT mice. Furthermore, AhRKO ovaries contain fewer corpora lutea compared to WT ovaries after 5 IU equine chorionic gonadotropin (eCG) treatment. Lastly, both AhRKO and WT mice ovulate a similar number of eggs in response to 5 IU human chorionic gonadotropin (hCG), but AhRKO mice ovulate fewer eggs than WT mice in response to 2.5 IU and 1.25 IU hCG. Collectively, these data indicate that AhRKO follicles have a reduced capacity to ovulate compared to WT follicles and that this is due to reduced responsiveness to gonadotropins. Thus, in addition to mediating toxicity of environmental chemicals, the Ahr is required for normal ovulation.

Alterations in Hormone Levels After Adjuvant Chemoradiation in Male Rectal Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Frederick H.; Perera, Francisco; Fisher, Barbara

Purpose: To evaluate follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels after postoperative chemoradiation in men with rectal cancer. Methods and Materials: Forty-three men with rectal cancer had baseline and postchemoradiation FSH, LH, and testosterone measured. Adjuvant chemoradiation consisted of two 5-day cycles of bolus 5-fluorouracil (5-FU) every 4 weeks at a dose of 500 mg/m{sup 2}/d followed by concurrent chemoradiation followed by two additional 5-day cycles of 5-FU at a dose of 450 mg/m{sup 2}/d. Continuous-infusion 5-FU at 225 mg/m{sup 2}/d was given during radiation. Pelvic radiation consisted of a three- or four-field technique with a median dosemore » of 54.0 Gy in 30 fractions. Results: Median follow-up was 6.1 years. Mean baseline FSH levels increased from 5.3 to a peak of 23.9 IU/L (p < 0.001) 13-24 months after chemoradiation. Mean baseline LH levels increased from 4.3 to a peak of 8.5 IU/L (p < 0.001) within 6 months after chemoradiation. Mean testosterone levels decreased from 15.4 nmol/L at baseline to 8.0 nmol/L more than 4 years after chemoradiation. Mean testosterone to mean LH ratio decreased from 4.4 at baseline to 1.1 after 48 months posttreatment, suggesting a continued decrease in Leydig cell function with time. Testicular dose was measured in 5 patients. Median dose was 4 Gy (range, 1.5-8.9 Gy). Conclusions: Chemoradiation in men with rectal cancer causes persistent increases in FSH and LH levels and decreases in testosterone levels.« less

Evaluation of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal axis.

PubMed

Ding, Yu; Li, Juan; Yu, Yongguo; Yang, Peirong; Li, Huaiyuan; Shen, Yongnian; Huang, Xiaodong; Liu, Shijian

2018-03-28

This study aimed to identify the predictive value of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal (HPG) axis in girls. Gonadotropin-releasing hormone (GnRH) stimulation tests were performed and evaluated in a total of 1750 girls with development of secondary sex characteristics. Correlation analyses were conducted between basal sex hormones and peak luteinizing hormone (LH) levels ≥5 IU/L during the GnRH stimulation test. Receiver operating characteristic (ROC) curves for basal levels of LH, follicle-stimulating hormone (FSH), LH/FSH, and estradiol (E2) before the GnRH stimulation test were plotted. The area under the curve (AUC) and 95% confidence intervals (CIs) were measured for each curve. The maximum AUC value was observed for basal LH levels (0.77, 95% CI: 0.74-0.79), followed by basal FSH levels (0.73, 95% CI: 0.70-0.75), the basal LH/FSH ratio (0.68, 95% CI: 0.65-0.71), and basal E2 levels (0.61, 95% CI: 0.59-0.64). The appropriate cutoff value of basal LH levels associated with a positive response of the GnRH stimulation test was 0.35 IU/L, with a sensitivity of 63.96% and specificity of 76.3% from the ROC curves when Youden's index showed the maximum value. When 100% of patients had peak LH levels ≥5 IU/L, basal LH values were >2.72 IU/L, but the specificity was only 5.45%. Increased basal LH levels are a significant predictor of a positive response during the GnRH stimulation test for assessing activation of the HPG axis in most girls with early pubertal signs.

Short communication: Follicle superstimulation before ovum pick-up for in vitro embryo production in Holstein cows.

PubMed

Oliveira, Louise H; Sanches, Carlos P; Seddon, Adriano S; Veras, Marcio B; Lima, Flávio A; Monteiro, Pedro L J; Wiltbank, Milo C; Sartori, Roberto

2016-11-01

The objective was to evaluate in vitro embryo production (IVEP) in nonlactating Holstein cows after ovarian superstimulation. Cows were randomly assigned in a crossover design to 1 of 2 groups: control (n=35), which was not synchronized and not treated with hormones before ovum pick-up (OPU), or hormone-treated (n=35), in which wave emergence was synchronized and animals treated with porcine (p)-FSH in the presence of norgestomet before OPU. In the hormone-treated group, all follicles ≥7mm in diameter were aspirated for synchronization of wave emergence and cows received a norgestomet ear implant. After 36h, treatment with p-FSH (6 doses of 40mg each, 12h apart, i.m.) started. Ovum pick-up from follicles >2mm in diameter was performed 44h after the last p-FSH (coasting). Then, IVEP was performed. The total number of cumulus-oocyte complexes recovered (16.0 vs. 20.5±2.2) and number of grades I to III (viable) oocytes (10.7 vs. 12.3±1.6) did not differ between hormone-treated and control groups Additionally, no differences were found in the number of blastocysts per cow per OPU (3.0 vs. 2.6±0.5) or in blastocyst rates (17.1 vs. 12.2±2.4%) between hormone-treated and control, respectively. Thus, in this study, ovarian follicle superstimulation with p-FSH followed by coasting in nonlactating Holstein cows that had synchronization of wave emergence and progestin supplementation did not improve oocyte quality or IVEP compared to no hormonal treatment. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Treatment Outcome of Ovulation-inducing Agents in Patients with Anovulatory Infertility: A Prospective, Observational Study

PubMed Central

Prajapati, Kinjal; Desai, Mira; Shah, Samidh; Choudhary, Sumesh; Aggarwal, Rohina; Mishra, Vineet

2017-01-01

Objective: To compare different treatment regimens on pregnancy rate and outcome in patients with anovulatory infertility. Patients and Methods: A prospective observational study was conducted on patients with infertility due to anovulation. Patients treated with clomiphene citrate (CC) 50/100 mg/day from 2nd to 6th day of menstrual cycle (MC) (n = 38), short gonadotropin-releasing hormone (GnRH) agonist regimen (leuprolide [0.5 mg subcutaneous] + recombinant follicle-stimulating hormone [rFSH] [225 IU intramuscular [IM] from 2nd to 10th day of MC [n = 32]), long GnRH agonist regimen (leuprolide from 21st day followed by leuprolide + rFSH from 2nd to 10th day of MC [n = 19]), and antagonist regimen (human menopausal gonadotropin [hMG] [150 IU IM] from 2nd day followed by hMG + cetrorelix from 7th to 10th day of MC) (n = 6) were recruited and followed up for follicular size, endometrial thickness, and pregnancy test. Data were analyzed using appropriate statistical test andP < 0.05 was considered statistically significant. Results: A significant increase in follicular diameter and endometrial thickness was observed in patients treated with gonadotropin regimens as compared to CC alone (P < 0.0001). The highest number of positive pregnancy test with ultrasonographic evidence of gestational sac was observed with leuprolide + rFSH (long regimen) (10/19, 52.6%) followed by leuprolide + rFSH (short regimen) (13/32, 40.6%) while least in antagonist regimen (2/6, 33.3%) and CC (1/38, 2.63%). All regimens were well tolerated. Conclusion: Treatment outcome was better with long agonist regimen. PMID:29081619

Influence of continuous illumination on estrous cycle of rats: time course of changes in levels of gonadotropins and ovarian steroids until occurrence of persistent estrus.

PubMed

Takeo, Y

1984-08-01

Plasma concentrations of LH, FSH, 17 beta-estradiol, estrone and progesterone were determined chronologically by radioimmunoassays in two groups of adult female rats exposed to continuous illumination (LL). Group 1 rats showing vaginal estrous cycles were sacrificed at 3- to 6-hour intervals during late proestrus through early estrus of the first 5 cycles after exposure to LL. Group 2 animals which displayed persistent vaginal estrus in an early period of exposure to LL were killed on the 2nd, 3rd, 4th, 5th and 7th days of vaginal estrus. In Group 1 rats, surges of the hormones, except estrone, took place in all the 5 cycles. The occurrence of peak hormone levels in each cycle was invariably delayed after transfer of animals to LL. According to regression analyses, the lengths of secretion cycles of LH, FSH, 17 beta-estradiol and progesterone in rats under LL were 100.89, 100.46, 101.14 and 101.06 h, respectively. Elevation of 17 beta-estradiol levels was observed prior to the LH surge, and peaks of progesterone and FSH occurred following it. However, the secretion patterns of these hormones appear to be disrupted with length of exposure to LL. In group 2 rats, the mean concentration of LH during persistent estrus was approximately similar to that on the morning of the days of proestrus of the 4-day cycles of rats placed under an alternating 12-hour light-dark regimen (LD), whereas the mean FSH concentration was continuously low. While the concentrations of 17 beta-estradiol and estrone in persistent-estrous rats were elevated, progesterone levels remained low.(ABSTRACT TRUNCATED AT 250 WORDS)

Multivariate analysis to predict letrozole efficacy in improving sperm count of non-obstructive azoospermic and cryptozoospermic patients: a pilot study

PubMed Central

Cavallini, Giorgio; Biagiotti, Giulio; Bolzon, Elisa

2013-01-01

We tested the hypothesis that letrozole increases sperm count in non-obstructive azoospermic or cryptozoospermic patients with a testosterone (T)/17-beta-2-oestradiol (E2) ratio <10. Forty-six patients with no chromosomal aberrations were randomized into two groups: 22 received letrozole 2.5 mg per day for 6 months (Group 1: 6 azoospermic+16 cryptozoospermic patients), while 24 received a placebo (Group 2: 5 azoospermic+19 cryptozoospermic patients). The following data were collected: two semen analyses, clinical history, scrotal Duplex scans, body mass index (BMI), Y microdeletion, karyotype and cystic fibrosis screens and follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, T and prolactin levels. Both before and after letrozole or placebo administration, the patients underwent two semen analyses and hormonal assessments. The differences were evaluated using the Mann–Whitney U test. The relationships between sperm concentration after letrozole administration with respect to FSH, T/E2 ratio, bilateral testicle volume and BMI before letrozole administration were assessed using multivariate analysis. The side effects were assessed using the chi-square test. Group 1 had sperm concentration (medians: 400–1.290×106 ml−1; P<0.01) and motility (medians: class A from 2% to 15% P<0.01), FSH, LH and T significantly increased, while Group 2 did not. E2 levels diminished significantly in Group 1, but not in Group 2. Eight patients in Group 1 demonstrated side effects, whereas no patient side effects were observed in Group 2. The sperm concentration after letrozole administration is inversely related to T/E2, FSH and BMI; a direct relationship emerged between sperm concentration and testicular volume. PMID:24121976

Androgen Stimulates Growth of Mouse Preantral Follicles In Vitro: Interaction With Follicle-Stimulating Hormone and With Growth Factors of the TGFβ Superfamily

PubMed Central

Laird, Mhairi; Thomson, Kacie; Fenwick, Mark; Mora, Jocelyn; Hardy, Kate

2017-01-01

Androgens are essential for the normal function of mature antral follicles but also have a role in the early stages of follicle development. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by androgen excess and aberrant follicle development that includes accelerated early follicle growth. We have examined the effects of testosterone and dihydrotestosterone (DHT) on development of isolated mouse preantral follicles in culture with the specific aim of investigating interaction with follicle-stimulating hormone (FSH), the steroidogenic pathway, and growth factors of the TGFβ superfamily that are known to have a role in early follicle development. Both testosterone and DHT stimulated follicle growth and augmented FSH-induced growth and increased the incidence of antrum formation among the granulosa cell layers of these preantral follicles after 72 hours in culture. Effects of both androgens were reversed by the androgen receptor antagonist flutamide. FSH receptor expression was increased in response to both testosterone and DHT, as was that of Star, whereas Cyp11a1 was down-regulated. The key androgen-induced changes in the TGFβ signaling pathway were down-regulation of Amh, Bmp15, and their receptors. Inhibition of Alk6 (Bmpr1b), a putative partner for Amhr2 and Bmpr2, by dorsomorphin resulted in augmentation of androgen-stimulated growth and modification of androgen-induced gene expression. Our findings point to varied effects of androgen on preantral follicle growth and function, including interaction with FSH-activated growth and steroidogenesis, and, importantly, implicate the intrafollicular TGFβ system as a key mediator of androgen action. These findings provide insight into abnormal early follicle development in PCOS. PMID:28324051

Androgen Stimulates Growth of Mouse Preantral Follicles In Vitro: Interaction With Follicle-Stimulating Hormone and With Growth Factors of the TGFβ Superfamily.

PubMed

Laird, Mhairi; Thomson, Kacie; Fenwick, Mark; Mora, Jocelyn; Franks, Stephen; Hardy, Kate

2017-04-01

Androgens are essential for the normal function of mature antral follicles but also have a role in the early stages of follicle development. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by androgen excess and aberrant follicle development that includes accelerated early follicle growth. We have examined the effects of testosterone and dihydrotestosterone (DHT) on development of isolated mouse preantral follicles in culture with the specific aim of investigating interaction with follicle-stimulating hormone (FSH), the steroidogenic pathway, and growth factors of the TGFβ superfamily that are known to have a role in early follicle development. Both testosterone and DHT stimulated follicle growth and augmented FSH-induced growth and increased the incidence of antrum formation among the granulosa cell layers of these preantral follicles after 72 hours in culture. Effects of both androgens were reversed by the androgen receptor antagonist flutamide. FSH receptor expression was increased in response to both testosterone and DHT, as was that of Star, whereas Cyp11a1 was down-regulated. The key androgen-induced changes in the TGFβ signaling pathway were down-regulation of Amh, Bmp15, and their receptors. Inhibition of Alk6 (Bmpr1b), a putative partner for Amhr2 and Bmpr2, by dorsomorphin resulted in augmentation of androgen-stimulated growth and modification of androgen-induced gene expression. Our findings point to varied effects of androgen on preantral follicle growth and function, including interaction with FSH-activated growth and steroidogenesis, and, importantly, implicate the intrafollicular TGFβ system as a key mediator of androgen action. These findings provide insight into abnormal early follicle development in PCOS.

Ultrasound features of polycystic ovaries relate to degree of reproductive and metabolic disturbance in polycystic ovary syndrome.

PubMed

Christ, Jacob P; Vanden Brink, Heidi; Brooks, Eric D; Pierson, Roger A; Chizen, Donna R; Lujan, Marla E

2015-03-01

To reexamine associations between polycystic ovarian morphology (PCOM) and degree of symptomatology in polycystic ovary syndrome (PCOS) using a well-defined PCOS population, newer ultrasound technology, and reliable offline assessments of sonographic parameters. Cross-sectional observational study. Academic hospital and clinical research unit. Forty-nine women with PCOS as defined by hyperandrogenism and oligoamenorrhea. None. Number of follicles per follicle size category, antral follicle count (AFC), ovarian volume (OV), follicle distribution pattern, stromal area, ovarian area, stromal to ovarian area ratio (S/A) and stromal echogenicity index (SI), total (TT), androstenedione, LH, FSH, cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, C-reactive protein, glucose, insulin, and hemoglobin A1C, menstrual cycle length, hirsutism score, body mass index (BMI), waist:hip ratio, and blood pressure. AFC, but not OV, was positively associated with TT (ρ = .610), androstenedione (ρ = .490), and LH:FSH (ρ = .402). SI was positively associated with androgen markers and LH:FSH, while S/A was negatively associated with these variables. Follicles ≤4 mm were negatively associated with various metabolic markers, whereas larger follicles (5-8 mm) showed positive associations. Stromal markers were not associated with cardiometabolic measures. LH:FSH best predicted follicles ≤4 mm, and BMI predicted 5- to 9-mm follicles. Dominant follicles ≥10 mm were best predicted by age. AFC, and not OV, reflected the severity of reproductive dysfunction in PCOS. Associations among different sized follicles were consistent with recruitable sized follicles, which reflects the severity of metabolic dysfunction in PCOS. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The aryl hydrocarbon receptor is required for normal gonadotropin responsiveness in the mouse ovary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barnett, Kimberly R.; Tomic, Dragana; Gupta, Rupesh K.

2007-08-15

The aryl hydrocarbon receptor (AHR) mediates the toxicity of a variety of environmental chemicals. Although little is known about the physiological role of the AHR, studies suggest that it plays an important role in regulating ovulation because Ahr deficient (AhRKO) mice have a reduced number of ovulations compared to wild-type (WT) mice. The reasons for the reduced ability of AhRKO mice to ovulate are unknown. Normal ovulation, however, requires estrous cyclicity, appropriate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and LH and FSH responsiveness. Thus, the purpose of this study was to test the hypothesis that Ahr deletion regulatesmore » ovulation by altering cyclicity, FSH and LH levels, follicle-stimulating hormone receptor (Fshr) and luteinizing hormone receptor (Lhcgr) levels and/or gonadotropin responsiveness. The data indicate that AhRKO and WT mice have similar levels of FSH and LH, but AhRKO mice have reduced Fshr and Lhcgr mRNA levels compared to WT mice. Furthermore, AhRKO ovaries contain fewer corpora lutea compared to WT ovaries after 5 IU equine chorionic gonadotropin (eCG) treatment. Lastly, both AhRKO and WT mice ovulate a similar number of eggs in response to 5 IU human chorionic gonadotropin (hCG), but AhRKO mice ovulate fewer eggs than WT mice in response to 2.5 IU and 1.25 IU hCG. Collectively, these data indicate that AhRKO follicles have a reduced capacity to ovulate compared to WT follicles and that this is due to reduced responsiveness to gonadotropins. Thus, in addition to mediating toxicity of environmental chemicals, the Ahr is required for normal ovulation.« less

Hypogonadism in DM1 and its relationship to erectile dysfunction.

PubMed

Antonini, Giovanni; Clemenzi, Alessandro; Bucci, Elisabetta; De Marco, Emanuela; Morino, Stefania; Di Pasquale, Antonella; Latino, Pamela; Ruga, Gilda; Lenzi, Andrea; Vanacore, Nicola; Radicioni, Antonio F

2011-07-01

Myotonic dystrophy type 1 (DM1) is characterized by both a premature appearance of age-related phenotypes and multiple organ involvement, which affects skeletal and smooth muscle as well as the eye, heart, central nervous system, and endocrine system. Although erectile dysfunction (ED) is a frequent complaint in patients with DM1, it has not been investigated in great depth. Hypogonadism, which is reported to be one of the physical causes of ED in the general population, frequently occurs in DM1. We planned this case-control study to evaluate the relationship between hypogonadism, as defined by the sexual hormone profile (FSH, LH, testosterone (T) and prolactin) and ED, as assessed by means of an internationally validated self-administered questionnaire (IIEF). DM1 patients had significantly increased mean levels of both gonadotropins (FSH and LH) (p < 0.0001) and a reduced mean level of T (p < 0.0001) when compared to controls. Twelve patients were eugonadic (normal LH, T, and FSH), while 18 displayed hormonal evidence of hypogonadism, characterized by tubular failure (increased FSH) in all the subjects and associated with interstitial failure in 14 subjects: seven with primary hypogonadism (increased LH and reduced T) and seven with compensated hypogonadism (increased LH and normal T). Patients with hormonal evidence of interstitial failure had a larger CTG expansion (p = 0.008), longer disease duration (p = 0.013), higher grade of disease (p = 0.004) and lower erectile function score (p = 0.02) than eugonadic patients. Impotence occurred in 13/14 hypogonadic patients with interstitial failure and in 5/12 eugonadic patients (p = 0.017, OR = 18.2).

Use of equine chorionic gonadotropin to control reproduction of the dairy cow: a review.

PubMed

De Rensis, F; López-Gatius, F

2014-04-01

Equine chorionic gonadotropin (eCG) is a member of the glycoprotein family of hormones along with LH, FSH and thyroid-stimulating hormone. In non-equid species, eCG shows high LH- and FSH-like activities and has a high affinity for both FSH and LH receptors in the ovaries. On the granulosa and thecal cells of the follicle, eCG has long-lasting LH- and FSH-like effects that stimulate oestradiol and progesterone secretion. Thus, eCG administration in dairy cattle results in fewer atretic follicles, the recruitment of more small follicles showing an elevated growth rate, the sustained growth of medium and large follicles and improved development of the dominant and pre-ovulatory follicle. In consequence, the quality of the ensuing CL is improved, and thereby progesterone secretion increased. Based on these characteristics, eCG treatment is utilized in veterinary medicine to control the reproductive activity of the cow by i) improving reproductive performance during early post-partum stages; ii) increasing ovulation and pregnancy rates in non-cyclic cows; iii) improving the conception rate in cows showing delayed ovulation; and finally, iv) eCG is currently included in protocols for fixed-time artificial insemination since after inducing the synchrony of ovulation using a progesterone-releasing device, eCG has beneficial effects on embryo development and survival. The above effects are not always observed in cyclic animals, but they are evident in animals in which LH secretion and ovarian activity are reduced or compromised, for instance, during the early post-partum period, under seasonal heat stress, in anoestrus animals or in animals with a low body condition score. © 2014 Blackwell Verlag GmbH.

Genotypically determined ancestry across an infertile population: ovarian reserve and response parameters are not influenced by continental origin.

PubMed

Olcha, Meir; Franasiak, Jason M; Shastri, Shefali; Molinaro, Thomas A; Congdon, Haley; Treff, Nathan R; Scott, Richard T

2016-08-01

To evaluate the relationship between genetic ethnicity using ancestry informative markers (AIMs) and ovarian reserve and response parameters as evidenced by FSH, antimüllerian hormone (AMH), basal antral follicle count (BAFC), and total oocyte yield in IVF. Retrospective. Academic medical center. A total of 2,508 infertile patients undergoing IVF at a single center. Patients were genotyped for 32 AIMs and analyzed for differences in allele frequencies. A validated Bayesian clustering algorithm was then used to assign individuals into one of four ethnic populations: European, African, Central/South Asian, or East Asian. FSH, AMH, BAFC, and oocyte yield variation. After controlling for age and body mass index, genetic ethnicity had no impact on AMH, BAFC, and oocyte yield. FSH was found to be lower in patients of Central/South Asian ancestry (6.46 ng/mL vs. 6.97 ng/mL); however, the absolute difference is of little clinical significance. Subgroup analyses of 1,327 patients restricted to those with limited genetic admixture as determined by AIMs indicated that FSH, AMH, BAFC, and oocyte yield were equivalent. When determining ethnicity using AIMs, ethnic background does not have an impact on markers of ovarian reserve or ovarian response. Specifically, no differences were found in AMH, BAFC, or oocyte yield relative to genotypic ethnicity. Using AIMs rather than self-reported ethnicity allows for elimination of reporting biases and nonreporting of ethnicity, which can confound data. Based upon these data, specific recommendations for ovarian reserve testing should thus be made based on other factors besides ethnic background. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Investigation into influence factors of wave velocity anisotropy for TCDP borehole

NASA Astrophysics Data System (ADS)

Wu, C. N.; Dong, J. J.; Yang, C. M.; Wu, W. J.

2015-12-01

The direction of fast horizontal shear wave velocity (FSH direction) is used as an indicator of the direction of maximum horizontal principal stress. However, the wave velocity anisotropy will be simultaneously dominated by the stress induced anisotropy and the inherent anisotropy which includes the effects of sedimentary and tectonic structures. In this study, the influence factors of wave velocity anisotropy will be analyzed in borehole-A of Taiwan Chelungpu-Fault Drilling Project (TCDP). The anisotropic compliance tensors of intact sandstones and mudrocks derived from the laboratory wave measurement are combined with the equivalent continuous model to evaluate the compliance tensor of jointed rock mass. Results show the lithology was identified as the most influential factor on the wave velocity anisotropy. Comparing the FSH direction logging data with our results, the wave velocity anisotropy in sandstones is mostly caused by inherent anisotropy of intact sandstones. The spatial variations of wave velocity anisotropy in mudrocks is caused by other relatively higher influence factors than inherent anisotropy of intact mudrocks. In addition, the dip angle of bedding plans is also important for wave velocity anisotropy of mudrocks because the FSH direction logging data seems dominated by the dip direction of bedding planes when the dip angle becomes steeper (at the depth greater than 1785 m). Surprisingly, the wave velocity anisotropy contributed by joints that we determined by equivalent continuous model is not significant. In this study, based on the TCDP borehole data, we conclude that determining the direction of maximum horizontal principal stress from the FSH directions should consider the influence of inherent anisotropy on rock mass.

Diagnosis and Treatment of Diminished Ovarian Reserve in ART Cycles of Women Up to Age 40 Years: The Role of Insurance Mandates

PubMed Central

Butts, Samantha F.; Ratcliffe, Sarah; Dokras, Anuja; Seifer, David B.

2012-01-01

Summary Objective To explore correlates of diminished ovarian reserve (DOR) and predictors of ART treatment outcome in DOR cycles using the SART-CORS database. We hypothesized that state insurance coverage for ART is associated with the prevalence of DOR diagnosis in ART cycles and with treatment outcomes in DOR cycles. Design Cross sectional study using ART cycles between 2004–2007. Setting United States ART registry data. Patients 182,779 fresh, non-donor, initial ART cycles in women up to age 40. Interventions None. Main Outcome Measures Prevalence of DOR and elevated FSH, odds ratio of DOR and elevated FSH in ART mandated vs. non-mandated states, live birth rates. Results Compared to cycles performed in states with mandated ART coverage, cycles in states with no ART mandate were more likely to have DOR (AOR 1.43 95% CI 1.37–1.5, p<0.0001) or elevated FSH (AOR 1.69 95% CI 1.56–1.85, p<0.0001) as the sole reason for treatment. A relationship between lack of mandated ART coverage and increased live birth rates in some, but not all DOR cycles. Conclusions A significant association was observed between lack of mandated insurance for ART and the proportion of cycles treating DOR or elevated FSH. The presence or absence of state mandated ART coverage could impact access to care and the mix of patients that pursue and initiate ART cycles. Additional studies are needed that consider the coalescence of insurance mandates, patient and provider factors, and state level variables on the odds of specific infertility diagnoses and treatment prognosis. PMID:23102859

Androgen receptor CAG repeat polymorphism and hypothalamic-pituitary-gonadal function in Filipino young adult males

PubMed Central

Ryan, Calen P.; McDade, Thomas W; Gettler, Lee T.; Eisenberg, Dan T.A.; Rzhetskaya, Margarita; Hayes, M. Geoffey; Kuzawa, Christopher W.

2016-01-01

Objectives Testosterone (T), the primary androgenic hormone in males, is stimulated through pulsatile secretion of LH and regulated through negative feedback inhibition at the hypothalamus and pituitary. The hypothalamic-pituitary-gonadal (HPG) axis also controls sperm production through the secretion of follicle-stimulating hormone (FSH). Negative feedback in the HPG axis is achieved in part through the binding of T to the androgen receptor (AR), which contains a highly variable trinucleotide repeat polymorphism (AR-CAGn). The number of repeats in the AR-CAGn inversely correlates with transcriptional activity of the AR. Thus, we predicted longer AR-CAGn to be associated with higher T, LH, and FSH levels. Methods We examined the relationship between AR-CAGn and total plasma T, LH, and FSH, as well as 'bioavailable' morning (AM-T) and evening (PM-T) testosterone in 722 young (21.5 ± 0.5 years) Filipino males. Results There was no relationship between AR-CAGn and total T, AM-T, or LH (P > 0.25 for all). We did observe a marginally non-significant (P = 0.066) correlation between AR-CAGn and PM-T in the predicted direction, and a negative correlation between AR-CAGn and FSH (P = 0.005). Conclusions Our results both support and differ from previous findings in this area, and study parameters that differ between our study and others, such as participant age, sample time, and the role of other hormones should be considered when interpreting our findings. While our data point to a modest effect of AR-CAGn on HPG regulation at best, the AR-CAGn may still affect somatic traits by regulating androgenic activity at peripheral tissues. PMID:27417274

Microdose flare protocol with interrupted follicle stimulating hormone and added androgen for poor responders--an observational pilot study.

PubMed

Mitri, Frederic; Behan, Lucy Ann; Murphy, Courtney A; Hershko-Klement, Anat; Casper, Robert F; Bentov, Yaakov

2016-01-01

To investigate whether temporarily withholding FSH and adding androgen could improve follicular response during a microdose flare protocol in women with slow follicular growth or asynchronous follicular development. Observational pilot study. University-affiliated private fertility center. Twenty-six women aged 34-47 years with poor response to stimulation or a previous cancelled IVF cycle and with slow or asynchronous follicular growth during a microdose flare cycle. For 13 women, after initiation of ovarian stimulation using the microdose flare protocol, gonadotropin administration was interrupted and transdermal testosterone gel was added for several days (4.4 ± 1.2 d) starting after cycle day 7 (mean cycle day 10 ± 2.6). FSH, E2, follicular growth, and total number of mature oocytes retrieved were determined for all of the patients. Cycle cancellation rate as well as pregnancy rate following embryo transfer were also documented when applicable. FSH levels declined (25.2 ± 6.5 to 6.8 ± 3.2 IU/L), E2 levels increased (896 ± 687 to 2,163 ± 1,667 pmol/L), and follicular growth improved significantly during gonadotropin interruption and were tracked for 2 days during this time frame. The average number of oocytes retrieved was 5.3 ± 2.6, and the ratio of mature to total oocytes was 4:5. Four of the 13 women in the interruption group conceived following frozen embryo transfer, whereas none in the control group did. The androgen-interrupted FSH protocol may improve follicular response to gonadotropins in cycles that might otherwise be cancelled. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Sequelae in male rabbits following developmental exposure to p,p'-DDT or a mixture of p,p'-DDT and vinclozolin: cryptorchidism, germ cell atypia, and sexual dysfunction.

PubMed

Veeramachaneni, D N R; Palmer, J S; Amann, R P; Pau, K-Y F

2007-01-01

Rabbit does (7-9 per group) were treated daily per orum from gestation day 15 through post-natal week 4 to provide per kg body wt 25 micaromol (low) or 250 micromol (high) p,p'-DDT or a mixture of DDT and vinclozolin (12.5 and 125 micromol each). Developmental as well as post-pubertal reproductive sequelae of male progeny were studied. Testicular descent in some pups was impaired by DDT. Serum LH or testosterone was not affected. FSH was lower in mixture- but not in DDT-exposed rabbits. Lack of sexual interest, penile erection and ejaculation were observed in some mixture rabbits. Sperm counts were unaffected, but morphologically normal spermatozoa were fewer; nuclear and acrosomal morphogenesis was disrupted. Atypical germ cells resembling carcinoma in situ were found. Also considering data for vinclozolin [Veeramachaneni DNR, Palmer JS, Amann RP, Kane CM, Higuchi TT, Pau K-YF. Disruption of sexual function, FSH secretion, and spermiogenesis in rabbits following developmental exposure to vinclozolin, a fungicide. Reproduction 2006;131:805-16], we concluded that DDT causes cryptorchidism and germ cell atypia, vinclozolin permanently disrupts FSH secretion and sexual function, and the mixture causes the full spectrum of dysgenesis.

Effectiveness of Acupuncture for Primary Ovarian Insufficiency: A Systematic Review and Meta-Analysis.

PubMed

Jo, Junyoung; Lee, Yoon Jae; Lee, Hyangsook

2015-01-01

Objective. This systematic review aimed to assess current evidence from randomized controlled trials (RCTs) on the effects of acupuncture for patients with primary ovarian insufficiency (POI). Methods. We searched twelve databases to identify relevant studies published before July 2014. The outcomes were serum follicle-stimulating hormone (FSH) levels and resumption of menstruation. Two reviewers independently assessed the risk of bias using the Cochrane's tool, extracted the results, and evaluated the overall level of the evidence using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Results. Eight RCTs were selected. Acupuncture significantly lowered serum FSH levels and more women receiving acupuncture reported resumption of menses. However, the results should be interpreted with caution due to a small number of participants, high risk of bias for blinding, and likely publication bias. The level of evidence for FSH level and resumption of menses were assessed as "low" using GRADE. Conclusion. The current evidence on acupuncture for POI is insufficient to draw a firm conclusion due to scarcity of studies with a low risk of bias and likely publication bias. Further rigorously designed and conducted studies are needed to confirm the effectiveness and safety of acupuncture in patients with POI.

In Utero Exposure to Di( n-butyl)phthalate Induces Morphological and Biochemical Changes in Rats Postpuberty.

PubMed

Okayama, Yuya; Wakui, Shin; Wempe, Michael F; Sugiyama, Mitsuru; Motohashi, Masaya; Mutou, Tomoko; Takahashi, Hiroyuki; Kume, Eisuke; Ikegami, Hiroshi

2017-06-01

Pregnant Sprague-Dawley rats were orally administered di( n-butyl)phthalate (DBP; 100 mg/kg/day) on gestation days (GD) 12 to 21. We investigated the male offspring and probed morphological alterations in Sertoli cells at 7, 9, 14, and 17 weeks of age. Parameters assessed in this study included offspring number, sex ratios, body weights, testis weights, seminiferous tubule (ST) profile numbers and diameters, number of vimentin-labeled Sertoli cells, and both testosterone and follicle-stimulating hormone (FSH) levels. Testicular weight/body weight ratios and the numbers and diameters of ST in maximum transverse testicular sections were statistically similar at weeks 7 and 9; however, at weeks 14 and 17, they were statistically different and displayed higher BrdU-positive Sertoli cells/Sertoli cell ratios in the DBP treatment group. Noteworthily, the serum FSH levels were higher and testicular testosterone levels were lower in the DBP treatment group. To our knowledge, the present study is the first to report that in utero DBP exposure significantly increased Sertoli cell numbers and their cellular proliferation from postpuberty to adulthood, with a significant decrease in testicular testosterone and an increase in FSH.

Serum hormone concentrations and ovarian follicular wave emergence in Jilin sika deer (Cervus nippon hortulorum) after synchronization of estrous cycles.

PubMed

Chen, X M; Wei, H J; Yang, Y F; Xue, H L; Zhao, W G; Zhao, M

2015-02-01

The study was conducted to investigate the serum hormone concentrations and follicular dynamics present after synchronous treatment (CIDR) in female Jilin sika deer (n = 15) of estrous cycles. Blood samples were collected to analyze the FSH, LH, estradiol and progesterone during the estrous cycles. Manual transrectal ultrasonography examination was conducted at least thrice weekly to monitor the follicular wave. Ultrasonography showed that follicle development occurred in waves, and most estrous cycles in Jilin sika deer consist of one, two, or three waves. The largest follicles of the interwaves of two- and three-wave cycles were different (P < 0.05). The mean interovulatory interval was 15.0 ± 4.6 d. There was a surge in circulating FSH in two- and three-wave cycles. The emergence of the largest follicle was related to the peak of serum concentration of estradiol. Serum progesterone concentrations were not different between one- and three-wave cycles (P < 0.05). We concluded that FSH and estradiol concentration may have an important role in controlling follicular development, that the estrous cycle in Jilin sika deer is characterized by one, two, or three waves of follicular development after synchronization. Copyright © 2015. Published by Elsevier B.V.

Purification and characterization of lutropin receptor from membranes of pig follicular fluid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yarney, T.A.; Sairam, M.R.; Bhargavi, G.N.

1990-04-10

Membranes derived from free floating granulosa cells in porcine ovarian follicular fluid were used as a starting material for structural characterization of both LH/hCG and FSH receptors. The receptors were highly hormone-specific and showed single classes of high-affinity binding sites. Their molecular weights as determined by affinity cross-linking with their respective {sup 125}I-ligands were similarly 70,000. The membrane-localized receptors could be solubilized with reduced Triton X-100 in the presence of 20% glycerol with good retention of hormone binding activity. The purified receptor exhibited a high specificity for hCG and hLH but not for hFSH bTSH. The purified receptor was iodinatedmore » and visualized to be composed of a major protein of M{sub r} 70,000 and other minor proteins of molecular weights ranging from 14,000 to 40,000. Except for the M{sub r} 14,000 protein, all other protein species bound to the concanavalin A-Sepharose column. The data suggest that the ovarian LH/hCG and FSH receptors are structurally similar and consist of a single polypeptide chain, as recently documented for the LH/hCG receptor.« less

Abnormal patterns of pulsatile luteinizing hormone in women with luteal phase deficiency.

PubMed

Soules, M R; Steiner, R A; Clifton, D K; Bremner, W J

1984-05-01

Luteal phase deficiency is usually a problem of inadequate progesterone production associated with inadequate ovarian follicular development. The hypothesis that luteal phase deficiency results from an abnormal secretion pattern of luteinizing hormone (LH) was tested in these women. To this end, the early follicular LH secretion pattern in four women with luteal phase deficiency was characterized and compared with patterns in normal women. Blood samples were obtained through indwelling catheters every ten minutes for eight hours (10 AM to 6 PM), and plasma levels of LH and FSH were measured. Luteinizing hormone and FSH secretion profiles were analyzed for pulse frequency, amplitude, and mean plasma level. A significantly greater LH pulse frequency in women with luteal phase deficiency was observed when compared with the frequency in normal controls (luteal phase deficiency, 10.5 pulses/eight hours; normal, 5.2 pulses/eight hours; P less than or equal to .05). The mean FSH concentration was less in the women with luteal phase deficiency, but the level was not significant. These data suggest that the abnormal LH secretion pattern observed in women with luteal phase deficiency is responsible for their inadequate luteal phase progesterone secretion and their infertility.

Pituitary and ovarian hormone activity during the 7-day hormone-free interval of various combined oral contraceptive regimens.

PubMed

Cho, Michael; Atrio, Jessica; Lim, Aaron H; Azen, Colleen; Stanczyk, Frank Z

2014-07-01

The objective was to investigate changes in luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and progesterone (P) during the hormone-free interval (HFI) of 6 combined oral contraceptives (COCs). Blood samples were obtained from 62 women. When COCs were grouped by ethinyl estradiol (EE) dose, there was a significant positive mean slope for LH and FSH during the HFI for the 30- and 35 mcg-EE doses, whereas 20 showed a gradual nonsignificant slope. All E2 slopes were significant. P remained suppressed with all doses. A more rapid rebound of gonadotropin levels is found with higher doses of EE during the HFI. This study showed a more rapid rebound of pituitary hormone levels among women using higher-EE-dosage formulations, which was demonstrated by the statistically significant slope for mean LH and FSH from day 1 to day 7 of the HFI. The degree of suppression did not vary across progestin generations. It remains to be established whether women who experience side effects during their HFI may benefit from using a COC with a lower EE dose to minimize changes in endogenous pituitary hormone levels. Copyright © 2014 Elsevier Inc. All rights reserved.

Possible Involvement of Photoperiodic Regulation in Reproductive Endocrine System of Female Olive Flounder Paralichthys olivaceus.

PubMed

Kim, Hyun Chul; Lee, Chi Hoon; Hur, Sung Pyu; Kim, Byeong Hoon; Park, Jun Young; Lee, Young Don

2015-03-01

This study investigated possible involvement of photoperiodic regulation in reproductive endocrine system of female olive flounder. To investigate the influence on brain-pituitary axis in endocrine system by regulating photoperiod, compared expression level of Kisspeptin and sbGnRH mRNA in brain and FSH-β, LH-β and GH mRNA in pituitary before and after spawning. Photoperiod was treated natural photoperiod and long photoperiod (15L:9D) conditions from Aug. 2013 to Jun. 2014. Continuous long photoperiod treatment from Aug. (post-spawning phase) was inhibited gonadal development of female olive flounder. In natural photoperiod group, the Kiss2 expression level a significant declined in Mar. (spawning period). And also, FSH-β, LH-β and GH mRNA expression levels were increasing at this period. However, in long photoperiod group, hypothalamic Kiss2, FSH-β, LH-β and GH mRNA expression levels did not show any significant fluctuation. These results suggest that expression of hypothalamic Kiss2, GtH and GH in the pituitary would change in response to photoperiod and their possible involvement of photoperiodic regulation in reproductive endocrine system of the BPG axis.

Honey and metformin ameliorated diabetes-induced damages in testes of rat; correlation with hormonal changes

PubMed Central

Nasrolahi, Ozra; Khaneshi, Fereshteh; Rahmani, Fatemeh; Razi, Mazdak

2013-01-01

Background: The global prevalence of diabetes mellitus is on rise. Diabetes-induced oxidative stress has been known to affect liver, pancreas, kidney and reproductive organs pathologically. Honey is a natural product of bee with antioxidant properties. Objective: Current study aimed to analyze the protective effects of Metformin (MF) alone and MF+ natural honey co-administration on diabetes-induced histological derangements in testis of rats. Materials and Methods: Thirty six, mature male Wistar rats were randomly divided into six groups including; control, honey-dosed non-diabetic, diabetes-induced (65 mg/kg, single dose), honey-administrated diabetic (1.0 g/kg/day), Metformin-received diabetic (100 mg/kg/day), Metformin and honey-co-treated diabetic which were followed 40 days. The animals were anesthetized by diethyl ether and the blood samples were collected. The serum levels of testosterone, Insulin, LH and FSH analyzed using antibody enzyme immunoassay method. The testicular tissues were dissected out and underwent to histological analyses. Results: The biochemical analyses revealed that the diabetes resulted in significantly reduced testosterone (p<0.01), LH and FSH (P<0.01, 0.001) levels in serum. Light microscopic analyses showed remarkable (p<0.01) reduction in seminiferous tubules diameter (STD), spermiogenesis index (SPI) and thickness of the epithelium in the diabetic group versus control and co-treated groups. Simultaneous administration of the honey with MF could fairly up-regulate testosterone, LH and FSH levels. The animals in metformin and honey-treated group exhibited with improved tubules atrophy, elevated spermiogenesis index and germinal epithelium thickness. Conclusion: Our data indicated that co-administration of Metformin and honey could inhibit the diabetes-induced damages in testicular tissue. Moreover, the simultaneous administration of metformin and honey up-regulated the diabetes-reduced insulin, LH, FSH and testosterone levels. This

Honey and metformin ameliorated diabetes-induced damages in testes of rat; correlation with hormonal changes.

PubMed

Nasrolahi, Ozra; Khaneshi, Fereshteh; Rahmani, Fatemeh; Razi, Mazdak

2013-12-01

The global prevalence of diabetes mellitus is on rise. Diabetes-induced oxidative stress has been known to affect liver, pancreas, kidney and reproductive organs pathologically. Honey is a natural product of bee with antioxidant properties. Current study aimed to analyze the protective effects of Metformin (MF) alone and MF+ natural honey co-administration on diabetes-induced histological derangements in testis of rats. Thirty six, mature male Wistar rats were randomly divided into six groups including; control, honey-dosed non-diabetic, diabetes-induced (65 mg/kg, single dose), honey-administrated diabetic (1.0 g/kg/day), Metformin-received diabetic (100 mg/kg/day), Metformin and honey-co-treated diabetic which were followed 40 days. The animals were anesthetized by diethyl ether and the blood samples were collected. The serum levels of testosterone, Insulin, LH and FSH analyzed using antibody enzyme immunoassay method. The testicular tissues were dissected out and underwent to histological analyses. The biochemical analyses revealed that the diabetes resulted in significantly reduced testosterone (p<0.01), LH and FSH (P<0.01, 0.001) levels in serum. Light microscopic analyses showed remarkable (p<0.01) reduction in seminiferous tubules diameter (STD), spermiogenesis index (SPI) and thickness of the epithelium in the diabetic group versus control and co-treated groups. Simultaneous administration of the honey with MF could fairly up-regulate testosterone, LH and FSH levels. The animals in metformin and honey-treated group exhibited with improved tubules atrophy, elevated spermiogenesis index and germinal epithelium thickness. Our data indicated that co-administration of Metformin and honey could inhibit the diabetes-induced damages in testicular tissue. Moreover, the simultaneous administration of metformin and honey up-regulated the diabetes-reduced insulin, LH, FSH and testosterone levels. This article extracted from M.Sc. thesis. (Ozra Nasrolahi).

Neonatal handling and reproductive function in female rats.

PubMed

Gomes, C M; Raineki, C; Ramos de Paula, P; Severino, G S; Helena, C V V; Anselmo-Franci, J A; Franci, C R; Sanvitto, G L; Lucion, A B

2005-02-01

Neonatal handling induces anovulatory estrous cycles and decreases sexual receptivity in female rats. The synchronous secretion of hormones from the gonads (estradiol (E2) and progesterone (P)), pituitary (luteinizing (LH) and follicle-stimulating (FSH) hormones) and hypothalamus (LH-releasing hormone (LHRH)) are essential for the reproductive functions in female rats. The present study aimed to describe the plasma levels of E2 and P throughout the estrous cycle and LH, FSH and prolactin (PRL) in the afternoon of the proestrus, and the LHRH content in the medial preoptic area (MPOA), median eminence (ME) and medial septal area (MSA) in the proestrus, in the neonatal handled rats. Wistar pup rats were handled for 1 min during the first 10 days after delivery (neonatal handled group) or left undisturbed (nonhandled group). When they reached adulthood, blood samples were collected through a jugular cannula and the MPOA, ME and MSA were microdissected. Plasma levels of the hormones and the content of LHRH were determined by RIA. The number of oocytes counted in the morning of the estrus day in the handled rats was significantly lower than in the nonhandled ones. Neonatal handling reduces E2 levels only on the proestrus day while P levels decreased in metestrus and estrus. Handled females also showed reduced plasma levels of LH, FSH and PRL in the afternoon of the proestrus. The LHRH content in the MPOA was significantly higher than in the nonhandled group. The reduced secretion of E2, LH, FSH and LHRH on the proestrus day may explain the anovulatory estrous cycle in neonatal handled rats. The reduced secretion of PRL in the proestrus may be related to the decreased sexual receptiveness in handled females. In conclusion, early-life environmental stimulation can induce long-lasting effects on the hypothalamus-pituitary-gonad axis.

Effect of recombinant human follicle-stimulating hormone and luteinizing hormone on in vitro maturation of porcine oocytes evaluated by the subsequent in vitro development of embryos obtained by in vitro fertilization, intracytoplasmic sperm injection, or parthenogenetic activation.

PubMed

Silvestre, M A; Alfonso, J; García-Mengual, E; Salvador, I; Duque, C C; Molina, I

2007-05-01

The aim of this work was to study the effect of recombinant human (rh) FSH and LH on in vitro maturation of pig oocytes compared with a conventional hormonal supplement based on equine (PMSG) and human chorionic gonadotropins (hCG), as evaluated by the developmental ability of 3 types of pig embryos obtained by in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), or artificial activation (ATA). In Exp. 1, one cumulus-oocyte complex group (A group) was supplemented with rh-FSH and rh-LH (0.1 IU/mL each), and the other group (B group) was supplemented with PMSG and hCG (10 IU/mL each). No differences in nuclear maturation between the A and B groups were observed (68.5 vs. 71.4%, respectively). No differences were detected between hormonal treatments in the rates of cleavage or blastocyst formation of ATA, IVF, and ICSI embryos. Total cell number of the embryos was not significantly different in any experimental group (A: 31.1, 28.5, and 19.8 vs. B: 25.2, 25.5, and 20.6 for ATA, IVF, and ICSI embryos, respectively). In Exp. 2, the effects of different concentrations of rh-FSH and rh-LH (0.5, 0.1, or 0.05 IU/mL) in maturation medium on nuclear maturation and in vitro development of embryos obtained by IVF were studied. No effect of different hormonal concentrations on blastocyst formation rates was observed (8.5, 13.0, and 5.7%, respectively). Blastocyst cell number was not different in any experimental group. In conclusion, the results obtained here permit us to substitute PMSG and hCG with rh-FSH and rh-LH and to produce pig embryos obtained by IVF, ICSI, or ATA.

Bone Morphogenetic Protein 15 in the Pro-Mature Complex Form Enhances Bovine Oocyte Developmental Competence

PubMed Central

Sudiman, Jaqueline; Sutton-McDowall, Melanie L.; Ritter, Lesley J.; White, Melissa A.; Mottershead, David G.; Thompson, Jeremy G.; Gilchrist, Robert B.

2014-01-01

Developmental competence of in vitro matured (IVM) oocytes needs to be improved and this can potentially be achieved by adding recombinant bone morphogenetic protein 15 (BMP15) or growth differentiation factor (GDF9) to IVM. The aim of this study was to determine the effect of a purified pro-mature complex form of recombinant human BMP15 versus the commercially available bioactive forms of BMP15 and GDF9 (both isolated mature regions) during IVM on bovine embryo development and metabolic activity. Bovine cumulus oocyte complexes (COCs) were matured in vitro in control medium or treated with 100 ng/ml pro-mature BMP15, mature BMP15 or mature GDF9 +/− FSH. Metabolic measures of glucose uptake and lactate production from COCs and autofluorescence of NAD(P)H, FAD and GSH were measured in oocytes after IVM. Following in vitro fertilisation and embryo culture, day 8 blastocysts were stained for cell numbers. COCs matured in medium +/− FSH containing pro-mature BMP15 displayed significantly improved blastocyst development (57.7±3.9%, 43.5±4.2%) compared to controls (43.3±2.4%, 28.9±3.7%) and to mature GDF9+FSH (36.1±3.0%). The mature form of BMP15 produced intermediate levels of blastocyst development; not significantly different to control or pro-mature BMP15 levels. Pro-mature BMP15 increased intra-oocyte NAD(P)H, and reduced glutathione (GSH) levels were increased by both forms of BMP15 in the absence of FSH. Exogenous BMP15 in its pro-mature form during IVM provides a functional source of oocyte-secreted factors to improve bovine blastocyst development. This form of BMP15 may prove useful for improving cattle and human artificial reproductive technologies. PMID:25058588

Bone morphogenetic protein 15 in the pro-mature complex form enhances bovine oocyte developmental competence.

PubMed

Sudiman, Jaqueline; Sutton-McDowall, Melanie L; Ritter, Lesley J; White, Melissa A; Mottershead, David G; Thompson, Jeremy G; Gilchrist, Robert B

2014-01-01

Developmental competence of in vitro matured (IVM) oocytes needs to be improved and this can potentially be achieved by adding recombinant bone morphogenetic protein 15 (BMP15) or growth differentiation factor (GDF9) to IVM. The aim of this study was to determine the effect of a purified pro-mature complex form of recombinant human BMP15 versus the commercially available bioactive forms of BMP15 and GDF9 (both isolated mature regions) during IVM on bovine embryo development and metabolic activity. Bovine cumulus oocyte complexes (COCs) were matured in vitro in control medium or treated with 100 ng/ml pro-mature BMP15, mature BMP15 or mature GDF9 +/- FSH. Metabolic measures of glucose uptake and lactate production from COCs and autofluorescence of NAD(P)H, FAD and GSH were measured in oocytes after IVM. Following in vitro fertilisation and embryo culture, day 8 blastocysts were stained for cell numbers. COCs matured in medium +/- FSH containing pro-mature BMP15 displayed significantly improved blastocyst development (57.7±3.9%, 43.5±4.2%) compared to controls (43.3±2.4%, 28.9±3.7%) and to mature GDF9+FSH (36.1±3.0%). The mature form of BMP15 produced intermediate levels of blastocyst development; not significantly different to control or pro-mature BMP15 levels. Pro-mature BMP15 increased intra-oocyte NAD(P)H, and reduced glutathione (GSH) levels were increased by both forms of BMP15 in the absence of FSH. Exogenous BMP15 in its pro-mature form during IVM provides a functional source of oocyte-secreted factors to improve bovine blastocyst development. This form of BMP15 may prove useful for improving cattle and human artificial reproductive technologies.

Pituitary-gonadal hormones during prolonged residency in Antarctica.

PubMed

Sawhney, R C; Malhotra, A S; Prasad, R; Pal, K; Kumar, R; Bajaj, A C

1998-08-01

Plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL) and testosterone levels were measured in nine eugonadal men in New Delhi and during the 1st week of different months of their stay at Dakshin Gangotri in Antarctica. During their 12-month stay in Antarctica, they were exposed to a severely cold climate, long polar nights and polar days, high wind velocity, increased amounts of solar and ultraviolet radiation and geomagnetism, as well as physical and social isolation. Plasma testosterone tended to increase in March, but a significant increase (P < 0.05) was not seen until April. The mean testosterone levels in May, June, September and November were also significantly higher than the March or New Delhi values. The absolute values of LH, FSH and PRL did not show any month-to-month changes in Antarctica. However, when the hormone levels were expressed as a percentage of the individual annual Antarctic mean, significant differences as a percentage of the individual annual Antarctic mean, significant differences were observed. The testosterone peak in April, May and June was associated with an increase in LH. The nadirs of testosterone, LH, FSH and PRL were seen in either July or August. FSH showed the highest values in March, whereas the highest PRL values were seen in November. These observations suggest the presence of circannual variations in gonadotropin, PRL and LH in Antarctica which are independent of polar days and polar nights. It appears that factors other than the duration of daylight might be involved in regulating these changes. The significance of maintenance of testosterone levels in the supra-physiological range in Antarctica remains unknown but may be important in acclimatization/habituation to the extreme polar cold by increasing basal metabolic rate, protein synthesis and erythropoiesis.

Perspectives on fish gonadotropins and their receptors.

PubMed

Levavi-Sivan, B; Bogerd, J; Mañanós, E L; Gómez, A; Lareyre, J J

2010-02-01

Teleosts lack a hypophyseal portal system and hence neurohormones are carried by nerve fibers from the preoptic region to the pituitary. The various cell types in the teleost pituitary are organized in discrete domains. Fish possess two gonadotropins (GtH) similar to FSH and LH in other vertebrates; they are heterodimeric hormones that consist of a common alpha subunit non-covalently associated with a hormone-specific beta subunit. In recent years the availability of molecular cloning techniques allowed the isolation of the genes coding for the GtH subunits in 56 fish species representing at least 14 teleost orders. Advanced molecular engineering provides the technology to produce recombinant GtHs from isolated cDNAs. Various expression systems have been used for the production of recombinant proteins. Recombinant fish GtHs were produced for carp, seabream, channel and African catfish, goldfish, eel, tilapia, zebrafish, Manchurian trout and Orange-spotted grouper. The hypothalamus in fishes exerts its regulation on the release of the GtHs via several neurohormones such as GnRH, dopamine, GABA, PACAP, IGF-I, norepinephrine, NPY, kisspeptin, leptin and ghrelin. In addition, gonadal steroids and peptides exert their effects on the gonadotropins either directly or via the hypothalamus. All these are discussed in detail in this review. In mammals, the biological activities of FSH and LH are directed to different gonadal target cells through the cell-specific expression of the FSH receptor (FSHR) and LH receptor (LHR), respectively, and the interaction between each gonadotropin-receptor couple is highly selective. In contrast, the bioactivity of fish gonadotropins seems to be less specific as a result of promiscuous hormone-receptor interactions, while FSHR expression in Leydig cells explains the strong steroidogenic activity of FSH in certain fish species. Copyright 2009 Elsevier Inc. All rights reserved.

Hormonal changes after localized prostate cancer treatment. Comparison between external beam radiation therapy and radical prostatectomy.

PubMed

Planas, J; Celma, A; Placer, J; Maldonado, X; Trilla, E; Salvador, C; Lorente, D; Regis, L; Cuadras, M; Carles, J; Morote, J

2016-11-01

To determine the influence of radical prostatectomy (RP) and external beam radiation therapy (EBRT) on the hypothalamic pituitary axis of 120 men with clinically localized prostate cancer treated with RP or EBRT exclusively. 120 patients with localized prostate cancer were enrolled. Ninety two patients underwent RP and 28 patients EBRT exclusively. We measured serum levels of luteinizing hormone, follicle stimulating hormone (FSH), total testosterone (T), free testosterone, and estradiol at baseline and at 3 and 12 months after treatment completion. Patients undergoing RP were younger and presented a higher prostate volume (64.3 vs. 71.1 years, p<0.0001 and 55.1 vs. 36.5 g, p<0.0001; respectively). No differences regarding serum hormonal levels were found at baseline. Luteinizing hormone and FSH levels were significantly higher in those patients treated with EBRT at three months (luteinizing hormone 8,54 vs. 4,76 U/l, FSH 22,96 vs. 8,18 U/l, p<0,0001) while T and free testosterone levels were significantly lower (T 360,3 vs. 414,83ng/dl, p 0,039; free testosterone 5,94 vs. 7,5pg/ml, p 0,018). At 12 months FSH levels remained significantly higher in patients treated with EBRT compared to patients treated with RP (21,01 vs. 8,51 U/l, p<0,001) while T levels remained significantly lower (339,89 vs. 402,39ng/dl, p 0,03). Prostate cancer treatment influences the hypothalamic pituitary axis. This influence seems to be more important when patients with prostate cancer are treated with EBRT rather than RP. More studies are needed to elucidate the role that prostate may play as an endocrine organ. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

[Effect of kuntai capsule on the number of retrieved oocytes, high-quality oocytes and embryos in in vitro fertilization of poor ovarian response patients].

PubMed

Lian, Fang; Jiang, Xiao-Yuan

2014-08-01

To observe the effect of Kuntai Capsule (KC) on the number of retrieved oocytes, the quality of high-quality oocytes and embryos in in vitro fertilization of poor ovarian response (POR) patients. Totally 70 POR patients preparing for in vitro fertilization-embryo transfer (IVF-ET) were randomly assigned to the observation group and the control group, 35 cases in each group. KC was administered to patients in the observation group in the preparation cycle (i.e., three menstrual cycles before IVF-ET) and during the superovulation process. Those in the control group took placebo during this period. Before and after medication the improvement of Shen yin deficiency syndrome (SYDS) was observed in the two groups. The basal follicle-stimulating hormone (bFSH), luteinizing hormone (LH), estradiol (E2), anti-Mullerian hormone (AMH), the ratio of FSH to LH, and antral follicle count (AFC) were observed. Besides, the E2 level of a single ovum on the day of HCG injection, the number of retrieved oocytes, the high-quality oocyte rate, and the high-quality embryos were observed. Compared with the control group, the SYDS, decreased bFSH and LH levels, increased ACF numbers, the E2 level of a single ovum on the day of HCG injection, the number of retrieved oocytes, high-quality oocytes, and high-quality embryos were superior in the observation group (P < 0.05). There was no statistical difference in the decreased FSH/LH level (P > 0.05). E2 and AMH increased after medication of KC in the observation group, while they decreased after administration of placebos in the control group. There was statistical difference in the post-pre treatment difference of E2 and AMH between the two groups (P < 0.05). KC could increase the number of retrieved oocytes, and elevate the quality of occytes and embryos in the IVF-ET.

Effects of 3-methyl-4-nitrophenol in diesel exhaust particles on the regulation of testicular function in immature male rats.

PubMed

Li, Chunmei; Taneda, Shinji; Suzuki, Akira K; Furuta, Chie; Watanabe, Gen; Taya, Kazuyoshi

2007-01-01

We investigated the effects of 3-methyl-4-nitrophenol (4-nitro-m-cresol, PNMC) isolated from diesel exhaust particles (DEP) on the reproductive functions of male rats. Twenty-eight-day-old rats were injected subcutaneously with PNMC (1, 10, or 100 mg/kg) daily for 5 days. The weights of the epididymis, seminal vesicle, and Cowper gland were significantly decreased in rats treated with 10 mg/kg PNMC. The plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were significantly increased by PNMC at 100 mg/kg. However, the plasma concentrations of testosterone and immunoreactive (ir)-inhibin were significantly decreased by PNMC at 100 mg/kg. The testosterone content of the testicles was significantly decreased in the group treated with 100 mg/kg PNMC compared with the control group. Furthermore, testicular concentration of ir-inhibin was significantly decreased by PNMC at 1 mg/kg or 100 mg/kg. To investigate the direct effects of PNMC on the secretion of LH and FSH from the anterior pituitary gland, and on the secretion of testosterone from the testes, we exposed cultured anterior pituitary and interstitial Leydig cells to PNMC (10(-6), 10(-5), 10(-4) M) with or without gonadotropin-releasing hormone (GnRH; 10 nM) (for the LH and FSH tests) and human chorionic gonadotropin (hCG; 0.1 IU/mL) (for the testosterone test) for 24 hours. PNMC did not change either the basal or GnRH-stimulated levels of FSH and LH secretion. However, PNMC significantly inhibited both basal and hCG-stimulated testosterone production. These findings suggest that PNMC has a direct effect on the testes of immature male rats, causing a reduction in testosterone secretion.

Relationships between obesity, lipids and fasting glucose in the menopause.

PubMed

Netjasov, Aleksandra Simoncig; Vujović, Svetlana; Ivović, Miomira; Tancić-Gajić, Milina; Marina, Ljiljana; Barać, Marija

2013-01-01

Menopause leads to the development of central adiposity, a more atherogenic lipid profile and increased incidence of metabolic syndrome independent of age and other factors. The aim of the study was to investigate the relationships between anthropometric characteristics, sex hormones, lipids and fasting glucose in menopausal women. The study included 87 menopausal women, who where divided into groups according to two criteria: BMI > or = 26.7 kg/m2 and BMI > or = 25 kg/m2. Anthropometric characteristics and blood pressure were measured. Blood was taken at 08.00 h for fasting glucose, triglycerides, cholesterol, HDL, LDL, apolipoprotein A, apolipoprotein B, lipoprotein(a) (Lp(a)), C-reactive protein, fibrinogen, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol, progesterone, testosterone and sex hormone binding globulin (SHBG). Significant differences between groups were found for weight, BMI, waist, hips circumference, waist/hip ratio (WHR), systolic and diastolic blood pressure, Lp(a), FSH, LH, PRL (for systolic blood pressure p < 0.05, for the rest p < 0.01) and fasting glucose (p < 0.05). In obese and overweight women with BMI > or = 26.7 kg/m2 significant negative correlations were found for FSH and glucose, SHBG and LDL, SHBG and total cholesterol, SHBG and glucose, BMI and HDL, WC and HDL. In obese and overweight women with BMI > or = 25 kg/m2 significant negative correlations were found for BMI and HDL, waist circumference (WC) and HDL, WHR and HDL, FSH and glucose, SHBG and glucose; significant positive correlations were between BMI and glucose, WC and glucose and WHR with triglycerides. Gaining weight and decreased SHBG are related to dyslipidemia and increased fasting glucose confirming increased incidence of metabolic abnormalities in the menopause.

Night shift work and hormone levels in women.

PubMed

Davis, Scott; Mirick, Dana K; Chen, Chu; Stanczyk, Frank Z

2012-04-01

Night shift work may disrupt the normal nocturnal rise in melatonin, resulting in increased breast cancer risk, possibly through increased reproductive hormone levels. We investigated whether night shift work is associated with decreased levels of urinary 6-sulfatoxymelatonin, the primary metabolite of melatonin, and increased urinary reproductive hormone levels. Participants were 172 night shift and 151 day shift-working nurses, aged 20-49 years, with regular menstrual cycles. Urine samples were collected throughout work and sleep periods and assayed for 6-sulfatoxymelatonin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrone conjugate (E1C). 6-Sulfatoxymelatonin levels were 62% lower and FSH and LH were 62% and 58% higher, respectively, in night shift-working women during daytime sleep than in day shift-working women during nighttime sleep (P ≤ 0.0001). Nighttime sleep on off-nights was associated with 42% lower 6-sulfatoxymelatonin levels among the night shift workers, relative to the day shift workers (P < 0.0001); no significant differences in LH or FSH were observed. 6-Sulfatoxymelatonin levels during night work were approximately 69% lower and FSH and LH were 35% and 38% higher, compared with day shift workers during nighttime sleep. No differences in E1C levels between night and day shift workers were observed. Within night shift workers, 6-sulfatoxymelatonin levels were lower and reproductive hormone levels were higher during daytime sleep and nighttime work, relative to nighttime sleep (P < 0.05). These results indicate that night shift workers have substantially reduced 6-sulfatoxymelatonin levels during night work and daytime sleep and that levels remain low even when a night shift worker sleeps at night. Shift work could be an important risk factor for many other cancers in addition to breast cancer. ©2012 AACR.

Prenatal diethylstilbestrol exposure and reproductive hormones in premenopausal women.

PubMed

Wise, L A; Troisi, R; Hatch, E E; Titus, L J; Rothman, K J; Harlow, B L

2015-06-01

Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women in the mid-1900s, is a potent endocrine disruptor. Prenatal DES exposure has been associated with reproductive disorders in women, but little is known about its effects on endogenous hormones. We assessed the association between prenatal DES exposure and reproductive hormones among participants from the Harvard Study of Moods and Cycles (HSMC), a longitudinal study of premenopausal women aged 36-45 years from Massachusetts (1995-1999). Prenatal DES exposure was reported at baseline (43 DES exposed and 782 unexposed). Early follicular-phase concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were measured at baseline and every 6 months during 36 months of follow-up. Inhibin B concentrations were measured through 18 months. We used multivariable logistic and repeated-measures linear regression to estimate odds ratios (OR) and percent differences in mean hormone values (β), respectively, comparing DES exposed with unexposed women, adjusted for potential confounders. DES-exposed women had lower mean concentrations of estradiol (pg/ml) (β=-15.6%, 95% confidence interval (CI): -26.5%, -3.2%) and inhibin B (pg/ml) (β=-20.3%, CI: -35.1%, -2.3%), and higher mean concentrations of FSH (IU/I) (β=12.2%, CI: -1.5%, 27.9%) and LH (IU/I) (β=10.4%, CI: -7.2%, 31.3%), than unexposed women. ORs for the association of DES with maximum FSH>10 IU/I and minimum inhibin B<45 pg/ml--indicators of low ovarian reserve--were 1.90 (CI: 0.86, 4.22) and 4.00 (CI: 0.88-18.1), respectively. Prenatal DES exposure was associated with variation in concentrations of FSH, estradiol and inhibin B among women of late reproductive age.

Insulin-like peptide 3 (INSL3) in men with congenital hypogonadotropic hypogonadism/Kallmann syndrome and effects of different modalities of hormonal treatment: a single-center study of 281 patients.

PubMed

Trabado, Séverine; Maione, Luigi; Bry-Gauillard, Hélène; Affres, Hélène; Salenave, Sylvie; Sarfati, Julie; Bouvattier, Claire; Delemer, Brigitte; Chanson, Philippe; Le Bouc, Yves; Brailly-Tabard, Sylvie; Young, Jacques

2014-02-01

Insulin-like factor 3 (INSL3) is a testicular hormone secreted during fetal life, the neonatal period, and after puberty. To measure INSL3 levels in a large series of men with congenital hypogonadotropic hypogonadism (CHH)/ Kallmann syndrome (KS), in order to assess its diagnostic value and to investigate its regulation. We studied 281 CHH/KS patients (91 untreated, 96 receiving T, and 94 receiving combined gonadotropin therapy [human chorionic gonadotropin, hCG, and FSH]) and 72 age-matched healthy men. Serum INSL3 was immunoassayed with a validated RIA. Mean (±SD) INSL3 levels (pg/mL) were 659 ± 279 in controls and lower (60 ± 43; P < .001) in untreated CHH/KS patients, with no overlap between the two groups, when the threshold of 250 pg/mL was used. Basal INSL3 levels were lower in both untreated CHH/KS men with cryptorchidism than in those with intrascrotal testes and in patients with testicular volumes below 4 mL. Significant positive correlations between INSL3 and both serum total T and LH levels were observed in untreated CHH/KS. Mean INSL3 levels remained low in T-treated CHH/KS patients and were significantly higher in men receiving combined hCG-FSH therapy (P < .001), but the increase was lower cryptorchid patients. FSH-hCG combination therapy or hCG monotherapy, contrary to T and FSH monotherapies, significantly increased INSL3 levels in CHH/KS. INSL3 is as sensitive a marker as T for the evaluation of altered Leydig cell function in CHH/KS patients. INSL3 levels correlate with LH levels in CHH/KS men showing, together with the rise in INSL3 levels during hCG therapy, that INSL3 secretion seems not constitutively secreted during adulthood but is dependence on pituitary LH.

Impact of thyroid function abnormalities on reproductive hormones during menstrual cycle in premenopausal HIV infected females at NAUTH, Nnewi, Nigeria

PubMed Central

Emelumadu, Obiageli Fidelia; Igwegbe, Anthony Osita; Monago, Ifeoma Nwamaka; Ilika, Amobi Linus

2017-01-01

Background This was a prospective study designed to evaluate the impact of thyroid function abnormalities on reproductive hormones during menstrual cycle in HIV infected females at Nnamdi Azikiwe University Teaching Hospital Nnewi, South-East Nigeria. Methods The study randomly recruited 35 Symptomatic HIV infected females and 35 Symptomatic HIV infected females on antiretroviral therapy (HAART) for not less than six weeks from an HIV clinic and 40 apparently heathy control females among the hospital staff of NAUTH Nnewi. They were all premenopausal females with regular menstrual cycle and aged between 15–45 years. Blood samples were collected at follicular and luteal phases of their menstrual cycle for assay of Thyroid indices (FT3, FT4 and TSH) and Reproductive indices (FSH, LH, Estrogen, Progesterone, Prolactin and Testosterone) using ELISA method. Results The result showed significantly higher FSH and LH but significantly lower progesterone (prog) and estrogen (E2) in the test females compared to control females at both phases of menstrual cycle (P<0.05). There was significantly lower FT3 but significantly higher TSH value in Symptomatic HIV females (P<0.05). FSH, LH and TSH values were significantly lowered while prog and FT3 were significantly higher in Symptomatic HIV on ART compared to Symptomatic HIV females (P<0.05). FT3, FT4, Prog and E2 were inversely correlated while FSH and LH were positively correlated with duration of HIV infection in HIV females (P<0.05 respectively). There was a direct correlation between CD4+ count and FT3 while inverse correlation was found between CD4+ count and TSH levels (P<0.05). Discussion The present study demonstrated hypothyroidism with a significant degree of primary hypogonadism in Symptomatic HIV infected females at both follicular and luteal phases of menstrual cycle which tends to normalize on treatments. PMID:28723963

Ovarian function after uterine artery embolization and hysterectomy.

PubMed

Healey, Sarah; Buzaglo, Karen; Seti, Laurent; Valenti, David; Tulandi, Togas

2004-08-01

To evaluate the effect of uterine artery embolization (UAE) and hysterectomy on ovarian function. Prospective case control study (Canadian Task Force classification II-2). University teaching hospital. Eighty-four healthy premenopausal women with symptomatic uterine myoma(s) undergoing UAE or hysterectomy. Patients had blood drawn to measure follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels and underwent transvaginal ultrasound to measure volume of the myoma(s) and uterus on cycle day 3 before the procedures. These measurements were repeated 3 and 6 months after treatment. The main outcome was the differences in serum FSH, LH, E2, and ultrasound findings before and after UAE or hysterectomy. Of the 68 patients who underwent UAE and 16 who underwent hysterectomy, 48 and 13 respectively, completed 6-month follow-up. The mean age of the patients in the UAE group was 44.9 +/- 3.8 years and 43.7 +/- 5.6 years in the hysterectomy group. There was no significant difference in serum FSH before (8.9 +/- 0.7 IU/L) and 6 months after UAE (9.9 +/- 1.0 lU/L), and between the baseline (10.4 +/- 1.8 lU/L) and 6 months posthysterectomy (7.8 +/- 1.8 lU/L). The uterine volume 6 months after UAE (361 +/- 50 mL) was significantly smaller than before UAE(538 +/- 38mL; p =.005, 95% CI 44-241). Compared with baseline (154 +/- 20 mL), the dominant myoma volume was smaller at 6 months after UAE (97 +/- 16 mL; p <.05, 95% CI 1.57-62). Uterine artery embolization is associated with a significant reduction in myoma and uterine volume. Ovarian function at 6 months, as indicated by day 3 FSH levels, is not affected by UAE or hysterectomy.

Prader-Willi syndrome with elevated follicle stimulating hormone levels and diabetes mellitus.

PubMed

Nagai, T; Mimura, N; Tomizawa, T; Monden, T; Mori, M

1998-12-01

A 21 -year-old man with Prader-Willi syndrome (PWS) was hospitalized due to hyperglycemia. After diet therapy and transient insulin administration, his blood glucose levels improved. Based on the fact that his urinary C-peptide levels increased, the diabetes mellitus may have been due to insulin resistance with obesity. In addition, his testes had become atrophied. Testosterone levels remained low even after human chorionic gonadotropin (HCG) administration. Luteinizing hormone (LH) levels were also low after LH releasing hormone (LHRH) administration. The LH response increased slightly after daily LHRH administration, indicating hypothalamic hypogonadism. Follicle stimulating hormone (FSH) levels were, however, high and increased after LHRH administration. The selective FSH elevation may have been due to the accompanying idiopathic oligospermia.

Malignant Brenner tumor. A histologic, morphometrical, immunohistochemical, and ultrastructural study.

PubMed

Seldenrijk, C A; Willig, A P; Baak, J P; Kühnel, R; Rao, B R; Burger, C W; van der Harten, J J; Dijkhuizen, G H; Meijer, C J

1986-08-01

The histologic, morphometric, immunohistochemical, and ultrastructural study of a malignant Brenner tumor in a postmenopausal women presenting with vaginal bleeding is described. A comparison with transitional cell carcinomas is made, and the use of morphometry in grading the urothelial-like epithelium in malignant Brenner tumors is suggested. High preoperative urinary estrogen, low serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels and histologically confirmed atypical endometrial hyperplasia suggested a hyperestrogenism. The reduction in urinary estrogen and the increase in serum LH and FSH after tumor removal and the presence of aromatase activity detected in tumor microsomes confirmed that the tumor was synthesizing estrogen. Estrogen receptors were undetectable both by biochemical and histochemical analysis in the tumor.

An introduction to global mental health.

PubMed

Patterson, Jo Ellen; Edwards, Todd M

2018-06-01

In general, readers of Families, Systems, and Health (FSH) practice in high income countries and in settings that have adequate resources. Providers can usually count on being able to offer the material resources and skills that patients need to heal. This bounty of resources is in contrast to many clinics in low- and middle-income countries (LMICs). The need for mental health services in LMICs is significant and growing because of upheaval caused by war and other disasters. The topics in this issue talk about the obstacles to obtaining mental health services, trends in global mental health, and FSH in the global mental health movement. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Possible role of serum testosterone, gonadotropins and prolactin in patients with premature ejaculation.

PubMed

Abu El-Hamd, M; Farah, A

2018-02-01

Premature ejaculation (PE) is the most common male sexual dysfunction. This study aimed to investigate the role of serum testosterone, gonadotropins and prolactin in patients with PE. In a prospective a case-controlled study, it was conducted on 90 male patients with PE and 90 male healthy participants as controls. Patients were evaluated by Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculatory latency time (IELT). Patients with mean IELT values ≤60 s and PEDT total scores ≥11 were considered to have PE. Serum levels of total testosterone (TT), free testosterone (FT), follicle-stimulating hormone (FSH), luteinising hormone (LH) and prolactin (PL) were investigated in patients with PE and controls. There was no statistically significant difference between patients with PE and controls regarding the serum levels of TT, FT, FSH, LH and PL (p value ˃.05). There was no significant correlation between the sex hormones levels (TT, FT, FSH, LH and PL) and (age, body mass index (BMI), IELTS and total PEDT scores of the patients; p value ˃.05). This study concluded that there was no disturbance in serum levels of testosterone, gonadotropins and prolactin in patients with PE and controls. These hormones could not relate to pathogenesis of PE. © 2017 Blackwell Verlag GmbH.

Expression of nerve growth factor and its receptor, tyrosine kinase receptor A, in rooster testes.

PubMed

Ma, Wei; Wang, Chunqiang; Su, Yuhong; Tian, Yumin; Zhu, Hongyan

2015-10-01

Nerve growth factor (NGF), which is required for the survival and differentiation of the nervous system, is also thought to play an important role in the development of mammalian reproductive tissues. To explore the function of NGF in the male reproductive system of non-mammalian animals, we determined the presence of NGF and its receptor, tyrosine kinase receptor A (TrkA), in rooster testes and investigated the regulation of NGF and TrkA expression by follicle-stimulating hormone (FSH). The mRNA and protein levels of NGF and TrkA in 6-week-old rooster testes were lower than those in 12-, 16- or 20-week age groups; levels were highest in the 16-week group. Immunohistochemistry showed that NGF and TrkA were both detected in spermatogonia, spermatocytes and spermatids. NGF immunoreactivity was observed in Leydig cells and strong TrkA signals were present in Sertoli cells. Meanwhile, FSH increased TrkA transcript levels in rooster testes in a dose-dependent manner. We present novel evidence for the developmental and FSH-regulated expression of the NGF/TrkA system, and our findings suggest that the NGF/TrkA system may play a prominent role in chicken spermatogenesis. Copyright © 2015 Elsevier B.V. All rights reserved.

Hormone secretion by euthyroid and hypothyroid rat ovaries during the early stages of hCG-induced ovarian cyst development.

PubMed

Bruot, B C

1987-02-01

This study was undertaken to examine ovarian steroid production during the early stages of hCG-induced ovarian cyst formation in the hypothyroid rat. Rats were placed into two groups with one group made hypothyroid by adding thiouracil to their diet. After 10 days, each group was divided into two subgroups with one subgroup receiving daily injections of hCG for 2 days and the other subgroup receiving saline. On the morning of Day 13, ovaries were removed and incubated for 2 hr. No significant difference in progesterone secretion was observed. However, ovaries from hypothyroid, hCG-treated rats secreted significantly more testosterone and estradiol than ovaries from vehicle-treated, hypothyroid rats and euthyroid, hCG-treated rats. In a second experiment, ovaries from euthyroid and hypothyroid rats treated with hCG were incubated in medium supplemented with 100 nM androstenedione and 0 or 100 ng FSH/ml. FSH failed to affect progesterone, testosterone, and estradiol secretions by ovaries from euthyroid, hCG-treated rats. In contrast, FSH significantly enhanced testosterone and estradiol secretion by ovaries from hypothyroid, hCG-treated rats. These results support the hypothesis that increased levels of testosterone and estradiol secretion have a central role in the induction of polycystic ovaries by hCG in the hypothyroid rat.

Responses to constant infusion of LH-RH in girls with primary hypogonadism.

PubMed

Reiter, E O; Duckett, G E; Root, A W

1980-09-01

To further assess quantitative pituitary gonadotropin release in patients with primary hypogonadism, a 3-hour constant infusion of the synthetic gonadotropin-releasing hormone, LH-RH, was administered to 12 functionally agonadal girls (11 with Turner syndrome and 1 who had been overiectomized), aged 9.5 to 19.42 years. Gonadotropin and sex steroid responses were determined before and during the infusion and contrasted to those in normal pubertal females. in girls with skeletal age under 11 years, mean control LH increased (P < .001) from 2.2 +/- 0.3 (mean +/- SEM) mIU/ml to 21.3 +/- 7.3 during LH-RH infusion, while luteinizing hormone (LH) rose (P < .001) from 89.2 +/- 24.6 to 276.5 +/- 42.6 girls with skeletal age over 11 years. This age-related augmentation is an exaggeration of data in normal girls and occcurs despite minimal gonadal secretion of sex steroids. A similar age-related discrepancy was not seen in follicle-stimulating hormone (FSH) secretion evoked by LH-RH; all girls had FSH increments into the castrate range with a rise from mean control levels of 78.6 +/- 6.7 to 133.9 +/- 8.3. These data demonstrate an age-related increase in LH-RH-evoked LH secretion, but not of FSH, in children and adolescents with primary hypogonadism.

Comparison of corifollitropin alfa and daily recombinant follicle-stimulating hormone in poor responder patients undergoing in vitro fertilization cycles.

PubMed

Akarsu, Süleyman; Demir, Sibel; Gode, Funda; Işık, Ahmet Zeki

2017-12-01

The aim of this study was to compare the effect of corifollitropin alfa (CFA) and recombinant follicle-stimulating hormone (rFSH) in poor-responder patients undergoing antagonist cycles. The study was a retrospective analysis of the treatment results of 214 poor responder patients who had been admitted to the In Vitro Fertilization Unit of İzmir Medical Park Hospital between November 2014 and November 2016. Intracytoplasmic sperm injections were performed in 38 patients (group 1) with CFA, and the remaining 176 (group 2) with rFSH for controlled ovarian hyperstimulation. The age, body mass index, anti-müllerian hormone level, duration of infertility, duration of induction and antral follicle number were similar in the two groups. There was no difference in the total aspirated oocyte counts, mature oocyte ratio, fertilization rate, implantation rate, and clinical pregnancy rates between the two groups. The implantation rate was 9/38 (23.6%) in group 1 and 42/176 (23.8%) in group 2, whereas the clinical pregnancy rates were 16.3% and 17.2%, respectively. No difference was found in terms of oocyte count, fertilization rate, implantation rate, and clinical pregnancy rates of CFA or rFSH use in the antagonist cycles in poor-responder patients.

Assisted Hatching and Intracytoplasmic Sperm Injection are not Associated with Improved Outcomes in ART Cycles for Diminished Ovarian Reserve: An Analysis of US Cycles from 2004–2011

PubMed Central

Butts, Samantha F.; Owen, Carter; Mainigi, Monica; Senapati, Suneeta; Seifer, David B.; Dokras, Anuja

2014-01-01

Objective To investigate the impact of intracytoplasmic sperm injection (ICSI) and assisted hatching (AH) on ART outcomes in cycles with diminished ovarian reserve (DOR) as the primary diagnosis. Design Retrospective cohort study of cycles from the SART-CORS database. Setting NA. Patient(s) A total of 422,949 fresh, non-donor, initial ART cycles of which 8,597 were diagnosed with only elevated FSH and 38,926 were diagnosed with only DOR according to the SART DOR categorization. Intervention(s) None. Main Outcome Measure(s) Live birth and clinical pregnancy rates. Result(s) ICSI and AH were associated with diminished odds of live birth in SART DOR only cycles (AOR, 95% CI 0.88, 0.81–0.96 for ICSI; AOR, 95% CI 0.77 0.71–0.84 for AH). No association between either ICSI or AH in Elevated FSH only cycles was observed. The combination of ICSI and AH resulted in significantly lower odds of live birth in SART DOR only cycles but not in Elevated FSH only cycles. Conclusion(s) In initial ART cycles for which the only indication relates to a diagnosis of diminished ovarian reserve, assisted hatching and ICSI are not associated with improved live birth rates. PMID:25086790

Development of rabbit embryos during a 96-h period of in vitro culture after superovulatory treatment under conditions of elevated ambient temperature.

PubMed

Cheng, H; Dooley, M P; Hopkins, S M; Anderson, L L; Yibchok-anun, S; Hsu, W H

1999-08-16

The effects of elevated ambient temperature on the response to exogenous gonadotropins were evaluated in female New Zealand White rabbits exposed to 33+/-1 degrees C (mean +/- SE) and 10-30% relative humidity (8 h/day) during a 5-day period. Does were treated with pFSH (0.3 mg/0.3 ml Standard Armour) twice daily during three consecutive days with a minimum interval of 8 h between injections. Six hours after the last FSH injection all does were removed from the experimental chamber, given hCG (25 IU/kg) and paired overnight. Nineteen hours after pairing, embryos were flushed from the reproductive tracts, evaluated, and subjected to in vitro culture during a 96-h period. The ovulatory responses to exogenous gonadotropins and fertilization rates did not differ significantly under conditions of elevated ambient temperature, whereas fewer blastocysts and increased number of degenerate embryos were observed after culture. We conclude that although hyperthermia was induced during exposure to elevated ambient temperature, it did not alter the ovulatory responses to gonadotropin treatment and plasma concentrations of FSH and LH compared with does in a thermoneutral environment. Exposure of donor rabbits to elevated ambient temperature before mating, however, increased embryonic degeneration.

Effects of Different Maturation Systems on Bovine Oocyte Quality, Plasma Membrane Phospholipid Composition and Resistance to Vitrification and Warming.

PubMed

Sprícigo, José F W; Diógenes, Mateus N; Leme, Ligiane O; Guimarães, Ana L; Muterlle, Carolle V; Silva, Bianca Damiani Marques; Solà-Oriol, David; Pivato, Ivo; Silva, Luciano Paulino; Dode, Margot A N

2015-01-01

The objective of this study was to evaluate the effects of different maturation systems on oocyte resistance after vitrification and on the phospholipid profile of the oocyte plasma membrane (PM). Four different maturation systems were tested: 1) in vitro maturation using immature oocytes aspirated from slaughterhouse ovaries (CONT; n = 136); 2) in vitro maturation using immature oocytes obtained by ovum pick-up (OPU) from unstimulated heifers (IMA; n = 433); 3) in vitro maturation using immature oocytes obtained by OPU from stimulated heifers (FSH; n = 444); and 4) in vivo maturation using oocytes obtained from heifers stimulated 24 hours prior by an injection of GnRH (MII; n = 658). A sample of matured oocytes from each fresh group was analyzed by matrix associated laser desorption-ionization (MALDI-TOF) to determine their PM composition. Then, half of the matured oocytes from each group were vitrified/warmed (CONT VIT, IMA VIT, FSH VIT and MII VIT), while the other half were used as fresh controls. Afterwards, the eight groups underwent IVF and IVC, and blastocyst development was assessed at D2, D7 and D8. A chi-square test was used to compare embryo development between the groups. Corresponding phospholipid ion intensity was expressed in arbitrary units, and following principal components analyses (PCA) the data were distributed on a 3D graph. Oocytes obtained from superstimulated animals showed a greater rate of developmental (P<0.05) at D7 (MII = 62.4±17.5% and FSH = 58.8±16.1%) compared to those obtained from unstimulated animals (CONT = 37.9±8.5% and IMA = 50.6±14.4%). However, the maturation system did not affect the resistance of oocytes to vitrification because the blastocyst rate at D7 was similar (P>0.05) for all groups (CONT VIT = 2.8±3.5%, IMA VIT = 2.9±4.0%, FSH VIT = 4.3±7.2% and MII VIT = 3.6±7.2%). MALDI-TOF revealed that oocytes from all maturation groups had similar phospholipid contents, except for 760.6 ([PC (34:1) + H]+), which was

Effects of Different Maturation Systems on Bovine Oocyte Quality, Plasma Membrane Phospholipid Composition and Resistance to Vitrification and Warming

PubMed Central

Sprícigo, José F. W.; Diógenes, Mateus N.; Leme, Ligiane O.; Guimarães, Ana L.; Muterlle, Carolle V.; Silva, Bianca Damiani Marques; Solà-Oriol, David; Pivato, Ivo; Silva, Luciano Paulino; Dode, Margot A. N.

2015-01-01

The objective of this study was to evaluate the effects of different maturation systems on oocyte resistance after vitrification and on the phospholipid profile of the oocyte plasma membrane (PM). Four different maturation systems were tested: 1) in vitro maturation using immature oocytes aspirated from slaughterhouse ovaries (CONT; n = 136); 2) in vitro maturation using immature oocytes obtained by ovum pick-up (OPU) from unstimulated heifers (IMA; n = 433); 3) in vitro maturation using immature oocytes obtained by OPU from stimulated heifers (FSH; n = 444); and 4) in vivo maturation using oocytes obtained from heifers stimulated 24 hours prior by an injection of GnRH (MII; n = 658). A sample of matured oocytes from each fresh group was analyzed by matrix associated laser desorption-ionization (MALDI-TOF) to determine their PM composition. Then, half of the matured oocytes from each group were vitrified/warmed (CONT VIT, IMA VIT, FSH VIT and MII VIT), while the other half were used as fresh controls. Afterwards, the eight groups underwent IVF and IVC, and blastocyst development was assessed at D2, D7 and D8. A chi-square test was used to compare embryo development between the groups. Corresponding phospholipid ion intensity was expressed in arbitrary units, and following principal components analyses (PCA) the data were distributed on a 3D graph. Oocytes obtained from superstimulated animals showed a greater rate of developmental (P<0.05) at D7 (MII = 62.4±17.5% and FSH = 58.8±16.1%) compared to those obtained from unstimulated animals (CONT = 37.9±8.5% and IMA = 50.6±14.4%). However, the maturation system did not affect the resistance of oocytes to vitrification because the blastocyst rate at D7 was similar (P>0.05) for all groups (CONT VIT = 2.8±3.5%, IMA VIT = 2.9±4.0%, FSH VIT = 4.3±7.2% and MII VIT = 3.6±7.2%). MALDI-TOF revealed that oocytes from all maturation groups had similar phospholipid contents, except for 760.6 ([PC (34:1) + H]+), which was

Inhibin binding protein in rats: alternative transcripts and regulation in the pituitary across the estrous cycle.

PubMed

Bernard, D J; Woodruff, T K

2001-04-01

Inhibin binding protein (InhBP) and the transforming growth factor-beta (TGF beta) type III receptor, beta glycan, have been identified as putative inhibin coreceptors. Here we cloned the InhBP cDNA in rats and predict that it encodes a large membrane-spanning protein that is part of the Ig superfamily, as has been described for humans. Two abundant InhBP transcripts (4.4 and 1.8 kb) were detected in the adult rat pituitary. The larger transcript encodes the full-length protein while the 1.8-kb transcript (InhBP-short or InhBP-S) corresponds to a splice variant of the receptor. This truncated isoform contains only the N-terminal signal peptide and first two (of 12) Ig-like domains observed in the full-length InhBP (InhBP-long or InhBP-L). InhBP-S does not contain a transmembrane domain and is predicted to be a soluble protein. Beta glycan was also detected in the pituitary; however, it was most abundant within the intermediate lobe. Although we also observed beta glycan immunopositive cells in the anterior pituitary, they rarely colocalized with FSH beta-producing cells. We next examined physiological regulation of the coreceptors across the rat estrous cycle. Like circulating inhibin A and inhibin B levels, pituitary InhBP-L and InhBP-S mRNA levels were dynamically regulated across the cycle and were negatively correlated with serum FSH levels. Expression of both forms of InhBP was also positively correlated with serum inhibin B, but not inhibin A, levels. These data are particularly interesting in light of our in vitro observations that InhBP may function as an inhibin B-specific coreceptor. Pituitary beta glycan mRNA levels did not fluctuate across the cycle nor did they correlate with serum FSH. These observations, coupled with its pattern of expression within the pituitary, indicate that beta glycan likely functions as more than merely an inhibin coreceptor within the pituitary. A direct role for InhBP or beta glycan in regulation of pituitary FSH by inhibin

Reproductive hormones of ICSI-conceived young adult men: the first results.

PubMed

Belva, Florence; Roelants, Mathieu; De Schepper, Jean; Van Steirteghem, André; Tournaye, Herman; Bonduelle, Maryse

2017-02-01

Are reproductive hormone levels (FSH, LH, inhibin B and testosterone) in male offspring conceived by ICSI because of male infertility comparable with those from peers born after spontaneous conception? In this cohort of 54 young men conceived by ICSI because of male-factor infertility, mean and median reproductive hormone levels were found to be comparable with results from spontaneously conceived peers, but ICSI-conceived men were more likely to have low inhibin B (<10th percentile) and high FSH (>90th percentile) levels. Since the worldwide oldest ICSI offspring have recently reached young adulthood, their reproductive health can now be investigated. This typically involves semen analysis and a hormonal profiling including the measurement of FSH, LH, inhibin B and testosterone. Circulating levels of FSH and inhibin B are generally known as markers of the exocrine function of the testis, i.e. spermatogenesis, while LH and testosterone reflect its endocrine function. We have previously observed a normal pubertal development and comparable levels of inhibin B and testosterone among pubertal ICSI boys when compared to spontaneously conceived peers. However, at present, information on the gonadal function of ICSI offspring in adulthood is still lacking. This study, conducted between March 2013 and April 2016 at the UZ Brussel, is part of a larger follow-up project focusing on reproductive and metabolic health of young adults between 18 and 22 years and conceived after ICSI because of male infertility. The ICSI men are part of a longitudinally followed cohort while the spontaneously conceived controls were recruited cross-sectionally. Results of a single fasting blood sample from 54 young adult ICSI men were compared to that of 57 spontaneously conceived peers. Reproductive hormone analysis involved FSH, LH, testosterone and inhibin B measurement. Furthermore, the association between their reproductive hormones and their sperm parameters was examined. Data were

Economic Evaluation of Three Frequently Used Gonadotrophins in Assisted Reproduction Techniques in the Management of Infertility in the Netherlands.

PubMed

Fragoulakis, Vassilis; Pescott, Chris P; Smeenk, Jesper M J; van Santbrink, Evert J P; Oosterhuis, G Jur E; Broekmans, Frank J M; Maniadakis, Nikos

2016-12-01

Subfertility represents a multidimensional problem associated with significant distress and impaired social well-being. In the Netherlands, an estimated 50,000 couples visit their general practitioner and 30,000 couples seek medical specialist care for subfertility. We conducted an economic evaluation comparing recombinant human follicle-stimulating hormone (follitropin alfa, r-hFSH, Gonal-F ® ) with two classes of urinary gonadotrophins-highly purified human menopausal gonadotrophin (hp-HMG, Menopur ® ) and urinary follicle-stimulating hormone (uFSH, Fostimon ® )-for ovarian stimulation in women undergoing in vitro fertilization (IVF) treatment in the Netherlands. A pharmacoeconomic model was developed, simulating each step in the IVF protocol from the start of therapy until either a live birth, a new IVF treatment cycle or cessation of IVF, following a long down-regulation protocol. A decision tree combined with a Markov model details progress through each health state, including ovum pickup, fresh embryo transfer, up to two subsequent cryo-preserved embryo transfers, and (ongoing) pregnancy or miscarriage. A health insurer perspective was chosen, and the time horizon was set at a maximum of three consecutive treatment cycles, in accordance with Dutch reimbursement policy. Transition probabilities and costing data were derived from a real-world observational outcomes database (from Germany) and official tariff lists (from the Netherlands). Adverse events were considered equal among the comparators and were therefore excluded from the economic analysis. A Monte Carlo simulation of 5000 iterations was undertaken for each strategy to explore uncertainty and to construct uncertainty intervals (UIs). All cost data were valued in 2013 Euros. The model's structure, parameters and assumptions were assessed and confirmed by an external clinician with experience in health economics modelling, to inform on the appropriateness of the outcomes and the applicability of the

[Effect of polycystic ovary syndrome treated with the periodic therapy of acupuncture].

PubMed

Yang, Danhong; Zhao, Mei; Tan, Jiahong

2017-08-12

To observe the effects differences for polycystic ovary syndrome (PCOS) between periodic therapy of acupuncture and diane-35 and to explore its mechanism. Sixty patients were randomly assigned into an acupuncture group and a western medication group, 30 cases in each one, 29 patients finally included with one case dropping out respectively. In the acupuncture group, periodic therapy was mainly used at bilateral Sanyinjiao (SP 6), Dahe (KI 12), Guilai (ST 29), Guanyuan (CV 4), Zhongji (CV 3), with different acupoints in the postmenstrual, intermenstrual, premenstrual periods, once every other day, 3 times a week. EA (2 Hz/100 Hz) was used at bilateral Dahe (KI 12) and Guilai (ST 29). If treatment, FSH increased and LH, LH/FSH, T decreased in the two groups (all P <0.05), but T level and the different value before and after treatment in the western medication group were better than those in the acupuncture group (both P <0.05). Periodic therapy of acupuncture is probably one of the effective methods for PCOS, which can improve patients' clinical symptoms, sex hormone level, and menstrual cycle. there was no discomfort during menstrual period, no treatment was given. In the western medication group, diane-35 was prescribed orally for 21 days as a course, with 7 days at interval, one tablet a day. All the treatment was started on the fifth day of the menstrual circle, for continuously 3 months. The indexes were observed before and after treatment, including the menstrual circle, acne score, body mass index (BMI), serum follicle stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH and testosterone (T). The effects of the two groups were compared. The total effective rate was 75.9% (22/29) in the acupuncture group, which was not significantly different from 79.3% (23/29) in the western medication group ( P >0.05). The menstrual cycles were shorter after treatment in the two groups (both P <0.05), with better effect and different value before and after treatment in

Anorchia

MedlinePlus

... stimulating hormone ( FSH ) and luteinizing hormone ( LH ) levels Surgery to look for male reproductive tissue Testosterone levels (low) Ultrasound or MRI to look for testes in the abdomen XY karyotype

[Genetic aspects of premature ovarian failure].

PubMed

Warenik-Szymankiewicz, Alina; Słopień, Radosław

2005-01-01

Among the causes of premature ovarian failure (POF) two groups of factors are reported: factors which lead to decrease of follicular number and factors which stimulate follicular atresia. In the first group genetic factors are the most important whereas in the second: enzymatic autoimmunological, iatrogenic, toxins and infections are reported. In 1986 familiar POF on the background of long arm of chromosome X deletion was reported. Other chromosomes which are important for normal ovarian function are: chromosome 21 (AIRE gene), chromosome 11 (gene of beta FSH, ATM gene), chromosome 3 (gene responsible for BEPS syndrome) and chromosome 2 (genes of FSH and LH receptors). In this review the role of these genes and results of several epidemiological studies are reported.

Evaluation of ovarian reserve tests in women with systemic lupus erythematosus.

PubMed

Ulug, Pasa; Oner, Gokalp; Kasap, Burcu; Akbas, Emin Murat; Ozcicek, Fatih

2014-07-01

Impact of systemic lupus erythematosus (SLE) on fertility may be negative, and ovarian function can be also reduced by autoimmune oophoritis. In this article, we evaluated the ovarian reserve of pre-menopausal women firstly diagnosed with systemic lupus erythematosus (SLE). This was a prospective controlled study which included twenty women with SLE and twenty healthy women as controls in the reproductive age. Basal levels of FSH, estradiol (E2), and LH on cycle day 3 were measured. All participants underwent transvaginal ultrasonographic examination on the third day of their menstrual periods for the determination of ovarian volume (OV) and total antral follicle count (AFC). A significant difference in FSH, LH, and E2 levels was observed between women with SLE and healthy controls. There was a statistically significant reduction in total AFC and OV in SLE group. Age was associated negatively with AFC, whereas positively with FSH and LH. Menstrual irregularity was significantly higher in SLE patients than control. AFC was the most reliable test to show the menstrual irregularity and negatively correlated each other in women with SLE. In this preliminary study, the first in SLE patients, we illustrated that women with SLE had lower ovarian reserves and higher menstrual irregularity compared with healthy controls according to hormonal and ultrasonographical evaluation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Active immunization with GnRH-tandem-dimer peptide in young male rats reduces serum reproductive hormone concentrations, testicular development and spermatogenesis.

PubMed

Han, Xing-Fa; Li, Jun-Li; Zhou, Yu-Qin; Ren, Xiao-Hua; Liu, Gong-Cheng; Cao, Xiao-Han; Du, Xiao-Gang; Zeng, Xian-Yin

2016-01-01

GnRH sterilization vaccines have been developed for various practical and clinical reasons. However, conjugation of GnRH peptide to carrier protein has many drawbacks, hampering the further commercialization of GnRH vaccines. In this study, a new nonconjugated GnRH vaccine, D-Lys6-GnRH-tandem-dimer peptide (TDK), emulsified in Specol adjuvant was investigated for its immunocastration efficacy in young male rats. Prepubertal male rats were randomly allocated into three groups (n = 12): control (no treatment), surgically castrated or immunized against 100 μg TDK in Specol adjuvant at 6 weeks of age (with a booster 8 weeks later). Blood samples (for antibody titers and hormone concentrations) were collected at 2-week intervals until rats were killed (18 weeks of age). Compared to intact controls, active immunization against TDK reduced (P < 0.05) serum concentrations of testosterone, inhibin B, LH and FSH, prevented the onset of spermatogenesis at puberty. Furthermore, mRNA expressions of GnRH receptor, LH-β and FSH-β in the pituitary, LH receptor, FSH receptor, inhibin α, βA and βB subunit in the testes were decreased in immunocastrated rats compared to intact controls (P < 0.05). These results demonstrate for the first time that GnRH-tandem-dimer peptide emulsified in Specol is a promising veterinary sterilization medicine.

Effects of Exercise Intervention on Preventing Letrozole-Exposed Rats From Polycystic Ovary Syndrome.

PubMed

Cao, Si-Fan; Hu, Wen-Long; Wu, Min-Min; Jiang, Li-Yan

2017-03-01

Polycystic ovary syndrome (PCOS) is a prevalent endocrinological disorder in reproductive-age women and is often associated with a metabolic syndrome. To investigate whether exercise intervention promotes PCOS prevention, a rat model was used. Polycystic ovary syndrome was induced by letrozole administration, and animals presented with obesity, sex hormone disorder, no ovulation, large cystic follicles, and increasing fasting insulin (FINS) and leptin levels. The intervention was set at 3 different intensities of swimming exercise: low (0.5 h/d), moderate (1 h/d), and high (2 h/d), and compared with a PCOS model group (letrozole administration without exercise intervention) and a control group. The exercise intervention in the low-intensity group did not produce changes in obesity, testosterone, progesterone (P), and follicle-stimulating hormone (FSH) levels. Moderate-intensity exercise reduced body weight, retained ovulation, and P levels were increased but remained lower than those in the control group. The FSH levels were significantly higher, and FINS and leptin levels were lower than in the model group ( P < 0.05) but not in the control group. The high-intensity group demonstrated the greatest effect of PCOS prevention. Testosterone, luteinizing hormone, FINS, and leptin levels were significantly lower in the high-intensity group, and FSH and P levels were higher compared with the model group. These results suggest that high-intensity exercise intervention can effectively prevent PCOS development.

Final height and gonad function after total body irradiation during childhood.

PubMed

Couto-Silva, A-C; Trivin, C; Esperou, H; Michon, J; Baruchel, A; Lemaire, P; Brauner, R

2006-09-01

Short stature and gonad failure can be a side effect of total body irradiation (TBI). The purpose of the study was to evaluate the factors influencing final height and gonad function after TBI. Fifty young adults given TBI during childhood were included. Twenty-seven had been treated with growth hormone (GH). Those given single 10 Grays (Gy) or fractionated 12 Gy TBI had similar characteristics, GH peaks, final heights and gonad function. After the end of GH treatment, 11/20 patients evaluated had GH peak >10 microg/l. Final height was <-2s.d. in 29 (58%). The height loss between TBI and final height (2.4+/-1.1 s.d.) was greater in those who were younger when irradiated (P<0.0001). When the GH-treated and -untreated patients were analyzed separately, this loss was correlated with the age at TBI at 4-8 years for the GH-treated and at 6-8 years for the untreated. Boys showed negative correlations between testicular volume and plasma follicle-stimulating hormone (FSH, P=0.0008) and between plasma FSH and inhibin B (P=0.005) concentrations. We concluded that the indications for GH treatment should be mainly based on the age at irradiation, taking into account the GH peak. The plasma FSH and inhibin B concentrations may predict sperm function. Published online 31 July 2006.

Postnatal Ovary Development in the Rat: Morphologic Study and Correlation of Morphology to Neuroendocrine Parameters

PubMed Central

Picut, Catherine A.; Dixon, Darlene; Simons, Michelle L.; Stump, Donald G.; Parker, George A.; Remick, Amera K.

2014-01-01

Histopathologic examination of the immature ovary is a required end point on juvenile toxicity studies and female pubertal and thyroid function assays. To aid in this evaluation and interpretation of the immature ovary, the characteristic histologic features of rat ovary through the developmental periods are described. These histologic features are correlated with published changes in neuroendocrine profiles as the hypothalamic–pituitary–gonadal axis matures. During the neonatal stage (postnatal day [PND] 0–7), ovarian follicle development is independent of pituitary gonadotropins (luteinizing hormone [LH] or follicle-stimulating hormone [FSH]), and follicles remain preantral. Antral development of “atypical” follicles occurs in the early infantile period (PND 8–14) when the ovary becomes responsive to pituitary gonadotropins. In the late infantile period (PND 15–20), the zona pellucida appears, the hilus forms, and antral follicles mature by losing their “atypical” appearance. The juvenile stage (PND 21–32) is the stage when atresia of medullary follicles occurs corresponding to a nadir in FSH levels. In the peripubertal period (PND 33–37), atresia subsides as FSH levels rebound, and LH begins its bimodal surge pattern leading to ovulation. This report will provide pathologists with baseline morphologic and endocrinologic information to aid in identification and interpretation of xenobiotic effects in the ovary of the prepubertal rat. PMID:25107574

Endocrine effects of adjuvant letrozole + triptorelin compared with tamoxifen + triptorelin in premenopausal patients with early breast cancer.

PubMed

Rossi, Emanuela; Morabito, Alessandro; De Maio, Ermelinda; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; Piccirillo, Maria Carmela; D'Aiuto, Giuseppe; D'Aiuto, Massimiliano; Rinaldo, Massimo; Botti, Gerardo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2008-01-10

To compare the endocrine effects of 6 months of adjuvant treatment with letrozole + triptorelin or tamoxifen + triptorelin in premenopausal patients with early breast cancer within an ongoing phase 3 trial (Hormonal Adjuvant Treatment Bone Effects study). Prospectively collected hormonal data were available for 81 premenopausal women, of whom 30 were assigned to receive tamoxifen + triptorelin and 51 were assigned letrozole + triptorelin +/- zoledronate. Serum 17-beta-estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), Delta4-androstenedione, testosterone, dehydroepiandrosterone-sulfate, progesterone, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline and after 6 months of treatment. For each hormone, 6-month values were compared between treatment groups by the Wilcoxon-Mann-Whitney exact test. Median age was 44 years for both groups of patients. Letrozole + triptorelin (+/- zoledronate) induced a stronger suppression of median E2 serum levels (P = .0008), LH levels (P = .0005), and cortisol serum levels (P < .0001) compared with tamoxifen + triptorelin. Median FSH serum levels were suppressed in both groups, but such suppression was lower among patients receiving letrozole, who showed significantly higher median FSH serum levels (P < .0001). No significant differences were observed for testosterone, progesterone, ACTH, androstenedione, and dehydroepiandrosterone between the two groups of patients. Letrozole in combination with triptorelin induces a more intense estrogen suppression than tamoxifen + triptorelin in premenopausal patients with early breast cancer.

Assessment of Estradiol Response after Depot Triptorelin Administration in Girls with Central Precocious Puberty.

PubMed

Freire, Analía Verónica; Gryngarten, Mirta Graciela; Ballerini, María Gabriela; Arcari, Andrea Josefina; Escobar, María Eugenia; Bergadá, Ignacio; Ropelato, María Gabriela

2016-01-01

Estradiol at baseline or after a classical gonadotropin-releasing hormone test did not reflect ovarian steroidogenesis in central precocious puberty (CPP) girls. To evaluate estradiol response to depot triptorelin, both at start and during therapy to determine how active ovarian steroidogenesis is at pubertal stage and under therapy. A prospective study was performed in 43 CPP girls. Serum luteinizing hormone and follicle-stimulating hormone at 3 h (LH-3h, FSH-3h) and estradiol at 24 h (E2-24h) after injection of depot triptorelin 3.75 mg were measured, at first dose and at 3, 6, 12, 18 and 24 months of treatment. E2-24h after depot triptorelin was >100 pg/ml after the first dose. Estradiol response (E2-24h) fell to levels <14 pg/ml in 78 out of 82 follow-up visits along 2 years of therapy. Concomitantly, LH-3h and FSH-3h were <4.0 and <6.3 IU/l, respectively. In 4 patients with inadequate treatment, E2-24h, LH-3h and FSH-3h rose to pubertal values similar to those observed at first dose. Estradiol (<14 pg/ml) assessment 24 h after depot triptorelin administration is a reliable and simple manner to confirm ovarian suppression in CPP girls during treatment. © 2015 S. Karger AG, Basel.

Bone health measured using quantitative ultrasonography in adult males with muscular dystrophy.

PubMed

Morse, C I; Smith, J; Denny, A; Tweedale, J; Searle, N D; Winwood, K; Onambele-Pearson, G L

2016-12-14

To compare muscle and bone health markers in adult males (aged 20-59 yrs) with and without muscular dystrophy (MD). Participants included 11 Fascioscapulohumeral (FSH), 11 Becker's (Be), 9 limb girdle (LG), 11 Duchenne (DMD), and 14 non-dystrophic controls (CTRL). Physical activity was assessed using Bone (BPAQ) and disability specific (PASIPD) questionnaires. Bone QUS provided T- and Z scores from the Distal Radius (DR) and Mid-shaft tibia (MST). Tibialis anterior cross sectional area (TA ACSA ) was measured using B-mode ultrasound. Grip strength was measured in all but DMD. Physical activity was lower in DMD, FSH and BeMD than CTRL (P<0.05), and lower in DMD than other MDs (P<0.01). T and Z scores were lower in DMD and Be than CTRL (DR, P<0.05); and lower in DMD than CTRL, LG, and FSH (MST, P<0.01). TA ACSA and grip strength was 35-59% and 50-58% smaller in MD than CTRL, respectively (P<0.01). Within MD, BPAQ correlated with bone QUS measures (r=0.42-0.38, P<0.01). PASIPD correlated with grip strength (r=0.65, P<0.01) and TA ACSA (r=0.46, P<0.01). Muscle size, strength, and bone health was lower in adult males with MD compared to adult males without MD, the extent of this is partially determined by physical activity.

Sertoli cell markers in the diagnosis of paediatric male hypogonadism.

PubMed

Grinspon, Romina P; Loreti, Nazareth; Braslavsky, Débora; Bedecarrás, Patricia; Ambao, Verónica; Gottlieb, Silvia; Bergadá, Ignacio; Campo, Stella M; Rey, Rodolfo A

2012-01-01

During childhood, the pituitary-testicular axis is partially dormant: testosterone secretion decreases following a drop in luteinising hormone levels; follicle-stimulating hormone (FSH) levels also go down. Conversely, Sertoli cells are most active, as revealed by the circulating levels of anti-Müllerian hormone (AMH) and inhibin B. Therefore, hypogonadism can best be evidenced, without stimulation tests, if Sertoli cell function is assessed. Serum AMH is high from fetal life until mid-puberty. Testicular AMH production increases in response to FSH and is potently inhibited by androgens. Inhibin B is high in the first years of life, then decreases partially while remaining clearly higher than in females, and increases again at puberty. Serum AMH and inhibin B are undetectable in anorchid patients. In primary or central hypogonadism affecting the whole gonad established in fetal life or childhood, all testicular markers are low. Conversely, when hypogonadism only affects Leydig cells, serum AMH and inhibin B are normal. In males of pubertal age with central hypogonadism, AMH and inhibin B are low. Treatment with FSH provokes an increase in serum levels of both Sertoli cell markers, whereas human chorionic gonadotrophin (hCG) administration increases testosterone levels. In conclusion, measurement of serum AMH and inhibin B is helpful in assessing testicular function, without need for stimulation tests, and orientates the aetiological diagnosis of paediatric male hypogonadism.

Masturbation Frequency and Sexual Function Domains Are Associated With Serum Reproductive Hormone Levels Across the Menopausal Transition

PubMed Central

Zheng, Huiyong; Avis, Nancy E.; Greendale, Gail A.; Harlow, Siobán D.

2015-01-01

Objective: To determine whether reproductive hormones are related to sexual function during the menopausal transition. Design: The Study of Women's Health Across the Nation (SWAN) is a multiethnic cohort study of the menopausal transition located at seven US sites. At baseline, the 3302 community-based participants, aged 42–52, had an intact uterus and at least one ovary and were not using exogenous hormones. Participants self-identified as White, Black, Hispanic, Chinese, or Japanese. At baseline and at each of the 10 follow-up visits, sexual function was assessed by self-administered questionnaires, and blood was drawn to assay serum levels of T, estradiol, FSH, SHBG, and dehydroepiandrosterone sulfate. Main Outcome Measures: Self-reported frequency of masturbation, sexual desire, sexual arousal, orgasm, and pain during intercourse. Results: Masturbation, sexual desire, and arousal were positively associated with T. Masturbation, arousal, and orgasm were negatively associated with FSH. Associations were modest. Estradiol was not related to any measured sexual function domain. Pain with intercourse was not associated with any hormone. Conclusions: Reproductive hormones were associated with sexual function in midlife women. T was positively associated, supporting the role of androgens in female sexual function. FSH was negatively associated, supporting the role of menopausal status in female sexual function. The modest associations in this large study suggest that the relationships are subtle and may be of limited clinical significance. PMID:25412335

Subtotal obstruction of the male reproductive tract.

PubMed

Dohle, G R; van Roijen, J H; Pierik, F H; Vreeburg, J T M; Weber, R F A

2003-03-01

Bilateral obstruction of the male reproductive tract is suspected in men with azoospermia, normal testicular volume and normal FSH. A testicular biopsy is required to differentiate between an obstruction and a testicular insufficiency. Unilateral or subtotal bilateral obstructions and epididymal dysfunction may cause severe oligozoospermia in men with a normal spermatogenesis. However, information on spermatogenesis in oligozoospermic men is lacking, since testicular biopsy is not routinely performed. Men with a sperm concentration of <1 x 10(6) spermatozoa/ml were investigated for possible partial obstruction by performing a testicular biopsy under local anaesthesia. Spermatogenesis was determined by the Johnsen scoring method. A testicular biopsy was performed in 78 men with severe oligozoospermia. The medical history showed male accessory gland infection in 12.8%, previous hernia repair in 14.1% and a history of cryptorchidism in 12.8%. A normal or slightly disturbed spermatogenesis (Johnsen score >8) was present in 39/78 (50%) of the men. Hernia repair occurred more often in men with normal spermatogenesis. A varicocele was predominantly seen in men with a disturbed spermatogenesis. FSH was significantly lower ( P<0.0001) in men with normal spermatogenesis. Subtotal obstruction of the male reproductive tract is a frequent cause of severe oligozoospermia in men with a normal testicular volume and a normal FSH. In other cases, an epididymal dysfunction might explain the oligozoospermia in men with a normal testicular biopsy score.

Masturbation frequency and sexual function domains are associated with serum reproductive hormone levels across the menopausal transition.

PubMed

Randolph, John F; Zheng, Huiyong; Avis, Nancy E; Greendale, Gail A; Harlow, Siobán D

2015-01-01

To determine whether reproductive hormones are related to sexual function during the menopausal transition. The Study of Women's Health Across the Nation (SWAN) is a multiethnic cohort study of the menopausal transition located at seven US sites. At baseline, the 3302 community-based participants, aged 42-52, had an intact uterus and at least one ovary and were not using exogenous hormones. Participants self-identified as White, Black, Hispanic, Chinese, or Japanese. At baseline and at each of the 10 follow-up visits, sexual function was assessed by self-administered questionnaires, and blood was drawn to assay serum levels of T, estradiol, FSH, SHBG, and dehydroepiandrosterone sulfate. Self-reported frequency of masturbation, sexual desire, sexual arousal, orgasm, and pain during intercourse. Masturbation, sexual desire, and arousal were positively associated with T. Masturbation, arousal, and orgasm were negatively associated with FSH. Associations were modest. Estradiol was not related to any measured sexual function domain. Pain with intercourse was not associated with any hormone. Reproductive hormones were associated with sexual function in midlife women. T was positively associated, supporting the role of androgens in female sexual function. FSH was negatively associated, supporting the role of menopausal status in female sexual function. The modest associations in this large study suggest that the relationships are subtle and may be of limited clinical significance.

Observations on the use of purified follicle-stimulating hormone in the treatment of luteal phase defects.

PubMed

Di Carlo, C; Affinito, P; Farace, M J; Gargiulo, A R; Zullo, F; Nappi, C

1995-06-01

We treated 18 infertile patients affected by histologically confirmed luteal phase deficiency with 75 IU of purified follicle-stimulating hormone (FSH) daily during the first 5 days of the cycle. Patients who were not pregnant after the first cycle of treatment underwent a second cycle. In the second cycle the daily doses of purified FSH were doubled if luteal phase deficiency had persisted during the first cycle. During the two cycles before treatment and during treatment, patients underwent an endometrial biopsy 1-3 days before the expected onset of menses. An assessment of progesterone serum concentrations was also performed on days 8, 6 and 4 before the expected onset of menses. Treatment was administered in a total of 33 cycles resulting in 30 ovulatory cycles. Six pregnancies were achieved. Among non-conception ovulatory cycles, 13 presented delayed endometrial dating and 11 normal endometrium. The mean +/- SD of the sum of the three progesterone determinations was 14.7 +/- 1.4 ng/ml in pretreatment cycles, 14.6 +/- 1.6 ng/ml in cycles with normalization of endometrial dating, 14.8 +/- 1.7 ng/ml in cycles with persistence of luteal phase deficiency and 30.4 +/- 3.0 ng/ml in conception cycles (P < 0.05 versus other groups). We conclude that purified FSH, if effective in the treatment of luteal phase deficiency, does not act through an increase in progesterone concentrations.

The use of Data Mining in the categorization of patients with Azoospermia.

PubMed

Mikos, Themistoklis; Maglaveras, Nikolaos; Pantazis, Konstantinos; Goulis, Dimitrios G; Bontis, John N; Papadimas, John

2005-01-01

Data Mining is a relatively new field of Medical Informatics. The aim of this study was to compare Data Mining diagnosis with clinical diagnosis by applying a Data Miner (DM) to a clinical dataset of infertile men with azoospermia. One hundred and forty-seven azoospermic men were clinically classified into four groups: a) obstructive azoospermia (n=63), b) non-obstructive azoospermia (n=71), c) hypergonadotropic hypogonadism (n=2), and d) hypogonadotropic hypogonadism (n=11). The DM (IBM's DB2/Intelligent Miner for Data 6.1) was asked to reproduce a four-cluster model. DM formed four groups of patients: a) eugonadal men with normal testicular volume and normal FSH levels (n=86), b) eugonadal men with significantly reduced testicular volume (median 6.5 cm3) and very high FSH levels (n=29), c) eugonadal men with moderately reduced testicular volume (median 14.5 cm3) and raised FSH levels (n=20), and d) hypogonadal men (n=12). Overall DM concordance rate in hypogonadal men was 92%, in obstructive azoospermia 73%, and in non-obstructive azoospermia 69%. Data Mining produces clinically meaningful results but different from those of the clinical diagnosis. It is possible that the use of large sets of structured and formalised data and continuous evaluation of DM results will generate a useful methodology for the Clinician.

Letrozole, an aromatase inhibitor, reduces post-peak age-related regression of rooster reproductive performance.

PubMed

Ali, Emad Abdulgabbar; Zhandi, Mahdi; Towhidi, Armin; Zaghari, Mojtaba; Ansari, Mahdi; Najafi, Mojtaba; Deldar, Hamid

2017-08-01

This study was designed to evaluate orally administrated Letrozole (Lz) on reproductive performance, plasma testosterone and estradiol concentrations and relative abundance of mRNA of GnRH, FSH and LH in roosters. Ross 308 roosters (n=32) that were 40-weeks of age were individually housed and received a basal standard diet supplemented different amounts of capsulated Lz [0 (Lz-0), 0.5 (Lz-0.5), 1 (Lz-1) or 1.5 (Lz-1.5), mg Lz/bird/day] for 12 weeks. Sperm quality variables and plasma testosterone and estradiol concentrations were assessed from the first to the tenth week of the treatment period. Semen samples from the 11th to 12th week were used for artificial insemination and eggs were collected and allotted to assess fertility and hatchability rates. Relative abundance of hypothalamic and pituitary GnRH, LH and FSH mRNA was evaluated at the end of 12th week. The results indicated that total and forward sperm motility as well as egg hatchability rate were greater in the Lz-0.5 group. Greater sperm concentrations, ejaculate volume, sperm plasma membrane integrity, testis index and fertility rates were recorded for both Lz-0.5 and Lz-1 groups compared with the Lz-0 group (P<0.05). Body weight, percentage of sperm abnormalities, and sperm plasma membrane functionality were not affected by treatment. Testosterone and estradiol concentrations were negatively related with greater testosterone concentrations in the Lz-1.5 group which had lesser estradiol concentrations. Relative mRNA transcript abundance for GnRH, LH and FSH was Lz dose responsive being greater in the treated groups; however, this trend plateaued for GnRH and for the relative abundance of both LH and FSH mRNA was less in the Lz-1.5 group than the other treatment groups. It is concluded that Lz may be an effective treatment to improve age related post-peak reproductive performance of roosters. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of exogenous hormones on spermatogenesis in the male prairie dog (Cynomys ludovicianus).

PubMed

Foreman, D

1998-01-01

Male prairie dogs (Cynomys ludovicianus) breed anually and have complete testicular regression. Changes in the seminiferous tubules during the annual cycle have been described recently (Foreman, 1997). This is the first description of spermatogenesis in such a species. The definition of tubular stages during the cycle allows for evaluation of the effects of exogenous hormones, hemicastration, and hemicryptorchidism on spermatogenesis during the annual cycle. Hemicastration was performed during stages of the annual cycle to determine effects of exogenous hormones on remaining testes. Hemicryptorchidism was also done during stages of the annual cycle. FSH, LH, and testosterone were given in high and low doses for short- or long-term treatment periods during stages of the annual cycle. Testicular weights and counts of cell types in tubules of control and treated testes were made on testis tissues. Hemicastration during the out-of-season period does not cause compensatory hypertrophy of the remaining testis, but during recrudescence, hypertrophy of the remaining testis occurs. Hemicastration does not prevent loss of weight by the remaining testis during regression. The seminiferous epithelium of hemicryptorchid prairie dog testes shows damage during spermatogenic activity but not during testicular inactivity. Similarly, hemicryptorchid 15-day-old rat testes do not show damage from hemicryptorchidism. Long-term treatment with FSH preparations during testicular inactivity increased testis weights, spermatogonial proliferation, and spermatocyte differentiation in conjunction with Sertoli cell differentiation. Short-term treatments with low doses increased spermatogonial proliferation and abnormal meiotic activity. Both long- and short-term treatments with LH caused increased sloughing of germ cells and stimulated Leydig and Sertoli cells. Testosterone propionate injections stimulated Sertoli secretions but not Leydig cell activity. Hemicastration during inactivity does

Exercise-induced stress responses of amenorrheic and eumenorrheic runners.

PubMed

Loucks, A B; Horvath, S M

1984-12-01

The role of stress in exercise-associated amenorrhea was investigated. Sex hormones [FSH, LH, androstenedione (A), testosterone, estrone, and 17 beta-estradiol (E2)], stress hormones [dehydroepiandrosterone, cortisol (F), PRL, norepinephrine, and epinephrine] and psychological status (Profile of Mood States and State-Trait Anxiety Inventory) were measured at rest and in response to a 40-min 80% of maximal aerobic power (VO2max) run in highly trained eumenorrheic (n = 8) and amenorrheic (n = 7) women runners matched for fatness [eumenorrheic, 16.5 +/- 2.3% (+/- SD); amenorrheic, 14.9 +/- 4.8] and maximal aerobic power (eumenorrheic, 58.9 +/- 5.7 ml/kg X min; amenorrheic, 59.8 +/- 4.6). Eumenorrheic runners were tested between days 3 and 8 of the follicular phase. At rest, decreased plasma FSH, LH, and E2 concentrations were found in amenorrheic women [eumenorrheic FSH, 10.5 +/- 4.1 mIU/ml; amenorrheic FSH, 4.9 +/- 1.6 (P less than 0.01); eumenorrheic LH, 14.1 +/- 6.1 mIU/ml; amenorrheic LH, 5.1 +/- 1.7 (P less than 0.01); eumenorrheic E2, 20 +/- 9 pg/ml; amenorrheic E2, 7 +/- 6 (P less than 0.05)]. Other sex and stress hormones and psychological measurements were similar in the two groups and were within the normal range. Ventilatory, cardiovascular, thermoregulatory, and psychological responses to the submaximal run were identical. Among eumenorrheic women, all stress hormones and A increased after exercise, but PRL, F, and A were unchanged among amenorrheic women. Estrone, E2, and testosterone did not change in either group. These observations are inconsistent with a general stress hypothesis of exercise-associated amenorrhea as well as with more specific hyperprolactinemic and hyperandrogenic hypotheses. In amenorrheic women, failure of PRL to increase in response to exercise may be due to their lack of E2, while failure of F and A to increase may indicate reduced adrenal 3 beta-hydroxysteroid dehydrogenase/isomerase activity.

Effect of early thermal experience on pituitary-gonadal axis in female rats.

PubMed

Kurowicka, Beata; Gajewska, Alina; Franczak, Anita

2006-03-01

The reproductive system fully develops during postnatal stages of life, and as such it may be susceptible to environmental cues such as high temperature. Thus, the purpose of the study was to compare how exposure to 34 degrees Celsius ambient temperature affects pituitary-gonadal axis of immature and adult female rats. Three groups of females at proestrous or metaestrous (n=38) were used in the study. The females were housed in ambient temperature of 34 degrees Celsius (WR group, n=10) or room temperature (CR group, n=16) from birth to adulthood. The females from the third group were acclimated to 34 degrees Celsius as adults (WA group, n=12). In the WR group the onset of puberty was delayed in comparison to the CR group. The plasma PRL level was lower during proestrous and higher during metaestrous in the WR group compared to the CR group. During metaestrous, lower FSH and higher progesterone (P(4)) plasma concentrations were found in the WR females. No changes in LH and oestradiol (E(2)) plasma concentrations were demonstrated. Higher in vitro E(2) and lower P(4) secretions under FSH stimulation were observed in the WR follicles compared to those of the CR group. The WR group also demonstrated higher basal and LH-stimulated luteal in vitro secretion of P(4) than controls. Plasma LH and FSH concentrations during metaestrous were higher in WA females than in the WR group, but PRL level was lower. Follicles of the WA group were unresponsive to FSH with respect to steroid secretion. In addition, LH stimulated luteal E(2) secretion in this group. P(4) release by luteal cells was lower in the WA than in the WR group. We concluded that WR females differ from WA in reproductive system adjustments to rearing temperature and that early thermal experience is more effective in antagonizing the effect of high temperature than acclimation of adult females.

Hypothalamic expression of KiSS-1 system and gonadotropin-releasing effects of kisspeptin in different reproductive states of the female Rat.

PubMed

Roa, J; Vigo, E; Castellano, J M; Navarro, V M; Fernández-Fernández, R; Casanueva, F F; Dieguez, C; Aguilar, E; Pinilla, L; Tena-Sempere, M

2006-06-01

Kisspeptins, products of the KiSS-1 gene with ability to bind G protein-coupled receptor 54 (GPR54), have been recently identified as major gatekeepers of reproductive function with ability to potently activate the GnRH/LH axis. Yet, despite the diversity of functional states of the female gonadotropic axis, pharmacological characterization of this effect has been mostly conducted in pubertal animals or adult male rodents, whereas similar studies have not been thoroughly conducted in the adult female. In this work, we evaluated maximal LH and FSH secretory responses to kisspeptin-10, as well as changes in sensitivity and hypothalamic expression of KiSS-1 and GPR54 genes, in different physiological and experimental models in the adult female rat. Kisspeptin-10 (1 nmol, intracerebroventricular) was able to elicit robust LH bursts at all phases of the estrous cycle, with maximal responses at estrus; yet, in diestrus LH, responses to kisspeptin were detected at doses as low as 0.1 pmol. In contrast, high doses of kisspeptin only stimulated FSH secretion at diestrus. Removal of ovarian sex steroids did not blunt the ability of kisspeptin to further elicit stimulated LH and FSH secretion, but restoration of maximal responses required replacement with estradiol and progesterone. Finally, despite suppressed basal levels, LH and FSH secretory responses to kisspeptin were preserved in pregnant and lactating females, although the magnitude of LH bursts and the sensitivity to kisspeptin were much higher in pregnant dams. Interestingly, hypothalamic KiSS-1 gene expression significantly increased during pregnancy, whereas GPR54 mRNA levels remained unaltered. In summary, our current data document for the first time the changes in hypothalamic expression of KiSS-1 system and the gonadotropic effects (maximal responses and sensitivity) of kisspeptin in different functional states of the female reproductive axis. The present data may pose interesting implications in light of the

Reproductive hormones in menstrual blood.

PubMed

Zhou, J P; Fraser, I S; Caterson, I; Grivas, A; McCarron, G; Norman, T; Tan, K

1989-08-01

Menstrual and peripheral blood samples were collected from 19 regularly cycling women on days 1-3 of the menstrual cycle. Menstrual samples were collected with a soft silicone rubber menstrual cup. Hematocrit, PRL, LH, FSH, estradiol (E2), and progesterone (P4) were measured in all samples. Validation studies were carried out for RIAs of PRL, LH, and FSH in menstrual plasma. The menstrual plasma PRL level was significantly higher than its peripheral blood level on day 1 (63.3 +/- 14.7 and 12.1 +/- 2.9 micrograms/L, respectively; t = 3.331; P less than 0.01), and menstrual PRL was significantly higher on day 1 than on day 2 (t = 3.340; P less than 0.01). There was a strong negative correlation between log menstrual PRL concentration and time of onset of menstruation (r = -0.596; P less than 0.01). Menstrual plasma FSH levels were significantly lower than peripheral levels on each of days 1-3 (day 1:t = 4.787; P less than 0.001), and there was a significant positive correlation between menstrual and peripheral levels (r = 0.607; P less than 0.01). By contrast, menstrual plasma LH was significantly higher than the peripheral level on days 1 and 2 (day 1:t = 3.105; day 2:t = 3.180; P less than 0.01), with no correlation between menstrual and peripheral levels. Menstrual E2 was slightly lower than and significantly positively correlated with peripheral E2 (r = 0.646; P less than 0.01). Menstrual P4 was lower than but showed no correlation with peripheral levels. As expected, the menstrual blood hematocrit was less than 0.20 and highly significantly lower than that of peripheral venous blood. These results suggest that PRL is released in substantial amounts from secretory endometrium into the menstrual flow during the first day of menstrual breakdown. LH may also be released in small amounts from menstrual endometrium, while menstrual FSH, E2, and P4 probably arise entirely from the peripheral circulation.

Does the degree of endocrine dyscrasia post-reproduction dictate post-reproductive lifespan? Lessons from semelparous and iteroparous species.

PubMed

Atwood, Craig S; Hayashi, Kentaro; Meethal, Sivan Vadakkadath; Gonzales, Tina; Bowen, Richard L

2017-02-01

Post-reproductive lifespan varies greatly among species; human post-reproductive lifespan comprises ~30-50% of their total longevity, while semelparous salmon and dasyurid marsupials post-reproductive lifespan comprises <4% of their total longevity. To examine if the magnitude of hypothalamic-pituitary-gonadal (HPG) axis dyscrasia at the time of reproductive senescence determines post-reproductive lifespan, we examined the difference between pre- and post-reproductive (1) circulating sex hormones and (2) the ratio of sex steroids to gonadotropins (e.g., 17β-estradiol/follicle-stimulating hormone (FSH)), an index of the dysregulation of the HPG axis and the level of dyotic (death) signaling post-reproduction. Animals with a shorter post-reproductive lifespan (<4% total longevity) had a more marked decline in circulating sex steroids and corresponding elevation in gonadotropins compared to animals with a longer post-reproductive lifespan (30-60% total longevity). In semelparous female salmon of short post-reproductive lifespan (1%), these divergent changes in circulating hormone concentration post-reproduction equated to a 711-fold decrease in the ratio of 17β-estradiol/FSH between the reproductive and post-reproductive periods. In contrast, the decrease in the ratio of 17β-estradiol/FSH in iteroparous female mammals with long post-reproductive lifespan was significantly less (1.7-34-fold) post-reproduction. Likewise, in male semelparous salmon, the decrease in the ratio of testosterone/FSH (82-fold) was considerably larger than for iteroparous species (1.3-11-fold). These results suggest that (1) organisms with greater reproductive endocrine dyscrasia more rapidly undergo senescence and die, and (2) the contribution post-reproduction by non-gonadal (and perhaps gonadal) tissues to circulating sex hormones dictates post-reproductive tissue health and longevity. In this way, reproduction and longevity are coupled, with the degree of non-gonadal tissue hormone

Sleep Symptoms During the Menopausal Transition and Early Postmenopause: Observations from the Seattle Midlife Women's Health Study

PubMed Central

Woods, Nancy Fugate; Mitchell, Ellen Sullivan

2010-01-01

Study Objectives: Describe the severity of getting to sleep, nighttime awakening, and early morning awakening across the menopausal transition (MT) and early postmenopause (PM) and their relationship to age, menopausal transition factors, symptoms, stress-related factors, and health related factors. Design: Cohort Setting: community Participants: 286 women from the Seattle Midlife Women's Health Study cohort Measurements: Participants completed annual menstrual calendars for MT staging, diaries in which they rated their symptoms, stress levels, and perceived health multiple times per year from 1990-2007 and provided first morning urine samples assayed for E1G, FSH, cortisol, and catecholamines. Multilevel modeling (R program) was used for data analysis. Results: Severity of self-reported problems going to sleep was associated with all symptoms, perceived stress, history of sexual abuse, perceived health (-), alcohol use (-) (all P < 0.001), and lower cortisol (P = 0.009), but not E1G or FSH. Severity of nighttime awakening was significantly associated with age, late MT stage. and early PM, FSH, E1G (-), hot flashes, depressed mood, anxiety, joint pain, backache, perceived stress, history of sexual abuse, perceived health (-), and alcohol use (-) (all P < 0.001, except E1G for which P = 0.030). Severity of early morning awakening was significantly associated with age, hot flashes, depressed mood anxiety, joint pain, backache, perceived stress, history of sexual abuse, perceived health (-) (all P ≤ 0.001, except E1G for which P = 0.02 and epinephrine (P = 0.038), but not MT stages or FSH. Multivariate models for each symptom included hot flashes, depressed mood, and perceived health. Conclusion: Sleep symptoms during the MT may be amenable to symptom management strategies that take into account the symptom clusters and promote women's general health rather than focusing only on the MT. Citation: Woods NF; Mitchell ES. Sleep symptoms during the menopausal transition

The association of endogenous hormone concentrations and bone mineral density measures in pre- and perimenopausal women of four ethnic groups: SWAN.

PubMed

Sowers, M R; Finkelstein, J S; Ettinger, B; Bondarenko, I; Neer, R M; Cauley, J A; Sherman, S; Greendale, G A

2003-01-01

We evaluated bone mineral density (BMD), hormone concentrations and menstrual cycle status to test the hypothesis that greater variations in reproductive hormones and menstrual bleeding patterns in mid-aged women might engender an environment permissive for less bone. We studied 2336 women, aged 42-52 years, from the Study of Women's Health Across the Nation (SWAN) who self-identified as African-American (28.2%), Caucasian (49.9%), Japanese (10.5%) or Chinese (11.4%). Outcome measures were lumbar spine, femoral neck and total hip BMD by dual-energy X-ray densitometry (DXA). Explanatory variables were estradiol, testosterone, sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) from serum collected in the early follicular phase of the menstrual cycle or menstrual status [premenopausal (menses in the 3 months prior to study entry without change in regularity) or early perimenopause (menstrual bleeding in the 3 months prior to study entry but some change in the regularity of cycles)]. Total testosterone and estradiol concentrations were indexed to SHBG for the Free Androgen Index (FAI) and the Free Estradiol Index (FEI). Serum logFSH concentrations were inversely correlated with BMD (r = -10 for lumbar spine [95% confidence interval (CI): -0.13, -0.06] and r = -0.08 for femoral neck (95% CI: -0.11, -0.05). Lumbar spine BMD values were approximately 0.5% lower for each successive FSH quartile. There were no significant associations of BMD with serum estradiol, total testosterone, FEI or FAI, respectively, after adjusting for covariates. BMD tended to be lower (p values = 0.009 to 0.06, depending upon the skeletal site) in women classified as perimenopausal versus premenopausal, after adjusting for covariates. Serum FSH but not serum estradiol, testosterone or SHBG were significantly associated with BMD in a multiethnic population of women classified as pre- versus perimenopausal, supporting the hypothesis that alterations in hormone environment

Hirsutism, virilism, polycystic ovarian disease, and the steroid-gonadotropin-feedback system: a career retrospective.

PubMed

Mahesh, Virendra B

2012-01-01

This career retrospective describes how the initial work on the mechanism of hormone action provided the tools for the study of hirsutism, virilism, and polycystic ovarian disease. After excessive ovarian and or adrenal androgen secretion in polycystic ovarian disease had been established, the question whether the disease was genetic or acquired, methods to manage hirsutism and methods for the induction of ovulation were addressed. Recognizing that steroid gonadotropin feedback was an important regulatory factor, initial studies were done on the secretion of LH and FSH in the ovulatory cycle. This was followed by the study of basic mechanisms of steroid-gonadotropin feedback system, using castration and steroid replacement and the events surrounding the natural onset of puberty. Studies in ovariectomized rats showed that progesterone was a pivotal enhancer of estrogen-induced gonadotropin release, thus accounting for the preovulatory gonadotropin surge. The effects of progesterone were manifested by depletion of the occupied estrogen receptors of the anterior pituitary, release of hypothalamic LHRH, and inhibition of enzymes that degrade LHRH. Progesterone also promoted the synthesis of FSH in the pituitary. The 3α,5α-reduced metabolite of progesterone brought about selective LH release and acted using the GABA(A) receptor system. The 5α-reduced metabolite of progesterone brought about selective FSH release; the ability of progesterone to bring about FSH release was dependent on its 5α-reduction. The GnRH neuron does not have steroid receptors; the steroid effect was shown to be mediated through the excitatory amino acid glutamate, which in turn stimulated nitric oxide. These observations led to the replacement of the long-accepted belief that ovarian steroids acted directly on the GnRH neuron by the novel concept that the steroid feedback effect was exerted at the glutamatergic neuron, which in turn regulated the GnRH neuron. The neuroprotective effects of

Comparing the Effects of Combined Oral Contraceptives Containing Progestins With Low Androgenic and Antiandrogenic Activities on the Hypothalamic-Pituitary-Gonadal Axis in Patients With Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis.

PubMed

Amiri, Mina; Ramezani Tehrani, Fahimeh; Nahidi, Fatemeh; Kabir, Ali; Azizi, Fereidoun

2018-04-25

Different products of combined oral contraceptives (COCs) can improve clinical and biochemical findings in patients with polycystic ovary syndrome (PCOS) through suppression of the hypothalamic-pituitary-gonadal (HPG) axis. This systematic review and meta-analysis aimed to compare the effects of COCs containing progestins with low androgenic and antiandrogenic activities on the HPG axis in patients with PCOS. We searched PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science databases (1980-2017) to identify randomized controlled trials or nonrandomized studies investigating the effect of COCs containing progestins with low androgenic and antiandrogenic activities, including the products containing desogestrel, cyproterone acetate, and drospirenone, on the HPG axis in patients with PCOS. In this meta-analysis, fixed and random effect models were used. Outcomes of interest were weighted mean differences (WMD) of hormonal parameters, including the follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH-to-FSH ratio, estradiol, total testosterone, and sex hormone-binding globulin. Potential sources of heterogeneity were investigated using meta-regression and subgroup analyses. Subgroup analyses were performed based on the used progestin compound and treatment duration. We assessed quality of included studies and their risk of bias using Cochrane guidelines. Publication bias was assessed using Egger test and funnel plot. COC use was significantly associated with a decrease in gonadotropin levels, including FSH and LH. Use of products containing cyproterone acetate was associated with a decrease in FSH levels after 3 months (WMD=-0.48; 95% CI -0.81 to -0.15), 6 months (WMD=-2.33; 95% CI -3.48 to -1.18), and 12 months (WMD=-4.70; 95% CI -4.98 to -4.42) and a decrease in LH levels after 3 months (WMD=-3.57; 95% CI -5.14 to -1.99), 6 months (WMD=-5.68; 95% CI -9.57 to -1.80), and 12 months (WMD=-11.60; 95% CI -17.60 to -5.60). Use of COCs containing

Hypopituitarism

MedlinePlus

... hormone (ACTH) -- stimulates the adrenal gland to release cortisol; cortisol helps to maintain blood pressure and blood sugar ... may include: Brain CT scan Pituitary MRI ACTH Cortisol Estradiol (estrogen) Follicle-stimulating hormone (FSH) Insulin-like ...

Ovarian and uterine alterations following forced swimming: An immunohistochemical study.

PubMed

Seyed Saadat, Seyedeh Nazanin; Mohammadghasemi, Fahimeh; Ebrahimi, Hannan; Rafati Sajedi, Hanieh; Chatrnour, Gelayol

2016-10-01

Physical exercise is known to be a stressor stimulus that leads to reproductive disruption. The aim of this study was to evaluate the effect of forced swimming on the uterus and ovaries in mice. Adult mice (N=24) were divided into the following three groups: A, control; B, swimming in water (10 o C); and C, swimming in water (23 o C). Swimmers swam for 5 min daily for 5 consecutive days/ wk during 2 wks. An enzyme linked immunosorbent assay was used to determine serum estradiol, follicle stimulating hormone (FSH) and testosterone levels. Immunohistochemistry was performed to study apoptotic cells or estrogen receptor (ER) expression in uterine epithelial cells and ovaries. ANOVA was used for statistical analysis. Swimming in both groups reduced the serum FSH and estradiol levels (p<0.01) without having a significant effect on the serum testosterone level or percentage of apoptosis in ovarian and uterine tissues (p<0.01) compared with controls. A significant reduction in the number of ERs in the uterus and ovaries, and secondary and graafian follicles were observed in groups B and C compared with controls (p<0.01); however the number of primordial and primary follicles were not significantly changed in the ovaries. Forced swimming of 2 wks duration reduces the serum levels of FSH and estradiol without having effects on apoptosis in the ovaries or uteri of mice. Over a long period of time, forced swimming may have an adverse effect on fertility.

Circadian Clock genes Per2 and clock regulate steroid production, cell proliferation, and luteinizing hormone receptor transcription in ovarian granulosa cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shimizu, Takashi, E-mail: shimizut@obihiro.ac.jp; Hirai, Yuko; Murayama, Chiaki

2011-08-19

Highlights: {yields} Treatment with Per2 and Clock siRNAs decreased the number of granulosa cells and LHr expression. {yields}Per2 siRNA treatment did not stimulate the production of estradiol and expression of P450arom. {yields} Clock siRNA treatment inhibited the production of estradiol and expression of P450arom mRNA. {yields}Per2 and Clock siRNA treatment increased and unchanged, respectively, progesterone production in FSH-treated granulosa cells. {yields} The expression of StAR mRNA was increased by Per2 siRNA and unchanged by Clock siRNA. -- Abstract: Circadian Clock genes are associated with the estrous cycle in female animals. Treatment with Per2 and Clock siRNAs decreased the number ofmore » granulosa cells and LHr expression in follicle-stimulating hormone FSH-treated granulosa cells. Per2 siRNA treatment did not stimulate the production of estradiol and expression of P450arom, whereas Clock siRNA treatment inhibited the production of estradiol and expression of P450arom mRNA. Per2 and Clock siRNA treatment increased and unchanged, respectively, progesterone production in FSH-treated granulosa cells. Similarly, expression of StAR mRNA was increased by Per2 siRNA and unchanged by Clock siRNA. Our data provide a new insight that Per2 and Clock have different action on ovarian granulosa cell functions.« less

Stimulation of in vitro steroidogenesis by pituitary hormones in a turtle (Trachemys scripta) within the temperature-sensitive period for sex determination.

PubMed

White, R B; Thomas, P

1992-12-01

To investigate the possible involvement of pituitary hormones in the regulation of steroidogenesis during reptilian sexual differentiation, we tested the ability of gonadotropin (ovine FSH), adrenocorticotropin (porcine ACTH), and growth hormone (bovine GH) to stimulate in vitro steroidogenesis in embryonic adrenal-kidney-gonad complexes (AKGs) of a turtle, Trachemys scripta, during and after the temperature-sensitive period for sex determination (TSP). Radioimmunoassays were used to measure progesterone, testosterone, estradiol, and corticosterone in incubation media; additionally, immunoreactive ACTH was measured in plasma. Presumptive male and female AKGs were stimulated by both FSH and ACTH at each stage investigated. Secretion of progesterone and corticosterone was usually far greater than that of testosterone or estradiol in both basal and hormone-stimulated incubations. In general, AKGs from presumptive males secreted more progesterone and corticosterone than AKGs from presumptive females. Progesterone and estradiol secretions were stimulated by both FSH and ACTH, but testosterone secretion was stimulated only by ACTH. Corticosterone secretion was strongly stimulated by ACTH. GH failed to significantly stimulate steroid secretion. Plasma ACTH levels were significantly higher in males than in females, and both sexes had significantly higher plasma levels of ACTH after the TSP compared to during the TSP. Our data demonstrate that during the temperature-sensitive period AKGs are responsive to both gonadotropin and ACTH, and that there are significant sex differences in steroidogenesis, sensitivity to gonadotropin and ACTH, and plasma ACTH levels.

A sea lamprey glycoprotein hormone receptor similar with gnathostome thyrotropin hormone receptor.

PubMed

Freamat, Mihael; Sower, Stacia A

2008-10-01

The specificity of the vertebrate hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid axes is explained by the evolutionary refinement of the specificity of expression and selectivity of interaction between the glycoprotein hormones GpH (FSH, LH, and TSH) and their cognate receptors GpH-R (FSH-R, LH-R, and TSH-R). These two finely tuned signaling pathways evolved by gene duplication and functional divergence from an ancestral GpH/GpH-R pair. Comparative analysis of the protochordate and gnathostome endocrine systems suggests that this process took place prior or concomitantly with the emergence of the gnathostome lineage. Here, we report identification and characterization of a novel glycoprotein hormone receptor (lGpH-R II) in the Agnathan sea lamprey. This 781 residue protein was found approximately 43% identical with mammalian TSH-R and FSH-R representative sequences, and similarly with these two classes of mammalian receptors it is assembled from ten exons. A synthetic ligand containing the lamprey glycoprotein hormone beta-chain tethered upstream of a mammalian alpha-chain activated the lGpH-R II expressed in COS-7 cells but in a lesser extent than lGpH-R I. Molecular phylogenetic analysis of vertebrate GpH-R protein sequences suggests a closer relationship between lGpH-R II and gnathostome thyrotropin receptors. Overall, the presence and characteristics of the lamprey glycoprotein hormone receptors suggest existence of a primitive functionally overlapping glycoprotein hormone/glycoprotein hormone receptor system in this animal.

Association between Th1/Th2 immune imbalance and obesity in women with or without polycystic ovary syndrome.

PubMed

Gong, Ping; Shi, Bingwei; Wang, Juan; Cao, Peixia; Diao, Zhenyu; Wang, Yuji; Hu, Yali; Li, Shuping

2018-02-15

This study aimed to investigate the Th1/Th2 cells in peripheral blood of PCOS patients, and assess the potential correlation between Th1/Th2 imbalance and obesity. Thirty-nine PCOS patients and 23 age-matched controls were enrolled. The PBMCs were obtained before pharmacological intervention in women with or without PCOS. The profiles of Th1 (IFN-γ) and Th2 (IL-4) cytokines of CD3 + CD - T lymphocyte subsets were analyzed by flow cytometry. Plasma sex hormones including E 2 , T, FSH, LH, and FINS, FPG were measured, together with BMI, WC, LH/FSH, E 2 /T and HOMA-IR index being calculated. Association between Th1/Th2 imbalance and BMI, WC were evaluated. The proportion of Th1 cells and Th1/Th2 ratio were significantly higher in PCOS patients than those in controls, accompanied by elevated T, LH, LH/FSH, FINS, HOMA-IR index and reduced E 2 /T. The Th1/Th2 ratio was increased when BMI and WC were enhanced in PCOS. Moreover, the significant difference of Th1/Th2 ratio was observed between WC subgroups of PCOS. It is concluded that Th1 type immunity is predominant in systemic immunization of PCOS patients. Th1/Th2 immune imbalance is connected with obesity, especially abdominal obesity, and may be one of the underlying mechanism for the pathogenesis of PCOS.

Early follicular phase hormone levels in relation to patterns of alcohol, tobacco, and coffee use.

PubMed

Lucero, J; Harlow, B L; Barbieri, R L; Sluss, P; Cramer, D W

2001-10-01

To examine the effects of alcohol, caffeine, and tobacco use on early follicular phase FSH, LH, E2, and sex hormone-binding globulin (SHBG). Cross-sectional study. Academic medical center. Four hundred ninety-eight women selected from the general population, ages 36-45, who were not currently pregnant, breast feeding, or using exogenous hormones. A general questionnaire assessing demography, anthropometry, and smoking habits and a standardized dietary questionnaire assessing food and beverage frequencies, including sources of alcohol and caffeine. FSH, LH, E2, and SHBG levels measured during the early follicular phase of the menstrual cycle. Significant associations observed in a univariate analysis included age > or =40 and current smoking associated with higher FSH; higher body mass index (BMI) associated with lower SHBG levels; and daily alcohol use, cholesterol consumption greater than the median, and coffee use >1 cup/d associated with higher E2 levels. In a multivariate model, total caffeine use was significantly associated with E2 levels after adjustment for age, BMI, total calories, current smoking, alcohol, cholesterol consumption, and day of sampling. Early follicular phase E2 increased from 28.2 pg/mL for women consuming < or =100 mg of caffeine to 45.2 pg/mL for women consuming > or =500 mg of caffeine per day, about a 70% increase. Coffee consumption and total caffeine use may increase early follicular phase E2 levels independent of related habits of alcohol or tobacco use.

[Patients with functional hypothalamic amenorrhea are characterized by low serum inhibin B concentrations].

PubMed

Podfigurna-Stopa, Agnieszka; Luisi, Stefano; Lazzeri, Lucia; Ciani, Valentina; Meczekalski, Błazej; Petraglia, Felice

2010-05-01

Functional hypothalamic disturbances may be the cause of secondary amenorrhea and are related to aberration in both the pattern of pulsatility and amplitude in the release of gonadotropin-releasing hormone (GnRH) in hypothalamus. Inhibin B, as an ovarian peptide plays a crucial role in reproduction function throughout regulation of folliculotropin (FSH) pituitary production and inhibiting GnRH secretion during the menstrual cycle. To measure and estimate serum inhibin B concentration in patients with functional hypothalamic amenorrhea. Material and methods. The study included 41 women suffering from functional hypothalamic amenorrhea. Secondary amenorrhea was defined as the lack of menstruation lasting at least 90 days not due to pregnancy, characterized by low serum concentrations of lutropin (LH < 5 mIU/ml)) and typical for functional hypothalamic disturbances anamnestic investigation. The control group consists of 40 healthy women with normal menstrual cycles and Body Mass Index (BMI between 18.5- 24.9 kg/m2). Medical history, examination and laboratory analysis of LH, FSH, estradiol (E), prolactin, testosterone and inhibin B were performed (ELISA--enzyme-linked immunosorbent assay). There are statistically lower serum inhibin B, FSH, LH, estradiol and prolactin concentrations in patients with functional hypothalamic amenorrhea in comparison to healthy women. Positive correlation between serum concentration of inhibin B and estradiol concentration was found in patients with functional hypothalamic amenorrhea. Patients with functional hypothalamic amenorrhea are characterized by statistical significant decrease in serum inhibin B concentration in comparison to the control group.

Bone health measured using quantitative ultrasonography in adult males with muscular dystrophy

PubMed Central

Morse, C.I.; Smith, J.; Denny, A.; Tweedale, J.; Searle, N.D.; Winwood, K.; Onambele-Pearson, G.L.

2016-01-01

Objectives: To compare muscle and bone health markers in adult males (aged 20-59 yrs) with and without muscular dystrophy (MD). Methods: Participants included 11 Fascioscapulohumeral (FSH), 11 Becker’s (Be), 9 limb girdle (LG), 11 Duchenne (DMD), and 14 non-dystrophic controls (CTRL). Physical activity was assessed using Bone (BPAQ) and disability specific (PASIPD) questionnaires. Bone QUS provided T- and Z scores from the Distal Radius (DR) and Mid-shaft tibia (MST). Tibialis anterior cross sectional area (TAACSA) was measured using B-mode ultrasound. Grip strength was measured in all but DMD. Results: Physical activity was lower in DMD, FSH and BeMD than CTRL (P<0.05), and lower in DMD than other MDs (P<0.01). T and Z scores were lower in DMD and Be than CTRL (DR, P<0.05); and lower in DMD than CTRL, LG, and FSH (MST, P<0.01). TAACSA and grip strength was 35-59% and 50-58% smaller in MD than CTRL, respectively (P<0.01). Within MD, BPAQ correlated with bone QUS measures (r=0.42-0.38, P<0.01). PASIPD correlated with grip strength (r=0.65, P<0.01) and TAACSA (r=0.46, P<0.01). Conclusion: Muscle size, strength, and bone health was lower in adult males with MD compared to adult males without MD, the extent of this is partially determined by physical activity. PMID:27973386

The rate of high ovarian response in women identified at risk by a high serum AMH level is influenced by the type of gonadotropin.

PubMed

Arce, Joan-Carles; Klein, Bjarke M; La Marca, Antonio

2014-06-01

The aim was to compare ovarian response and clinical outcome of potential high-responders after stimulation with highly purified menotropin (HP-hMG) or recombinant follicle-stimulating hormone (rFSH) for in vitro fertilisation/intracytoplasmic sperm injection. Retrospective analysis was performed on data collected in two randomized controlled trials, one conducted following a long GnRH agonist protocol and the other with an antagonist protocol. Potential high-responders (n = 155 and n = 188 in the agonist and antagonist protocol, respectively) were defined as having an initial anti-Müllerian hormone (AMH) value >75th percentile (5.2 ng/ml). In both protocols, HP-hMG stimulation in women in the high AMH category was associated with a significantly lower occurrence of high response (≥15 oocytes retrieved) than rFSH stimulation; 33% versus 51% (p = 0.025) and 31% versus 49% (p = 0.015) in the long agonist and antagonist protocol, respectively. In the potential high-responder women, trends for improved live birth rate were observed with HP-hMG compared with rFSH (long agonist protocol: 33% versus 20%, p = 0.074; antagonist protocol: 34% versus 23%, p = 0.075; overall population: 34% versus 22%, p = 0.012). In conclusion, the type of gonadotropin used for ovarian stimulation influences high-response rates and potentially clinical outcome in women identified as potential high-responders.

Spontaneous recovery from isolated post-traumatic central hypogonadism in a woman.

PubMed

Ruggeri, Rosaria M; Smedile, Giovanni; Granata, Francesca; Longo, Marcello; Cannaíò, Salvatore; Sarlis, Nicholas J; Trimarchi, Francesco; Benvenga, Salvatore

2010-01-01

Hypopituitarism is a recognized complication of Traumatic Brain Injury (TBI). Resolution of established anterior pituitary hormones deficiency is rare. A woman was initially presented at the age of 22 years with amenorrhoea. Two years earlier she had been involved in a car accident with consequent TBI. At our evaluation, serum oestradiol (E2) was low (3 pmol/l), Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) were borderline low [1.7 and 2.5 mIU/l, normal range (NR) for 20-35 yr old women being 1.4-13 and 2.5-13, respectively] with poor response to Gonadotropin Releasing Hormone (GnRH) (ΔLH = 2.4 and, ΔFSH = 4.0 mIU/l), while serum Prolactin (PRL) was elevated (951 mIU/l; NR: 102-496). No other pituitary hormone deficiencies were observed. Magnetic resonance imaging (MRI) showed a partially empty sella and very thin stalk. Ten years later a new endocrine evaluation was performed. On day 4 of her menstrual cycle, serum values of PRL (196 mIU/l), FSH (4.7 mIU/l), LH (4.8 mIU/l) and E2 (103 pmol/l) were within normal limits for women aged 20-35. Six months after this evaluation (that is, 12 years after trauma), the patient became pregnant and delivered a healthy baby. Our case shows that spontaneous resolution of post-head trauma anterior hypopituitarism occur even many years after head injury. Medicolegal implications are self-evident.

Biological mechanisms of premature ovarian failure caused by psychological stress based on support vector regression

PubMed Central

Wang, Xiu-Feng; Zhang, Lei; Wu, Qing-Hua; Min, Jian-Xin; Ma, Na; Luo, Lai-Cheng

2015-01-01

Psychological stress has become a common and important cause of premature ovarian failure (POF). Therefore, it is very important to explore the mechanisms of POF resulting from psychological stress. Sixty SD rats were randomly divided into control and model groups. Biomolecules associated with POF (β-EP, IL-1, NOS, NO, GnRH, CRH, FSH, LH, E2, P, ACTH, and CORT) were measured in the control and psychologically stressed rats. The regulation relationships of the biomolecules were explored in the psychologically stressed state using support vector regression (SVR). The values of β-EP, IL-1, NOS, and GnRH in the hypothalamus decreased significantly, and the value of NO changed slightly, when the values of 3 biomolecules in the hypothalamic-pituitary-adrenal axis decreased. The values of E2 and P in the hypothalamic-pituitary-ovarian axis decreased significantly, while the values of FSH and LH changed slightly, when the values of the biomolecules in the hypothalamus decreased. The values of FSH and LH in the pituitary layer of the hypothalamic-pituitary-ovarian axis changed slightly when the values of E2 and P in the target gland layer of the hypothalamic-pituitary-ovarian axis decreased. An Imbalance in the neuroendocrine-immune bimolecular network, particularly the failure of the feedback action of the target gland layer to pituitary layer in the pituitary-ovarian axis, is possibly one of the pathogenic mechanisms of POF. PMID:26885082

Male patients with partial androgen insensitivity syndrome: a longitudinal follow-up of growth, reproductive hormones and the development of gynaecomastia.

PubMed

Hellmann, Philip; Christiansen, Peter; Johannsen, Trine Holm; Main, Katharina M; Duno, Morten; Juul, Anders

2012-05-01

To describe the natural history of phenotype, growth and gonadal function in patients with partial androgen insensitivity syndrome. Tertiary paediatric endocrine centre. Retrospective evaluation of 14 male patients with partial androgen insensitivity syndrome (PAIS) with verified androgen receptor (AR) mutations. The authors recorded phenotypic characteristics at birth and external masculinisation score (EMS), registered longitudinal growth, circulating levels of testosterone, estradiol, luteinising hormone (LH), follicle-stimulating hormone (FSH), inhibin-B and sex hormone binding globulin (SHBG), in addition to phenotype at postpubertal follow up. The EMS ranged from 5 to 12 in PAIS at birth. Six patients were born with hypospadias and all patients developed gynaecomastia in puberty. Eight of the patients received testosterone treatment. At follow-up penile size was impaired irrespective of EMS at birth, but responded to pubertal androgen therapy in some of the patients. Serum levels of testosterone, estradiol, SHBG and LH, but not FSH and inhibin B, were markedly elevated in puberty. Final height was 181.3 cm (165.7-190.5 cm) corresponding to an SD score of 0.7 (-2.1 to +2.1 SD, n=10). Gynaecomastia and impaired phallic growth are frequently observed in adults with PAIS, but may be ameliorated by androgen therapy. The authors suggest that male patients presenting with gynaecomastia in puberty, and elevated circulating levels of testosterone, estradiol and LH in puberty, but normal FSH, should be suspected of having PAIS and undergo genetic testing for AR mutations.

Obesity independently influences gonadal function in very long-term adult male survivors of childhood cancer.

PubMed

Blijdorp, Karin; van Dorp, Wendy; Laven, Joop S E; Pieters, Rob; de Jong, Frank H; Pluijm, Saskia M F; van der Lely, Aart Jan; van den Heuvel-Eibrink, Marry M; Neggers, Sebastian J C M M

2014-08-01

Although obesity is associated with gonadal dysfunction in the general population, gonadotoxic treatment might diminish the impact of obesity in childhood cancer survivors (CCS). The aim was to evaluate whether altered body composition is associated with gonadal dysfunction in male CCS, independent of gonadotoxic cancer treatment. Three hundred fifty-one male CCS were included. Median age at diagnosis was 5.9 years (0-17.8) and median age at follow-up 25.6 years (18.0-45.8). Total and non-SHBG-bound testosterone, sex hormone-binding globulin, inhibin B, and follicle-stimulating hormone (FSH) were studied. Potential determinants were BMI, waist circumference, waist-hip ratio, and body composition measures (dual energy X-ray absorptiometry). Non-SHBG-bound testosterone was significantly decreased in survivors with BMI ≥ 30 kg/m(2) (adjusted mean 9.1 nmol/L vs. 10.2 nmol/L, P = 0.015), high fat percentage (10.0 vs. 11.2, P = 0.004), and high waist circumference (>102 cm) (9.0 vs. 11.0, P = 0.020). Survivors with high fat percentage (≥25%) had significantly lower inhibin B/FSH ratios (inhibin B/FSH ratio: β -34%, P = 0.041). Obesity is associated with gonadal dysfunction in male CCS, independent of the irreversible effect of previous cancer treatment. Randomized controlled trials are required to evaluate whether weight normalization could improve gonadal function, especially in obese survivors with potential other mechanisms than lifestyle causing their obesity. Copyright © 2014 The Obesity Society.

Intact follicular maturation and defective luteal function in mice deficient for cyclin- dependent kinase-4.

PubMed

Moons, David S; Jirawatnotai, Siwanon; Tsutsui, Tateki; Franks, Roberta; Parlow, A F; Hales, Dale B; Gibori, Geula; Fazleabas, Asgerally T; Kiyokawa, Hiroaki

2002-02-01

Cell cycle progression of granulosa cells is critical for ovarian function, especially follicular maturation. During follicular maturation, FSH induces cyclin D2, which promotes G1 progression by activating cyclin-dependent kinase-4 (Cdk4). Because cyclin D2-deficient mice exhibit a block in follicular growth, cyclin D2/Cdk4 has been hypothesized to be required for FSH-dependent proliferation of granulosa cells. Here we investigate ovarian function in Cdk4-knockout mice we recently generated. Cdk4(-/-) females were sterile, but the morphology of their ovaries appeared normal before sexual maturation. The number of preovulatory follicles and the ovulation efficiency were modestly reduced in gonadotropin-treated Cdk4(-/-) mice. However, unlike cyclin D2-deficient mice, Cdk4(-/-) mice showed no obvious defect in FSH-induced proliferation of granulosa cells. Cdk4(-/-) ovaries displayed normal preovulatory expression of aromatase, PR, and cyclooxygenase-2. Postovulatory progesterone secretion was markedly impaired in Cdk4(-/-) mice, although granulosa cells initiated luteinization with induction of p450 side-chain cleavage cytochrome and p27(Kip1). Progesterone treatment rescued implantation and restored fertility in Cdk4(-/-) mice. Serum PRL levels after mating were significantly reduced in Cdk4(-/-) mice, suggesting the involvement of perturbed PRL regulation in luteal failure. Thus, Cdk4 is critical for luteal function, and some redundant protein(s) can compensate for the absence of Cdk4 in proliferation of granulosa cells.

Evaluation of the pituitary-gonadal response to GnRH, and adrenal status, in the leopard (Panthera pardus japonensis) and tiger (Panthera tigris).

PubMed

Brown, J L; Goodrowe, K L; Simmons, L G; Armstrong, D L; Wildt, D E

1988-01-01

Frequent blood samples were collected to study hormonal responses to GnRH in male and female leopards and tigers. Animals were anaesthetized with ketamine-HCl and blood samples were collected every 5 min for 15 min before and 160 min after i.v. administration of GnRH (1 micrograms/kg body weight) or saline. No differences in serum cortisol concentrations were observed between sexes within species, but mean cortisol was 2-fold greater in leopards than tigers. GnRH induced a rapid rise in LH in all animals (18.3 +/- 0.9 min to peak). Net LH peak height above pretreatment levels was 3-fold greater in males than conspecific females and was also greater in tigers than leopards. Serum FSH increased after GnRH, although the magnitude of response was less than that observed for LH. Basal LH and FSH and GnRH-stimulated FSH concentrations were not influenced by sex or species. Serum testosterone increased within 30-40 min after GnRH in 3/3 leopard and 1/3 tiger males. Basal testosterone was 3-fold greater in tiger than leopard males. LH pulses (1-2 pulses/3 h) were detected in 60% of saline-treated animals, suggesting pulsatile gonadotrophin secretion; however, in males concomitant testosterone pulses were not observed. These results indicate that there are marked sex and species differences in basal and GnRH-stimulated hormonal responses between felids of the genus Panthera which may be related to differences in adrenal activity.

Using the ovarian sensitivity index to define poor, normal, and high response after controlled ovarian hyperstimulation in the long gonadotropin-releasing hormone-agonist protocol: suggestions for a new principle to solve an old problem.

PubMed

Huber, Malin; Hadziosmanovic, Nermin; Berglund, Lars; Holte, Jan

2013-11-01

To explore the utility of using the ratio between oocyte yield and total dose of FSH, i.e., the ovarian sensitivity index (OSI), to define ovarian response patterns. Retrospective cross-sectional study. University-affiliated private center. The entire unselected cohort of 7,520 IVF/intracytoplasmic sperm injection treatments (oocyte pick-ups [OPUs]) during an 8-year period (long GnRH agonist-recombinant FSH protocol). None. The distribution of the OSI (oocytes recovered × 1,000/total dose of FSH), the cutoff levels for poor and high response, set at ±1 SD, and the relationship between OSI and treatment outcome. OSI showed a log-normal distribution with cutoff levels for poor and high response at 1.697/IU and 10.07/IU, respectively. A nomogram is presented. Live-birth rates per OPU were 10.5 ± 0.1%, 26.9 ± 0.6%, and 36.0 ± 1.4% for poor, normal, and high response treatments, respectively. The predictive power (C-statistic) for OSI to predict live birth was superior to that of oocyte yield. The OSI improves the definition of ovarian response patterns because it takes into account the degree of stimulation. The nomogram presents evidence-based cutoff levels for poor, normal, and high response and could be used for unifying study designs involving ovarian response patterns. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Influence of age, strain and season on circadian periodicity of pituitary, gonadal and adrenal hormones in the serum of male laboratory rats.

PubMed

Wong, C C; Döhler, K D; Geerlings, H; von zur Mühlen, A

1983-01-01

The influence of age, strain and season on the circadian pattern of serum levels of LH, FSH, prolactin androgens and corticosterone was studied in five groups of male laboratory rats. Significant 24-hour periodicity was observed for serum levels of corticosterone in all five groups, for androgen levels in four, for prolactin levels in three, for LH levels in two and for FSH levels in one group of rats. There were significant influences of age, strain and season on the temporal patterns and/or on 24-hour mean serum hormone levels. The results indicate that some of the disagreements on existence or nonexistence of circadian rhythms and on rhythm patterns in serum hormone levels may be explained by the fact that animals of different ages or strains had been used or that experiments were performed at different times of the year.

[The role of gonadal peptides in clinical investigation].

PubMed

Lahlou, N; Bouvattier, C; Linglart, A; Rodrigue, D; Teinturier, C

2009-01-01

Inhibins, activins, and anti-Mullerian hormone (AMH) are gonadal dimeric peptides produced in ovaries and testes by homologous cells, granulosa cells and Sertoli cells, respectively. The production of inhibins is driven by FSH, that of AMH may indirectly depends on FSH, while it is down regulated, at least in the male, by testosterone. In the past decade, measurements of serum inhibin and AMH have provided useful tools for clinical investigation in gonadal disorders: pseudohermaphroditism, androgen insensitivity, anorchidism, gonadal dysgenesis, disorders of pubertal developpement. Inhibins, activins, and AMH are also reliable markers of gonadal tumors. They are extensively used as indexes of fertility: in the male the production of inhibin B reflects the spermatogenetic activity, in women both inhibin B and AMH levels are correlated with the number of preantral and early antral follicles and reflect the ovarian reserve of follicles available for recruitment.

LH (Luteinizing Hormone) Test

MedlinePlus

... to predict ovulation by detecting a woman's monthly pre-ovulation LH surge. It indicates ovulation but cannot, however, be used to confirm that ovulation has occurred. Why would a man need a test for FSH and LH; I thought these were ...

Comparing the Effects of Combined Oral Contraceptives Containing Progestins With Low Androgenic and Antiandrogenic Activities on the Hypothalamic-Pituitary-Gonadal Axis in Patients With Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis

PubMed Central

Amiri, Mina; Nahidi, Fatemeh; Kabir, Ali; Azizi, Fereidoun

2018-01-01

Background Different products of combined oral contraceptives (COCs) can improve clinical and biochemical findings in patients with polycystic ovary syndrome (PCOS) through suppression of the hypothalamic-pituitary-gonadal (HPG) axis. Objective This systematic review and meta-analysis aimed to compare the effects of COCs containing progestins with low androgenic and antiandrogenic activities on the HPG axis in patients with PCOS. Methods We searched PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science databases (1980-2017) to identify randomized controlled trials or nonrandomized studies investigating the effect of COCs containing progestins with low androgenic and antiandrogenic activities, including the products containing desogestrel, cyproterone acetate, and drospirenone, on the HPG axis in patients with PCOS. In this meta-analysis, fixed and random effect models were used. Outcomes of interest were weighted mean differences (WMD) of hormonal parameters, including the follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH-to-FSH ratio, estradiol, total testosterone, and sex hormone–binding globulin. Potential sources of heterogeneity were investigated using meta-regression and subgroup analyses. Subgroup analyses were performed based on the used progestin compound and treatment duration. We assessed quality of included studies and their risk of bias using Cochrane guidelines. Publication bias was assessed using Egger test and funnel plot. Results COC use was significantly associated with a decrease in gonadotropin levels, including FSH and LH. Use of products containing cyproterone acetate was associated with a decrease in FSH levels after 3 months (WMD=−0.48; 95% CI −0.81 to −0.15), 6 months (WMD=−2.33; 95% CI −3.48 to −1.18), and 12 months (WMD=−4.70; 95% CI −4.98 to −4.42) and a decrease in LH levels after 3 months (WMD=−3.57; 95% CI −5.14 to −1.99), 6 months (WMD=−5.68; 95% CI −9.57 to −1.80), and 12

Density gradient centrifugation prior to cryopreservation and hypotaurine supplementation improve post-thaw quality of sperm from infertile men with oligoasthenoteratozoospermia.

PubMed

Brugnon, F; Ouchchane, L; Pons-Rejraji, H; Artonne, C; Farigoule, M; Janny, L

2013-08-01

Can selection of spermatozoa by density gradient centrifugation prior to cryopreservation and/or hypotaurine supplementation improve the post-thaw quality of sperm from infertile men with oligoasthenoteratozoospermia? Sperm selection by density gradient centrifugation before freezing and supplementation of the media by hypotaurine is beneficial for the cryopreservation of semen samples of patients with oligoasthenoteratozoospermia. Sperm from men with oligoasthenoteratozoospermia are more susceptible than normal to cryoinjury. Density gradient centrifugation before sperm freezing may allow the selection of a subpopulation of spermatozoa more resistant to cryopreservation. Hypotaurine is an antioxidant with a protective effect on sperm functions. The experiment was carried out according to a factorial design involving two binary factors resulting in four treatment combinations which were randomly allocated in oligoasthenoteratozoospermia sperm samples from 64 patients recruited between January 2009 and June 2010. Semen was provided by 64 men undergoing evaluation for infertility at the Centre for Reproductive Medicine of the University Hospital in Clermont-Ferrand, France, between January 2009 and June 2010. Four treatment combinations were tested: sperm freezing before selection without (F-S/H-; n = 16) and with hypotaurine supplementation (F-S/H+; n = 16); sperm selection before freezing without (S-F/H-; n = 16) and with hypotaurine supplementation (S-F/H+; n = 16). Measurements of sperm recovery rates and markers of apoptosis (externalization of phosphatidylserine (PS), mitochondrial membrane potential and DNA fragmentation) were compared in recovered spermatozoa after each procedure. Higher recovery rates of progressive and total motile spermatozoa were observed when sperm selection was performed before freezing (P < 0.05). The protective effect of hypotaurine was only observed on the percentage of live spermatozoa with PS externalization among total live

Effect of inhibitors of prostaglandin synthesis on gonadotropin release in the rat.

PubMed

Ojeda, S R; Harms, P G; McCann, S M

1975-10-01

To study the effect of blockade of prostaglandin (PG) synthesis on gonadotropin release in the rat, inhibitors of PG synthesis were injected by various routes in various experimental conditions. The injection of 5-, 8-, 11-, 14-eicosatetraynoic acid (TYA) into the third ventricle (3rd V) significantly decreased plasma LH of ovariectomized (OVX) rats 1, 2, and 4 h following its injection; however, TYA failed to alter plasma LH in OVX rats when administered as a single sc injection and also failed to prevent the post-castration rise in plasma LH when administered sc once daily for 4 days to short-term OVX rats. None of these treatments altered plasma FSH concentrations. Indomethacin (Id) injected into the 3rd V or implanted into the medial basal hypothalamus (MBH) of OVX rats depressed plasma LH 1--6 h later. This effect was no longer observed 24--72 h following its implantation in the MBH. When different doses of Id were administered as single sc injections to OVX rats, plasma LH titers were depressed 24--32 h later, whereas plasma FSH remained either unaltered or was slightly increased. Similarly, the post-castration rise of plasma LH but not that of FSH in male rats was suppressed by a single sc injection of Id given 6 h before orchidectomy. Id administered acutely iv failed to modify the pulsatile release of LH in OVX rats, but it effectively inhibited this release when injected sc 20--30 h before the initiation of blood collection. Moreover, Id blocked the progesterone-induced LH and FSH release in OVX estrogen-primed rats when given sc 24 h before progesterone, but not when it was injected either sc or iv shortly (2 h) before or shortly after (1--3 h) progesterone treatment. Rats treated with Id showed a decrease in BW 24--32 h afters its sc injection. However, the effects of Id on LH release could not be explained by lack of food intake since fasted controls showed LH titers similar to fed rats. Id did not significantly inhibit the LH release in response to

Corpora lutea in superovulated ewes fed different planes of nutrition.

PubMed

Kraisoon, A; Redmer, D A; Bass, C S; Navanukraw, C; Dorsam, S T; Valkov, V; Reyaz, A; Grazul-Bilska, A T

2018-01-01

The corpus luteum (CL) is an ovarian structure which is critical for the maintenance of reproductive cyclicity and pregnancy support. Diet and/or diet components may affect some luteal functions. FSH is widely used to induce multiple follicle development and superovulation. We hypothesized that FSH would affect luteal function in ewes fed different nutritional planes. Therefore, the aim of this study was to determine if FSH-treatment affects (1) ovulation rate; (2) CL weight; (3) cell proliferation; (4) vascularity; (5) expression of endothelial nitric oxide (eNOS) and soluble guanylate cyclase (sGC) proteins; and (6) luteal and serum progesterone (P4) concentration in control (C), overfed (O), and underfed (U) ewes at the early- and mid-luteal phases. In addition, data generated from this study were compared to data obtained from nonsuperovulated sheep and described by Bass et al. Ewes were categorized by weight and randomly assigned into nutrition groups: C (2.14 Mcal/kg; n = 11), O (2xC; n = 12), and U (0.6xC; n = 11). Nutritional treatment was initiated 60 d prior to day 0 of the estrous cycle. Ewes were injected with FSH on day 13-15 of the first estrous cycle, and blood samples and ovaries were collected at early- and mid-luteal phases of the second estrous cycle. The number of CL/ewe was determined, and CL was dissected and weighed. CL was fixed for evaluation of expression of Ki67 (a proliferating cell marker), CD31 (an endothelial cell marker), and eNOS and sGC proteins using immunohistochemistry and image analysis. From day 0 until tissue collection, C maintained, O gained, and U lost body weight. The CL number was greater (P < 0.03) in C and O than U. Weights of CL, cell proliferation, vascularity, and eNOS but not sGC expression were greater (P < 0.001), and serum, but not luteal tissue, P4 concentrations tended to be greater (P = 0.09) at the early- than mid-luteal phase. Comparisons of CL measurements demonstrated greater (P < 0.01) cell

Daily testosterone and gonadotropin levels are similar in azoospermic and nonazoospermic normal men administered weekly testosterone: implications for male contraceptive development.

PubMed

Amory, J K; Anawalt, B D; Bremner, W J; Matsumoto, A M

2001-01-01

Weekly intramuscular administration of testosterone esters such as testosterone enanthate (TE) suppresses gonadotropins and spermatogenesis and has been studied as a male contraceptive. For unknown reasons, however, some men fail to achieve azoospermia with such regimens. We hypothesized that either 1) daily circulating serum fluoroimmunoreactive gonadotropins were higher or testosterone levels were lower during the weekly injection interval, or 2) monthly circulating bioactive gonadotropin levels were higher in nonazoospermic men. We therefore analyzed daily testosterone and fluoroimmunoreactive gonadotropin levels as well as pooled monthly bioactive and fluoroimmunoreactive gonadotropin levels in normal men receiving chronic TE injections and correlated these levels with sperm production. After a 3-month control period, 51 normal men were randomly assigned to receive intramuscular TE at 25 mg (n = 10), 50 mg (n = 9), 100 mg (n = 10), 300 mg (n = 10), or placebo (n = 12) weekly for 6 months. After 5 months of testosterone administration, morning testosterone and fluoroimmunoreactive follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured daily for a 1-week period between TE injections. In addition, fluoroimmunoreactive and bioactive FSH and LH levels were measured in pooled monthly blood samples drawn just before the next TE injection. In the 100-mg and 300-mg TE groups, mean monthly fluoroimmunoreactive FSH and LH levels were suppressed by 86%-97%, bioactive FSH and LH levels by 62%-80%, and roughly half the subjects became azoospermic. In the 1-week period of month 6, daily testosterone levels between TE injections were within the normal range in men receiving placebo, or 25 or 50 mg of weekly TE, but were significantly elevated in men receiving 100 or 300 mg of weekly TE. At no point during treatment, however, were there significant differences in daily testosterone or fluoroimmunoreactive gonadotropin levels, or monthly bioactive

Urinary sexual steroids associated with bisphenol A (BPA) exposure in the early infant stage: Preliminary results from a Daishan birth cohort.

PubMed

Wang, Heng; Liu, Liangpo; Wang, Jianyue; Tong, Zhendong; Yan, Jianbo; Zhang, Tongjie; Qin, Ying; Jiang, Tingting; She, Jianwen; Shen, Heqing

2017-12-01

Many surveys have shown that older children are ubiquitously exposed to bisphenol A (BPA), and many laboratory studies have shown that BPA exposure has adverse effects related to estrogenic disruption, whereas the evidence in infants has not yet been observed. Women in early pregnancy were recruited by the Maternal and Child Health and Family Planning Service Center, Daishan, China, from March 2012 to December 2014. After delivery, urine samples were collected from the diapers of 59 infants (0 to 6months of age). Urinary BPA, estradiol (E 2 ), testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and creatinine were analyzed. The partial correlation and multivariable linear regression were applied to assess the associations of BPA with E 2 , T, FSH, and LH for each of the development stages: at birth, 14days, 28days, 42days, 3months, and 6months. For both genders from birth to 6months, infants showed randomly changed urinary BPA but regularly changed hormones, i.e., the monotonic decreasing E 2 and T, the "U" shaping E 2 /T and upside down "U" shaping FSH and LH with extreme values at approximately the 14-day stage, respectively. However, the creatinine-adjusted FSH for all stages and E 2 from 6months were genders different. After adjustment for creatinine, gender, and infant body mass index, BPA was positively associated with E 2 both in male (for 14-, 28-, and 42-day stages) and female (for 14-, 28-, 42-day, and 3-month stages) infants; positively associated with E 2 /T ratio in both male (for 14- and 28-day stages) and female (for 14-day stage) infants; and positively associated with T in female (for 3-month stage) infants. To the best of our knowledge, this is the first time that associations of BPA with E 2 , E 2 /T, and T in infant urine were observed. The results suggested that the infants first demonstrate a surge of steroids after leaving the maternal uterus's steroidogenic environment (i.e., mini-puberty) and may be affected by

Establishing reference intervals for hCG in postmenopausal women.

PubMed

Patel, Khushbu K; Qavi, Abraham J; Hock, Karl G; Gronowski, Ann M

2017-03-01

Plasma concentrations of human chorionic gonadotropin (hCG) have been shown to increase with age due to pituitary secretion. We previously recommended that an hCG cutoff of 14.0IU/L be used for women ≥55years of age. However, it remains unknown whether concentrations >14.0IU/L can be expected in women with advanced age. Our objectives were to establish plasma hCG reference intervals and correlate follicle stimulating hormone (FSH) and hCG concentrations in postmenopausal females ≥55years. Residual plasma samples from 798 women ≥55years were utilized with 303, 269, and 226 samples belonging to the age groups 55-69, 70-84, and ≥85years, respectively. FSH and hCG were measured using the Abbott ARCHITECT. All positive hCG samples (hCG ≥5IU/L) were analyzed for potential heterophile antibody interference and 3 were excluded. Electronic medical records were reviewed and patients with malignancy were excluded. 8% (56/666) of women age≥55years had plasma hCG ≥5IU/L. There were 19, 16, and 21 patients with hCG ≥5IU/L in the age groups 55-69, 70-84, and ≥85years, respectively. The highest hCG concentrations observed in each age group were: 55-69years maximum=11.7IU/L and 97.5th percentile=9.6IU/L; 70-84years maximum=18.09IU/L, 97.5th percentile=6.2IU/L; ≥85years maximum=11.1IU/L and 97.5th percentile=10.0IU/L, and the overall 97.5th percentile=8.5IU/L for all women ≥55years of age. Neither hCG nor FSH concentrations continued to increase with age in women ≥55years. The prevalence of positive hCG in women ≥55years is 8%. This study confirms our previously recommended cutoff of 14IU/L for women ≥55years of age. In women ≥55years of age, FSH concentrations do not predict hCG concentrations. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Comparative morphophysiological evaluation of the testis of adult Wistar rats fed low protein-energy diet and dosed with aqueous extracts of Cuscuta australis.

PubMed

Ozegbe, P C; Omirinde, J O

2012-12-18

Cuscuta australis (C. australis) seed and stem are historically used by the local population as dietary supplement for the management of infertility. This study, therefore, evaluated the effect of orally administered aqueous extracts of C. australis seed and stem, 300 mg/kg body weight/day for seven days, on the testis of the adult Wistar rat fed either low or normal protein-energy diets. The control group received water. The relative weight of the testis was non-significantly increased (p>0.05) in the Low Protein-energy diet-Water-treated (LPWA), Low Protein-energy diet-Seed-treated (LPSE) and Normal Protein-energy diet-Seed-treated (NPSE) groups relative to the Normal Protein-energy diet-Water-treated (NPWA). The weight of the testis was also non-significantly increased (p˃0.05) in the Low Protein-energy diet-Stem-treated (LPST), but decreased in the Normal Protein-energy diet-Stem-treated (NPST), relative to LPWA and NPWA. Heights of germinal epithelium were significantly decreased (p<0.05) in the LPWA, LPSE and LPST relative to the NPWA, NPSE and NPST. Diet significantly influenced (p<0.001) the effect of stem extract on the height of germinal epithelium. The NPSE, LPSE, NPST, LPST and LPWA showed significantly decreased (p<0.001) plasma levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) relative to NPWA. The LPWA, LPSE and NPST also showed significantly decreased (p<0.001) levels of testosterone relative to NPWA and LPST. Diet significantly influenced (p<0.001) the effect of seed on the level of LH. Seed-diet interactions significantly affected the levels of FSH (p<0.001) and LH (p<0.05), but not testosterone. Diet significantly influenced (p<0.001) the effects of stem extract on the levels of FSH, LH and testosterone. Stem-diet interactions significantly affected (p<0.001) the levels of FSH, LH and testosterone. Our data suggest that the aqueous extract of C. australis stem is more potent than the seed extract and that dietary protein

Analyses of risk factors for polycystic ovary syndrome complicated with non-alcoholic fatty liver disease.

PubMed

Zhang, Jianhai; Hu, Jian; Zhang, Chunxia; Jiao, Yanni; Kong, Xiang; Wang, Wei

2018-05-01

The risk factors related to polycystic ovary syndrome (PCOS) patients complicated with non-alcoholic fatty liver disease (NAFLD) were investigated. A total of 188 PCOS patients treated in Shengli Oilfield Central Hospital (Dongying, China) from February 2014 to February 2015 were retrospectively analyzed as PCOS group, and PCOS group was further divided into NAFLD group and non-NAFLD (N-NAFLD) group according to the liver B ultrasound. In the same time-period, 65 healthy people were selected as normal control group. The differences of clinical, biochemical and metabolic indexes were compared. The levels of luteinizing hormone (LH), LH/follicle stimulating hormone (FSH), testosterone (T), free androgen index (FAI), fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) index in PCOS group were higher than those in normal control group, but the sex hormone binding globulin (SHBG) level was lower than that in normal control group (P<0.05); there were no statistically significant differences in comparisons of age, body mass index (BMI), waist-hip ratio (WHR), FSH, dehydroepiandrosterone sulfate (DHEAs) and fasting blood glucose (FBG) between the two groups (P>0.05). The prevalence rate of NAFLD in PCOS group (44.68%) was significantly higher than that in control group (24.62%) (P<0.05). The proportion of NAFLD in PCOS patients in obesity group (63.51%) was significantly higher than that in non-obesity group (15.79%) (P<0.05). In PCOS group, NAFLD patients had more obvious metabolic abnormalities [high BMI, WHR, FBG, FINS, HOMA-IR index, total cholesterol (TC) and triglyceride (TG), and low high-density lipoprotein HDL and SHBG] and androgen excess compared with those in N-NAFLD patients (P<0.05). The levels of LH, LH/FSH, FINS and HOMA-IR index in PCOS group complicated with NAFLD were higher than those in control group complicated with NAFLD (P<0.05), but the differences in age, BMI, WHR, FSH and FBG levels were not statistically

Pharmacokinetics and Bioavailability of the GnRH Analogs in the Form of Solution and Zn2+-Suspension After Single Subcutaneous Injection in Female Rats.

PubMed

Suszka-Świtek, Aleksandra; Ryszka, Florian; Dolińska, Barbara; Dec, Renata; Danch, Alojzy; Filipczyk, Łukasz; Wiaderkiewicz, Ryszard

2017-04-01

Although many synthetic gonadoliberin analogs have been developed, only a few of them, including buserelin, were introduced into clinical practice. Dalarelin, which differs from buserelin by just one aminoacid in the position 6 (D-Ala), is not widely used so far. Gonadotropin-releasing hormone (GnRH) analogs are used to treat many different illnesses and are available in different forms like solution for injection, nasal spray, microspheres, etc. Unfortunately, none of the above drug formulations can release the hormones for 24 h. We assumed that classical suspension could solve this problem. Two sets of experiments were performed. In the first one, buserelin and dalarelin were injected into mature female rats in two forms: suspension, in which the analogs are bounded by Zn 2+ ions and solution. The pharmacokinetic parameters and bioavailability of the analogs were calculated, based on their concentration in the plasma measured by high-performance liquid chromatography method (HPLC). In the second experiment, the hormones in two different forms were injected into superovulated immature female rats and then the concentration of Luteinizing hormone (LH), Follicle-stimulating hormone (FSH) and 17β-estradiol in the serum was measured by radioimmunological method. The Extent of Biological Availability (EBA), calculated on the base of AUC 0-∞ , showed that in the form of solution buserelin and dalarelin display, respectively, only 13 and 8 % of biological availability of their suspension counterparts. Comparing both analogs, the EBA of dalarelin was half (53 %) that of buserelin delivered in the form of solution and 83 % when they were delivered in the form of suspension. The injection of buserelin or dalarelin, in the form of solution or suspension, into superovulated female rats increased LH, FSH and estradiol concentration in the serum. However, after injection of the analogs in the form of suspension, the high concentration of LH and FSH in the serum persisted

MULTIPLE STABLE PERIODIC SOLUTIONS IN A MODEL FOR THE HORMONAL REGULATION OF THE MENSTRUAL CYCLE

EPA Science Inventory

ABSTRACT

The pituitary hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the ovarian hormones, estradiol (E2), progesterone (P4), and inhibin (Ih), are five hormones important for the regulation and maintenance of the human menstrual cycle. The...

Effects of long-term fasting on female hormone levels: Ramadan model.

PubMed

Cağlayan, E K; Göçmen, A Y; Delibas, N

2014-01-01

Ramadan fasting is a special model of hunger and particularly affects metabolic processes, including carbohydrate and lipid levels. Endocrine changes induced by Ramadan fasting are not well known. The aim of this article was to evaluate the changes in hormone levels in women before and after the special Muslim fasting period of Ramadan. This study was performed in 30 healthy women in Obstetrics and Gynecology department during the Ramadan month of2011. Patients during and after the first menstrual period had menstrual cycles fasting blood samples taken on the same days. Luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), testosterone, and prolactin (PRL) levels were determined. Before and during fasting LH, FSH, E2, testosterone and PRL levels were not statistically different. Despite the limited available studies on these subjects in women, effect of Ramadan fasting on hormone levels were found to be within the normal limits.

Gonadotropin levels in urine during early postnatal period in small for gestational age preterm male infants with fetal growth restriction.

PubMed

Nagai, S; Kawai, M; Myowa-Yamakoshi, M; Morimoto, T; Matsukura, T; Heike, T

2017-07-01

The objective of this study was to estimate gonadotropin concentrations in small for gestational age (SGA) male infants with the reactivation of the hypothalamic-pituitary-gonadal axis during the first few months of life that is important for genital development. We prospectively examined 15 SGA and 15 appropriate for gestational age (AGA) preterm male infants between 2013 and 2014 at Kyoto University Hospital. Gonadotropin concentrations (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) were measured in serial urine samples from the postnatal days 7 to 168 and compared between SGA and AGA infants using the Mann-Whitney test. A longitudinal analysis showed that SGA infants had higher LH and lower FSH concentrations (P=0.004 and P=0.006, respectively) than AGA infants. Male infants who are SGA at birth because of fetal growth restriction have gonadotropin secretion abnormalities in the first few months of life.

Insulin signalling and glucose transport in the ovary and ovarian function during the ovarian cycle

PubMed Central

Dupont, Joëlle; Scaramuzzi, Rex J.

2016-01-01

Data derived principally from peripheral tissues (fat, muscle and liver) show that insulin signals via diverse interconnecting intracellular pathways and that some of the major intersecting points (known as critical nodes) are the IRSs (insulin receptor substrates), PI3K (phosphoinositide kinase)/Akt and MAPK (mitogen-activated protein kinase). Most of these insulin pathways are probably also active in the ovary and their ability to interact with each other and also with follicle-stimulating hormone (FSH) and luteinizing hormone (LH) signalling pathways enables insulin to exert direct modulating influences on ovarian function. The present paper reviews the intracellular actions of insulin and the uptake of glucose by ovarian tissues (granulosa, theca and oocyte) during the oestrous/menstrual cycle of some rodent, primate and ruminant species. Insulin signals through diverse pathways and these are discussed with specific reference to follicular cell types (granulosa, theca and oocyte). The signalling pathways for FSH in granulosa cells and LH in granulosa and theca cells are summarized. The roles of glucose and of insulin-mediated uptake of glucose in folliculogenesis are discussed. It is suggested that glucose in addition to its well-established role of providing energy for cellular function may also have insulin-mediated signalling functions in ovarian cells, involving AMPK (AMP-dependent protein kinase) and/or hexosamine. Potential interactions of insulin signalling with FSH or LH signalling at critical nodes are identified and the available evidence for such interactions in ovarian cells is discussed. Finally the action of the insulin-sensitizing drugs metformin and the thiazolidinedione rosiglitazone on follicular cells is reviewed. PMID:27234585

Protective effects of persian honey, Apis Mellifera Meda Skorikov on side effects of chemotherapy and ischemia/reperfusion induced testicular injury.

PubMed

Gholami, Mohammadreza; Abbaszadeh, Abolfazl; Baharvand, Parastoo; Hasanvand, Afshin; Hasanvand, Amin; Gharravi, Anneh Mohammad

2018-05-23

Introduction The aim of the present study was to survey the protective effect of pretreatment with Persian honey on amelioration of side effects of chemotherapy and ischemia/reperfusion induced testicular injury. Materials and methods Forty adult's male wistar rats were divided into four groups of ischemia-reperfusion (IR), honey + ischemia-reperfusion (HIR), Busulfan (B) and Busulfan intraperitoneally+ honey (BH). The seminiferous tubules were rated for their modified spermatogenesis index (SI) by Johnsons score. Detection of single- and double-stranded DNA breaks at the early stages of apoptosis was performed using the in-situ cell death detection kit. Total serum concentration of Follicle-stimulating hormone (FSH) , Luteinizing hormone (LH) and testosterone was measured using ELISA. All data were expressed as mean ± SD and significance was set at p≤0.05. Results Honey improved SI in the HIR and BH groups and serum levels of FSH and LH in the BH and HIR groups (p<0.001). Also, serum levels of testosterone were significantly higher in BH and HIR groups. But, apoptotic cells in IR and B groups significantly increased (p<0.001), while in HIR and BH groups, the number of apoptotic cells decreased and the positive cells of TUNEL (TdT-mediated dUTP-X nick end labelling) staining were detected in spermatocytes and spermatid. Discussion Pretreatment with honey protect testis against chemotherapy and testicular IR injury, increase FSH and LH and testosterone and decrease the cellular damage and apoptosis. Honey can decrease the side effects of chemotherapy on reproductive system and prevent sterility.

Effects of exosome-like vesicles on cumulus expansion in pigs in vitro.

PubMed

Matsuno, Yuta; Onuma, Asuka; Fujioka, Yoshie A; Yasuhara, Kazuma; Fujii, Wataru; Naito, Kunihiko; Sugiura, Koji

2017-02-16

Cell-secreted vesicles, such as exosomes, have recently been recognized as mediators of cell communication. A recent study in cattle showed the involvement of exosome-like vesicles in the control of cumulus expansion, a prerequisite process for normal ovulation; however, whether this is the case in other mammalian species is not known. Therefore, this study aimed to examine the presence of exosome-like vesicles in ovarian follicles and their effects on cumulus expansion in vitro in pigs. The presence of exosome-like vesicles in porcine follicular fluid (pFF) was confirmed by transmission electron microscopic observation, the detection of marker proteins, and RNA profiles specific to exosomes. Fluorescently labeled exosome-like vesicles isolated from pFF were incorporated into both cumulus and mural granulosa cells in vitro. Exosome-like vesicles were not capable of inducing cumulus expansion to a degree comparable to that induced by follicle-stimulating hormone (FSH). Moreover, exosome-like vesicles had no significant effects on the expression levels of transcripts required for the normal expansion process (HAS2, TNFAIP6, and PTGS2). Interestingly, FSH-induced expression of HAS2 and TNFAIP6 mRNA, but not of PTGS2 mRNA, was significantly increased by the presence of exosome-like vesicles; however, the degree of FSH-induced expansion was not affected. In addition, porcine exosome-like vesicles had no significant effects on the expansion of mouse cumulus-oocyte complexes. Collectively, the present results suggest that exosome-like vesicles are present in pFF, but they are not efficient in inducing cumulus expansion in pigs.

Ovarian and uterine alterations following forced swimming: An immunohistochemical study

PubMed Central

Seyed Saadat, Seyedeh Nazanin; Mohammadghasemi, Fahimeh; Ebrahimi, Hannan; Rafati Sajedi, Hanieh; Chatrnour, Gelayol

2016-01-01

Background: Physical exercise is known to be a stressor stimulus that leads to reproductive disruption. Objective: The aim of this study was to evaluate the effect of forced swimming on the uterus and ovaries in mice. Materials and Methods: Adult mice (N=24) were divided into the following three groups: A, control; B, swimming in water (10oC); and C, swimming in water (23oC). Swimmers swam for 5 min daily for 5 consecutive days/ wk during 2 wks. An enzyme linked immunosorbent assay was used to determine serum estradiol, follicle stimulating hormone (FSH) and testosterone levels. Immunohistochemistry was performed to study apoptotic cells or estrogen receptor (ER) expression in uterine epithelial cells and ovaries. ANOVA was used for statistical analysis. Results: Swimming in both groups reduced the serum FSH and estradiol levels (p<0.01) without having a significant effect on the serum testosterone level or percentage of apoptosis in ovarian and uterine tissues (p<0.01) compared with controls. A significant reduction in the number of ERs in the uterus and ovaries, and secondary and graafian follicles were observed in groups B and C compared with controls (p<0.01); however the number of primordial and primary follicles were not significantly changed in the ovaries. Conclusion: Forced swimming of 2 wks duration reduces the serum levels of FSH and estradiol without having effects on apoptosis in the ovaries or uteri of mice. Over a long period of time, forced swimming may have an adverse effect on fertility. PMID:27921086

Functional Gonadotroph Adenomas: Case Series and Report of Literature

PubMed Central

Cote, David J.; Smith, Timothy R.; Sandler, Courtney N.; Gupta, Tina; Bale, Tejus A.; Bi, Wenya Linda; Dunn, Ian F.; De Girolami, Umberto; Woodmansee, Whitney W.; Kaiser, Ursula B.; Laws, Edward R.

2016-01-01

Background Functional gonadotroph adenomas (FGA) are rare tumors of the pituitary gland that secrete biologically active gonadotropins. Objective To advance clinical understanding of FGA. Methods We performed a retrospective review of adult patients who underwent resection of a pituitary lesion between August 1997 and October 2014 and remain under care at our center. We identified patients who had pathologic and biochemical confirmation of FGA, as defined by lack of serum LH/FSH suppression in the setting of elevated gonadal steroids, associated clinical symptoms, or both. Results FGA was documented in seven patients (five men, two women) over a 17-year period. Clinical findings at presentation included visual field deficits in five patients, headache in three, sexual dysfunction in three, and ovarian cysts in both women. Each patient underwent lesional resection (six by the endonasal transsphenoidal approach, one by craniotomy with transsphenoidal reoperation). Analysis of tumor samples revealed immunopositivity for FSH/LH in five patients and FSH only in two patients. Post-operative follow-up (median 10 mo, range 4-213 mo) indicated remission in six of seven patients. Conclusion FGA can pose both a diagnostic and therapeutic challenge. The tumor is often diagnosed as a nonfunctioning macroadenoma after presenting with non-specific symptoms, and is the cause of significant morbidity. FGA should be considered in the differential diagnosis of patients harboring pituitary adenomas with reproductive dysfunction. Transsphenoidal resection is the initial treatment of choice, and can reduce endocrine dysfunction, resolve headaches, improve visual impairment, and provide tissue for detailed analysis. PMID:26692108

The effect of lead intoxication on endocrine functions.

PubMed

Doumouchtsis, K K; Doumouchtsis, S K; Doumouchtsis, E K; Perrea, D N

2009-02-01

Studies on the effects of lead on the endocrine system are mainly based on occupationally lead-exposed workers and experimental animal models. Although evidence is conflicting, it has been reported that accumulation of lead affects the majority of the endocrine glands. In particular, it appears to have an effect on the hypothalamic-pituitary axis causing blunted TSH, GH, and FSH/LH responses to TRH, GHRH, and GnRH stimulation, respectively. Suppressed GH release has been reported, probably caused by reduced synthesis of GHRH, inhibition of GHRH release or reduced somatotrope responsiveness. Higher levels of PRL in lead intoxication have been reported. In short-term lead-exposed individuals, high LH and FSH levels are usually associated to normal testosterone concentrations, whereas in long-term exposed individuals' low testosterone levels do not induce high LH and FSH concentrations. These findings suggest that lead initially causes some subclinical testicular damage, followed by hypothalamic or pituitary disturbance when longer periods of exposure take place. Similarly, lead accumulates in granulosa cells of the ovary, causing delays in growth and pubertal development and reduced fertility in females. In the parenchyma of adrenals histological and cytological changes are demonstrated, causing changes in plasma basal and stress-mediated corticosterone concentrations and reduced cytosolic and nuclear glucocorticoid receptor binding. Thyroid hormone kinetics are also affected. Central defect of the thyroid axis or an alteration in T4 metabolism or binding to proteins may be involved in derangements in thyroid hormone action. Lead toxicity involves alterations on calcitropic hormones' homeostasis, which increase the risk of skeletal disorders.

Effects of exosome-like vesicles on cumulus expansion in pigs in vitro

PubMed Central

MATSUNO, Yuta; ONUMA, Asuka; FUJIOKA, Yoshie A; YASUHARA, Kazuma; FUJII, Wataru; NAITO, Kunihiko; SUGIURA, Koji

2017-01-01

Cell-secreted vesicles, such as exosomes, have recently been recognized as mediators of cell communication. A recent study in cattle showed the involvement of exosome-like vesicles in the control of cumulus expansion, a prerequisite process for normal ovulation; however, whether this is the case in other mammalian species is not known. Therefore, this study aimed to examine the presence of exosome-like vesicles in ovarian follicles and their effects on cumulus expansion in vitro in pigs. The presence of exosome-like vesicles in porcine follicular fluid (pFF) was confirmed by transmission electron microscopic observation, the detection of marker proteins, and RNA profiles specific to exosomes. Fluorescently labeled exosome-like vesicles isolated from pFF were incorporated into both cumulus and mural granulosa cells in vitro. Exosome-like vesicles were not capable of inducing cumulus expansion to a degree comparable to that induced by follicle-stimulating hormone (FSH). Moreover, exosome-like vesicles had no significant effects on the expression levels of transcripts required for the normal expansion process (HAS2, TNFAIP6, and PTGS2). Interestingly, FSH-induced expression of HAS2 and TNFAIP6 mRNA, but not of PTGS2 mRNA, was significantly increased by the presence of exosome-like vesicles; however, the degree of FSH-induced expansion was not affected. In addition, porcine exosome-like vesicles had no significant effects on the expansion of mouse cumulus-oocyte complexes. Collectively, the present results suggest that exosome-like vesicles are present in pFF, but they are not efficient in inducing cumulus expansion in pigs. PMID:28163264

Triple X syndrome and puberty: focus on the hypothalamus-hypophysis-gonad axis.

PubMed

Stagi, Stefano; di Tommaso, Mariarosaria; Scalini, Perla; Lapi, Elisabetta; Losi, Stefania; Bencini, Erica; Masoni, Fabrizio; Dosa, Laura; Becciani, Sabrina; de Martino, Maurizio

2016-06-01

To evaluate the hypothalamus-hypophysis-gonad axis in a cohort of children and adolescents with nonmosaic triple X syndrome. Cross-sectional study with retrospective analysis. University pediatric hospital. Fifteen prepubertal subjects (median age 9.0 years, range 6.9-11.9 years) with nonmosaic triple X syndrome and age- and pubertal-matched control group (30 girls, median age 9.1 y, range 6.9-11.6 years). None. We evaluated FSH, LH, and E2 levels and performed an autoimmunity screening as well as a pelvic ultrasonography and an LH-releasing hormone stimulation test. All triple X patients (with and without pubertal signs) showed a pubertal LH peak level that was significantly different from controls. Triple X patients showed increased basal and peak FSH and LH values compared with control subjects. However, the mean E2 level was significantly lower than control subjects. However, triple X patients showed reduced DHEAS levels and reduced inhibin levels compared with control subjects. Finally, triple X patients had a significantly reduced ovarian volume compared with control subjects, in both prepubertal and pubertal patients. Triple X patients showed premature activation of the GnRH pulse generator, even without puberty signs. Both basal and peak LH and FSH levels were higher than in control subjects, and E2 and inhibin levels and ovarian volume were reduced, which led to a reduced gonadal function. Other studies and a longitudinal evaluation is necessary to better understand the endocrinologic features of these subjects. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

rs4889 polymorphism in KISS1 gene, its effect on polycystic ovary syndrome development and anthropometric and hormonal parameters in Saudi women.

PubMed

Albalawi, Fadwa S; Daghestani, Maha H; Daghestani, Mazin H; Eldali, Abdelmoneim; Warsy, Arjumand S

2018-05-30

Kisspeptin is involved in female reproduction. This study was designed to i- estimate kisspeptin levels in women with polycystic ovary syndrome (PCOS), in comparison with controls, ii- study the correlations between kisspeptin and PCOS-related reproductive hormones, and iii- investigate the relation between KISS1 gene polymorphisms and hormone levels in women suffering from PCOS. The investigation was a clinically designed study on 28 women with PCOS, and 30 normal, healthy women with no signs of PCOS as controls. Blood samples were collected between day 3 and day 6 of the menstrual cycle in both groups at 8:00 a.m., and circulating levels of LH, FSH and kisspeptin were estimated. DNA was extracted from whole blood and all coding exons of KISS1 gene were sequenced. Women with PCOS had higher LH levels and BMI compared to controls. Plasma kisspeptin levels were positively correlated with LH levels. There was no statistically significant difference between the groups in terms of kisspeptin and FSH levels. The SNP rs4889 C/G, a non-synonymous SNP, was investigated in the PCOS group. The frequency of GG genotype was significantly higher in the PCOS compared to the controls. These patients were more obese, had higher kisspeptin and FSH levels. The results of the study show that the genetic variation of KISS1 gene may be a factor contributing to PCOS development. The association between the gene and the gene variation and PCOS need further validation in large-scaled and functional studies.

A novel homozygous mutation in the FSHR gene is causative for primary ovarian insufficiency.

PubMed

Liu, Hongli; Xu, Xiaofei; Han, Ting; Yan, Lei; Cheng, Lei; Qin, Yingying; Liu, Wen; Zhao, Shidou; Chen, Zi-Jiang

2017-12-01

To identify the potential FSHR mutation in a Chinese woman with primary ovarian insufficiency (POI). Genetic and functional studies. University-based reproductive medicine center. A POI patient, her family members, and another 192 control women with regular menstruation. Ovarian biopsy was performed in the patient. Sanger sequencing was carried out for the patient, her sister, and parents. The novel variant identified was further confirmed with the use of control subjects. Sanger sequencing and genotype analysis to identify the potential variant of the FSHR gene; hematoxylin and eosin staining of the ovarian section to observe the follicular development; Western blotting and immunofluorescence to detect FSH receptor (FSHR) expression; and cyclic adenosine monophosphate (cAMP) assay to monitor FSH-induced signaling. Histologic examination of the ovaries in the patient revealed follicular development up to the early antral stage. Mutational screening and genotype analysis of the FSHR gene identified a novel homozygous mutation c.175C>T (p.R59X) in exon 2, which was inherited in the autosomal recessive mode from her heterozygous parents but was absent in her sister and the 192 control women. Functional studies demonstrated that in vitro the nonsense mutation caused the loss of full-length FSHR expression and that p.R59X mutant showed no response to FSH stimulation in the cAMP level. The mutation p.R59X in FSHR is causative for POI by means of arresting folliculogenesis. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Pubertal development and primary ovarian insufficiency in female survivors of embryonal brain tumors following risk-adapted craniospinal irradiation and adjuvant chemotherapy.

PubMed

DeWire, Mariko; Green, Daniel M; Sklar, Charles A; Merchant, Thomas E; Wallace, Dana; Lin, Tong; Vern-Gross, Tamara; Kun, Larry E; Krasin, Matthew J; Boyett, James M; Wright, Karen D; Wetmore, Cynthia; Broniscer, Alberto; Gajjar, Amar

2015-02-01

Female survivors of central nervous system (CNS) tumors are at an increased risk for gonadal damage and variations in the timing of puberty following radiotherapy and alkylating agent-based chemotherapy. Clinical and laboratory data were obtained from 30 evaluable female patients with newly diagnosed embryonal CNS tumors treated on a prospective protocol (SJMB 96) at St. Jude Children's Research Hospital (SJCRH). Pubertal development was evaluated by Tanner staging. Primary ovarian insufficiency (POI) was determined by Tanner staging and FSH level. Females with Tanner stage I-II and FSH > 15 mIU/ml, or Tanner stage III-V, FSH > 25 mIU/ml and FSH greater than LH were defined to have ovarian insufficiency. Recovery of ovarian function was defined as normalization of FSH without therapeutic intervention. Median length of follow-up post completion of therapy was 7.2 years (4.0-10.8 years). The cumulative incidence of pubertal onset was 75.6% by the age of 13. Precocious puberty was observed in 11.1% and delayed puberty in 11.8%. The cumulative incidence of POI was 82.8%, though recovery was observed in 38.5%. Treatment for primary CNS embryonal tumors may cause variations in the timing of pubertal development, impacting physical and psychosocial development. Female survivors are at risk for POI, a subset of whom will recover function over time. Further refinement of therapies is needed in order to reduce late ovarian insufficiency. Pediatr Blood Cancer 2015;62:329-334. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Serum Leptin and Ghrelin Levels in Women with Polycystic Ovary Syndrome: Correlation with Anthropometric, Metabolic, and Endocrine Parameters

PubMed Central

Houjeghani, Shiva; Pourghassem Gargari, Bahram; Farzadi, Laya

2012-01-01

Background Polycystic ovary syndrome (PCOS) patients are more prone to abnormal production of some regulatory peptides. In these patients, studies on the serum levels of leptin and ghrelin are controversial. This study aims to investigate serum levels of leptin and ghrelin and their correlation with metabolic and endocrine indices in PCOS. Materials and Methods This case-control study was conducted on 60 women; 30 with PCOS and 30 healthy women whose age and body mass index (BMI) were matched and who were referred to Alzahra Hospital, Tabriz, Iran. Serum levels of leptin, ghrelin, insulin, luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and testosterone were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Descriptive statistics and correlations were performed using SPSS 12.0 for Windows. Results In PCOS women, serum levels of leptin, insulin, HOMA-IR, testosterone, LH, and LH/FSH were significantly higher, while SHBG was lower than in healthy women. Ghrelin and FSH were similar in both groups. Serum levels of leptin correlated with BMI (r=0.85, p<0.001), waist to hip ratio (WHR) (r=0.55, p<0.01), insulin levels (r=0.85, p<0.001) and HOMA-IR (r=0.67, p<0.01), while ghrelin levels had an inverse association with testosterone (r=-0.32, p=0.04). Conclusion The results showed increased leptin levels while ghrelin remained unchanged in PCOS patients. In PCOS patients, leptin positively correlated with BMI, WHR, insulin, and insulin resistance, while ghrelin was only associated with serum testosterone levels. PMID:25493169

Interpretation of serum gonadotropin levels in hyperprolactinemia.

PubMed

Abbara, Ali; Clarke, Sophie A; Nesbitt, Alexander; Ali, Sabreen; Comninos, Alexander N; Hatfield, Emma; Martin, Niamh; Sam, Amir; Meeran, Karim; Dhillo, Waljit S

2018-04-16

Background/Aims: Hyperprolactinemia is a common cause of amenorrhea due to hypogonadotropic hypogonadism. Prolactin is hypothesized to impede the reproductive axis through an inhibitory action at the hypothalamus. However, limited data exists to aid the interpretation of serum gonadotropins in the context of hyperprolactinemia. Serum gonadotropin values were reviewed in 243 patients with elevated serum monomeric prolactin due to discrete etiologies at a tertiary reproductive endocrine centre between 2012 and 2015. The cause of hyperprolactinemia was categorized by an experienced endocrinologist / pituitary multidisciplinary team, unless superseded by histology. The most frequently encountered diagnoses were Microprolactinoma (n=88), Macroprolactinoma (n=46), Non-Functioning Pituitary Adenoma (NFPA) (n=72), Drug-Induced Hyperprolactinemia (DIH) (n=22) and Polycystic Ovarian Syndrome (PCOS) (n=15). In patients with prolactinoma and modestly raised serum prolactin levels (<4000 mU/L), increasingly FSH-predominant gonadotropin values were observed with rising prolactin level, consistent with a progressive reduction in hypothalamic GnRH pulsatility. Patients with prolactinoma and higher prolactin values (>4000 mU/L) were more likely to have a reduction in serum levels of both FSH and LH, consistent with direct pituitary gonadotrope dysfunction. Patients with macroadenoma and extremes of serum gonadotropin values (either serum FSH or LH >8 IU/L) were more likely to have NFPA than prolactinoma. Patients with polycystic ovarian syndrome (PCOS) and hyperprolactinemia had LH-predominant secretion in keeping with increased GnRH pulsatility despite a raised prolactin level. The pattern of gonadotropin secretion in patients may reflect the etiology of hyperprolactinemia.
. ©2018S. Karger AG, Basel.

Plasticity of the reproductive axis caused by social status change in an african cichlid fish: I. Pituitary gonadotropins.

PubMed

Maruska, Karen P; Levavi-Sivan, Berta; Biran, Jakob; Fernald, Russell D

2011-01-01

Social position in a dominance hierarchy is often tightly coupled with fertility. Consequently, an animal that can recognize and rapidly take advantage of an opportunity to rise in rank will have a reproductive advantage. Reproduction in all vertebrates is controlled by the brain-pituitary-gonad axis, and in males of the African cichlid fish Astatotilapia burtoni, GnRH1 neurons at the apex of this axis are under social control. However, little is known about how quickly social information is transformed into functional reproductive change, or about how socially controlled changes in GnRH1 neurons influence downstream actions of the brain-pituitary-gonad axis. We created an opportunity for reproductively suppressed males to ascend in status and then measured how quickly the perception of this opportunity caused changes in mRNA and protein levels of the pituitary gonadotropins. mRNA levels of the β-subunits of LH and FSH rose rapidly in the pituitary 30 min after suppressed males perceived an opportunity to ascend. In contrast, mRNA levels of GnRH receptor-1 remained unchanged during social transition but were higher in stable dominant compared with subordinate males. In the circulation, levels of both LH and FSH were also quickly elevated. There was a positive correlation between mRNA in the pituitary and circulating protein levels for LH and FSH, and both gonadotropins were positively correlated with plasma 11-ketotestosterone. Our results show that the pituitary is stimulated extremely rapidly after perception of social opportunity, probably to allow suppressed males to quickly achieve reproductive success in a dynamic social environment.

Evaluation of irregular menses in perimenarcheal girls: a pilot study.

PubMed

Browner-Elhanan, Karen J; Epstein, Jonathan; Alderman, Elizabeth M

2003-12-01

Acyclic vaginal bleeding in girls within three years of menarche is most commonly attributed to an immature hypothalamic-pituitary-ovarian axis. Assuming this diagnosis may preclude the practitioner from performing more definitive studies and thereby diagnosing other, treatable causes of menstrual irregularities. A retrospective chart review of 178 girls presenting to an inner-city hospital-based adolescent clinic within three years of menarche was performed. Personal and family medical and menarcheal history was assessed, and findings on physical and laboratory examination performed were evaluated. Of the 178 girls still perimenarcheal at presentation, 47 were the focus of this study. Of these, 39 had no significant findings on physical examination, while 3 had signs of functional ovarian hyperandrogenism (FOH) including obesity, hirsutism, and moderate acne with corresponding LH/FSH ratios>3, although pelvic ultrasound examination revealed normal ovaries. Four of the 39 patients with normal physical exams had LH/FSH testing done, and 1 of the 4 had an abnormal LH/FSH ratio, indicating possible FOH. Two of the 47 patients were pregnant. Other laboratory abnormalities included microcytic, hypochromic anemia in patients, and an elevated Erythrocyte Sedimentation Rate in a patient later diagnosed with a rheumatologic disorder. Those perimenarcheal girls presenting with irregular menses and findings including obesity, acne, or pallor, were likely to have treatable causes of menstrual irregularities. In one of the four girls with a normal physical examination, hormonal testing indicated possible FOH, thus suggesting that hormonal evaluation of perimenarcheal girls with menstrual irregularities may be justified, as it may reveal previously unsuspected pathology.

Functional genetic polymorphisms and female reproductive disorders: Part I: polycystic ovary syndrome and ovarian response

PubMed Central

Simoni, M.; Tempfer, C.B.; Destenaves, B.; Fauser, B.C.J.M.

2008-01-01

BACKGROUND The identification of polymorphisms associated with a disease can help to elucidate its pathogenesis, and this knowledge can be used to improve prognosis for women with a particular disorder, such as polycystic ovary syndrome (PCOS). Since an altered response to ovarian stimulation is also a characteristic of the disease, further knowledge about its aetiology could help in defining the parameters that determine the response of an individual to ovarian stimulation. METHODS PubMed and EMBASE databases were systematically searched for gene association studies published until the end of August 2007, using search criteria relevant to PCOS and ovarian response to stimulation. Data from additional papers identified through hand searches were also included; 139 publications were reviewed. RESULTS Several genes involved in ovarian function and metabolism are associated with increased susceptibility to PCOS, but none is strong enough to correlate alone with susceptibility to the disease, or response to therapy. A single-nucleotide polymorphism in exon 10 of the FSH receptor (FSHR) gene, FSHR p.N680S, was consistently identified as having a significant association with ovarian response to FSH. CONCLUSIONS No consistent association between gene polymorphism and PCOS could be identified. The FSHR gene may play a significant role in the success of ovarian stimulation, and can be used as a marker to predict differences in FSHR function and ovarian response to FSH. Genotyping the FSHR p.N680S polymorphism may provide a means of identifying a population of poor responders before in vitro fertilization procedures are initiated. PMID:18603647

Occult Form of Premature Ovarian Insufficiency in Women with Infertility and Oligomenorrhea as Assessed by Poor Ovarian Response Criteria.

PubMed

Izhar, Rubina; Husain, Samia; Tahir, Suhaima; Husain, Sonia

2017-01-01

The purpose of this study was to evaluate the ability of poor ovarian response criteria to classify women presenting with infertility and oligomenorrhea as having "occult" premature ovarian insufficiency. This was a cross sectional study conducted at Aziz Medical Center, Karachi, Pakistan from 1st August 2015 to 31st July 2016. Women with infertility and oligomenorrhea were included. All eligible women underwent day 2 FSH level and an early follicular phase transvaginal ultrasound to assess the antral follicular count (AFC). All women then underwent the confirmatory test, of Anti-Mullerian Hormone (AMH) level. The main outcome measure was assignment to occult premature ovarian insufficiency (POI) after screening that used the criteria set out in fertility guideline for predicting the likely ovarian response to gonadotrophin stimulation. Another measure was to compare the sensitivity and specificity of the two index criteria, of FSH and AFC, relative to the emerging reference standard, of the AMH criterion. The three criteria together classified 59 (34.91%) women as occult POI in those with oligomenorrhea. The sensitivity, specificity, negative predictive value and positive predictive value of FSH relative to AMH for these women were 77.8%, 95.7%, 90.2% and 89.4%, respectively whereas the same values of AFC relative to AMH were 92.6%, 99.1 %, 96.6% and 98%, respectively. Women with menstrual irregularity and infertility are at a higher risk for satisfying criteria of poor ovarian response irrespective of age. A policy incorporating these surrogate markers can be used to screen these women for occult premature ovarian insufficiency.

Effects of a single use of the GnRH analog buserelin on the induction of ovulation and endocrine profiles in heavy draft mares.

PubMed

Miki, Wataru; Oniyama, Hiroyuki; Takeda, Naomasa; Kimura, Yuki; Haneda, Shingo; Matsui, Motozumi; Taya, Kazuyoshi; Nambo, Yasuo

2016-01-01

We observed structural changes in the follicles and uterus of heavy draft mares during estrus and examined the effect of a single injection of the gonadotropin-releasing hormone analog buserelin on ovulation and endocrine profiles. Twenty-two heavy draft mares were divided into a buserelin-treated group (n=8) and a control group (n=14). Mares were given an intramuscular injection of 40 µg buserelin when they presented signs of estrus to a teaser stallion, had ≥45 mm diameter follicles, and presented decreased uterine edema compared with the previous examination. The follicles and uterus were monitored using transrectal ultrasound imaging and measurement of blood levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone, and estradiol-17β. The ovulation rates within 48 hr was significantly higher in the treated group (100%, 8/8) than in the control group (57.1%, 8/14; P=0.051). The mean ± SEM time before confirmation of ovulation was 29 ± 9 hr for the treated group and 59 ± 7 hr for the control group. There were no significant differences in mating frequency, double ovulation rate, or fertility rate between the two groups. One to two days after administering buserelin, LH and FSH temporarily increased, and in the control group, LH was high during ovulation, whereas FSH temporarily increased with the growth of the follicle. These results indicate that a single injection of 40 µg buserelin when follicles are at least 45 mm in diameter and uterine edema is decreased is effective for inducing ovulation.

Pivagabine decreases stress-related hormone secretion in women with hypothalamic amenorrhea.

PubMed

Genazzani, A D; Stomati, M; Bersi, C; Luisi, S; Fedalti, M; Santuz, M; Esposito, G; Petraglia, F; Genazzani, A R

2000-09-01

Stress-induced neuroendocrine activities influence the regulation of endocrine glands and axes. Weight loss-related hypothalamic amenorrhea is a typical stress-induced physiopathological condition. It is characterized by increased adrenal cortex activation and by reduced GH, LH, FSH and gonadal steroid hormone levels. The aim of the present study was to investigate the effects of pivagabine, a neurotropic drug (1800 mg/day for 7 days) or placebo administration on ACTH, cortisol, GH, LH, FSH and PRL plasma levels in patients with hypothalamic amenorrhea related to weight loss. Hormonal parameters and the pulsatile release of cortisol (6-hour pulsatility, sampling every 10 minutes) were evaluated before and after 7 days of treatment. Pivagabine administration significantly reduced mean plasma ACTH (from 21.7+/-1.7 to 15.4+/-1.2 pg/ml, p<0.05) and cortisol levels (from 12.2+/-0.7 to 9.7+/-0.7 ng/ml, p<0.05) and increased GH levels (from 1.4+/-0.5 to 3.0+/-0.9 ng/ml, p<0.05). A significant reduction of cortisol pulse amplitude was observed (p<0.01) while no change in pulse frequency occurred. No changes were observed in placebo-treated subjects. LH, FSH and PRL levels were not modified by placebo or pivagabine administration. In conclusion, in patients with hypothalamic amenorrhea related to weight loss pivagabine induced a significant decrease of cortisol secretion and an increase of GH release by pivagabine administration, suggesting that this drug exerts a specific neuroendocrine modulatory role.

Dose-Dependent Suppression of Gonadotropins and Ovarian Hormones by Elagolix in Healthy Premenopausal Women.

PubMed

Ng, Juki; Chwalisz, Kristof; Carter, David C; Klein, Cheri E

2017-05-01

Elagolix is a nonpeptide, oral gonadotropin-releasing hormone (GnRH) antagonist being developed for sex-hormone-dependent diseases in women. We evaluated the pharmacokinetics and pharmacodynamics of elagolix. This study was a randomized, double-blind, placebo-controlled, multiple-ascending dose study in 45 healthy premenopausal women at a research unit. Elagolix [150 mg once daily or 100, 200, 300, or 400 mg twice daily (BID)] or placebo was administered for 21 days. Main outcome measures were elagolix pharmacokinetics, suppression of gonadotropics [follicle-stimulating hormone (FSH), luteinizing hormone (LH)] and ovarian hormones [estradiol (E2), progesterone (P)], and adverse events. Elagolix was rapidly absorbed after oral dosing, reaching maximum concentrations at 1.0 to 1.5 hours, with a half-life of 4 to 6 hours. FSH, LH, and E2 were suppressed within hours of elagolix administration on day 1. Dose-dependent suppression of E2 was observed, with maximum suppression achieved with elagolix 200 mg BID. Dose-dependent suppression of FSH and LH was also observed, with maximal or near-maximal suppression achieved at 300 mg BID and 200 mg BID, respectively. At elagolix doses ≥100 mg BID, P concentrations remained at anovulatory levels throughout 21 days of dosing. The most frequently reported adverse events were headache and hot flush. Elagolix administration allows for modulation of gonadotropin and ovarian hormone concentrations, from partial suppression at lower doses to nearly full suppression at higher doses. The results of this study provide a rationale for elagolix dose selection for treatment of sex hormone-dependent diseases in women. Copyright © 2017 Endocrine Society

The G-protein coupled estrogen receptor (GPER/GPR30) is a gonadotropin receptor dependent positive prognosticator in ovarian carcinoma patients.

PubMed

Heublein, Sabine; Mayr, Doris; Vrekoussis, Thomas; Friese, Klaus; Hofmann, Simone S; Jeschke, Udo; Lenhard, Miriam

2013-01-01

Follicle stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHCGR) were demonstrated to impact upon survival of patients suffering from epithelial ovarian cancer (EOC). Though structure wise the G-protein coupled estrogen receptor (GPER/GPR30) is related to FSHR/LHCGR, its prognostic impact in EOC remains controversial. We recently found that FSHR negative patients represent a specific EOC subgroup that may behave differently in respect to both treatment response and prognosis. Hence, the current study aimed to analyze how GPER may interact with the FSHR/LHCGR system in EOC and whether the prognostic significance of GPER in EOC cases (n=151) may be dependent on the FSHR/LHCGR immunophenotype of the tumor. Ovarian cancer cell lines were used to study how FSH and LH regulate GPER and whether GPER activation differentially affects in vitro cell proliferation in presence/absence of activated FSHR/LHCGR. In EOC tissue, GPER correlated with FSHR/LHCGR and was related to prolonged overall survival only in FSHR/LHCGR negative patients. Although GPER was found to be specifically induced by LH/FSH, GPER agonists (4-Hydroxy-Tamoxifen, G1) reduced EOC cell proliferation only in case of LH/FSH unstimulated pathways. To the same direction, only patients characterized as LHCGR/FSHR negative seem to gain from GPER in terms of survival. Our combined tissue and in vitro results support thus the hypothesis that GPER activation could be of therapeutic benefit in LHCGR/FSHR negative EOC patients. Further studies are needed to evaluate the impact of GPER activation on a clinical scheme.

The G-Protein Coupled Estrogen Receptor (GPER/GPR30) is a Gonadotropin Receptor Dependent Positive Prognosticator in Ovarian Carcinoma Patients

PubMed Central

Heublein, Sabine; Mayr, Doris; Vrekoussis, Thomas; Friese, Klaus; Hofmann, Simone S.

2013-01-01

Follicle stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHCGR) were demonstrated to impact upon survival of patients suffering from epithelial ovarian cancer (EOC). Though structure wise the G-protein coupled estrogen receptor (GPER/GPR30) is related to FSHR/LHCGR, its prognostic impact in EOC remains controversial. We recently found that FSHR negative patients represent a specific EOC subgroup that may behave differently in respect to both treatment response and prognosis. Hence, the current study aimed to analyze how GPER may interact with the FSHR/LHCGR system in EOC and whether the prognostic significance of GPER in EOC cases (n = 151) may be dependent on the FSHR/LHCGR immunophenotype of the tumor. Ovarian cancer cell lines were used to study how FSH and LH regulate GPER and whether GPER activation differentially affects in vitro cell proliferation in presence/absence of activated FSHR/LHCGR. In EOC tissue, GPER correlated with FSHR/LHCGR and was related to prolonged overall survival only in FSHR/LHCGR negative patients. Although GPER was found to be specifically induced by LH/FSH, GPER agonists (4-Hydroxy-Tamoxifen, G1) reduced EOC cell proliferation only in case of LH/FSH unstimulated pathways. To the same direction, only patients characterized as LHCGR/FSHR negative seem to gain from GPER in terms of survival. Our combined tissue and in vitro results support thus the hypothesis that GPER activation could be of therapeutic benefit in LHCGR/FSHR negative EOC patients. Further studies are needed to evaluate the impact of GPER activation on a clinical scheme. PMID:23951246

Supplementation with a recombinant human chorionic gonadotropin microdose leads to similar outcomes in ovarian stimulation with recombinant follicle-stimulating hormone using either a gonadotropin-releasing hormone agonist or antagonist for pituitary suppression.

PubMed

Cavagna, Mario; Maldonado, Luiz Guilherme Louzada; de Souza Bonetti, Tatiana Carvalho; de Almeida Ferreira Braga, Daniela Paes; Iaconelli, Assumpto; Borges, Edson

2010-06-01

To compare the outcomes of protocols for ovarian stimulation with recombinant hCG microdose, with GnRH agonists and antagonists for pituitary suppression. Prospective nonrandomized clinical trial. A private assisted reproduction center. We studied 182 patients undergoing intracytoplasmic sperm injection (ICSI) cycles, allocated into two groups: GnRH agonist group, in which patients received a GnRH agonist (n = 73), and a GnRH antagonist group, in which patients were administered a GnRH antagonist for pituitary suppression (n = 109). Pituitary suppression with GnRH agonist or GnRH antagonist. Ovarian stimulation carried out with recombinant FSH and supplemented with recombinant hCG microdose. Total dose of recombinant FSH and recombinant hCG administered; E(2) concentrations and endometrial width on the day of hCG trigger; number of follicles aspirated, oocytes and mature oocytes retrieved; fertilization, pregnancy (PR), implantation, and miscarriage rates. The total dose of recombinant FSH and recombinant hCG administered were similar between groups, as were the E(2) concentrations and endometrial width. The number of follicles aspirated, oocytes, and metaphase II oocytes collected were also comparable. There were no statistically significant differences in fertilization, PR, implantation, and miscarriage rates in the GnRH agonist and GnRH antagonist groups. When using recombinant hCG microdose supplementation for controlled ovarian stimulation (COS), there are no differences in laboratory or clinical outcomes with the use of either GnRH antagonist or agonist for pituitary suppression. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A decade review of publications in Families, Systems, & Health: 2005-2015.

PubMed

Mendenhall, Tai J; Li, Yiting; Schulz, Catherine L

2016-09-01

The purpose of this investigation was to review recent publication content and trends in Families, Systems, & Health ( FSH ). How do the journal’s articles reflect current and emerging challenges in health care? We hope that our findings can guide special issues and content foci. All work published in FSH between 2005 and 2015 was included (n = 452); each piece was coded for article type, general foci, and specific foci. The most common type of article published over the 10-year time frame was research reports (43%; n = 195), followed by other types (e.g., tribute pieces, poems), commentaries, conceptual/theory papers, literature reviews, and case studies. The most common general focus included family health and/or functioning (28%; n = 128). The most common specific foci centered on children (15%; n = 55). Common themes found in FSH ’s most frequently cited publications included family relationships in care, chronic physical illnesses, and mental health. Marked trends in journal content included increases in articles targeting family health and/or functioning and primary care and decreased attention to theory. FSH’s emphasis on research reports to inform current and evolving interventions that target contemporary health challenges suggests that the journal is keeping stride with the most pressing issues in health care today. Future special issues can continue to serve and meet these needs. FSH’s robust inclusion of other article types sustains the journal’s mission to advance multiple ways of understanding health-care phenomena. PsycINFO Database Record (c) 2016 APA, all rights reserved

Iron overload detection using pituitary and hepatic MRI in thalassemic patients having short stature and hypogonadism.

PubMed

Mousa, Amany A; Ghonem, Mohamed; Elhadidy, El Hadidy M; Azmy, Emad; Elbackry, Magda; Elbaiomy, Azza A; Elzehery, Rasha R; Shaker, Gehan A; Saleh, Omyma

2016-05-01

to assess the growth and pubertal development among a group of patients with β-Thalassemia Major (β-TM) and to evaluate the role of the pituitary gland and liver MRI signal intensity (SI) reduction in assessing and predicting the clinical severity of growth and pubertal dysfunctions. Thirty-eight patients with β-TM were examined and divided into two groups: Group I patients were of normal height and puberty and Group II patients had short statures and hypogonadism. Laboratory investigations included serum ferritin, LH, FSH, prolactin, TSH, and basal and dynamic growth hormones. Pituitary and liver MRIs were performed to assess the pituitary to fat (P/F) and liver to muscle (L/M) signal intensities (SI), respectively. Fifteen healthy and sex- and age-matched subjects were included as controls. Both patient groups had significantly elevated serum ferritin and significantly decreased prolactin and IGF1 compared to control subjects. Group II showed a significant reduction in LH, FSH, and IGF1 and a significant increase in ferritin in comparison with Group I and the control group, and it had a highly significant reduction in both P/F and L/M SI in comparison with Group I (p<0.001 and 0.008, respectively). The reduced P/F ratio was significantly correlated with FSH and LH, and a cutoff for a P/F ratio ≥0.94 was obtained to differentiate between Group I and II. MRI in conjunction with the P/F signal intensity ratio is a useful and noninvasive tool for the early diagnosis of pituitary iron overload.

Effects of Metformin on Endocrine and Metabolic Parameters in Patients with Polycystic Ovary Syndrome.

PubMed

Zahra, M; Shah, M; Ali, A; Rahim, R

2017-02-01

The present study was designed to evaluate the effects of metformin on metabolic and endocrine parameters in patients with polycystic ovary syndrome (PCOS). The study included 40 patients with PCOS. Patients were divided into 2 groups based on whether they will receive metformin (500 mg 3 times a day, n=20) or placebo (n=20) for 3 consecutive months. Serum concentrations of fasting blood glucose, insulin, HOMA-IR, INSL-3, visfatin, FSH, and LH were measured at baseline and after 3 months of therapy. The key endocrine and metabolic parameters significantly changed after metformin treatment. The systolic and diastolic blood pressures were significantly reduced in the metformin group after treatment compared to placebo (p<0.001). A significant reduction in the size of the right ovary was observed after metformin treatment (p=0.05), while no change was found in the size of left ovary (p>0.12). Moreover, a significant reduction was observed in the serum levels of FSH (p>0.01), LH (p>0.001), and visfatin (p>0.001) after metformin treatment. However, HOMA-IR (which is used to assess insulin resistance) failed to reach the statistical significance (p=0.20). We conclude that metformin treatment in females with PCOS showed significant improvement in systolic and diastolic blood pressures. In addition, an improvement in the hormonal profile in the form of reduction in LH, FSH, and visfatin levels was observed. Thus, therapeutic intervention with metformin could be of clinical importance in high-risk group of young females with PCOS. © Georg Thieme Verlag KG Stuttgart · New York.

36 CFR 215.17 - Informal disposition.

Code of Federal Regulations, 2011 CFR

2011-07-01

... distances, alternative types of meetings (such as telephone conferences or video conferences) may be... and reconsideration of decisions to take action guidance in FSH 1909.15, Chapter 10, section 18, and... and disposition of the unresolved portion of the appeal shall continue (§ 215.18). ...

36 CFR 215.17 - Informal disposition.

Code of Federal Regulations, 2014 CFR

2014-07-01

... distances, alternative types of meetings (such as telephone conferences or video conferences) may be... and reconsideration of decisions to take action guidance in FSH 1909.15, Chapter 10, section 18, and... and disposition of the unresolved portion of the appeal shall continue (§ 215.18). ...

36 CFR 215.17 - Informal disposition.

Code of Federal Regulations, 2013 CFR

2013-07-01

... distances, alternative types of meetings (such as telephone conferences or video conferences) may be... and reconsideration of decisions to take action guidance in FSH 1909.15, Chapter 10, section 18, and... and disposition of the unresolved portion of the appeal shall continue (§ 215.18). ...

36 CFR 215.17 - Informal disposition.

Code of Federal Regulations, 2010 CFR

2010-07-01

... distances, alternative types of meetings (such as telephone conferences or video conferences) may be... and reconsideration of decisions to take action guidance in FSH 1909.15, Chapter 10, section 18, and... and disposition of the unresolved portion of the appeal shall continue (§ 215.18). ...

36 CFR 215.17 - Informal disposition.

Code of Federal Regulations, 2012 CFR

2012-07-01

... distances, alternative types of meetings (such as telephone conferences or video conferences) may be... and reconsideration of decisions to take action guidance in FSH 1909.15, Chapter 10, section 18, and... and disposition of the unresolved portion of the appeal shall continue (§ 215.18). ...

Ovulation

MedlinePlus Videos and Cool Tools

... sequence of hormonal responses. Located deep within the brain, the pituitary gland releases the hormones FSH and LH, which travel through the blood stream to the ovaries. These hormones signal the development and release a single egg cell from one of the ovaries. The sweeping motion ...

Effects of Space Flight on Ovarian-Hypophyseal Function in Postpartum Rats

NASA Technical Reports Server (NTRS)

Burden, H. W.; Zary, J.; Lawrence, I. E.; Jonnalagadda, P.; Davis, M.; Hodson, C. A.

1997-01-01

The effect of space flight in a National Aeronautics and Space Administration (NASA) shuttle was studied in pregnant rats. Rats were launched on day 9 of gestation and recovered on day 20 of gestation. On day 20 of gestation, rats were unilaterally hysterectomized and subsequently allowed to go to term and deliver vaginally. There was no effect of space flight on pituitary and ovary mass postpartum. In addition, space flight did not alter healthy and atretic ovarian antral follicle populations, fetal wastage in utero, plasma concentrations of progesterone and luteinizing hormone (LH) or pituitary content of follicle stimulating hormone (FSH). Space flight significantly increased plasma concentrations of FSH and decreased pituitary content of LH at the postpartum sampling time. Collectively, these data show that space flight, initiated during the postimplantation period of pregnancy, and concluded before parturition, is compatible with maintenance of pregnancy and has minimal effects on postpartum hypophyseal parameters; however, none of the ovarian parameters examined was altered by space flight.

Therapeutic effect of ozone and rutin on adriamycin-induced testicular toxicity in an experimental rat model.

PubMed

Salem, E A; Salem, N A; Hellstrom, W J

2017-02-01

To evaluate the cytoprotective effects of rutin, ozone and their combination on adriamycin (ADR)-induced testicular toxicity, 50 male albino rats were classified into five groups of ten animals each as follows: placebo group; ADR group; ADR + rutin group; ADR + ozone group and ADR + rutin + ozone group. Sperm functions, testosterone (T), luteinising hormone (LH), follicle stimulating hormone (FSH), testicular enzymes, oxidant/antioxidant status, C-reactive protein, monocyte chemoattractant proteins-1 and leukotriene B4 were determined. After ADR injection, a decline in sperm functions was observed. FSH and LH levels were increased, T level and testicular enzymes were decreased, significant enhancement in oxidative stress with subsequent depletion in antioxidants was detected and inflammatory markers were significantly elevated. Treatment with rutin and/or ozone, however, improved the aforementioned parameters. Ozone therapy alone almost completely reversed the toxic effects of ADR and restored all parameters to normal levels. © 2016 Blackwell Verlag GmbH.

Ovarian size and response to laparoscopic ovarian electro-cauterization in polycystic ovarian disease.

PubMed

Alborzi, S; Khodaee, R; Parsanejad, M E

2001-09-01

To evaluate endocrine and ovulatory changes in polycystic ovarian disease (PCOD) in relation to patients' ovarian size. Three hundred and seventy-one women with clomiphene citrate-resistant PCOD underwent laparoscopic ovarian cauterization [type I or typical with ovarian volume >8 cm(3) or cross-sectional area >10 cm(2) (n=211), type II with normal size ovary (n=160)]. Serum levels of LH, FSH, DHEAS, PRL, and T before and 10 days after ovarian cautery, spontaneous and induced ovulation and pregnancy rates were compared. Both groups responded to therapy in a similar manner, with a marked decrease in LH, FSH, DHEAS and T levels, with ovulation rates in type I 90.99%, type II 88.75% and pregnancy rates, 73.45% and 71.25%, respectively, with no statistical differences. Hormonal changes, ovulation and pregnancy rates were similar in the two types of PCOD, therefore it can be concluded that ovarian size is not a prognostic factor for response of PCOD patients to laparoscopic ovarian electro-cauterization.

Effect of aerobic exercises versus laser acupuncture in treatment of postmenopausal hot flushes: a randomized controlled trial.

PubMed

Elhosary, Eman Abdelfatah Mohamed; Ewidea, Mahmoud Mohamed; Ahmed, Hamada Ahmed Hamada; El Khatib, Ayman

2018-02-01

[Purpose] To compare the effect of aerobic exercises versus laser acupuncture in treatment of postmenopausal hot flushes. [Subjects and Methods] This study was designed as single blind randomized controlled trial. A total of 48 postmenopausal women complained of hot flushes. Their ages ranged between 45 to 55 years and were randomly assigned into 2 equal groups: group (A), which received an aerobic exercises, and group (B), which received laser acupuncture. Both groups recieved 3 sessions per week for two months. The level of follicular stimulating hormone, lutelizing hormone, and hot flushes dairy card were assessed the severity of hot flahes before and after treatment program. [Results] There were Significant reduction in FSH, LH, and menopausal daily hot flush scale in group A compared with group B at the post treatment. [Conclusion] Eight week program of an aerobic exercises yields improvement in FSH, LH, and decrease in severity of hot flushes assessed by hot flush dairy card than laser acupuncture in the treatment of postmenopausal hot flashes.

Preservation of fertility in women affected by cancer. An audit of the cryopreservation services provided for women at Human Assisted Reproduction Ireland.

PubMed

O'Donovan, M; Harrison, R F

2005-10-01

There has been a remarkable improvement in survival rates for adult and childhood cancers, due to progress in cancer treatments. However multiagent chemotherapy and radiotherapy are associated with gonadal failure. Whereas sperm banking is commonly performed, female gametes are not so amenable to cryopreservation. Options available to women for fertility preservation include, embryo and oocyte cryopreservation. Our unit established an oocyte/embryo cryopreservation service for women affected by cancer in October 2003. Ninteen women have been referred and five (26%) women have had oocytes cryopreserved. The mean age of women in the group cryopreserved was 34 years (range 21-41). Their mean day 3 FSH was 6.2 IU (range 5.5-6.8). The mean dose of rFSH used was 1870 units (range 1500-2600). The mean number of oocytes cryopreserved was 8 (range 3-16). Preservation of fertility is of major concern to women affected by cancer. This service offers them hope for their future fertility.

Ovulation induction in normogonadotropic anovulation (PCOS).

PubMed

van Santbrink, Evert J P; Fauser, Bart C J M

2006-06-01

Treatment of normogonadotropic anovulatory infertility (World Health Organization class 2, or WHO2) is by induction of ovulation using clomiphene citrate (CC), followed by follicle-stimulating hormone (FSH) in cases of treatment failure. Not all patients will become ovulatory or will conceive with this treatment. Others, exhibiting multifollicular instead of monofollicular development, may encounter complications such as ovarian hyperstimulation and multiple pregnancy. Recently introduced alternative treatment interventions-such as insulin-sensitizing drugs, aromatase inhibitors, or laparoscopic electrocautery of the ovaries-may offer the possibility of improving the efficacy of the classical ovulation induction algorithm. Based on initial patient characteristics, it may be possible to identify specific patient subgroups with altered chances of success or complications while using one of these interventions. Regarding CC and FSH ovulation induction, this has been performed using multivariate prediction models. This approach may enable us to improve safety, cost-effectiveness, and patient convenience in future ovulation induction.

Ovulation induction: a mini review.

PubMed

Messinis, Ioannis E

2005-10-01

Ovulation induction is the method for treating anovulatory infertility. For patients with hypogonadotrophic hypogonadism, the treatment involves administration of both FSH and LH, while HCG is injected for follicle rupture. Pulsatile GnRH has the same effectiveness as gonadotrophins and the advantage of the low multiple pregnancy rate. In polycystic ovary syndrome (PCOS), the first treatment choice is clomiphene citrate. With this drug, in properly selected patients, the cumulative pregnancy rate approaches that of normal women. Low-dose protocols of FSH are the second line of treatment, effective in inducing monofollicular development. Laparoscopic ovarian drilling can be an alternative but not as a first choice treatment in clomiphene-resistant patients. Other treatments, such as pulsatile GnRH and GnRH agonists, are hardly used today in PCOS. However, in obese women with PCOS, weight loss and exercise should be recommended as the first line of therapy. Newer agents including aromatase inhibitors and insulin sensitizers, although promising, need further evaluation.

Clinical characteristics in Taiwanese women with polycystic ovary syndrome

PubMed Central

2015-01-01

Polycystic ovary syndrome (PCOS) is one of the most common hormonal endocrine disorders in women of reproductive age. It consists of a heterogeneous collection of signs and symptoms that together form a disorder spectrum. The diagnosis of PCOS is principally based on clinical and physical findings. The extent of metabolic abnormalities in women with PCOS varies with phenotype, body weight, age, and ethnicity. For general population, the prevalence of hyperandrogenism and oligomenorrhea decreases with age, while complications such as insulin resistance and other metabolic disturbances increase with age. Obese women with PCOS have a higher risk of developing oligomenorrhea, amenorrhea, hyperandrogenemia, insulin resistance, and lower luteinizing hormone (LH) to follicle stimulation hormone (FSH) ratios than non-obese women with PCOS. The LH to FSH ratio is a valuable diagnostic tool in evaluating Taiwanese women with PCOS, especially in the diagnosis of oligomenorrhea. Overweight/obesity is the major determinant of cardiovascular and metabolic disturbances in women of reproductive age. PMID:26473107

Changes of blood levels of several hormones, catecholamines, prostaglandins, electrolytes and cAMP in man during emotional stress.

PubMed

Tigranian, R A; Orloff, L L; Kalita, N F; Davydova, N A; Pavlova, E A

1980-01-01

The levels of several hormones (ACTH, GH, TSH, FSH, LH, parathyroid hormone--PTH, insulin, thyroxine--T4, triiodothyronine--T3, cortisol, testosterone, aldosterone, renin), catecholamines (epinephrine, norepinephrine, dopamin), prostaglandins (F1 alpha, F2 alpha, A + E), electrolytes (Na, K, Ca, Mg), cAMP and glucose in blood were measured before and immediately after the examination in 15 male students aged 28 to 35 years. Simultaneously the blood pressure was measured and hemodynamic measures were registered with the aid of echocardiography. A remarkable increase of catecholamines, ACTH, renin, T3, PTH, cAMP, PG F1 alpha, PG F2 alpha and Ca was found before the examination together with the increase of blood pressure. After the examination the levels of catecholamines, renin, aldosterone, T3, PTH, GH, FSH, LH, testosterone, PG A + E, glucose and Ca were found to be increased, while these of insulin, Na, PG F1 alpha, PG F2 alpha were decreased. The decrease of blood pressure was also found.

Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus.