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Sample records for gonadotropins pituitary

  1. Gonadotropin-releasing hormone agonist-induced pituitary apoplexy

    PubMed Central

    Keane, Fergus; Navin, Patrick; Brett, Francesca; Dennedy, Michael C

    2016-01-01

    Summary Pituitary apoplexy represents an uncommon endocrine emergency with potentially life-threatening consequences. Drug-induced pituitary apoplexy is a rare but important consideration when evaluating patients with this presentation. We describe an unusual case of a patient with a known pituitary macroadenoma presenting with acute-onset third nerve palsy and headache secondary to tumour enlargement and apoplexy. This followed gonadotropin-releasing hormone (GNRH) agonist therapy used to treat metastatic prostate carcinoma. Following acute management, the patient underwent transphenoidal debulking of his pituitary gland with resolution of his third nerve palsy. Subsequent retrospective data interpretation revealed that this had been a secretory gonadotropinoma and GNRH agonist therapy resulted in raised gonadotropins and testosterone. Hence, further management of his prostate carcinoma required GNRH antagonist therapy and external beam radiotherapy. This case demonstrates an uncommon complication of GNRH agonist therapy in the setting of a pituitary macroadenoma. It also highlights the importance of careful, serial data interpretation in patients with pituitary adenomas. Finally, this case presents a unique insight into the challenges of managing a hormonal-dependent prostate cancer in a patient with a secretory pituitary tumour. Learning points While non-functioning gonadotropinomas represent the most common form of pituitary macroadenoma, functioning gonadotropinomas are exceedingly rare. Acute tumour enlargement, with potential pituitary apoplexy, is a rare but important adverse effect arising from GNRH agonist therapy in the presence of both functioning and non-functioning pituitary gonadotropinomas. GNRH antagonist therapy represents an alternative treatment option for patients with hormonal therapy-requiring prostate cancer, who also have diagnosed with a pituitary gonadotropinoma. PMID:27284452

  2. Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function.

    PubMed

    Themmen APN; Huhtaniemi, I T

    2000-10-01

    The recent unraveling of structures of genes for the gonadotropin subunits and gonadotropin receptors has provided reproductive endocrinologists with new tools to study normal and pathological functions of the hypothalamic-pituitary-gonadal axis. Rare inactivating mutations that produce distinctive phenotypes of isolated LH or FSH deficiency have been discovered in gonadotropin subunit genes. In addition, there is a common polymorphism in the LHbeta subunit gene with possible clinical significance as a contributing factor to pathologies of LH-dependent gonadal functions. Both activating and inactivating mutations have been detected in the gonadotropin receptor genes, a larger number in the LH receptor gene, but so far only a few in the gene for the FSH receptor. These mutations corroborate and extend our knowledge of clinical consequences of gonadotropin resistance and inappropriate gonadotropin action. The information obtained from human mutations has been complemented by animal models with disrupted or inappropriately activated gonadotropin ligand or receptor genes. These clinical and experimental genetic disease models form a powerful tool for exploring the physiology and pathophysiology of gonadotropin function and provide an excellent example of the power of molecular biological approaches in the study of pathogenesis of diseases.

  3. Stimulation of Spermiation by Human Chorionic Gonadotropin and Carp Pituitary Extract in Grass Puffer, Takifugu niphobles

    PubMed Central

    Goo, In Bon; Park, In-Seok; Gil, Hyun Woo; Im, Jae Hyun

    2015-01-01

    Spermiation was stimulated in the mature grass puffer, Takifugu niphobles, with an injection of human chorionic gonadotropin (HCG) or carp pituitary extract (CPE). Spermatocrit and sperm density were reduced, but milt production was increased in both the HCG and CPE treatment groups relative to those in the control group (P <0.05). These results should be useful for increasing the fertilization efficiency in grass puffer breeding programs. PMID:26973977

  4. The forkhead transcription factor, FOXP3, is required for normal pituitary gonadotropin expression in mice.

    PubMed

    Jung, Deborah O; Jasurda, Jake S; Egashira, Noboru; Ellsworth, Buffy S

    2012-05-01

    The hypothalamic-pituitary-gonadal axis is central to normal reproductive function. This pathway begins with the release of gonadotropin-releasing hormone in systematic pulses by the hypothalamus. Gonadotropin-releasing hormone is bound by receptors on gonadotroph cells in the anterior pituitary gland and stimulates the synthesis and secretion of luteinizing hormone and, to some extent, follicle-stimulating hormone. Once stimulated by these glycoprotein hormones, the gonads begin gametogenesis and the synthesis of sex hormones. In humans, mutations of the forkhead transcription factor, FOXP3, lead to an autoimmune disorder known as immunodysregulation, polyendocrinopathy, and enteropathy, X-linked syndrome. Mice with a mutation in the Foxp3 gene have a similar autoimmune syndrome and are infertile. To understand why FOXP3 is required for reproductive function, we are investigating the reproductive phenotype of Foxp3 mutant mice (Foxp3(sf/Y)). Although the gonadotroph cells appear to be intact in Foxp3(sf/Y) mice, luteinizing hormone beta (Lhb) and follicle-stimulating hormone beta (Fshb) expression are significantly decreased, demonstrating that these mice exhibit a hypogonadotropic hypogonadism. Hypothalamic expression of gonadotropin-releasing hormone is not significantly decreased in Foxp3(sf/Y) males. Treatment of Foxp3(sf/Y) males with a gonadotropin-releasing hormone receptor agonist does not rescue expression of Lhb or Fshb. Interestingly, we do not detect Foxp3 expression in the pituitary or hypothalamus, suggesting that the infertility seen in Foxp3(sf/Y) males is a secondary effect, possibly due to loss of FOXP3 in immune cells. Pituitary expression of glycoprotein hormone alpha (Cga) and prolactin (Prl) are significantly reduced in Foxp3(sf/Y) males, whereas the precursor for adrenocorticotropic hormone, pro-opiomelanocortin (Pomc), is increased. Human patients diagnosed with IPEX often exhibit thyroiditis due to destruction of the thyroid gland by

  5. Differential social regulation of two pituitary gonadotropin-releasing hormone receptors.

    PubMed

    Au, Teresa M; Greenwood, Anna K; Fernald, Russell D

    2006-06-30

    In many vertebrates, social interactions regulate reproductive capacity by altering the activity of the hypothalamic-pituitary-gonadal (HPG) axis. To better understand the mechanisms underlying social regulation of reproduction, we investigated the relationship between social status and one main component of the HPG axis: expression levels of gonadotropin-releasing hormone receptor (GnRH-R). Social interactions dictate reproductive capacity in the cichlid fish Astatotilapia burtoni. Reproductively active territory holders suppress the HPG axis of non-territorial males through repeated aggressive encounters. To determine whether the expression of GnRH-R is socially regulated, we quantified mRNA levels of two GnRH-R variants in the pituitaries and brains of territorial (T) and non-territorial (NT) A. burtoni males. We found that T males had significantly higher levels of pituitary GnRH-R1 mRNA than NT males. In contrast, GnRH-R2 mRNA levels in the pituitary did not vary with social status. Pituitaries from both T and NT males expressed significantly higher mRNA levels of GnRH-R1 than GnRH-R2. GnRH mRNA levels in the brain correlated positively with GnRH-R1 mRNA levels in the pituitary but did not correlate with pituitary GnRH-R2. Measurements of GnRH-R1 and GnRH-R2 mRNA levels across the whole brain revealed no social status differences. These results show that, in addition to the known effects of social status on other levels of the HPG axis, GnRH receptor in the pituitary is also a target of social regulation.

  6. Regulation of genes encoding steroidogenic factor-1 (SF-1) and gonadotropin subunits in the ovine pituitary gland.

    PubMed

    Baratta, M; Turzillo, A M; Arreguin-Arevalo, A; Clay, C M; Nett, T M

    2003-07-01

    Steroidogenic factor-1 (SF-1) is a transcription factor originally characterized as a mediator of gene expression in steroidogenic tissues. Studies in SF-1 knockout mice revealed that SF-1 has additional roles at multiple levels of the hypothalamic-pituitary-gonadal axis, including regulation of gene expression in pituitary gonadotropes. Specific binding sites for SF-1 have been demonstrated in several pituitary genes with essential roles in gonadotropin synthesis, including alpha subunit, LHbeta subunit, and GnRH receptor. In studies aimed at identifying physiological factors controlling pituitary expression of SF-1, GnRH has been implicated as a co-regulator of SF-1 and gonadotropin subunit genes. In both rats and ewes, elevated endogenous secretion of GnRH following ovariectomy was associated with increased amounts of SF-1 mRNA in the anterior pituitary gland. Conversely, removal of GnRH input to the pituitary gland by hypothalamic-pituitary disconnection (HPD) in ovariectomized (OVX) ewes reduced SF-1 expression. Despite these changes, however, treatment of OVX ewes with GnRH following HPD only partially restored levels of SF-1 mRNA in the pituitary gland. Therefore, it is possible that regulation of SF-1 gene expression by GnRH during the estrous cycle may involve ovarian hormones or other hypothalamic factors. Additional studies are required to further define the physiological roles of SF-1 in regulation of the hypothalamic-pituitary-gonadal axis in domestic ruminants.

  7. Gonadotropin releasing hormone stimulates the formation of inositol phosphates in rat anterior pituitary tissue.

    PubMed Central

    Schrey, M P

    1985-01-01

    The production of inositol phosphates in response to gonadotropin releasing hormone (GnRH) was studied in rat anterior pituitary tissue preincubated with [3H]inositol. Prelabelled paired hemipituitaries from prepubertal female rats were incubated in the presence or absence of GnRH in medium containing 10 mM-Li+ X Li+, which inhibits myo-inositol-1-phosphatase, greatly amplified the stimulation of inositol phosphate production by GnRH (10(-7) M) to 159, 198 and 313% of paired control values for inositol 1-phosphate, inositol bisphosphate and inositol trisphosphate respectively after 20 min. The percentage distribution of [3H]inositol within the phosphoinositides was 91.3, 6.3 and 2.4 for phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate respectively and was unaffected by GnRH. The stimulation of inositol trisphosphate production by GnRH was evident after 5 min incubation, was dose-dependent with a half-maximal effect around 11 nM, and was not inhibited by removal of extracellular Ca2+. Elevation of cytosolic Ca2+ by membrane depolarization with 50 mM-K+ had no significant effect on inositol phosphate production. These findings are consistent with the hypothesis that GnRH action in the anterior pituitary involves the hydrolysis of phosphatidylinositol 4,5-bisphosphate. The resulting elevation of inositol trisphosphate may in turn lead to intracellular Ca2+ mobilization and subsequent stimulation of gonadotropin secretion. PMID:2986599

  8. Leptin and the hypothalamic-pituitary regulation of the gonadotropin-gonadal axis.

    PubMed

    Chan, J L; Mantzoros, C S

    2001-01-01

    Leptin is an adipocyte-derived protein hormone which not only conveys a signal of the amount of energy stores to the central nervous system but also plays an important role in regulating neuroendocrine function. The importance of leptin in the reproductive system has been suggested by the reproductive dysfunction associated with leptin deficiency and resistance in both animal models and humans as well as the ability of leptin to accelerate the onset of reproductive function in normal mice. Transgenic mice overexpressing leptin also have accelerated puberty, and leptin administration reverses the fasting-induced suppression of sexual maturation in rodents, indicating that leptin may serve as the critical link between sufficient energy stores and proper functioning of the reproductive system. Normal women have a pulsatile release pattern of leptin that is significantly associated with the variations in luteinizing hormone (LH) and estradiol levels. In various animal models, leptin administration restores the LH pulsatility pattern which is suppressed during fasting, indicating a hypothalamic site of action since LH pulsatility is under the control of gonadotropin-releasing hormone (GnRH). In humans, leptin has been administered to a 9-year-old leptin-deficient girl, resulting in a gonadotropin secretory pattern consistent with early puberty. While in vitro experiments with hypothalamic explants and a GnRH-secreting neuronal cell line have shown that leptin can directly stimulate GnRH secretion, the lack of leptin receptors on GnRH neurons suggests that leptin may act through other hypothalamic neuropeptides. Several neuropeptides which act as downstream effectors of leptin have been investigated, and recent studies indicate that cocaine and amphetamine-regulated transcript may be such a mediator of leptin's effect on GnRH. Leptin receptors have also been identified in human pituitaries, and leptin may influence LH release from the pituitary. However, the current

  9. Neutralization of gonadotropin-releasing hormone in neonatal rats with permanent impairment of the hypothalamic-pituitary-testicular axis.

    PubMed

    Bercu, B B

    1982-05-01

    Males rats were passively immunized at 5 days of age with a single 0.25 ml i.p. injection of gonadotropin-releasing hormone (GnRH) antiserum. Control animals were given an equal volume of normal rabbit serum (NRS). Serial blood determinations of gonadotropins, testosterone and dihydrotestosterone (DHT) were obtained at intervals ranging from early in life through adult life. Gonadotropin secretion was reduced (P less than 0.025) up to 35 days of age. Androgen secretion (testosterone) was reduced (P less than 0.05) at 10 and 33 days of age. When hCG was given to 54-day-old (young adult), and 100-day-old and 15-month-old animals, testosterone concentrations were similar in both experimental and control groups 1 h after hCG stimulation. As adults, basal gonadotropins were the same in both groups; however, after GnRH stimulation, the GnRH antiserum-treated groups showed an increased gonadotropin response when compared to the NRS control group. In order to determine whether there was an alteration in steroid feedback, other animals were castrated at adult age (approximately 100 days old), and exogenous testosterone was given in increasing increments. However, serum gonadotropins decreased similarly in treated and control groups. These data indicate that a single injection of GnRH antiserum early in life decreased gonadotropin secretion temporarily during prepubertal sexual development and caused a permanent alteration in hypothalamic-pituitary-testicular function.

  10. Changes in brain gonadotropin-releasing hormone, pituitary and plasma gonadotropins, and plasma thyroxine during smoltification in chinook salmon (Oncorhynchus tschawytscha).

    PubMed

    Lewis, K A; Swanson, P; Sower, S A

    1992-09-01

    Concentrations of brain salmon gonadotropin-releasing hormone (sGnRH), plasma gonadotropin I (GTH I), and pituitary GTH I and GTH II were determined in yearling chinook salmon (Oncorhynchus tschawytscha) during the parr-smolt transformation in two successive seasons. There were significant elevations in brain sGnRH content from February to March in 1988, and from February to April in 1989. Increases in brain sGnRH content coincided with elevations in plasma thyroxine levels that occurred from February to March, 1988 and 1989. Plasma GTH levels were relatively constant (1-2 ng/ml) throughout the period of sampling. However, during 1988, plasma concentrations of GTH I decreased significantly between late March and early April. During 1989, plasma GTH I levels appeared to reach a peak (2 ng/ml) in mid-February, but otherwise remained near 1 ng/ml. Previous studies have shown that GTH II was not detectable in plasma at this stage. During 1989, pituitary GTH I concentrations were 50- to 70-fold higher than that of GTH II, and increased, though not significantly, from February through April. Although GTH II was detected in the pituitary by RIA, it is likely that the measurable levels are due to GTH I cross-reaction in the GTH II RIA. Histological examination of the gonads indicated that throughout smoltification the oocytes remained in the perinucleolar stage of oogenesis and the testes were in the spermatogonial stage of spermatogenesis. Although no observable changes in gametogenesis occurred, the changes in brain sGnRH content, plasma GTH I levels, and pituitary GTH content suggest that some changes in the hypothalamic-pituitary axis may occur during smoltification.

  11. Beta human chorionic gonadotropin (beta-hCG) expression in pituitary adenomas: relationship to endocrine function and tumour recurrence.

    PubMed

    Doyle, Paul M; Thiryayi, Waziq A; Joshi, Abhijit; du Plessis, Daniel; Kearney, Tara; Gnanalingham, Kanna K

    2009-01-01

    The beta subunit of human chorionic gonadotropin (beta-hCG) is a marker of malignancies. Recent studies have also reported its expression in pituitary adenomas, although its significance is unclear. In this retrospective study, the authors quantitatively investigated the immunohistochemical expression of beta-hCG in 123 patients undergoing surgery for pituitary adenomas and explored its relationship to the rest of the endocrine function, tumour recurrence and Ki-67 nuclear labelling. Based on the endocrine profile and immunohistochemistry, the pituitary adenomas were grouped into non-functioning (NFPA; N = 78) and functioning pituitary adenomas (N = 45). The latter included, 20 growth hormone (GH), 12 prolactin (PRL), 8 adreno-corticotrophin hormone (ACTH) and 5 mixed GH-PRL-producing adenomas. Ninety-three (76%) tumours were classified as primary and 30 (24%) tumours classified as recurrent adenomas. Immunohistochemically, 107 (87%) of pituitary adenomas expressed beta-hCG, which was more common in NFPA (91%) than functioning pituitary adenomas (80%). beta-hCG expression was not different between primary (86%) and recurrent pituitary adenomas (90%) and it was also not related to raised Ki-67 labelling. But, Ki-67 labelling was raised in recurrent pituitary adenomas (33%), compared to primary pituitary adenomas (11%). Although, beta-hCG is expressed in the majority of pituitary adenomas, more especially in NFPA, it is un-related to the risk of tumour recurrence or cellular proliferation as measured by Ki-67 nuclear labelling. The high incidence of beta-hCG expression in pituitary adenomas may provide a target for specific beta-hCG-directed tumour therapies in the future. PMID:19005764

  12. Circulating kisspeptin and pituitary adenylate cyclase-activating polypeptide (PACAP) do not correlate with gonadotropin serum levels.

    PubMed

    Kanasaki, Haruhiko; Purwana, Indri N; Oride, Aki; Mijiddorj, Tselmeg; Sukhbaatar, Unurjargal; Miyazaki, Kohji

    2013-06-01

    Kisspeptins are known to be the principle regulators of the hypothalamic-pituitary gonadal (HPG) axis. In addition, the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the regulation of pituitary gonadotropins has been elucidated. We measured plasma concentrations of kisspeptin and PACAP and determined whether the levels of these peptides varied in proportion to circulating gonadotropin levels. Plasma luteinizing hormone (LH) levels were higher in postmenopausal women and in patients with premature ovarian failure (POF) and lower in patients with idiopathic hypogonadotropic hypogonadism (IHH) compared with the LH level in normally menstruating women. Similarly, serum follicle-stimulating hormone levels were higher in postmenopausal women and in patients with POF but lower in pregnant women and patients with IHH compared with normally menstruating women. Plasma levels of kisspeptins were significantly higher in pregnant women compared with normally menstruating women. However, no significant differences were observed in postmenopausal women, patients with POF, and patients with IHH. On the other hand, plasma levels of PACAP were significantly lower in pregnant women, patients with POF, and in IHH patients when compared with normally menstruating women. No significant differences were observed in PACAP concentration between postmenopausal women and in normally menstruating women. Our observations suggest that the serum levels of kisspeptins and PACAP did not correlate with variations in serum gonadotropin levels.

  13. Fundulus heteroclitus gonadotropins.5: Small scale chromatographic fractionation of pituitary extracts into components with different steroidogenic activities using homologous bioassays

    PubMed Central

    Lin, Yu-Wai Peter; Petrino, Teresa R; Wallace, Robin A

    2004-01-01

    Fractionation and characterization of gonadotropins (GtH) from Fundulus heteroclitus pituitary extracts were carried out using a biocompatible liquid chromatographic procedure (Pharmacia FPLC system). Chromatographic fractions were monitored for gonadotropic activities (induction of oocyte maturation and steroid production) using homologous follicle bioassays in vitro. Size-exclusion chromatography eluted gonadotropic activity in one major protein peak (Mr ~ 30,000). Anion-exchange and hydrophobic-interaction chromatography (HIC) yielded two distinct peaks of 17beta-estradiol (E2)- and 17alpha-hydroxy,20beta-dihydroprogesterone (DHP)-promoting activity with associated oocyte maturation. Two-dimensional chromatography (chromatofocusing followed by HIC) resolved pituitary extracts into two active fractions; both induced E2 synthesis, but one was relatively poor in eliciting DHP and testosterone production. Thus, using homologous bioassays, at least two quantitatively different gonadotropic (steroidogenic) activities: an E2-promoting gonadotropin (GtH I-like) and a DHP-promoting gonadotropin (GtH II-like), which has a lower isoelectric point but greater hydrophobicity than the former, can be distinguished from F. heteroclitus pituitaries by a variety of chromatographic procedures. This study complements previous biochemical and molecular data in F. heteroclitus and substantiates the duality of GtH function in a multiple-spawning teleost. PMID:15040801

  14. Anterior pituitary leptin expression changes in different reproductive states: in vitro stimulation by gonadotropin-releasing hormone.

    PubMed

    Akhter, Noor; Johnson, Brandy W; Crane, Christopher; Iruthayanathan, Mary; Zhou, Yi-Hong; Kudo, Akihiko; Childs, Gwen V

    2007-02-01

    This study was designed to learn more about the changes in expression of rat anterior pituitary (AP) leptin during the estrous cycle. QRT-PCR assays of cycling rat AP leptin mRNA showed 2-fold increases from metestrus to diestrus followed by an 86% decrease on the morning of proestrus. Percentages of leptin cells increased in proestrus and pregnancy to 55-60% of AP cells. Dual labeling for leptin proteins and growth hormone (GH) or gonadotropins showed that the rise in leptin protein-bearing cells from diestrus to proestrus was mainly in GH cells. Only 10-20% of leptin cells in male or cycling female rats coexpress gonadotropins. In contrast, 50-73% of leptin cells from pregnant or lactating females coexpress gonadotropins and only 19% coexpress GH, indicating plasticity in the distribution of leptin. Leptin cells expressed GnRH receptors, and estrogen and GnRH together increased the coexpression of leptin mRNA and gonadotropins. GnRH increased cellular leptin proteins three to four times and mRNA 9.8 times in proestrous rats and stimulated leptin secretion in cultures from diestrous, proestrous, and pregnant rats. These regulatory influences, and the high expression of AP leptin during proestrus and pregnancy, suggest a supportive role for leptin during key events involved with reproduction.

  15. Expression of the putative gonadotropin-inhibitory hormone receptor, NPFFR1, in the anterior pituitary gland of the gilt is affected by age and sexual maturation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gonadotropin-inhibitory hormone (GnIH) purportedly suppresses secretion of luteinizing hormone (LH) by acting through a G-protein coupled receptor (NPFFR1) in the anterior pituitary gland and hypothalamus. The objective of these studies was to determine if expression of mRNA for NPFFR1 in the reprod...

  16. Endocrine disrupting effects of dichlorodiphenyltrichloroethane analogues on gonadotropin hormones in pituitary gonadotrope cells.

    PubMed

    Zhou, Jinghua; Yang, Ye; Xiong, Kang; Liu, Jing

    2014-05-01

    It has been shown that exposure to dichlorodiphenyltrichloroethane (DDT) analogues leads to disharmony of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, the effects and mechanisms of DDT analogues on the expression of gonadotropin genes (FSHβ, LHβ and Cgα), which is the rate-limiting step of FSH and LH biosynthesis, remain unknown. In this study, we assessed the effects of p,p'-DDT, o,p'-DDT, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and methoxychlor (MXC) on gonadotropin genes expression and hormones synthesis in gonadotrope cells. p,p'-DDT and MXC at test concentrations ranging from 10(-9) to 10(-7)mol/L, stimulated gonadotropin genes expression and hormones synthesis in a dose-dependent manner. The activation of extracellular signal-regulated kinase (ERK) was required for the induction of gonadotropin genes expression and hormones synthesis by p,p'-DDT or MXC exposure. This study showed for the first time that p,p'-DDT and MXC regulated gonadotropin genes expression and hormones synthesis through ERK pathway in gonadotrope cells.

  17. Dexamethasone suppresses gonadotropin-releasing hormone (GnRH) secretion and has direct pituitary effects in male rats: differential regulation of GnRH receptor and gonadotropin responses to GnRH.

    PubMed

    Rosen, H; Jameel, M L; Barkan, A L

    1988-06-01

    Endogenous or exogenous glucocorticoid excess leads to the development of hypogonadotropic hypogonadism, but the site(s) and mechanisms of glucocorticoid action are uncertain. We studied the effects of various doses of dexamethasone (Dex) on the hypothalamic-pituitary-gonadal axis in intact and castrate testosterone-replaced (cast + T) male rats and attempted to determine possible sites of Dex effects. A dose-dependent suppression of basal gonadotropin secretion was induced by 5 days of Dex treatment (20, 100, 500, or 2,500 micrograms/kg.day), and the highest dose completely abolished the postcastration rise in pituitary GnRH receptor number (GnRH-R) and serum gonadotropin levels. Administration of exogenous GnRH (0.02-200 micrograms/day over 2 days) resulted in a dose-dependent induction in GnRH-R in both intact and cast + T rats, but the effect was significantly (P less than 0.01) augmented in Dex-treated animals. In contrast, acute LH and FSH responses to GnRH (10, 25, 50, 100, or 250 ng, iv) were significantly blunted in Dex-treated rats. The data suggest that 1) Dex suppresses hypothalamic GnRH secretion, thereby preventing the postcastration rises in GnRH-R and gonadotropins; 2) at the pituitary level, Dex dissociates GnRH-R and gonadotropin responses to GnRH, augmenting GnRH-R induction by GnRH and suppressing gonadotropin responses to GnRH at a postreceptor site; and 3) the model of Dex-treated rats may be useful to study differential GnRH regulation of GnRH-R and gonadotropin secretion.

  18. Wastewater treatment plant effluent alters pituitary gland gonadotropin mRNA levels in juvenile coho salmon (Oncorhynchus kisutch).

    PubMed

    Harding, Louisa B; Schultz, Irvin R; da Silva, Denis A M; Ylitalo, Gina M; Ragsdale, Dave; Harris, Stephanie I; Bailey, Stephanie; Pepich, Barry V; Swanson, Penny

    2016-09-01

    It is well known that endocrine disrupting compounds (EDCs) present in wastewater treatment plant (WWTP) effluents interfere with reproduction in fish, including altered gonad development and induction of vitellogenin (Vtg), a female-specific egg yolk protein precursor produced in the liver. As a result, studies have focused on the effects of EDC exposure on the gonad and liver. However, impacts of environmental EDC exposure at higher levels of the hypothalamic-pituitary-gonad axis are less well understood. The pituitary gonadotropins, follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) are involved in all aspects of gonad development and are subject to feedback from gonadal steroids making them a likely target of endocrine disruption. In this study, the effects of WWTP effluent exposure on pituitary gonadotropin mRNA expression were investigated to assess the utility of Lh beta-subunit (lhb) as a biomarker of estrogen exposure in juvenile coho salmon (Oncorhynchus kisutch). First, a controlled 72-h exposure to 17α-ethynylestradiol (EE2) and 17β-trenbolone (TREN) was performed to evaluate the response of juvenile coho salmon to EDC exposure. Second, juvenile coho salmon were exposed to 0, 20 or 100% effluent from eight WWTPs from the Puget Sound, WA region for 72h. Juvenile coho salmon exposed to 2 and 10ng EE2L(-1) had 17-fold and 215-fold higher lhb mRNA levels relative to control fish. Hepatic vtg mRNA levels were dramatically increased 6670-fold, but only in response to 10ng EE2L(-1) and Fsh beta-subunit (fshb) mRNA levels were not altered by any of the treatments. In the WWTP effluent exposures, lhb mRNA levels were significantly elevated in fish exposed to five of the WWTP effluents. In contrast, transcript levels of vtg were not affected by any of the WWTP effluent exposures. Mean levels of natural and synthetic estrogens in fish bile were consistent with pituitary lhb expression, suggesting that the observed lhb induction may be due to

  19. Wastewater treatment plant effluent alters pituitary gland gonadotropin mRNA levels in juvenile coho salmon (Oncorhynchus kisutch).

    PubMed

    Harding, Louisa B; Schultz, Irvin R; da Silva, Denis A M; Ylitalo, Gina M; Ragsdale, Dave; Harris, Stephanie I; Bailey, Stephanie; Pepich, Barry V; Swanson, Penny

    2016-09-01

    It is well known that endocrine disrupting compounds (EDCs) present in wastewater treatment plant (WWTP) effluents interfere with reproduction in fish, including altered gonad development and induction of vitellogenin (Vtg), a female-specific egg yolk protein precursor produced in the liver. As a result, studies have focused on the effects of EDC exposure on the gonad and liver. However, impacts of environmental EDC exposure at higher levels of the hypothalamic-pituitary-gonad axis are less well understood. The pituitary gonadotropins, follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) are involved in all aspects of gonad development and are subject to feedback from gonadal steroids making them a likely target of endocrine disruption. In this study, the effects of WWTP effluent exposure on pituitary gonadotropin mRNA expression were investigated to assess the utility of Lh beta-subunit (lhb) as a biomarker of estrogen exposure in juvenile coho salmon (Oncorhynchus kisutch). First, a controlled 72-h exposure to 17α-ethynylestradiol (EE2) and 17β-trenbolone (TREN) was performed to evaluate the response of juvenile coho salmon to EDC exposure. Second, juvenile coho salmon were exposed to 0, 20 or 100% effluent from eight WWTPs from the Puget Sound, WA region for 72h. Juvenile coho salmon exposed to 2 and 10ng EE2L(-1) had 17-fold and 215-fold higher lhb mRNA levels relative to control fish. Hepatic vtg mRNA levels were dramatically increased 6670-fold, but only in response to 10ng EE2L(-1) and Fsh beta-subunit (fshb) mRNA levels were not altered by any of the treatments. In the WWTP effluent exposures, lhb mRNA levels were significantly elevated in fish exposed to five of the WWTP effluents. In contrast, transcript levels of vtg were not affected by any of the WWTP effluent exposures. Mean levels of natural and synthetic estrogens in fish bile were consistent with pituitary lhb expression, suggesting that the observed lhb induction may be due to

  20. Pyroglutamylated RFamide peptide 43 stimulates the hypothalamic-pituitary-gonadal axis via gonadotropin-releasing hormone in rats.

    PubMed

    Patel, Sejal R; Murphy, Kevin G; Thompson, Emily L; Patterson, Michael; Curtis, Annette E; Ghatei, Mohammad A; Bloom, Stephen R

    2008-09-01

    Although it is established that other members of the RFamide family stimulate the hypothalamic-pituitary-gonadal axis, the influence of the novel pyroglutamylated RFamide peptide 43 (QRFP43) is not known. We show intracerebroventricular (icv) administration of QRFP43 (2 nmol) to male rats increased plasma LH and FSH levels at 40 min after injection. icv administration of 3 nmol QRFP43 did not affect food intake in ad-libitum-fed male rats. The icv administration of 2 nmol QRFP43 did not significantly influence behavior in male rats. Intraperitoneal administration of doses up to 1200 nmol/kg QRFP43 in male rats did not significantly influence circulating gonadotropin or sex steroid levels. In vitro, QRFP43 stimulated GnRH release from hypothalamic explants from male rats and from GT1-7 cells. Pretreatment with a GnRH receptor antagonist, cetrorelix, blocked the increase in plasma LH levels after icv administration of QRFP43 (2 nmol). These results suggest that icv QRFP43 activates the hypothalamic-pituitary-gonadal axis via GnRH.

  1. Regulation and distribution of squirrel monkey chorionic gonadotropin and secretogranin II in the pituitary

    PubMed Central

    Vasauskas, Audrey A.; Hubler, Tina R.; Mahanic, Christina; Gibson, Susan; Kahn, Andrea G.; Scammell, Jonathan G.

    2011-01-01

    Secretogranin II (SgII) is a member of the granin family of proteins found in neuroendocrine and endocrine cells. The expression and storage of SgII in the pituitary gland of Old World primates and rodents have been linked with those of luteinizing hormone (LH). However, New World primates including squirrel monkeys do not express LH in the pituitary gland, but rather CG is expressed. If CG takes on the luteotropic role of LH in New World primates, SgII may be associated with the expression and storage of CG in the pituitary gland. The goal of this study was to evaluate the regulation and distribution of CG and SgII in the squirrel monkey. A DNA fragment containing approximately 750 bp of squirrel monkey SgII promoter was isolated from genomic DNA and found to contain a cyclic AMP response element that is also present in the human SgII promoter and important for GnRH responsiveness. The squirrel monkey and human SgII promoters were similarly activated by GnRH in luciferase reporter gene assays in LβT2 cells. Double immunofluorescence microscopy demonstrated close association of SgII and CG in gonadotrophs of squirrel monkey pituitary gland. These results suggest that CG and SgII have a similar intercellular distribution and are coregulated in squirrel monkey pituitary gland. PMID:21095191

  2. Influence of estradiol, progesterone, and nutrition on concentrations of gonadotropins and GnRH receptors, and abundance of mRNA for GnRH receptors and gonadotropin subunits in pituitary glands of beef cows.

    PubMed

    Looper, M L; Vizcarra, J A; Wettemann, R P; Malayer, J R; Braden, T D; Geisert, R D; Morgan, G L

    2003-01-01

    Nutritionally induced anovulatory cows (n = 28) were used to determine the effect of steroids on regulation of synthesis and secretion of gonadotropins. Anovulatory cows were ovariectomized and received intravaginal inserts containing estradiol (E2), progesterone (P4), E2 and P4 (E2P4), or a sham intravaginal insert (C) for 7 d. Concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were quantified in serum and E2 and P4 were quantified in plasma. Cows were exsanguinated within 1 to 2 h after removal of intravaginal inserts and pituitary glands were collected and stored at -80 degrees C until messenger ribonucleic acid (mRNA) for gonadotropin-releasing hormone receptor (GnRH-R) and gonadotropin subunits, pituitary content of GnRH-R, and LH and FSH were quantified. Pituitary glands from five proestrous cows were harvested to compare gonadotropin characteristics between ovariectomized, anovulatory cows and intact cows. Plasma concentrations of E2 were greater (P < 0.05) in E2-treated cows than in sham-treated cows. Concentrations of P4 were greater (P < 0.05) in cows treated with P4 than in sham-treated cows. Mean serum concentrations of LH and FSH were not significantly influenced by steroid treatments. However, frequency of LH pulses of ovariectomized, nutritionally induced anovulatory cows was increased (P < 0.05) by treatment with E2 and amplitude of LH pulses was greater (P < 0.05) in cows treated with E2 or P4 than in cows treated with E2P4 or sham-treated. Quantity of mRNA for LHbeta in the pituitary gland was greater when cows were treated with P4. Concentrations of LH in the pituitary gland were not affected by steroid treatments; however, pituitary concentrations of FSH were less (P < 0.1) in E2 cows than in sham-treated cows. The number of GnRH-R was increased (P < 0.05) in cows treated with E2, but P4 treatment did not influence the number of GnRH-R. Abundance of mRNA for GnRH-R, common alpha-subunit, and FSHbeta were not

  3. Prenatal development of gonadotropin-releasing hormone receptors in the rat anterior pituitary

    SciTech Connect

    Jennes, L. )

    1990-02-01

    The development of pituitary GnRH receptors was studied in the rat with in vitro and in vivo autoradiography. GnRH receptors were first seen in pituitary primordia of 13-day-old fetuses. The binding was specific and saturable and was abolished in the presence of 10 microM synthetic GnRH. To examine whether GnRH was available to the fetus, amnionic fluid was collected on days E 12-18. RIA analyses showed that GnRH levels in the amnionic fluid were low on days 12 and 13 (0-20 pM/ml) and rose to 225 pM/ml on day E 16 before they declined to 110 pM/ml on fetal day E 18. The highest levels of GnRH in the amnionic fluid on day E 16 coincided with the first appearance of immunoreactive LH cells, as determined by immunohistochemistry. Intravenous injection of 500 microliters amnionic fluid into pentobarbital-anesthetized adult rats caused a transient 40-60% increase in circulating serum LH in the recipient animal. To show that GnRH from the amnionic fluid has access to the developing pituitary, the 125I-labeled GnRH agonist Buserelin was injected into the amnionic fluid of 13-, 14-, and 15-day-old fetuses in the presence or absence of 10 microM unlabeled GnRH. Autoradiographic analysis of the fetal tissue indicated that the labeled GnRH agonist bound to specific receptors in the primordial pituitaries. The results suggest that the pituitary gonadotropes are differentiated before day E 13 because the expression of GnRH receptors is already an indication of cell determination. Since GnRH is present in the amnionic fluid in a biologically active form and can reach the fetal pituitary, it is concluded that GnRH may be an important factor determining the onset LH synthesis, but not the differentiation, of primordial pituitary cells.

  4. PPARG regulates gonadotropin-releasing hormone signaling in LbetaT2 cells in vitro and pituitary gonadotroph function in vivo in mice.

    PubMed

    Sharma, Shweta; Sharma, Prem M; Mistry, Devendra S; Chang, R Jeffery; Olefsky, Jerrold M; Mellon, Pamela L; Webster, Nicholas J G

    2011-03-01

    Peroxisome proliferators-activated receptor gamma (PPARG) ligands improve insulin sensitivity in type 2 diabetes and polycystic ovarian syndrome (PCOS). Despite clinical studies showing normalization of pituitary responsiveness to gonadotropin-releasing hormone (GnRH) in patients with PCOS, the precise role of PPARG in regulating the hypothalamic-pituitary-gonadal axis remains unclear. In the present study, we tested the hypothesis that the PPARG agonist rosiglitazone has a direct effect on the pituitary. In mouse LbetaT2 immortalized gonadotrophs, rosiglitazone treatment inhibited GnRH stimulation of the stress kinases p38MAPK and MAPKs/JNKs, but did not alter activation of ERKs, both in the presence and absence of activin. Furthermore, p38MAPK signaling was critical for both Lhb and Fshb promoter activity, and rosiglitazone suppressed the GnRH-mediated induction of Lhb and Fshb mRNA. Depletion of PPARG using a lentivirally encoded short hairpin RNA abolishes the effect of rosiglitazone to suppress activation of JNKs and induction of the transcription factors EGR1 and FOS as well as the gonadotropin genes Lhb and Fshb. Lastly, we show conditional knockout of Pparg in pituitary gonadotrophs caused an increase in luteinizing hormone levels in female mice, a decrease in follicle-stimulating hormone in male mice, and a fertility defect characterized by reduced litter size. Taken together, our data support a direct role for PPARG in modulating pituitary function in vitro and in vivo.

  5. Molecular cloning of pituitary glycoprotein alpha-subunit and follicle stimulating hormone and chorionic gonadotropin beta-subunits from New World squirrel monkey and owl monkey.

    PubMed

    Scammell, Jonathan G; Funkhouser, Jane D; Moyer, Felricia S; Gibson, Susan V; Willis, Donna L

    2008-02-01

    The goal of this study was to characterize the gonadotropins expressed in pituitary glands of the New World squirrel monkey (Saimiri sp.) and owl monkey (Aotus sp.). The various subunits were amplified from total RNA from squirrel monkey and owl monkey pituitary glands by reverse transcription-polymerase chain reaction and the deduced amino acid sequences compared to those of other species. Mature squirrel monkey and owl monkey glycoprotein hormone alpha-polypeptides (96 amino acids in length) were determined to be 80% homologous to the human sequence. The sequences of mature beta subunits of follicle stimulating hormone (FSHbeta) from squirrel monkey and owl monkey (111 amino acids in length) are 92% homologous to human FSHbeta. New World primate glycoprotein hormone alpha-polypeptides and FSHbeta subunits showed conservation of all cysteine residues and consensus N-linked glycosylation sites. Attempts to amplify the beta-subunit of luteinizing hormone from squirrel monkey and owl monkey pituitary glands were unsuccessful. Rather, the beta-subunit of chorionic gonadotropin (CG) was amplified from pituitaries of both New World primates. Squirrel monkey and owl monkey CGbeta are 143 and 144 amino acids in length and 77% homologous with human CGbeta. The greatest divergence is in the C terminus, where all four sites for O-linked glycosylation in human CGbeta, responsible for delayed metabolic clearance, are predicted to be absent in New World primate CGbetas. It is likely that CG secreted from pituitary of New World primates exhibits a relatively short half-life compared to human CG.

  6. Gonadotropin-Releasing hormones in the brain and pituitary of the white sucker

    USGS Publications Warehouse

    Robinson, T. Craig; Tobet, Stuart A.; Chase, Cindy; Waldron, Travis; Sower, Stacia A.

    2000-01-01

    The present study investigated GnRH forms within the brain of a representative of the order Cypriniformes, the white sucker, Catostomus commersoni, using HPLC, RIA, andimmunocytochemistry. Several immunoreactive (ir) GnRH forms were identified in the brain of the white sucker by chromatography and radioimmunoassay, including ir-salmon GnRH, ir-lamprey GnRH-I and -III, and ir-chicken GnRH-II. Results from immunocytochemical studies were consistent with multiple GnRH forms distributed in different patterns, particularly for fibers. Neuronal perikarya containing ir-salmon GnRH and ir-lamprey-like GnRH were found laterally within the preoptic area and rostralhypothalamus. Cells containing exclusively ir-salmon GnRH appeared slightly more rostrally, but in the same region. Fibers containing ir-salmon GnRH and ir-lamprey-like GnRH were seen throughout the caudal telencephalon and extended into thediencephalon, toward the pituitary. Fibers containing ir-chicken-II-like GnRH were also seen in the caudal telencephalon, but were concentrated more dorsally in the diencephalon. Within the pituitary, fibers containing ir-salmon GnRH and ir-lamprey-like GnRH entered the neurohypophysis, but differed in their destinations. Fibers containing ir-salmon GnRH remained within the neurohypophysis, while fibers containing ir-lamprey-like GnRH targeted adenohypophyseal tissue. These findings are consistent with the hypothesis that multiple GnRH forms with multiple functions exist within the brain and pituitary of teleosts and provide further evidence of a lamprey-like GnRH within an early evolved teleost species.

  7. Reduction in size of a thyrotropin- and gonadotropin-secreting pituitary adenoma treated with octreotide acetate (somatostatin analog).

    PubMed

    Sy, R A; Bernstein, R; Chynn, K Y; Kourides, I A

    1992-03-01

    TSH as well as alpha-subunit, secretion has been shown to decrease after the administration of the somatostatin analog octreotide acetate (SMS 201-995). We have studied a 59-yr-old, male patient with a TSH- and gonadotropin-secreting tumor who, because of severe cardiomyopathy, was treated with long-term somatostatin analog rather than surgical resection of the pituitary tumor. Thirteen weeks of treatment with thrice daily sc injection of 100 micrograms octreotide acetate resulted in decreased TSH and alpha-subunit secretion, normal serum thyroid hormone levels, reduction in LH and testosterone level, and significant tumor size reduction. Long-term treatment for 51 weeks has not been associated with any significant side effects. We have shown that octreotide acetate may be a therapeutically valuable modality for certain patients with neoplastic inappropriate secretion of TSH (NIST). A probable effect of octreotide acetate on neoplastic gonadotropes, as evidenced by the reduction of the LH level with a concomitant decrease in testosterone level, is, likewise, suggested.

  8. Feedback inhibition of gonadotropins by testosterone in men with hypogonadotropic hypogonadism: comparison to the intact pituitary-testicular axis in primary hypogonadism.

    PubMed

    Shimon, Ilan; Lubina, Alexandra; Gorfine, Malka; Ilany, Jacob

    2006-01-01

    Men with hypogonadotropic hypogonadism (HH) due to hypothalamic-pituitary disease present with low serum testosterone levels combined with undetectable, low, or normal gonadotropin levels. Treatment consists of testosterone replacement to reverse the symptoms of androgen deficiency. The aim of this study was to examine the dynamics and feedback inhibition of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in relation to testosterone in 38 men with HH treated with testosterone. Findings were compared with 11 men with primary hypergonadism (PH). Testosterone replacement led to a suppression of FSH levels from 2.8 IU/L at baseline to 1.1 IU/L and to a suppression of LH levels from 2.3 to 0.8 IU/L. There was a linear correlation between levels of FSH and LH (after natural log transformation for both) and testosterone levels in both the HH and PH groups. However, the differences in intercepts and slopes between the groups were significant. To determine whether nonsuppressed FSH or LH during testosterone replacement reduces the probability of eugonadism, as reflected by normal testosterone levels, gonadotropin levels were measured and categorized as low (<0.5 IU/L), medium (0.5-2 IU/L), and high levels (>2 IU/L). The higher FSH or LH levels were found to significantly decrease the chance for achieving eugonadism. In conclusion, in men with HH due to hypothalamic-pituitary disease or injury, the pituitary-testicular hormonal axis maintains its physiological negative feedback between testosterone and gonadotropins. Thus, gonadotropin levels in men with HH might be useful, together with testosterone concentrations, for assessing the adequacy of androgen replacement.

  9. Role of calcium in gonadotropin releasing hormone-induced luteinizing hormone secretion from the bovine pituitary

    SciTech Connect

    Kile, J.P.

    1986-01-01

    The hypothesis was tested that GnRH acts to release LH by increasing calcium uptake by gonadotroph which in turn stimulates calcium-calmodulin activity and results in LH release from bovine pituitary cells as it does in the rat. Pituitary glands of calves (4-10 months of age) were enzymatically dispersed (0.2% collagenase) and grown for 5 days to confluency in multiwell plates (3 x 10/sup 5//well). Cells treated with GnRH Ca/sup + +/ ionophore A23187, and ouabain all produced significant releases of LH release in a pronounced all or none fashion, while thorough washing of the cells with 0.5 mM EGTA in Ca/sup + +/-free media prevented the action of GnRH. GnRH caused a rapid efflux of /sup 45/Ca/sup + +/. Both GnRH-stimulated /sup 45/Ca efflux and LH release could be partially blocked by verapamil GnRH-induced LH release could also be blocked by nifedipine and tetrodotoxin, although these agents did not affect /sup 45/Ca efflux. The calmodulin antagonists calmidazolium and W7 were found to block GnRH induced LH release, as well as LH release induced by theophylline, KC PGE/sub 2/ and estradiol. These data indicated that: (1) calcium is required for GnRH action, but extracellular Ca/sup + +/ does not regulate LH release; (2) GnRH elevates intracellular Ca/sup + +/ by opening both voltage sensitive and receptor mediated Ca/sup + +/ channels; (3) activation of calmodulin is one mechanism involved in GnRH-induced LH release.

  10. Molecular cloning and characterization of the gonadotropin subunits GPα, FSHβ, and LHβ genes in the stinging catfish Heteropneustes fossilis: phylogeny, seasonal expression and pituitary localization.

    PubMed

    Acharjee, Arup; Chaube, Radha; Joy, Keerikkattil Paily

    2015-10-01

    Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and consist of a common glycoprotein hormone alpha (GPα) and the function-specific follicle-stimulating hormone beta subunit (FSHβ) or luteinizing hormone beta subunit (LHβ). In the present study, the subunit protein genes were cloned and characterized from the pituitary of the catfish Heteropneustes fossilis. Full-length cDNAs of GPα, FSHβ, and LHβ are 511 base pairs (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature proteins, respectively. GPα has 10 cysteines with 2 N-linked glycosylation sites while LHβ contains 12 cysteines with a single N-linked glycosylation site. In contrast, FSHβ has 13 cysteines, 1 additional over the conserved 12 cysteines of other vertebrates, and a single glycosylation site between Cys 3 and Cys 4. Phylogenetic analyses of the deduced proteins confirm their homology and relationships with the respective gonadotropin subunit proteins of gnathostome vertebrates. Tissue expression analysis by semi-quantitative RT-PCR shows that GPα mRNA is expressed only in the pituitary while both FSHβ and LHβ mRNA are expressed in extra-pituitary sites. The subunit mRNAs show both seasonal and sex dimorphic variations especially in the expression of FSHβ and LHβ transcripts. In the sexually quiescent phase, the transcript expression is low while in the recrudescent phase, the expressions are differential, high, and varied with regard to sex and reproductive phase. In situ hybridization of the mRNAs gave positive signals in gonadotropes in the pars distalis of the pituitary, which exhibited seasonal variation in staining intensity and numbers. PMID:26205349

  11. GnRH-Induced Ca2+ Signaling Patterns and Gonadotropin Secretion in Pituitary Gonadotrophs. Functional Adaptations to Both Ordinary and Extraordinary Physiological Demands

    PubMed Central

    Durán-Pastén, Maria Luisa; Fiordelisio, Tatiana

    2013-01-01

    Pituitary gonadotrophs are a small fraction of the anterior pituitary population, yet they synthesize gonadotropins: luteinizing (LH) and follicle-stimulating (FSH), essential for gametogenesis and steroidogenesis. LH is secreted via a regulated pathway while FSH release is mostly constitutive and controlled by synthesis. Although gonadotrophs fire action potentials spontaneously, the intracellular Ca2+ rises produced do not influence secretion, which is mainly driven by Gonadotropin-Releasing Hormone (GnRH), a decapeptide synthesized in the hypothalamus and released in a pulsatile manner into the hypophyseal portal circulation. GnRH binding to G-protein-coupled receptors triggers Ca2+ mobilization from InsP3-sensitive intracellular pools, generating the global Ca2+ elevations necessary for secretion. Ca2+ signaling responses to increasing (GnRH) vary in stereotyped fashion from subthreshold to baseline spiking (oscillatory), to biphasic (spike-oscillatory or spike-plateau). This progression varies somewhat in gonadotrophs from different species and biological preparations. Both baseline spiking and biphasic GnRH-induced Ca2+ signals control LH/FSH synthesis and exocytosis. Estradiol and testosterone regulate gonadotropin secretion through feedback mechanisms, while FSH synthesis and release are influenced by activin, inhibin, and follistatin. Adaptation to physiological events like the estrous cycle, involves changes in GnRH sensitivity and LH/FSH synthesis: in proestrus, estradiol feedback regulation abruptly changes from negative to positive, causing the pre-ovulatory LH surge. Similarly, when testosterone levels drop after orquiectomy the lack of negative feedback on pituitary and hypothalamus boosts both GnRH and LH secretion, gonadotrophs GnRH sensitivity increases, and Ca2+ signaling patterns change. In addition, gonadotrophs proliferate and grow. These plastic changes denote a more vigorous functional adaptation in response to an extraordinary functional

  12. Distribution of LPXRFa, a gonadotropin-inhibitory hormone ortholog peptide, and LPXRFa receptor in the brain and pituitary of the tilapia.

    PubMed

    Ogawa, Satoshi; Sivalingam, Mageswary; Biran, Jakob; Golan, Matan; Anthonysamy, Rachel Shalini; Levavi-Sivan, Berta; Parhar, Ishwar S

    2016-10-01

    In vertebrates, gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH), respectively, regulate reproduction in positive and negative manners. GnIH belongs to the LPXRFa family of peptides previously identified in mammalian and nonmammalian vertebrates. Studying the detailed distribution of LPXRFa as well as its receptor (LPXRFa-R) in the brain and pituitary is important for understanding their multiple action sites and potential functions. However, the distribution of LPXRFa and LPXRFa-R has not been studied in teleost species, partially because of the lack of fish-specific antibodies. Therefore, in the present study, we generated specific antibodies against LPXRFa and its receptor from Nile tilapia (Oreochromis niloticus), and examined their distributions in the brain and pituitary by immunohistochemistry. Tilapia LPXRFa-immunoreactive neurons lie in the posterior ventricular nucleus of the caudal preoptic area, whereas LPXRFa-R-immunoreactive cells are distributed widely. Double immunofluorescence showed that neither LPXRFa-immunoreactive fibers nor LPXRFa-R is closely associated or coexpressed with GnRH1, GnRH3, or kisspeptin (Kiss2) neurons. In the pituitary, LPXRFa fibers are closely associated with gonadotropic endocrine cells [expressing luteinizing hormone (LH) and follicle-stimulating hormone (FSH)], with adrenocorticomelanotropic cells [corticotropin (ACTH) and α-melanotropin (α-MSH)], and with somatolactin endocrine cells. In contrast, LPXRFa-R are expressed only in LH, ACTH, and α-MSH cells. These results suggest that LPXRFa and LPXRFa-R signaling acts directly on the pituitary cells independent from GnRH or kisspeptin and could play multiple roles in reproductive and nonreproductive functions in teleosts. J. Comp. Neurol. 524:2753-2775, 2016. © 2016 Wiley Periodicals, Inc. PMID:26917324

  13. 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.

  14. Environmental impacts on the gonadotropic system in female Atlantic salmon (Salmo salar) during vitellogenesis: Photothermal effects on pituitary gonadotropins, ovarian gonadotropin receptor expression, plasma sex steroids and oocyte growth.

    PubMed

    Taranger, Geir Lasse; Muncaster, Simon; Norberg, Birgitta; Thorsen, Anders; Andersson, Eva

    2015-09-15

    The gonadotropic system and ovarian growth and development were studied during vitellogenesis in female Atlantic salmon subjected to either simulated natural photoperiod and ambient water temperature (NL-amb), or an accelerating photoperiod (short day of LD8:16 from May 10) combined with either warmed (ca 2°C above ambient; 8L-warm) or cooled water (ca 2°C below ambient; 8L-cold) from May to September. Monthly samples were collected from 10 females/group for determination of transcript levels of pituitary gonadotropin subunits (fshb and lhb) and ovarian gonadotropin receptors (fshr and lhr), plasma sex steroids (testosterone: T and estradiol-17β: E2), gonadosomatic index (GSI) and oocyte size. Short day in combination with either warmed or cooled water induced an earlier increase in pituitary fshb and lhb levels compared with NL-amb controls, and advanced ovarian growth and the seasonal profiles of T, E2. By contrast only minor effects were seen of the photothermal treatments on ovarian fshr and lhr. The 8L-cold had earlier increase in fshb, lhb and E2, but similar oocyte and gonadal growth as 8L-warm, suggesting that the 8L-cold group tried to compensate for the lower water temperature during the period of rapid gonadal growth by increasing fshb and E2 production. Both the 8L-warm and 8L-cold groups showed incomplete ovulation in a proportion of the females, possibly due to the photoperiod advancement resulting in earlier readiness of spawning occurring at a higher ambient temperature, or due to some reproductive dysfunction caused by photothermal interference with normal neuroendocrine regulation of oocyte development and maturation.

  15. Atrazine inhibits pulsatile luteinizing hormone release without altering pituitary sensitivity to a gonadotropin-releasing hormone receptor agonist in female Wistar rats.

    PubMed

    Foradori, Chad D; Hinds, Laura R; Hanneman, William H; Legare, Marie E; Clay, Colin M; Handa, Robert J

    2009-07-01

    Atrazine [2-chloro-4-(ethylamino)-6-(isopropylamino)-s-tri-azine] is one of the most commonly used herbicides in the United States. Atrazine has been shown to suppress luteinizing hormone (LH) release and can lead to a prolongation of the estrous cycle in the rat. The objectives of this study were to examine the effects of atrazine on normal tonic release of LH and to elucidate the site of action of atrazine in the hypothalamic-pituitary-gonadal axis. Episodic release of gonadotropin-releasing hormone (GnRH) and the corresponding release of LH from the anterior pituitary gland are required for normal reproductive function. To determine if atrazine affects pulsatile LH release, ovariectomized adult female Wistar rats were administered atrazine (50, 100, or 200 mg/kg of body weight daily by gavage) or vehicle control for 4 days. On the final day of atrazine treatment, blood samples were obtained using an indwelling right atrial cannula. In the group receiving 200 mg/kg, there was a significant reduction in LH pulse frequency and a concomitant increase in pulse amplitude. To determine if the effects of atrazine on LH release were due to changes at the level of the pituitary, animals were passively immunized against endogenous GnRH, treated with atrazine, and challenged with a GnRH receptor agonist. Atrazine failed to alter pituitary sensitivity to the GnRH receptor agonist at any dose used. Taken together, these findings demonstrate that high doses of atrazine affect the GnRH pulse generator in the brain and not at the level of gonadotrophs in the pituitary.

  16. Alterations in hypothalamus-pituitary-adrenal/thyroid axes and gonadotropin-releasing hormone in the patients with primary insomnia: a clinical research.

    PubMed

    Xia, Lan; Chen, Gui-Hai; Li, Zhi-Hua; Jiang, Song; Shen, Jianhua

    2013-01-01

    The hypothalamus-pituitary-target gland axis is thought to be linked with insomnia, yet there has been a lack of further systematic studies to prove this. This study included 30 patients with primary insomnia (PI), 30 patients with depression-comorbid insomnia (DCI), and 30 healthy controls for exploring the alterations in the hypothalamus-pituitary-adrenal/thyroid axes' hormones and gonadotropin-releasing hormone (GnRH). The Pittsburgh Sleep Quality Index was used to evaluate sleep quality in all subjects. The serum concentrations of corticotrophin-releasing hormone (CRH), thyrotrophin-releasing hormone (TRH), GnRH, adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), cortisol, total triiodothyronine (TT3), and total thyroxine (TT4) in the morning (between 0730 h and 0800 h) were detected. Compared to the controls, all hormonal levels were elevated in the insomniacs, except ACTH and TSH in the PI group. Compared to the DCI patients, the PI patients had higher levels of CRH, cortisol, TT3, and TT4 but lower levels of TRH, GnRH, and ACTH. Spearman's correlation analysis indicated that CRH, TRH, GnRH, TSH, cortisol, TT4, and TT3 were positively correlated with the severity of insomnia. The linear regression analysis showed that only CRH, GnRH, cortisol, and TT3 were affected by the PSQI scores among all subjects, and only CRH was included in the regression model by the "stepwise" method in the insomnia patients. Our results indicated that PI patients may have over-activity of the hypothalamus-pituitary-adrenal/thyroid axes and an elevated level of GnRH in the morning.

  17. Dose-response relationship of 15alpha-hydroxylated sex steroids to gonadotropin-releasing hormones and pituitary extract in male sea lampreys (Petromyzon marinus).

    PubMed

    Young, Bradley A; Bryan, Mara B; Glenn, Jessica R; Yun, Sang Seon; Scott, Alexander P; Li, Weiming

    2007-03-01

    The sea lamprey (Petromyzon marinus) is one of the earliest extant vertebrates for which the hypothalamic-pituitary-gonadal (HPG) axis has been shown to control and regulate reproduction in a similar fashion to gnathostome vertebrates. While the two forms of gonadotropin-releasing hormones in the sea lamprey (GnRH I and GnRH III) have been studied extensively, their in vivo effect on synthesis of 15alpha-hydroxytestosterone (15alpha-T) and 15alpha-hydroxyprogesterone (15alpha-P) have only been partially characterized. In the present study, plasma concentrations of 15alpha-T and 15alpha-P were measured in prespermiating sea lampreys that were given a single injection of either GnRH I or GnRH III in doses ranging from 5 to 100 microg/kg, or of pituitary extract (as a source of gonadotropin). Plasma was sampled at 1-6h and 6-48 h post-injection, in separate experiments, in order to characterize the peak and duration of responses. 15alpha-T plasma concentrations increased slightly in response to all three treatments, but not in a dose-dependent manner, and the timing of peak concentrations varied between doses. However, 15alpha-P plasma concentrations showed a greater range of response (between 1 and 100 ng/ml) and were clearly correlated with the injection dose. Plasma concentrations of 15alpha-P also responded to far lower doses of GnRH I and GnRH III than any other steroid previously investigated in lampreys. The plasma concentrations of 15alpha-P peaked at 6h after injection for all three treatments, and levels reached a mean of 53.1 ng/ml. In female lampreys that were injected twice with 50 microg/ml GnRH I or III, 15alpha-T concentrations did not exceed 0.5 ng/ml and 15alpha-P concentrations did not exceed 1 ng/ml. These results lend further support to the hypothesis that 15alpha-P plays an important role in the reproductive endocrinology of male lampreys.

  18. Long-term GnRH-induced gonadotropin secretion in a novel hypothalamo-pituitary slice culture from tilapia brain.

    PubMed

    Bloch, Corinne L; Kedar, Noa; Golan, Matan; Gutnick, Michael J; Fleidervish, Ilya A; Levavi-Sivan, Berta

    2014-10-01

    Organotypic cultures, prepared from hypothalamo-pituitary slices of tilapia, were developed to enable long-term study of secretory cells in the pituitary of a teleost. Values of membrane potential at rest were similar to those recorded from acute slices, and cells presented similar spontaneous spikes and spikelets. Some cells also exhibited slow spontaneous oscillations in membrane potential, which may be network-driven. Long-term (6days) continuous exposure to GnRH induced increases in LH and FSH secretion. FSH levels reached the highest levels after 24h of exposure to GnRH, and the highest secretion of LH was observed in days 4 and 5 of the experiment. Since slices were viable for several weeks in culture, maintaining the original cytoarchitecture, electrical membrane properties and the ability to secrete hormones in response to exogenous GnRH, this technique is ideal for studying the mechanisms regulating cell-to-cell communication under conditions resembling the in vivo tissue organization.

  19. Sex steroid levels, oocyte maturation and spawning performance in Waigieu seaperch (Psammoperca waigiensis) exposed to thyroxin, human chorionic gonadotropin, luteinizing hormone releasing hormone and carp pituitary extract.

    PubMed

    Pham, Hung Quoc; Nguyen, Anh Tuong; Nguyen, Mao Dinh; Arukwe, Augustine

    2010-02-01

    In the present study, we have investigated the sex steroid hormone levels, oocyte maturation and spawning performance in Waigieu seaperch (Psammoperca waigiensis) exposed to different doses (0, (control), 0.05, 0.25 and 0.5 mg/kg fish) of thyroxin (T(4)) both through diet (continuously) and injection (single injection). In addition, we also studied plasma steroid hormone levels and spawning performances in female fish injected with a single dose of D-Ala(6), Pro(9)-Net-mGnRH (LHRHa: 50 microg/kg), human chronic gonadotropin (HCG: 1,500 IU/kg) and carp pituitary extract (CPE: 10 mg/kg). In all experiments, samples were collected at 0, 6, 12, 24 and 48 h after exposure. T4 exposure via dietary route produced differential and enhanced effects, compared with when the compound was injected to the broodstock. A significant association between exposure to dietary T4, elevated plasma steroid hormone levels, maturation-, spawning-, fertilization- and hatching rate, egg diameter, embryogenesis and larval growth were observed. Interestingly, we observed that broodstock groups fed with T4 doses spawned 20 days earlier than the control group. Thus, we propose that these differences may be attributed to higher systemic availability of T4 due to dietary exposure that is easily transferable to eggs and embryos, as opposed to injection that require absorption to increase bioavailability. Furthermore, our results show that LHRHa, CPE and HCG produced significant increase in spawning rate, but significantly reduced fertilization- and hatching rates. Waigieu seaperch is a new candidate for marine aquaculture in Vietnam and relatively little is known about the reproductive biology and endocrinology of this species. Therefore, the present study forms an integral basis for understanding the reproductive endocrinology of a tropical marine finfish with increasing aquaculture prospects and may also contribute in the development of sustainable aquaculture of this species in a developing

  20. Effect of very high dose D-leucine6-gonadotropin-releasing hormone proethylamide on the hypothalamic-pituitary testicular axis in patients with prostatic cancer.

    PubMed

    Warner, B; Worgul, T J; Drago, J; Demers, L; Dufau, M; Max, D; Santen, R J

    1983-06-01

    Potent synthetic analogs of gonadotropin-releasing hormone produce parodoxical antireproductive effects when administered chronically. These compounds are minimally toxic and may exhibit no plateau of the dose-response curve even at very high doses. These considerations served as the basis for our systematic evaluation of [D-leucine6-desarginine-glycine-NH2(10)]gonadotropin-releasing hormone (GnRH-A) proethylamide in the very high dose range (i.e., 10-fold larger amounts than previously used). In rats given the analog for 12 wk, prostate, testis, and seminal vesicle weights were suppressed to a greater extent with 200 micrograms q.d. than with 40 micrograms q.d. (P less than 0.01 prostate, less than 0.01 testis, less than 0.01 seminal vesicles), indicating dose-response effects in the very high dose range. 200 micrograms of [D-Leu6-des-Gly-NH2(10]-GnRH-A consistently suppressed leutinizing hormone (LH) values at 6 and 12 wk (basal 71 +/- 9.5; 6 wk 34 +/- 3.8; 12 wk 28 +/- 5 ng/ml) whereas 40 micrograms suppressed LH variably (basal 33 +/- 3.8; 6 wk 17 +/- 3.9; 12 wk 32 +/- 5.2). Testosterone fell to 15 +/- 2.4 and 19 +/- 2.0 ng/100 ml in response to 200 micrograms q.d. and to 27 +/- 6.4 and 22 +/- 7.4 ng/100 ml with the 40-micrograms dose. These findings in the rodent prompted treatment of stage D prostate cancer patients with similarly high doses of [D-Leu6-des-Gly-NH2(10)]-GnRH-A. After treatment for 11 wk with 1,000 or 10,000 micrograms/d of the analog, testosterone and dihydrotestosterone levels transiently rose and then fell into the surgically castrate range (testosterone 19 +/- 4.4 ng/100 ml [D-Leu6-des-Gly-NH2(10)]-GnRH-A vs. surgically castrate 11 +/- 0.9 ng/100 ml, P = NS; dihydrotestosterone 15 +/- 1.7 ng/100 ml GnRH-A vs. surgically castrate 15 +/- 4.1 ng/100 ml. P = NS). However, unlike the chronic stimulatory effect on the pituitary at lower doses, very high dose therapy resulted in profound suppression of plasma and urine LH. Plasma levels fell to

  1. Multihormonal pituitary adenomas.

    PubMed

    Heitz, P U

    1979-01-01

    66 pituitary tumors detected at autopsy were investigated for the presence of corticotropin, beta-lipotrophin, growth hormone, prolactin, thyrotropin and gonadotropins by immunocytochemistry. 56 tumors contained hormone-producing cells; 45 were found to contain 2 or more hormones. This finding confirms and extends previous morphologic and clinical observations. The majority of pituitary tumors are mixed and they probably arise from impaired regulation at the hypothalamic and/or pituitary level.

  2. The chronic intracerebroventricular infusion of interleukin-1 beta alters the activity of the hypothalamic-pituitary-gonadal axis of cycling rats. I. Effect on LHRH and gonadotropin biosynthesis and secretion.

    PubMed

    Rivest, S; Lee, S; Attardi, B; Rivier, C

    1993-12-01

    We have previously reported that the acute injection of interleukin-1 beta (IL-1 beta) into the brain ventricles of intact female rats promptly decreases LHRH release and inhibits gene expression of this peptide in the medial preoptic area (MPOA). The present studies were therefore designed to determine whether continuous exposure to the cytokine would disrupt the estrous cycle. IL-1 beta was injected intracerebroventricularly for 4-6 days at a rate of 4 ng/h. Daily vaginal smears were obtained to follow the cycle; pituitary LH and FSH secretion were measured at regular intervals. Steady state levels of LH and FSH messenger RNA (mRNA) in the pituitary, and LHRH gene expression in the MPOA, were measured at the end of the treatment. Infusion of IL-1 beta caused a total disruption of the estrous cycle, characterized by persistent smears indicative of the diestrus stage. When compared to animals treated with the vehicle, rats infused with IL-1 beta showed a significant decrease in circulating LH concentrations, which was accompanied by lowered mRNA levels in the pituitary. This statistical difference (P < 0.01) persisted even when treated rats were compared to control in a similar stage of the cycle (i.e. diestrus). Plasma FSH levels remained low at all times after IL-1 beta infusion but showed the expected cyclic changes in control animals. At the end of treatment, LHRH gene expression was also markedly suppressed in LHRH neurons distributed between the rostral preoptic area/organum vasculosum of the lamina terminalis and the MPOA of these animals. These results indicate that prolonged infusion of IL-1 beta into brain ventricles disrupts the estrous cycle, an event accompanied by decreased biosynthesis/release of LHRH and gonadotropins. We report in a related study that IL-1-treated rats also show increased plasma progesterone levels. However, it is improbable that this change was responsible for the interruption of the cycle described here; indeed we have previously

  3. Intracellular mechanisms involved in copper-gonadotropin-releasing hormone (Cu-GnRH) complex-induced cAMP/PKA signaling in female rat anterior pituitary cells in vitro.

    PubMed

    Gajewska, Alina; Zielinska-Gorska, Marlena; Wolinska-Witort, Ewa; Siawrys, Gabriela; Baran, Marta; Kotarba, Grzegorz; Biernacka, Katarzyna

    2016-01-01

    The copper-gonadotropin-releasing hormone molecule (Cu-GnRH) is a GnRH analog, which preserves its amino acid sequence, but which contains a Cu(2+) ion stably bound to the nitrogen atoms including that of the imidazole ring of Histidine(2). A previous report indicated that Cu-GnRH was able to activate cAMP/PKA signaling in anterior pituitary cells in vitro, but raised the question of which intracellular mechanism(s) mediated the Cu-GnRH-induced cAMP synthesis in gonadotropes. To investigate this mechanism, in the present study, female rat anterior pituitary cells in vitro were pretreated with 0.1 μM antide, a GnRH antagonist; 0.1 μM cetrorelix, a GnRH receptor antagonist; 0.1 μM PACAP6-38, a PAC-1 receptor antagonist; 2 μM GF109203X, a protein kinase C inhibitor; 50 mM PMA, a protein kinase C activator; the protein kinase A inhibitors H89 (30 μM) and KT5720 (60 nM); factors affecting intracellular calcium activity: 2.5 mM EGTA; 2 μM thapsigargin; 5 μM A23187, a Ca(2+) ionophore; or 10 μg/ml cycloheximide, a protein synthesis inhibitor. After one of the above pretreatments, cells were incubated in the presence of 0.1 μM Cu-GnRH for 0.5, 1, and 3 h. Radioimmunoassay analysis of cAMP confirmed the functional link between Cu-GnRH stimulation and cAMP/PKA signal transduction in rat anterior pituitary cells, demonstrating increased intracellular cAMP, which was reduced in the presence of specific PKA inhibitors. The stimulatory effect of Cu-GnRH on cAMP production was partly dependent on GnRH receptor activation. In addition, an indirect and Ca(2+)-dependent mechanism might be involved in intracellular adenylate cyclase stimulation. Neither activation of protein kinase C nor new protein synthesis was involved in the Cu-GnRH-induced increase of cAMP in the rat anterior pituitary primary cultures. Presented data indicate that conformational changes of GnRH molecule resulting from cooper ion coordination affect specific pharmacological properties of Cu

  4. Pulsatile administration of gonadotropin-releasing hormone does not alter the follicle-stimulating hormone (FSH) isoform distribution pattern of pituitary or circulating FSH in nutritionally growth-restricted ovariectomized lambs.

    PubMed

    Hassing, J M; Kletter, G B; I'Anson, H; Wood, R I; Beitins, I Z; Foster, D L; Padmanabhan, V

    1993-04-01

    The experimental induction of puberty by GnRH administration to prepubertal lambs increases serum bioactive FSH (B-FSH) as measured in the rat Sertoli cell aromatase induction bioassay. Serum immunoreactive FSH (I-FSH) levels are unchanged. The increase in serum B-FSH is associated with an increase in the proportion of less acidic and more biopotent FSH serum isoforms. However, it is unknown if this effect of GnRH on serum FSH microheterogeneity is direct or mediated by gonadal factors. We have used the nutritionally growth-restricted ovariectomized lamb as a model of the neuroendocrine regulation of FSH isoform microheterogeneity. With this model, the hypothalamic-pituitary component of the neuroendocrine axis may be isolated from gonadal factors. In the present study, using the nutritionally growth-restricted ovariectomized lamb as a model, we investigated the role of GnRH on the regulation of FSH microheterogeneity. Specifically, we tested the hypothesis that GnRH increases the proportion of the less acidic (more biopotent) serum FSH isoforms. As an in vitro correlate, we investigated the effect of GnRH on gonadotropin secretion and FSH isoform distribution in ovine pituitary explant cultures. Seven ovariectomized nutritionally restricted lambs were administered GnRH (i.v., 2 ng/kg) for 36 h (at 2-h intervals for 24 h, then hourly for the final 12 h). Six others served as controls. Blood samples were withdrawn at 12-min intervals during the last 4 h for the measurement of serum immunoactive LH (I-LH) and I-FSH. Pituitary homogenates and serum from four animals from each group were individually chromatofocused, and the FSH isoform distribution patterns were determined. Pulsatile administration of GnRH to nutritionally growth-restricted lambs increased circulating I-LH concentrations from 0.6 +/- 1.0 to 5.9 +/- 3.1 ng/ml (P < 0.01), but did not significantly change circulating I-FSH (4.9 +/- 1.8 vs. 11.5 +/- 4.2 ng/ml) nor B-FSH concentrations (3.9 +/- 1.2 vs. 5

  5. Novel evidence that pituitary gonadotropins directly stimulate human leukemic cells-studies of myeloid cell lines and primary patient AML and CML cells

    PubMed Central

    Abdelbaset-Ismail, Ahmed; Borkowska, Sylwia; Janowska-Wieczorek, Anna; Tonn, Torsten; Rodriguez, Cesar; Moniuszko, Marcin; Bolkun, Lukasz; Koloczko, Janusz; Eljaszewicz, Andrzej; Ratajczak, Janina; Ratajczak, Mariusz Z.; Kucia, Magda

    2016-01-01

    We recently reported that normal hematopoietic stem cells express functional pituitary sex hormone (SexH) receptors. Here we report for the first time that pituitary-secreted gonadotrophins stimulate migration, adhesion, and proliferation of several human myeloid and lymphoid leukemia cell lines. Similar effects were observed after stimulation of human leukemic cell lines by gonadal SexHs. This effect seems to be direct, as the SexH receptors expressed by leukemic cells responded to stimulation by phosphorylation of MAPKp42/44 and AKTser473. Furthermore, in parallel studies we confirmed that human primary patient-derived AML and CML blasts also express several functional SexH receptors. These results shed more light on the potential role of SexHs in leukemogenesis and, in addition, provide further evidence suggesting a developmental link between hematopoiesis and the germline. PMID:26701888

  6. Suppression of the hypothalamic-pituitary-gonadal axis by TAK-385 (relugolix), a novel, investigational, orally active, small molecule gonadotropin-releasing hormone (GnRH) antagonist: studies in human GnRH receptor knock-in mice.

    PubMed

    Nakata, Daisuke; Masaki, Tsuneo; Tanaka, Akira; Yoshimatsu, Mie; Akinaga, Yumiko; Asada, Mari; Sasada, Reiko; Takeyama, Michiyasu; Miwa, Kazuhiro; Watanabe, Tatsuya; Kusaka, Masami

    2014-01-15

    TAK-385 (relugolix) is a novel, non-peptide, orally active gonadotropin-releasing hormone (GnRH) antagonist, which builds on previous work with non-peptide GnRH antagonist TAK-013. TAK-385 possesses higher affinity and more potent antagonistic activity for human and monkey GnRH receptors compared with TAK-013. Both TAK-385 and TAK-013 have low affinity for the rat GnRH receptor, making them difficult to evaluate in rodent models. Here we report the human GnRH receptor knock-in mouse as a humanized model to investigate pharmacological properties of these compounds on gonadal function. Twice-daily oral administration of TAK-013 (10mg/kg) for 4 weeks decreased the weights of testes and ventral prostate in male knock-in mice but not in male wild-type mice, demonstrating the validity of this model to evaluate antagonists for the human GnRH receptor. The same dose of TAK-385 also reduced the prostate weight to castrate levels in male knock-in mice. In female knock-in mice, twice-daily oral administration of TAK-385 (100mg/kg) induced constant diestrous phases within the first week, decreased the uterus weight to ovariectomized levels and downregulated GnRH receptor mRNA in the pituitary after 4 weeks. Gonadal function of TAK-385-treated knock-in mice began to recover after 5 days and almost completely recovered within 14 days after drug withdrawal in both sexes. Our findings demonstrate that TAK-385 acts as an antagonist for human GnRH receptor in vivo and daily oral administration potently, continuously and reversibly suppresses the hypothalamic-pituitary-gonadal axis. TAK-385 may provide useful therapeutic interventions in hormone-dependent diseases including endometriosis, uterine fibroids and prostate cancer.

  7. Developmental expression of three forms of gonadotropin-releasing hormone and ontogeny of the hypothalamic-pituitary-gonadal axis in gilthead seabream (Sparus aurata).

    PubMed

    Wong, Ten-Tsao; Gothilf, Yoav; Zmora, Nilli; Kight, Katherine E; Meiri, Iris; Elizur, Abigail; Zohar, Yonathan

    2004-09-01

    To address the complexity of the origin of the GnRH system in perciforms, we investigated the ontogenic expression of three GnRHs in gilthead seabream. Using in situ hybridization, chicken (c) GnRH-II mRNA-expressing cells were detected in the hindbrain at 1.5 days postfertilization (DPF) and in the midbrain at 2 DPF and thereafter; the hindbrain signals became undetectable after 10 DPF. Salmon (s) GnRH mRNA-expressing cells were first seen in the olfactory placode at 3 DPF, started caudal migration at 14 DPF, and reached the preoptic areas at 59 DPF. Seabream (sb) GnRH mRNA-expressing cells were first detected in the terminal nerve ganglion cells (TNgc), ventral part of the ventral telencephalon, nucleus preopticus parvocellularis, and thalamus at 39 DPF, and extended to the nucleus preopticus magnocellularis at 43 DPF, ventrolateral hypothalamus at 51 DPF, and nucleus lateralis tuberis and posterior tuberculum at 59 DPF. Coexpression of sbGnRH and sGnRH transcripts was found in the TNgc. Using real-time fluorescence-based quantitative polymerase chain reaction, transcript levels of cGnRH-II and sGnRH were first detected at 1 and 1.5 DPF, respectively, and increased and remained high thereafter. Transcript levels of sbGnRH remained low after first detection at 1 DPF. Furthermore, these GnRH expression profiles were correlated with the expression profiles of reproduction-related genes in which at least four concomitant increases of GnRH, GnRH receptor, gonadotropin, gonadotropin receptor, and Vasa transcripts were found at 5, 8, 14, and 28 DPF. Our data provide an expanded view of the ontogeny of the GnRH system and reproductive axis in perciforms.

  8. Does a nonclassical signaling mechanism underlie an increase of estradiol-mediated gonadotropin-releasing hormone receptor binding in ovine pituitary cells?

    PubMed

    Davis, Tracy L; Whitesell, Jennifer D; Cantlon, Jeremy D; Clay, Colin M; Nett, Terry M

    2011-10-01

    Estradiol-17beta (E2) is the major regulator of GnRH receptor (GnRHR) gene expression and number during the periovulatory period; however, the mechanisms underlying E2 regulation of the GNRHR gene remain undefined. Herein, we find that E2 conjugated to BSA (E2-BSA) mimics the stimulatory effect of E2 on GnRH binding in primary cultures of ovine pituitary cells. The time course for maximal GnRH analog binding was similar for both E2 and E2-BSA. The ability of E2 and E2-BSA to increase GnRH analog binding was blocked by the estrogen receptor (ER) antagonist ICI 182,780. Also, increased GnRH analog binding in response to E2 and the selective ESR1 agonist propylpyrazole triol was blocked by expression of a dominant-negative form of ESR1 (L540Q). Thus, membrane-associated ESR1 is the likely candidate for mediating E2 activation of the GNRHR gene. As cAMP response element binding protein (CREB) is an established target for E2 activation in gonadotrophs, we next explored a potential role for this protein as an intracellular mediator of the E2 signal. Consistent with this possibility, adenoviral-mediated expression of a dominant-negative form of CREB (A-CREB) completely abolished the ability of E2 to increase GnRH analog binding in primary cultures of ovine pituitary cells. Finally, the presence of membrane-associated E2 binding sites on ovine pituitary cells was demonstrated using a fluorescein isothiocyanate conjugate of E2-BSA. We suggest that E2 regulation of GnRHR number during the preovulatory period reflects a membrane site of action and may proceed through a nonclassical signaling mechanism, specifically a CREB-dependent pathway.

  9. Involvement of pituitary gonadotropins, gonadal steroids and breeding season in sex change of protogynous dusky grouper, Epinephelus marginatus (Teleostei: Serranidae), induced by a non-steroidal aromatase inhibitor.

    PubMed

    Garcia, Carlos Eduardo de O; Araújo, Bruno C; Mello, Paulo H; Narcizo, Amanda de M; Rodrigues-Filho, Jandyr A; Medrado, Andreone T; Zampieri, Ricardo A; Floeter-Winter, Lucile M; Moreira, Renata Guimarães

    2013-10-01

    Two experiments were performed using the aromatase inhibitor (AI) letrozole (100mg/kg) to promote sex change, from female-to-male, in protogynous dusky grouper. One experiment was performed during the breeding season (spring) and the other at the end of the breeding season (summer). During the spring, AI promoted sex change after 9 weeks and the sperm produced was able to fertilize grouper oocytes. During the summer, the sex change was incomplete; intersex individuals were present and sperm was not released by any of the animals. Sex changed gonads had a lamellar architecture; cysts of spermatocytes and spermatozoa in the lumen of the germinal compartment. In the spring, after 4 weeks, 11ketotestosterone (11KT) levels were higher in the AI than in control fish, and after 9 weeks, coincident with semen release, testosterone levels increased in the AI group, while 11KT returned to the initial levels. Estradiol (E2) levels remained unchanged during the experimental period. Instead of decreasing throughout the period, as in control group, 17 α-OH progesterone levels did not change in the AI-treated fish, resulting in higher values after 9 weeks when compared with control fish. fshβ and lhβ gene expression in the AI animals were lower compared with control fish after 9 weeks. The use of AI was effective to obtain functional males during the breeding season. The increase in androgens, modulated by gonadotropins, triggered the sex change, enabling the development of male germ cells, whereas a decrease in E2 levels was not required to change sex in dusky grouper.

  10. Mutations affecting gonadotropin secretion and action.

    PubMed

    Huhtaniemi, Ilpo

    2003-01-01

    A number of mutations are known to disturb the development and function of the hypothalamic-pituitary-gonadal axis. They affect hypothalamic-pituitary-gonadal function at multiple levels, from the migration of gonadotropin releasing hormone neurons to the hypothalamus right through to gonadotropin action in the ovary and testis. Most of the mutations are inactivating, causing various forms of hypogonadism. Exceptions are the activating mutations of the luteinizing hormone receptor, causing male-limited gonadotropin-independent precocious puberty. The human mutations and genetically modified animal models have clarified the molecular pathogenesis of hypogonadism and such disorders can now be diagnosed using molecular biological techniques, enabling selection of specific treatments and appropriate counselling of patients and their families.

  11. Gonadotropin response to gonadotropin releasing hormone in acute schizophrenia.

    PubMed

    Cantalamessa, L; Catania, A; Silva, A; Orsatti, A; Baldini, M; Mosca, G; Zanussi, C; Cazzullo, C L

    1984-01-01

    To evaluate hypothalamic-pituitary-gonadal axis in acute schizophrenia, plasma FSH and LH concentrations were estimated both in basal conditions and after stimulation with gonadotropin releasing hormone (GnRH, 200 micrograms i.v.) in 14 young male patients with acute schizophrenia and in a age-matched group of 14 healthy male controls. Basal plasma PRL and testosterone levels were also measured. The mean basal levels of LH and FSH were slightly lower in schizophrenics, while the mean testosterone and prolactin levels were similar in the two groups. The FSH response to GnRH was significantly reduced in patients with acute schizophrenia, while the response of LH was similar in schizophrenics and in the controls. The possible significance of these findings is discussed in the contest of the complex neuroendocrine regulation of gonadotropin secretion and the overactivity of dopaminergic systems in acute schizophrenia.

  12. Five-day pulsatile gonadotropin-releasing hormone administration unveils combined hypothalamic-pituitary-gonadal defects underlying profound hypoandrogenism in men with prolonged critical illness.

    PubMed

    van den Berghe, G; Weekers, F; Baxter, R C; Wouters, P; Iranmanesh, A; Bouillon, R; Veldhuis, J D

    2001-07-01

    . Serum interleukin-1beta concentrations were normal, whereas interleukin-6 and tumor necrosis factor-alpha were elevated. Serum tumor necrosis factor-alpha was positively correlated with the molar E(2)/testosterone ratio and with type 1 procollagen; the latter was elevated, whereas osteocalcin was decreased. Ureagenesis and breakdown of bone were increased. C-Reactive protein and white blood cell counts were elevated; serum lactate levels were normal. Intermittent iv GnRH administration increased pulsatile LH secretion compared with placebo by an increment of +8.1 +/- 8.1 IU/L at 24 h (P = 0.001). This increase was only partially maintained after 5 days of treatment. GnRH pulses transiently increased serum testosterone by +174% on day 2 (P = 0.05), whereas all other endocrine parameters remained unaltered. GnRH tended to increase type 1 procollagen (P = 0.06), but did not change serum osteocalcin levels or bone breakdown. Ureagenesis was suppressed (P < 0.0001), and white blood cell count (P = 0.0001), C-reactive protein (P = 0.03), and lactate level (P = 0.01) were increased by GnRH compared with placebo infusions. In conclusion, hypogonadotropic hypogonadism in prolonged critically ill men is only partially overcome with exogenous iv GnRH pulses, pointing to combined hypothalamic-pituitary-gonadal origins of the profound hypoandrogenism evident in this context. In view of concomitant central hyposomatotropism and hypothyroidism, evaluating the effectiveness of pulsatile GnRH intervention together with GH and TSH secretagogues will be important.

  13. [Anterior pituitary hypersecretion syndromes].

    PubMed

    Gómez, F; Steinhäuslin, F; Crottaz, B; Temler, E

    1987-01-17

    Anterior pituitary hypersecretion can be due to abnormal hypothalamic regulation, decreased peripheral hormone feedback or pituitary tumor. In some cases hypersecretion gives rise to a typical clinical syndrome involving acromegaly, hyperprolactinemia, and excess corticotropin (ACTH). The etiology of acromegaly is a growth hormone (GH)-secreting pituitary tumor in the vast majority of cases. Hyperprolactinemia and excess cortisol, however, may be due to many causes among which prolactin (PRL)- and ACTH-secreting pituitary tumors are not frequent. Glycoprotein-secreting pituitary tumors, especially gonadotropin (LH and FSH) and free subunits usually do not cause a typical excess hormone syndrome. Perhaps for this reason they are seldom recognized clinically, although histopathological studies are increasingly disclosing the gonadotrope nature of many pituitary tumors. Mixed hormonal secretions are common. When pituitary hormone secretion can be selectively suppressed by medical therapy, a significant reduction of tumor size is by no means rare. In other cases, pituitary irradiation or surgery, or even treatment aimed at a peripheral target gland, may be necessary. PMID:3029861

  14. Neuroendocrine regulation of gonadotropin secretion in seasonally breeding birds

    PubMed Central

    Ubuka, Takayoshi; Bentley, George E.; Tsutsui, Kazuyoshi

    2013-01-01

    Seasonally breeding birds detect environmental signals, such as light, temperature, food availability, and presence of mates to time reproduction. Hypothalamic neurons integrate external and internal signals, and regulate reproduction by releasing neurohormones to the pituitary gland. The pituitary gland synthesizes and releases gonadotropins which in turn act on the gonads to stimulate gametogenesis and sex steroid secretion. Accordingly, how gonadotropin secretion is controlled by the hypothalamus is key to our understanding of the mechanisms of seasonal reproduction. A hypothalamic neuropeptide, gonadotropin-releasing hormone (GnRH), activates reproduction by stimulating gonadotropin synthesis and release. Another hypothalamic neuropeptide, gonadotropin-inhibitory hormone (GnIH), inhibits gonadotropin synthesis and release directly by acting on the pituitary gland or indirectly by decreasing the activity of GnRH neurons. Therefore, the next step to understand seasonal reproduction is to investigate how the activities of GnRH and GnIH neurons in the hypothalamus and their receptors in the pituitary gland are regulated by external and internal signals. It is possible that locally-produced triiodothyronine resulting from the action of type 2 iodothyronine deiodinase on thyroxine stimulates the release of gonadotropins, perhaps by action on GnRH neurons. The function of GnRH neurons is also regulated by transcription of the GnRH gene. Melatonin, a nocturnal hormone, stimulates the synthesis and release of GnIH and GnIH may therefore regulate a daily rhythm of gonadotropin secretion. GnIH may also temporally suppress gonadotropin secretion when environmental conditions are unfavorable. Environmental and social milieus fluctuate seasonally in the wild. Accordingly, complex interactions of various neuronal and hormonal systems need to be considered if we are to understand the mechanisms underlying seasonal reproduction. PMID:23531789

  15. Genetically modified mouse models addressing gonadotropin function.

    PubMed

    Ratner, Laura D; Rulli, Susana B; Huhtaniemi, Ilpo T

    2014-03-01

    The development of genetically modified animals has been useful to understand the mechanisms involved in the regulation of the gonadotropin function. It is well known that alterations in the secretion of a single hormone is capable of producing profound reproductive abnormalities. Human chorionic gonadotropin (hCG) is a glycoprotein hormone normally secreted by the human placenta, and structurally and functionally it is related to pituitary LH. LH and hCG bind to the same LH/hCG receptor, and hCG is often used as an analog of LH to boost gonadotropin action. There are many physiological and pathological conditions where LH/hCG levels and actions are elevated. In order to understand how elevated LH/hCG levels may impact on the hypothalamic-pituitary-gonadal axis we have developed a transgenic mouse model with chronic hCG hypersecretion. Female mice develop many gonadal and extragonadal phenotypes including obesity, infertility, hyperprolactinemia, and pituitary and mammary gland tumors. This article summarizes recent findings on the mechanisms involved in pituitary gland tumorigenesis and hyperprolactinemia in the female mice hypersecreting hCG, in particular the relationship of progesterone with the hyperprolactinemic condition of the model. In addition, we describe the role of hyperprolactinemia as the main cause of infertility and the phenotypic abnormalities in these mice, and the use of dopamine agonists bromocriptine and cabergoline to normalize these conditions.

  16. Reduced gonadotropins in athymic mice: prevention by thymic transplantation.

    PubMed

    Rebar, R W; Morandini, I C; Benirschke, K; Petze, J E

    1980-12-01

    The reduction in pituitary concentrations of gonadotropins observed in 20-day old congenitally athymic nude mice in comparison to their normal heterozygous littermates was completely prevented in females and partially prevented in males by thymic transplantation on the first day of life. Those athymic mice receiving transplants but in which no thymic tissue could be found at sacrifice had reduced pituitary gonadotropin concentrations equivalent to sham-operated athymic animals. From these data we infer that the reduced concentrations of gonadotropins seen in the athymic animals are causally related to the absence of the thymus and suggest that the thymus, directly or indirectly, is necessary for development of normal function of the hypothalamic-pituitary-gonadal axis in mice.

  17. Gonadotropin-dependent precocious puberty: neoplastic causes and endocrine considerations.

    PubMed

    Stephen, Matthew D; Zage, Peter E; Waguespack, Steven G

    2011-01-01

    Premature activation of the hypothalamic-pituitary-gonadal (HPG) axis manifests as gonadotropin-dependent precocious puberty. The mechanisms behind HPG activation are complex and a clear etiology for early activation is often not elucidated. Though collectively uncommon, the neoplastic and developmental causes of gonadotropin-dependent precocious puberty are very important to consider, as a delay in diagnosis may lead to adverse patient outcomes. The intent of the current paper is to review the neoplastic and developmental causes of gonadotropin-dependent precocious puberty. We discuss the common CNS lesions and human chorionic gonadotropin-secreting tumors that cause sexual precocity, review the relationship between therapeutic radiation and gonadotropin-dependent precocious puberty, and finally, provide an overview of the therapies available for height preservation in this unique patient population.

  18. Regulation of gonadotropins by corticotropin-releasing factor and urocortin.

    PubMed

    Kageyama, Kazunori

    2013-01-01

    While stress activates the hypothalamic-pituitary-adrenal (HPA) axis, it suppresses the hypothalamic-pituitary-gonadal (HPG) axis. Corticotropin-releasing factor (CRF) is a major regulatory peptide in the HPA axis during stress. Urocortin 1 (Ucn1), a member of the CRF family of peptides, has a variety of physiological functions and both CRF and Ucn1 contribute to the stress response via G protein-coupled seven transmembrane receptors. Ucn2 and Ucn3, which belong to a separate paralogous lineage from CRF, are highly selective for the CRF type 2 receptor (CRF(2) receptor). The HPA and HPG axes interact with each other, and gonadal function and reproduction are suppressed in response to various stressors. In this review, we focus on the regulation of gonadotropins by CRF and Ucn2 in pituitary gonadotrophs and of gonadotropin-releasing hormone (GnRH) via CRF receptors in the hypothalamus. In corticotrophs, stress-induced increases in CRF stimulate Ucn2 production, which leads to the inhibition of gonadotropin secretion via the CRF(2) receptor in the pituitary. GnRH in the hypothalamus is regulated by a variety of stress conditions. CRF is also involved in the suppression of the HPG axis, especially the GnRH pulse generator, via CRF receptors in the hypothalamus. Thus, complicated regulation of GnRH in the hypothalamus and gonadotropins in the pituitary via CRF receptors contributes to stress responses and adaptation of gonadal functions.

  19. Pituitary gland

    MedlinePlus

    ... glands. Located above the pituitary gland is the hypothalamus. The hypothalamus decides which hormones the pituitary should release by ... messages. In response to hormonal messages from the hypothalamus, the pituitary gland releases the following hormones: GH ( ...

  20. Hypothalamic-pituitary function in the Bardet-Biedl syndrome.

    PubMed

    Leroith, D; Farkash, Y; Bar-Ziev, J; Spitz, I M

    1980-07-01

    Four siblings with classic Bardet-Biedl syndrome were studied. The brother had hypogonadism of testiculr origin, with high gonadotropin levels and exaggerated responses to luteinizing-hormone-releasing hormone, whereas the three sisters showed a normal hypothalamic-pituitary-gonadal axis. The remaining pituitary hormone function was intact.

  1. Tissue-specific expression of squirrel monkey chorionic gonadotropin

    PubMed Central

    Vasauskas, Audrey A.; Hubler, Tina R.; Boston, Lori; Scammell, Jonathan G.

    2010-01-01

    Pituitary gonadotropins LH and FSH play central roles in reproductive function. In Old World primates, LH stimulates ovulation in females and testosterone production in males. Recent studies have found that squirrel monkeys and other New World primates lack expression of LH in the pituitary. Instead, chorionic gonadotropin (CG), which is normally only expressed in the placenta of Old World primates, is the active luteotropic pituitary hormone in these animals. The goal of this study was to investigate the tissue-specific regulation of squirrel monkey CG. We isolated the squirrel monkey CGβ gene and promoter from genomic DNA from squirrel monkey B-lymphoblasts and compared the promoter sequence to that of the common marmoset, another New World primate, and human CGβ and LHβ. Using reporter gene assays, we found that a squirrel monkey CGβ promoter fragment (−1898/+9) is active in both mouse pituitary LβT2 and human placenta JEG3 cells, but not in rat adrenal PC12 cells. Furthermore, within this construct separate cis-elements are responsible for pituitary- and placenta-specific expression. Pituitary-specific expression is governed by Egr-1 binding sites in the proximal 250 bp of the promoter, whereas placenta-specific expression is controlled by AP-2 sites further upstream. Thus, selective expression of the squirrel monkey CGβ promoter in pituitary and placental cells is governed by distinct cis-elements that exhibit homology with human LHβ and marmoset CGβ promoters, respectively. PMID:21130091

  2. Gonadotropin-releasing hormone analogs: Understanding advantages and limitations.

    PubMed

    Kumar, Pratap; Sharma, Alok

    2014-07-01

    Pituitary stimulation with pulsatile gonadotropin-releasing hormone (GnRH) analogs induces both follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Pituitary gonadotropin secretions are blocked upon desensitization when a continuous GnRH stimulus is provided by means of an agonist or when the pituitary receptors are occupied with a competitive antagonist. GnRH antagonists were not available originally; therefore, prolonged daily injections of agonist with its desensitizing effect were used. Today, single- and multiple-dose injectable antagonists are also available to block the LH surge and thus to cause desensitization. This review provides an overview of the use of GnRH analogs which is potent therapeutic agents that are considerably useful in a variety of clinical indications from the past to the future with some limitations. These indications include management of endometriosis, uterine leiomyomas, hirsutism, dysfunctional uterine bleeding, premenstrual syndrome, assisted reproduction, and some hormone-dependent tumours, other than ovulation induction.

  3. Pituitary Disorders

    MedlinePlus

    ... the "master control gland" - it makes hormones that affect growth and the functions of other glands in the body. With pituitary disorders, you often have too much or too little of one of your hormones. Injuries can cause pituitary disorders, but the most common cause is a pituitary tumor.

  4. Hypothalamic-pituitary-gonadal axis in thalassemic patients with secondary amenorrhea.

    PubMed

    De Sanctis, V; Vullo, C; Katz, M; Wonke, B; Hoffbrand, A V; Bagni, B

    1988-10-01

    Eight thalassemic patients, aged 24-35 years, who developed amenorrhea 2-15 years after menarche, were studied. Mean basal serum LH and FSH levels and the peak levels after gonadotropin-releasing hormone were significantly less than corresponding values in normal controls. All patients showed low basal serum levels of estradiol and six had a poor or absent response to human menopausal gonadotropin. One subject had intact pituitary-gonadal function and one patient had an impaired LH and FSH response to gonadotropin-releasing hormone in the presence of a significant increase of estradiol after human menopausal gonadotropin stimulation. The findings regarding pituitary hormones other than gonadotropins suggest that iron overload damages tropic cells unequally and inconsistently. We conclude that both pituitary and gonadal damage may be responsible for the secondary amenorrhea in thalassemic patients.

  5. Genetic insights into human isolated gonadotropin deficiency.

    PubMed

    Trarbach, Ericka Barbosa; Silveira, Leticia Gontijo; Latronico, Ana Claudia

    2007-01-01

    The identification of naturally occurring genetic mutations has provided unique insight into the current knowledge of the human hypothalamic-pituitary-gonadal axis. In the past decade, several monogenic causes have been reported in patients with isolated gonadotropin deficiency. Kallmann Syndrome is a clinically and genetically heterogeneous disorder, characterized by isolated hypogonadotropic hypogonadism and anosmia or hyposmia. To date, loss-of-function mutations in the genes encoding anosmin-1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1) have been described in the X-linked and autosomal dominant forms of this syndrome, respectively. More recently, several heterozygous, homozygous or compound heterozygous mutations in the G protein-coupled prokineticin receptor-2 (PROKR2) and one of its ligands, prokineticin-2 (PROK2) were described in Kallmann syndrome. In addition, complex genetic transmission (digenic inheritance) was recently demonstrated in this condition. Regarding isolated hypogonadotropic hypogonadism without olfactory abnormalities, loss-of-function mutations in the Gonadotropin-releasing hormone (GnRH) receptor (GnRH-R) or the G-protein coupled receptor 54 (GPR54) genes, both encoding transmembrane receptors, have been described, as well as FGFR1 mutations. Finally, mutations of the beta sub-units of LH and FSH have been described in patients with selective gonadotropin deficiency. We review the role of these distinct genetic factors in human isolated hypogonadotropic hypogonadism.

  6. Effect of gonadotropin secretion rate on the radiosensitivity of the rat luteinizing hormone-releasing hormone neuron and gonadotroph

    SciTech Connect

    Winterer, J.; Barnes, K.M.; Lichter, A.S.; Deluca, A.M.; Loriaux, D.L.; Cutler, G.B. Jr.

    1988-03-01

    To test the hypothesis that the functional state of hypothalamic LHRH neurons and pituitary gonadotrophs might alter their radiosensitivity, we determined the experimental conditions under which the gonadotropin response to castration could be impaired by a single dose of cranial irradiation. Single doses of cranial irradiation greater than 2000 rads were lethal to unshielded rats. Shielding of the oropharynx and esophagus allowed the animals to survive doses up to 5000 rads. Doses between 2000 and 5000 rads had no effect on basal gonadotropin levels for as long as 3 months after irradiation. Irradiation caused a dose- and time-dependent impairment, however, in the gonadotropin response to castration. Impairment of the gonadotropin levels of castrate animals occurred in animals that were irradiated either before or after castration. However, rats irradiated in the castrate state showed a decreased susceptibility to irradiation damage. Additionally, stimulation of the pituitary by LHRH agonist (LHRHa) 3 h before irradiation significantly reduced the impairment of gonadotropin secretion 12-20 weeks after irradiation (P less than 0.05). Thus, increased functional activity of the rat hypothalamus or pituitary at the time of irradiation, induced by either castration or acute LHRHa administration, was associated with some protection against the gonadotropin-lowering effect of irradiation. Based upon these data, we hypothesize that stimulation of gonadotropin secretion at the time of therapeutic cranial irradiation in humans might protect against subsequent impairment of gonadotropin secretion.

  7. Perinatal activity of the hypothalamic-pituitary-gonadal axis in the lamb. II. In vitro testicular response to human chorionic gonadotropin and choleratoxin in the first 2 months of life.

    PubMed

    Savoie, S; Forest, M G; Bourel, B; Haour, F; Saez, J M; Collu, R; Bertrand, J; Ducharme, J R

    1980-01-01

    Testicular response to human chorionic gonadotropin (hCG) was studied in male lambs. Adenosine 3':5'-cyclic monophosphate (cAMP), testosterone (T), delta 4-androstenedione and 17 alpha-hydroxyprogesterone content and cAMP and T production by dispersed interstitial cells were assessed in control and hCG-pretreated animals. Plasma T levels increased after hCG at 1, 4 and 8 weeks. Increments in the testicular content of cAMP, delta 4-androstenedione, and T were greater at 8 weeks and that of 17 alpha-hydroxyprogesterone and 125I-hCG binding to dispersed interstitial cells were identical at all ages. cAMP and T production by dispersed interstitial cells from nonstimulated animals and the response to hCG and choleratoxin were similar in all lambs. In contrast, cAMP and T production were higher at 1 week only in animals pretreated with hCG in vivo. These data are compatible with hCG-induced desensitization at 4 and 8 weeks.

  8. Regulation of tonic gonadotropin release in prepubertal female hamsters

    SciTech Connect

    Smith, S.G.; Matt, K.S.; Prestowitz, W.F.; Stetson, M.H.

    1982-04-01

    Basal serum gonadotropin levels were monitored weekly in female hamsters from birth to 10 weeks of age. Hamsters raised on three different photoperiods presented uniform pre- and postpubertal patterns of serum LH and FSH, suggesting that gonadotropin release in the young hamster occurs independently of ambient photoperiod. In all groups, serum LH levels increased gradually in animals up to 4 weeks of age, after which levels plateaued at 50--100 ng/ml. Serum FSH was markedly elevated in 2- and 3-week-old hamsters (800--1200 ng/ml), but remained at 200--400 ng/ml in all other groups. We next examined the change in the responsiveness of the pituitary to exogenous gonadotropin-releasing hormone (GnRH) challenge. Female hamsters 2 days of age failed to respond to any dose (0.025--1000 ng) of GnRH, while 10-day old females responded in typical dose-dependent fashion. GnRH-stimulated LH release first occurred in 6-day-old hamsters and was maximal by day 9, whereas FSH release first occurred on day 8 and was maximal by day 9. The prepubertal pattern of gonadotropin release can, in part, be explained on the basis of the development of pituitary GnRH sensitivity, which occurs independently of photoperiod.

  9. Gonadotropin and estradiol secretion during the week of placebo therapy in oral contraceptive pill users.

    PubMed

    van der Spuy, Z M; Sohnius, U; Pienaar, C A; Schall, R

    1990-12-01

    The changes in the hypothalamic-pituitary-ovarian axis during the placebo week in oral contraceptive pill users were assessed. Fifteen women using the combined oral contraceptive pill were studied for eight hours at the start and at the end of the placebo week and gonadotropin secretion and estradiol concentrations were compared with those in control women in the follicular phase of an unmedicated menstrual cycle. Both gonadotropin and estradiol concentrations were suppressed at the start of the placebo week. By day 7 of placebo, gonadotropin concentrations and pulse patterns were indistinguishable from those of the control subjects although estradiol concentrations were still significantly lower.

  10. Hypothalamic and pituitary dysfunction in obese males.

    PubMed

    Amatruda, J M; Hochstein, M; Hsu, T H; Lockwood, D H

    1982-01-01

    Previous studies have indicated dysfunction of the hypothalamic-hypophyseal axis in obesity. We have studied 12 obese males to further characterize the extent of this dysfunction. The hypothalamic-hypophyseal-gonadal axis is normal as determined by the testicular response to human chorionic gonadotropin (hCG), the pituitary response to 200 micrograms gonadotropin-releasing hormone (GnRH), and the hypothalamic-pituitary-testicular response to clomiphene. Although L-dopa suppresses prolactin normally, the ability of thyrotropin releasing hormone (TRH) to stimulate the release of prolactin and thyroid stimulating hormone (TSH) is blunted. These latter responses are inversely related to the degree of obesity. The response to chlorpromazine, a hypothalamic stimulus for prolactin secretion, is also blunted, and to a greater extent than the prolactin response to TRH. These data indicate that exogenous obesity in males is associated with more extensive hypothalamic and pituitary dysfunction than previously realized. The abnormalities with regard to prolactin and TSH release become progressively worse when body weight exceeds 200 percent of ideal. In addition, when evaluating pituitary function with regard to gonadotropin release, obese males may have an abnormal response to 100 micrograms GnRH but respond normally to 200 micrograms.

  11. Pituitary responsiveness to luteinizing-hormone-releasing hormone in different reproductive disorders. A review.

    PubMed

    Vasquez, J M; Greenblatt, R B

    1985-08-01

    As a result of the use of synthetic luteinizing-hormone-releasing hormone (LHRH) (and its analogs), significant advances in modern clinical practice are being realized. We studied the use of LHRH as a test for pituitary reserve for gonadotropin secretion in different reproductive disorders. Synthetic LHRH was used as a diagnostic test for discriminating pituitary from hypothalamic disorders. After appropriate LHRH priming of the pituitary, LHRH was used to document hypothalamic dysfunction in patients with Kallmann's syndrome who had normal gonadotropin responsiveness to LHRH. The gonadotropin responsiveness to 100 micrograms of LHRH was impaired or absent in patients with panhypopituitarism, craniopharyngiomas, hemochromatosis and acromegaly accompanied by abnormal lactation. In women with gonadal dysgenesis, the absence of gonadal steroid feedback exacerbated the pituitary responsiveness to LHRH. Women with hyperprolactinemia are also known to have a blunted gonadotropin response to endogenous and exogenous LHRH. An experimental rat model was developed in our laboratory to study the site of prolactin action on gonadotropin secretion. LHRH challenge tests during perphenazine-induced hyperprolactinemia in rats indicated that prolactin may decrease pituitary sensitivity to LHRH. Additional experiments indicated that the increased progesterone produced in these hyperprolactinemic (pseudopregnant) rats was probably responsible for the decreased pituitary responsiveness to LHRH. Further studies will be necessary to determine whether prolactin, which can alter ovarian steroidogenesis in vitro, interferes with ovulation directly in addition to affecting the hypothalamic-pituitary axis.

  12. Does the impairment of the hypothalamic-pituitary-gonadal axis in anorexia nervosa depend on increased sensitivity to endogenous melatonin?

    PubMed

    Pawlikowski, M; Zarzycki, J

    1999-02-01

    The authors hypothesize that the impairment of hypothalamic-pituitary-gonadal axis in patients suffering from anorexia nervosa depends (at least in part) on the increased sensitivity to endogenous melatonin. The hypothesis is based mainly on the following facts: (1) melatonin is well known to exert an inhibitory effect on gonadotropin secretion; (2) melatonin binding is increased in brains of fasted rats; (3) undernutrition dramatically increases the inhibitory effect of exogenous melatonin on gonadotropin-releasing hormone-induced gonadotropin secretion in female rats; (4) the administration of propranolol in girls suffering from anorexia nervosa diminishes the nocturnal peak of melatonin and, in parallel, restores the gonadotropin response to gonadotropin-releasing hormone.

  13. Gonadotropin hormone and receptor sequences from model teleost species.

    PubMed

    Wong, Andrew C; Van Eenennaam, Alison L

    2004-01-01

    Fish offer some advantages for the study of vertebrate reproductive physiology. Only a few of the genes encoding the components of the hypothalamic-pituitary-gonadal axis have been identified from model teleosts. This study describes a combination of database searching and molecular approaches to identify the FSH and LH gonadotropin beta-subunits (fshb and lhb, respectively), and the LH receptor (lhr) from two model teleost species: zebrafish (Danio rerio) and Fugu (Takifugu rubripes). Sequence and phylogenetic analyses were used to examine the relationships that exist between gonadotropins and their receptors from species representing several piscine orders. The gonadotropin alpha-subunit (Cga) is highly conserved among teleosts and tetrapods. The presence of a genomic pseudogene (cgap) was also noted in zebrafish. Generally, teleostean FSHbeta protein sequences share less identity with each other than do LHbeta protein sequences, supporting the hypothesis that FSHbeta diverged more rapidly during teleost evolution. Interestingly, and uniquely, zebrafish Fshb lacked two highly conserved cysteine residues in the "determinant loop" which is thought to contribute towards receptor binding and specificity. Teleost gonadotropin receptor sequences clearly diverged into two distinct groups, FSHR and LHR. As has been seen with mammalian gonadotropin receptor transcripts, splice variants of zebrafish lhr were also observed.

  14. Pituitary Tumors

    MedlinePlus

    ... pituitary is the "master control gland" - it makes hormones that affect growth and the functions of other glands in the body. Pituitary tumors are common, but often they don't cause health ... tumor produces hormones and disrupts the balance of hormones in your ...

  15. Hypothalamic and pituitary function in hypogonadotropic hypogonadism.

    PubMed

    Paulson, D F; Wiebe, H R; Hammond, C B

    1975-09-01

    Hypogonadotropic hypogonadism has been identified as a cause of partial or complete failure of puberty, may be familial and may have other associated abnormalities of hyposmia, intellectual retardation, perceptive deafness, color blindness, skeletal deformities, and gynecomastia. Pituitary function is usually normal with the primary defect believed to be hypothalamic. A twenty-year-old white male with a clinical diagnosis of hypogonadotropic hypogonadism and anosmia under-went complete endocrine evaluation with evaluation of the pituitary response to luteinizing hormone-releasing hormone. FSH (follicle-stimulating hormone) and LH (luteinizing hormone) release after luteinizing hormone-releasing hormone did occur, but the response was less than that seen in normal controls. Evaluation demonstrated that the pituitary-gonadal axis was intact with the hypothalamic-pituitary axis being defective. Therapy with the synthetic decapeptide (luteinizing hormone-releasing hormone) is correct theoretically and may be superior to therapy with exogenous gonadotropins.

  16. Dual pathways of calcium entry in spike and plateau phases of luteinizing hormone release from chicken pituitary cells: sequential activation of receptor-operated and voltage-sensitive calcium channels by gonadotropin-releasing hormone

    SciTech Connect

    Davidson, J.S.; Wakefield, I.K.; King, J.A.; Mulligan, G.P.; Millar, R.P.

    1988-04-01

    It has previously been shown that, in pituitary gonadotrope cells, the initial rise in cytosolic Ca2+ induced by GnRH is due to a Ca2+ mobilization from intracellular stores. This raises the possibility that the initial transient spike phase of LH release might be fully or partially independent of extracellular Ca2+. We have therefore characterized the extracellular Ca2+ requirements, and the sensitivity to Ca2+ channel blockers, of the spike and plateau phases of secretion separately. In the absence of extracellular Ca2+ the spike and plateau phases were inhibited by 65 +/- 4% and 106 +/- 3%, respectively. Both phases exhibited a similar dependence on concentration of extracellular Ca2+. However, voltage-sensitive Ca2+ channel blockers D600 and nifedipine had a negligible effect on the spike phase, while inhibiting the plateau phase by approximately 50%. In contrast, ruthenium red, Gd3+ ions, and Co2+ ions inhibited both spike and plateau phases to a similar extent as removal of extracellular Ca2+. A fraction (35 +/- 4%) of spike phase release was resistant to removal of extracellular Ca2+. This fraction was abolished after calcium depletion of the cells by preincubation with EGTA in the presence of calcium ionophore A23187, indicating that it depends on intracellular Ca2+ stores. Neither absence of extracellular Ca2+, nor the presence of ruthenium red or Gd3+ prevented mobilization of 45Ca2+ from intracellular stores by GnRH. We conclude that mobilization of intracellular stored Ca2+ is insufficient by itself to account for full spike phase LH release.

  17. Significance of the secretion of human prolactin and gonadotropin for puerperal lactational infertility.

    PubMed

    Tyson, J E; Freedman, R S; Perez, A; Zacur, H A; Zanartu, J

    1976-01-01

    The causes of puerperal infertility in lactating women are poorly understood. The controlling centres may be either the hypothalamic-pituitary axis or the ovary (or both). We studied the secretory dynamics of prolactin and gonadotropins in healthy, normal, lactating and non-lactating women after administering either gonadoliberin to assess pituitary responsiveness or human menopausal gonadotropins to assess ovarian responsiveness during the puerperium. A reciprocal relationship was observed between the secretion of gonadotropins and the secretion of prolactin after the nipples of mothers who were breast-feeding had been stimulated for 30 min. The absence of a short-loop negative feedback control by prolactin for gonadotropin secretion was not confirmed because cyclic secretion of gonadotropin was not necessarily impaired by hyperprolactinaemia. Hyperprolactinaemia did, however, appear to impair the function of the corpus luteum in women suffering from non-puerperal galactorrhoea. We postulate a multifactorial mechanism for puerperal infertility based initially on the peripheral concentration of prolactin and gonadotropins and, in some poorly defined way, on the cerebral concentration of catecholamines.

  18. Altered pulsatile gonadotropin signaling in nutritional deficiency in the male.

    PubMed

    Bergendahl, M; Veldhuis, J D

    1995-07-01

    Reproduction cannot occur without adequate nutrition. Diets that are nutritionally inadequate delay and disrupt the pubertal development of the reproductive processes of immature experimental animals and humans, and impair the function of the hypothalamic-pituitary-gonadal axis in adults. Although there is a general understanding of the linkages between nutrition and reproduction, there is a lack of detailed knowledge of the exact mechanisms that couple these two systems. The major effects of malnutrition on the hypothalamic-pituitary-gonadal axis reported in the literature are, for the most part, manifested as reduced gonadotropin secretion. Malnutrition results in decreased circulating gonadotropin concentrations. These changes in the reproductive system are associated with impaired gonadal function and subsequent secondary sex organ atrophy and lead, ultimately, to poor reproduction. Decreased hypothalamic release of gonadotropin-releasing hormone (GnRH) has been proposed as the most important etiologic factor for the fasting-induced suppression of pituitary-testicular function. In the human, hypogonadism and infertility develop in both sexes during chronic malnutrition. Most studies on the effects of malnutrition on the reproductive hormones have been performed in women, perhaps because malnutrition in women is promptly accompanied by amenorrhea, whereas in men hypogonadism develops gradually and becomes clinically evident only during more severe malnutrition. With the advent of sensitive assays for measuring reproductive hormones and of modern computerized methods for analyzing the pulsatile secretion of these hormones, however, the function of the hypothalamic-pituitary-testicular axis has been scrutinized and it has, indeed, been observed that this system is disturbed even during acute malnutrition. Here, we review the effects of malnutrition on reproductive function, especially on the pulsatile pattern of LH secretion, in humans and in experimental animals.

  19. Pituitary Tumors

    MedlinePlus

    ... or milk production), sex hormones (control the menstrual cycle and other sexual functions), thyroid gland hormones (control the thyroid gland), adrenal gland hormones, and vasopressin (a hormone involved in water and electrolyte balance). Symptoms of pituitary adenoma and ...

  20. Dioxin Silences Gonadotropin Expression in Perinatal Pups by Inducing Histone Deacetylases

    PubMed Central

    Takeda, Tomoki; Fujii, Misaki; Taura, Junki; Ishii, Yuji; Yamada, Hideyuki

    2012-01-01

    Maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes the impairment of reproduction and development in the pups. Our previous studies have revealed that maternal treatment with TCDD attenuates the fetal production of pituitary gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone) at gestational day (GD) 20, leading to the impairment of sexual behavior in adulthood. However, the mechanism underlying such a reduction has remained unknown until now. When pregnant rats at GD15 were given an oral dose of TCDD (1 μg/kg), the testicular expression of steroidogenic proteins was reduced between GD20 and postnatal days (PND) 2. In accordance with this, the pituitary expression of gonadotropin β-subunit and serum gonadotropin were also attenuated from GD20 to PND0 in a pup-specific fashion. To identify the target genes linked to a fetal reduction in gonadotropin β-subunit, we performed a DNA microarray analysis using the fetal pituitary and its regulatory organ, the hypothalamus. The results obtained showed that TCDD induced histone deacetylases (HDACs) in the fetal pituitary. In support with this, TCDD markedly deacetylated histones H3 and H4 twined around the promoter of the fetal LHβ gene. This effect was fetus- and LHβ-specific, and this was not observed in the maternal pituitary or for other pituitary hormone genes. Finally, an LHβ reduction caused by TCDD was completely restored by maternal co-treatment with valproic acid, an HDAC inhibitor. These results strongly suggest that the increased deacetylation of histone owing to HDAC induction plays a critical role in the TCDD-induced reduction in LHβ in the fetal pituitary. PMID:22493514

  1. Contemporary issues in the evaluation and management of pituitary adenomas.

    PubMed

    Pekic, S; Stojanovic, M; Popovic, V

    2015-12-01

    Pituitary adenomas are common benign monoclonal neoplasms accounting for about 15% of intracranial neoplasms. Data from postmortem studies and imaging studies suggest that 1 of 5 individuals in the general population may have pituitary adenoma. Some pituitary adenomas (mainly microadenomas which have a diameter of less than 1 cm) are exceedingly common and are incidentally diagnosed on magnetic resonance imaging (MRI) performed for an unrelated reason (headache, vertigo, head trauma). Most microadenomas remain clinically occult and stable in size, without an increase in tumor cells and without local mass effects. However, some pituitary adenomas grow slowly, enlarge by expansion and become demarcated from normal pituitary (macroadenomas have a diameter greater than 1 cm). They may be clinically silent or secrete anterior pituitary hormones in excess such as prolactin, growth hormone (GH), or adrenocorticotropic hormone (ACTH) causing diseases like prolactinoma, acromegaly, Cushing's disease or rarely thyroid-stimulating hormone (TSH) or gonadotropins (LH, FSH). The incidence of the various subtypes of pituitary adenoma varies but the most common is prolactinoma. Clinically non-functioning pituitary adenomas (NFPAs), which do not secrete hormones often cause local mass symptoms and represent one-third of pituitary adenomas. Given the high prevalence of pituitary adenomas and their heterogeneity (different tumor subtypes), it is critical that clinicians have a thorough understanding of the potential abnormalities in pituitary function and prognostic factors for behavior of pituitary adenomas in order to timely implement specific treatment modalities. Regarding pathogenesis of these tumors genetics, epigenetics and signaling pathways are the focus of current research yet our understanding of pituitary tumorigenesis remains incomplete. Although several genes and signaling pathways have been identified as important factors in the development of pituitary tumors, current

  2. 21 CFR 522.1079 - Serum gonadotropin and chorionic gonadotropin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Serum gonadotropin and chorionic gonadotropin. 522.1079 Section 522.1079 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... (i) Gilts. For induction of fertile estrus (heat) in healthy prepuberal (noncycling) gilts. (ii)...

  3. Non-functioning pituitary adenomas.

    PubMed

    Chanson, P; Brochier, S

    2005-01-01

    The vast majority (>80%) of clinically non-functioning pituitary adenomas (NFPAs) are gonadotroph-cell adenomas, as demonstrated by immunocytochemistry. However, they are rarely associated with increased levels of dimeric LH or FSH. Increased levels of uncombined subunits (free alpha-subunit mainly, LH-beta subunit more rarely) are more frequently encountered, but are generally modest. The main problems raised by NFPA are mass effects problems, responsible for optic chiasm compression or deficient hormone secretion resulting from compression of normal anterior pituitary cells. The therapeutic management of NFPA may require combination of different options. The strategy of observation only for patients with incidentally discovered pituitary adenomas may be appropriate, provided that the tumor is well-delimited, small, has no extension with risk of neurological or visual chiasm compression, and that a meticulous hormonal work-up has ruled out the possibility of a minimal hormonal hypersecretion. Transsphenoidal surgery allows improvement in visual disturbances due to chiasmal syndrome in most patients, and sometimes, in pituitary function. After surgery alone, nearly 30% (between 10 and 69%, according to the series) of patients relapse within 5 to 10 yr. Radiotherapy is proposed either as a systematic adjunct or only if a significant remnant persists. Systematic radiation therapy is supported by the low relapse rate (mean, 11%; range, 6-21%) observed when radiation therapy is systematically associated with surgery. However, irradiation is almost always followed by hypopituitarism which might be associated with a reduction in life expectancy, despite appropriate replacement therapy. Results of medical treatment are disappointing. Dopamine agonist bromocriptine decreases gonadotropin and alpha-subunit in vitro and in vivo, but, in clinical studies, was poorly effective in reducing supranormal gonadotropins and free subunits levels, and rarely produced a minimal tumoral

  4. Pituitary Apoplexy.

    PubMed

    Briet, Claire; Salenave, Sylvie; Bonneville, Jean-François; Laws, Edward R; Chanson, Philippe

    2015-12-01

    Pituitary apoplexy, a rare clinical syndrome secondary to abrupt hemorrhage or infarction, complicates 2%-12% of pituitary adenomas, especially nonfunctioning tumors. Headache of sudden and severe onset is the main symptom, sometimes associated with visual disturbances or ocular palsy. Signs of meningeal irritation or altered consciousness may complicate the diagnosis. Precipitating factors (increase in intracranial pressure, arterial hypertension, major surgery, anticoagulant therapy or dynamic testing, etc) may be identified. Corticotropic deficiency with adrenal insufficiency may be life threatening if left untreated. Computed tomography or magnetic resonance imaging confirms the diagnosis by revealing a pituitary tumor with hemorrhagic and/or necrotic components. Formerly considered a neurosurgical emergency, pituitary apoplexy always used to be treated surgically. Nowadays, conservative management is increasingly used in selected patients (those without important visual acuity or field defects and with normal consciousness), because successive publications give converging evidence that a wait-and-see approach may also provide excellent outcomes in terms of oculomotor palsy, pituitary function and subsequent tumor growth. However, it must be kept in mind that studies comparing surgical approach and conservative management were retrospective and not controlled. PMID:26414232

  5. The effect of ovariectomy on gonadotropin release

    PubMed Central

    Yen, S. S. C.; Tsai, C. C.

    1971-01-01

    The sequential changes in the concentration and pattern of circulating luteinizing hormone (LH) and follicle-stimulating hormone (FSH)1 following bilateral ovariectomy were determined in 10 premenopausal women. The initial (1st wk) and delayed (3 wk) secretory responses of serum LH and FSH as related to the phases of the menstrual cycle were examined. Ovariectomy during follicular phase was accompanied by a prompt and much greater rise in both LH and FSH during the 1st wk. This rapid rise was followed by a transient decline between the 7th and 10th day which resulted in a biphasic pattern. In contrast, a slower and progressive rise in serum LH and FSH was observed in subjects ovariectomized during luteal phase of the cycle. The quantitative secretion (area under the curve) during the 1st wk after ovariectomy was significantly greater in patients operated on during the follicular phase than during the luteal phase for both LH (P < 0.05) and FSH (P < 0.01). Thereafter, a similar pattern of gonadotropin rise was observed for patients ovariectonized during either phase of the cycle and reached a plateau by the end of the 3rd wk. At this time, the mean LH concentration increased 6-fold for follicular phase surgery and 8-fold for luteal phase surgery. The mean serum FSH concentration increased 8-fold for follicular phase surgery and 12-fold for luteal phase surgery. The net increase in serum FSH level was higher than that in the serum LH level after surgery in both phases of the cycle and thus a reversal of FSH/LH ratio occurred. These data provide indirect evidence that the phase of ovarian steroid secretion may exert a quantitative influence on the gonadotropin turnover rate within the hypothalamic-pituitary system. The augmented gonadotropin release and the reversal of FSH/LH ratio following ovariectomy presumably could be due to an increased gonadotropin net synthesis which is more pronounced for FSH than for LH. Images PMID:5552412

  6. Regulation of gonadotropin gene expression by Mullerian inhibiting substance.

    PubMed

    Bédécarrats, Grégoy Y; O'Neill, Francis H; Norwitz, Errol R; Kaiser, Ursula B; Teixeira, Jose

    2003-08-01

    In addition to its role in causing Müllerian duct regression, Müllerian inhibiting substance (MIS) is implicated in the regulation of steroidogenesis, breast and prostate growth, and ovarian follicle recruitment, all of which are processes controlled or influenced by the hypothalamic-pituitary-gonadal axis. Whereas the direct effect of MIS on gonadal, prostate, and breast cells is under investigation, the ability of MIS to modulate pituitary function, thereby affecting those tissues indirectly, has not yet been studied. Using LbetaT2 cells, a murine gonadotrope-derived cell line, we have evaluated the effects of MIS on the expression of the gonadotropin genes. We show that both LbetaT2 cells and adult rat pituitaries express MIS type II receptor (MISRII) mRNA. Within 2 h, follicle-stimulating hormone beta subunit (FSHbeta) mRNA levels are significantly induced by addition of MIS to LbetaT2 cells and remain elevated through 8 h of treatment. Transcriptional activation of both the FSHbeta and luteinizing hormone beta subunit (LHbeta) gene promoters was observed by MIS, which enhances the effect of gonadotropin-releasing hormone (GnRH) agonist on the FSHbeta gene promoter and synergizes with the GnRH agonist to stimulate LHbeta gene promoter activity. Addition of MIS to LbetaT2 cells stimulates the activity of the rat LHbeta gene promoter with as little as 1 microg/ml and in a dose-dependent manner. These studies report both MISRII expression in rat pituitary cells and a gonadotrope-derived cell line and MIS-mediated activation of LHbeta and FSHbeta gene expression, and suggest that MIS may modulate the hypothalamic-pituitary-gonadal axis at more than one level.

  7. Effects of dopamine blockade on gonadotropins and testosterone in men.

    PubMed

    Siris, S G; Siris, E S; van Kammen, D P; Docherty, J P; Alexander, P E; Bunney, W E

    1980-02-01

    The authors found that plasma luteinizing hormone (LH), prolactin, and testosterone were initially normal in nine acutely psychotic males with schizophrenia or schizo-affective disorder; follicle-stimulating hormone (FSH) was normal in eight of the nine. When patients were treated with pimozide, a relatively specific dopamine receptor blocker, there were statistically significant declines in FSH and LH, although levels remained within normal limits. Prolactin rose significantly, but testosterone did not change. The observed reductions in FSH and LH concentrations are consistent with the hypotheses that dopamine and/or prolactin play a role in gonadotropin secretion. The maintenance of normal levels of gonadotropins and testosterone, however, suggests that these patients possessed relatively normal hypothalamic-pituitary-gonadal axis function before and during a course of neuroleptic treatment.

  8. Gonadotropins: a cohesive gender-based etiology of Alzheimer disease.

    PubMed

    Webber, Kate M; Casadesus, Gemma; Atwood, Craig S; Bowen, Richard L; Perry, George; Smith, Mark A

    2007-01-01

    While there is ample experimental evidence supporting the role of estrogen in the pathogenesis of Alzheimer disease, recent inconclusive data regarding hormone replacement therapy (HRT), specifically, the unexpected results of the Women's Health Initiative (WHI) Memory Study has raised serious questions regarding the protective effects of estrogen. Because of this and other inconsistencies in the estrogen hypothesis, we propose that another hormone of the hypothalamic-pituitary-gonadal axis, luteinizing hormone, is a major factor in the pathogenesis of Alzheimer disease. Specifically, we suspect that the increase in gonadotropin concentrations, and not the decrease in steroid hormone (e.g., estrogen) production following menopause/andropause, is a primary causative factor for the development of Alzheimer disease. In this review, we examine how the gonadotropins may play a central and determining role in modulating the susceptibility to, and progression of, Alzheimer disease.

  9. Binding sites for gonadotropins in human postmenopausal ovaries

    SciTech Connect

    Nakano, R.; Shima, K.; Yamoto, M.; Kobayashi, M.; Nishimori, K.; Hiraoka, J.

    1989-02-01

    The binding of human LH and human FSH to postmenopausal ovarian tissue from 21 patients with cervical carcinoma was analyzed. The binding sites for FSH and LH were demonstrated in postmenopausal ovarian tissue. The surface-binding sites for gonadotropins were localized in the cells of cortical stroma of the postmenopausal ovary. In addition, diffuse cytoplasmic staining of endogenous estrogen and 3 beta-hydroxysteroid dehydrogenase activity were detected immunohistochemically and histochemically in the cells of the cortical stroma. Electron microscopic study also suggested steroidogenic function in the cells of the cortical stroma. The results of the present study suggest that postmenopausal ovaries contain specific binding sites for pituitary gonadotropins and play a role in ovarian steroidogenesis.

  10. Pituitary tumor

    MedlinePlus

    ... visual field loss, drooping eyelids or changes in color vision Headache Lack of energy Nasal drainage of clear fluid Nausea and vomiting Problems with the sense of smell In rare cases, these symptoms occur suddenly and can be severe ( pituitary apoplexy ).

  11. Gonadotropins and Alzheimer's disease: the link between estrogen replacement therapy and neuroprotection.

    PubMed

    Webber, Kate M; Bowen, Richard; Casadesus, Gemma; Perry, George; Atwood, Craig S; Smith, Mark A

    2004-01-01

    The search for a definitive gender bias in Alzheimer's disease has resulted in a multitude of epidemiological findings that point to a higher prevalence and incidence of Alzheimer's disease in women. Due to this reported predisposition of women to Alzheimer's disease, the sex steroid estrogen has become the primary focus of research in this field, however, inconclusive data regarding estrogen replacement therapy has lead some researchers to further investigate the role of the other hormones of the hypothalamic-pituitary-gonadal (HPG) axis that have been, for the most, part overlooked. The hormones of the HPG axis, such as the gonadotropin, (luteinizing hormone and follicle-stimulating hormone), are involved in regulating reproductive function via a complex feedback loop. We propose that it is in fact the increase in gonadotropin concentrations and not the decrease in steroid hormone (e.g., estrogen) production following menopause/andropause that results in an increased risk of Alzheimer's disease. Furthermore, when the role of gonadotropins is taken into account, the data obtained from recent epidemiological studies and randomized trials suggesting the ineffectiveness estrogen may indeed be misinterpreted. In this review, we examine how hormones of the hypothalamic-pituitary-gonadal axis, in particular the gonadotropins, play a central and determining role in modulating the susceptibility to and progression of Alzheimer's disease. Based on this, we suggest that therapeutic interventions targeted at gonadotropins could both prevent disease in those patients currently asymptomatic or halt, and even reverse, disease in those currently afflicted.

  12. Gonadotropin secretion in bulimia nervosa.

    PubMed

    Schweiger, U; Pirke, K M; Laessle, R G; Fichter, M M

    1992-05-01

    Twenty-two normal weight women with bulimia nervosa (BN) were studied (mean age, 25 +/- 5 yr; body mass index, 20.2 +/- 2.6 kg/m2). Sixteen of them reported menstrual cycles in the range of 21-42 days, and 6 had experienced absence of menstruation for at least 3 months. Twenty-one healthy women with regular menstrual cycles (mean age, 23 +/- 2 yr; body mass index, 20.7 +/- 1.4) served as the control subjects. Frequent morning blood samples for estradiol (E2) and progesterone (P4) determinations were obtained for the duration of 1 menstrual cycle or for 6 weeks in the case of amenorrhea. LH, FSH, cortisol, and insulin secretion were studied on day 3, 4, or 5 after the onset of a menstrual cycle or on a random day in the 6 BN women with amenorrhea. Blood samples were collected at 15-min intervals from 1800-0600 h for LH and FSH and at 30-min intervals from 2400-0600 h for cortisol and insulin. Nineteen of the 21 controls, but only 10 of the 22 BN women, fulfilled the following standard criteria: maximum E2 above 440 pmol/L, maximum P4 above 19 nmol/L, and luteal phase length of 9 days or more. The 10 BN women with normal menstrual cycles had lower mean insulin concentrations than the controls (70 +/- 20 vs. 120 +/- 30 pmol/L; P less than 0.01), but gonadotropin secretion, cortisol, and T3 concentrations were similar. The 8 BN women with amenorrhea or ovulatory dysfunction (maximum E2, less than 440 pmol/L; maximum P4, less than 6 nmol/L) displayed decreased mean LH pulse frequency (2.6 +/- 2.4 vs. 5.7 +/- 2.0 pulses/12 h; P less than 0.01), increased mean cortisol (120 +/- 40 vs. 80 +/- 20 nmol/L; P less than 0.01), decreased mean insulin (90 +/- 40 vs. 120 +/- 30 pmol/L; P less than 0.05), and decreased mean T3 concentrations (1.5 +/- 0.3 vs. 1.8 +/- 0.2 nmol/L; P less than 0.01). The data suggest that BN in normal weight women is associated with an increased rate of ovarian dysfunction; decreased pulsatile LH secretion seems to be an important mechanism. Increased

  13. Ghrelin and anterior pituitary function.

    PubMed

    Lanfranco, Fabio; Motta, Giovanna; Baldi, Matteo; Gasco, Valentina; Grottoli, Silvia; Benso, Andrea; Broglio, Fabio; Ghigo, Ezio

    2010-01-01

    Ghrelin, a 28-amino-acid octanoylated peptide predominantly produced by the stomach, was discovered to be the natural ligand of the type 1a GH secretagogue receptor. Thus, it was considered as a natural GH secretagogue (GHS) additional to GHRH, although later on ghrelin has mostly been considered a major orexigenic factor. The GH-releasing action of ghrelin takes place both directly on pituitary cells and through modulation of GHRH from the hypothalamus; some functional anti-somatostatin action has also been shown. However, even at the neuroendocrine level, ghrelin is much more than a natural GHS. In fact, it significantly stimulates prolactin secretion in humans, independent of both gender and age and probably involving a direct action on somatomammotroph cells. Above all, ghrelin and synthetic GHS possess an acute stimulatory effect on the activity of the hypothalamus-pituitary-adrenal axis in humans, which is, at least, similar to that of the opioid antagonist naloxone, arginine vasopressin and even corticotropin-releasing hormone. Also, ghrelin plays a relevant role in the modulation of the hypothalamic-pituitary-gonadal function, with a predominantly CNS-mediated inhibitory effect upon the gonadotropin pulsatility both in animals and in humans.

  14. Rheumatic manifestations of pituitary tumors.

    PubMed

    Stavrou, S; Kleinberg, D L

    2001-10-01

    Pituitary tumors may cause rheumatologic problems as a result of under production or overproduction of one pituitary hormone. Excessive growth hormone causes destruction of cartilage by a direct action. Facial and acral changes and arthralgias may be some of the first symptoms of acromegaly. The arthritis associated with acromegaly is often devastating. Carpal tunnel syndrome is very common in patients with acromegaly. Adrenocorticotropin (ACTH) has indirect effects via the action of glucocorticoid on bones, muscles, and the immune system. Proximal muscle weakness is a characteristic feature of Cushing's syndrome. Patients with Cushing's syndrome commonly have osteopenia and osteoporosis that lead to an increase in bone fractures. Avascular necrosis is associated with exogenous steroid administration. The effects of too much glucocorticoid or too rapid withdrawal can be severe. Gonadotropins act via the gonadal steroids and protect bone mass from loss. Prolactin is less involved in rheumatologic disease; the data for which are limited in humans. Pituitary tumors can have manifestations similar to rheumatologic disorders and should be included in the differential diagnosis of these diseases.

  15. Pituitary incidentaloma.

    PubMed

    Orija, Israel B; Weil, Robert J; Hamrahian, Amir H

    2012-02-01

    Pituitary incidentalomas (PIs) are commonly encountered in clinical practice. While most are microincidentalomas (<1 cm) and not functional, in some cases their identification may lead to discovery of unrecognized abnormalities such as pituitary hormonal deficiencies, excess hormone secretion or visual field defects. Although the majority are pituitary adenomas, the potential list of differential diagnosis is extensive. A limited biochemical work up for asymptomatic patients with microincidentalomas, to include measurement of prolactin and IGF-1, is reasonable, with further studies to be tailored based on the clinical picture. All patients with macroincidentalomas (≥1 cm) should be evaluated for hypopituitarism and undergo visual field testing if the sellar mass abuts or compresses the optic chiasm. Most PIs can be followed, closely without surgery over time, but some may require surgical removal, especially if they are found to be macroincidentalomas at presentation, encroaching on or abutting the optic chiasm, or are found to be functional, excluding prolactinomas. Recovery of pituitary function may be seen in some patients with mass effect following resection of a sellar mass. The association of headache and pituitary incidentalomas remains a diagnostic challenge. There are no randomized controlled studies to guide the follow up approach when surgery is not indicated; most of the follow up algorithms in the literature are based on personal experience. Most retrospective series on natural history indicate that microincidentalomas tend not to grow; without a need for long-term follow up unless the patient becomes symptomatic. Macroincidentalomas, on the other hand, have a propensity to grow and need a more aggressive follow up approach to minimize morbidity. PMID:22305452

  16. Gonadotropin-releasing hormone-stimulated gonadotropin levels in women with premenstrual dysphoria.

    PubMed

    Smith, M J; Schmidt, P J; Su, T P; Rubinow, D R

    2004-12-01

    Despite consistent evidence that premenstrual dysphoria (PMD) is not characterized by abnormalities in basal ovarian hormone secretion, the possibility remains that PMD is associated with an abnormality in the regulation of the hypothalamic-pituitary-ovarian (HPO) axis. We studied HPO axis regulation in 11 women with prospectively confirmed PMD and 20 asymptomatic controls, during both the follicular and luteal phases of the menstrual cycle. Plasma levels of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), were obtained before and after stimulation with gonadotropin-releasing hormone (GnRH) (100 microg intravenously). Potential diagnostic- and menstrual cycle phase-related diferences in basal and plasma hormone levels were analyzed by repeated-measures analysis of variance. No significant differences were observed between women with PMD and controls in either basal or stimulated levels of FSH and LH. Stimulated FSH was significantly increased and stimulated LH was significantly decreased during the follicular compared with the luteal phase in both women with PMD and controls. These data are consistent with prior findings of normal basal reproductive hormone levels in women with PMD. Our data suggest the absence in women with PMD of an abnormality of dynamic ovarian function as measured by GnRH stimulation.

  17. Cysteamine reduces serum gonadotropin concentrations in adult male rats.

    PubMed

    Badger, T M; Sagar, S M; Millard, W J; Martin, J B; Rosenblum, P

    1982-01-18

    We have examined the effects of cysteamine on the hypothalamic-pituitary-gonadal axis of the adult male rat. A single subcutaneous injection of cysteamine (300 mg/kg) reduces significantly (p less than or equal to 0.05 serum concentrations of LH, FSH and T. Cysteamine blocked LH secretion induced by castration and administration of naloxone and LHRH. Neither acute nor chronic treatment (7 days) altered the hypothalamic LHRH content. These results suggest that cysteamine acts to reduce pituitary responsiveness to LHRH, resulting in lower mean serum gonadotropin and testosterone concentrations. It is possible, however, that cysteamine acts also at the hypothalamus to reduce LHRH secretion and/or at the testes to reduce testosterone release.

  18. The hormonal basis of reproductive defects in athymic mice: diminished gonadotropin concentrations in prepubertal females.

    PubMed

    Rebar, R W; Morandini, I C; Erickson, G F; Petze, J E

    1981-01-01

    Congenitally nude athymic female mice are known to have severe deficiencies in reproductive function, including reduced ovarian weight, increased follicular atresia, decreased fertility, and premature ovarian failure, in comparison to their phenotypically normal heterozygous littermates. To determine the hormonal basis for these reproductive defects, pituitary and circulating concentrations of gonadotropins and circulating levels of gonadal steroids were quantitated in 132 congenitally athymic mice and 126 of their normal heterozygous littermates, ranging in age from 1-120 days. Although prepubertal increases in both circulating LH and FSH, which were maximal at 10 days of age, were observed in both athymic and heterozygous females, the concentrations were reduced significantly in the athymic animals (P less than 0.01). Dramatic increases in the pituitary concentrations of both LH and FSH followed at 20 days, with the concentrations in heterozygotes being 3-fold greater than those in the athymic mice (P less than 0.01 for LH; P less than 0.001 for FSH). These abnormalities in pituitary gonadotropin concentrations in the athymic mice were followed by a 2- to 3-fold reduction in the secretion of estrone but not estradiol in athymic females 30 days and older. Serum androgen levels were also reduced. From these data we infer that the reduced gonadotropin concentrations observed in the athymic animals are responsible for their increased follicular atresia and premature ovarian failure and that the thymus gland appears to be essential for normal development of the hypothalamic-pituitary-ovarian axis.

  19. Absence of pubertal gonadotropin secretion in girls with McCune-Albright syndrome.

    PubMed

    Foster, C M; Ross, J L; Shawker, T; Pescovitz, O H; Loriaux, D L; Cutler, G B; Comite, F

    1984-06-01

    Precocious puberty in girls with McCune-Albright syndrome has been attributed in some cases to early activation of the hypothalamic-pituitary-gonadal axis and in other cases to sex steroid secretion by apparently autonomous ovarian cysts. We evaluated serum gonadotropins and sex steroids in six girls (aged 1-9 yr) with McCune-Albright syndrome. The children had Tanner stage II-IV pubertal development. In five patients, nocturnal gonadotropin concentrations and the gonadotropin response to LHRH were within the normal range for prepubertal children. Thus, the precocious puberty in these patients could not be explained by activation of the hypothalamic-pituitary-ovarian axis. One child had high amplitude nocturnal pulses of serum LH and a LH-predominant response to LHRH. She was the oldest of the six girls and had a bone age of 13.5 yr which is within the range in which hypothalamic-pituitary-ovarian activation normally occurs. The children all had ovarian enlargement and ovarian cysts determined by ultrasound. It appears that precocious puberty in McCune-Albright syndrome may result from ovarian estrogen secretion in the absence of normal pubertal activation of the hypothalamic-pituitary-ovarian axis.

  20. The gonadotropin connection in Alzheimer's disease.

    PubMed

    Meethal, Sivan Vadakkadath; Smith, Mark A; Bowen, Richard L; Atwood, Craig S

    2005-04-01

    Although not traditionally thought of as regulators of neuronal function, the hypothalamic-pituitary-gonadal (HPG) hormones luteinizing hormone (LH), gonadotropin-releasing hormone (GnRH), and activins possess neuronal receptors. These receptors are found throughout the limbic system on a number of different cell types, and, like reproductive tissues, the expression of these receptors is regulated by hormonal feedback loops. These hormones and their receptors regulate structure and a diverse range of functions in the brain. Therefore, it is not surprising that the dysregulation of the HPG axis with menopause and andropause (leading to elevated LH, GnRH, and activin signaling but decreased sex steroid signaling) might promote alterations in both the structure and function of neuronal cells. To date, most evidence has accumulated for a role of LH in promoting neurodegenerative changes. LH is known to cross the blood-brain barrier, receptors for LH are most concentrated in the hippocampus, that region of the brain most vulnerable to Alzheimer's disease (AD) and LH is significantly elevated in both the serum and the pyramidal neurons of AD subjects. LH promotes the amyloidogenic processing of the amyloid-beta precursor protein in vitro, and the antigonadotropin leuprolide acetate decreases amyloid generation in mice. Moreover, leuprolide acetate improves the cognitive performance and decreases amyloid-beta deposition in aged transgenic mice carrying the Swedish AbetaPP mutation. Therefore, the elevation of LH with the dysregulation of the HPG axis at menopause and andropause is a physiologically relevant signal that could promote neurodegeneration. Epidemiological support for a role of LH/GnRH in AD is evidenced by a reduction in neurodegenerative disease among prostate cancer patients a group known to GnRH agonists. Clinical trials are underway for the treatment of AD using GnRH analogs and should provide further insights into the gonadotropin connection in AD.

  1. Pituitary gigantism.

    PubMed

    Daughaday, W H

    1992-09-01

    Pituitary gigantism is a rare condition whose association with McCune-Albright syndrome suggests that mutations in alpha-subunit of a Gs protein are an important cause of this condition. In addition to somatotroph adenoma, it is now recognized that somatotroph hyperplasia can also result from increased levels of growth hormone-releasing hormone. Transgenic rats with hypersomatotrophism are prone to renal and hepatic pathology. PMID:1521516

  2. A rare case of type 1 diabetes mellitus with pituitary hypoplasia.

    PubMed

    Pinto, Jostol; Sudeep, K; Venkatesha, B M

    2014-01-01

    Growth failure and pubertal abnormalities are not uncommon in chronic uncontrolled metabolic diseases like diabetes mellitus. We present a young girl with uncontrolled type 1 diabetes mellitus, who presented with short stature and primary amenorrhea, and on evaluation was found to have anterior pituitary hypoplasia. In addition to uncontrolled diabetes mellitus, she presented with early onset growth failure and lack of spontaneous secondary sexual characteristics. She had central hypothyroidism and inappropriately normal gonadotropin levels. However her serum cortisol levels were normal. MRI of the sellar-suprasellar region revealed a small anterior pituitary gland with thinning of the pituitary stalk consistent with pituitary hypoplasia. While uncontrolled type 1 diabetes itself may cause growth retardation and pubertal abnormalities, this girl had coexisting pituitary maldevelopment - a rare co-existence of two major illnesses of unrelated etiologies. The partial pituitary hormonal deficiency, which spared the hypothalamo-pituitary-adrenal axis, may be due to a transcription factor defect.

  3. Molecular mechanisms of gonadotropin-releasing hormone receptor gene regulation.

    PubMed

    Norwitz, E R; Jeong, K H; Chin, W W

    1999-01-01

    GnRH plays a critical role in regulating mammalian reproductive development and function. At the level of the anterior pituitary, GnRH binds to the GnRH receptor (GnRHR) on the cell surface of pituitary gonadotropes. Here, it activates intracellular signal transduction pathways to effect both the synthesis and intermittent release of the gonadotropins LH and FSH. These hormones then enter the systemic circulation to regulate gonadal function, including steroid hormone synthesis and gametogenesis. The response of pituitary gonadotropes to GnRH correlates directly with the concentration of GnRHR on the cell surface, which is mediated, at least in part, at the level of gene expression. A number of endocrine, paracrine, and autocrine factors are known to regulate GnRHR gene expression. This article reviews in detail the role of the GnRHR in the hypothalamic-pituitary-gonadal axis and the factors mediating expression of this gene. A better understanding of the molecular mechanisms that regulate transcription of the GnRHR gene will further our knowledge about the role of this receptor in mammalian reproductive physiology in health and disease.

  4. Stages of Pituitary Tumors

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  5. Gonadotropin-releasing hormone and its analogs.

    PubMed

    Conn, P M; Crowley, W F

    1994-01-01

    GnRH and its analogues have led to exciting new avenues of therapy in virtually every subspecialty of internal medicine as well as in gynecology, pediatrics, and urology. Since their discovery in 1971, it has been demonstrated that GnRH and its analogues enable medical professionals to influence the hypothalamic-pituitary-gonadal axis in two distinct classes of therapeutic applications. The first provides natural sequence GnRH in a pulsatile fashion via portable infusion pumps to mimic the normal physiology of hypothalamic GnRH secretion and restores reproductive potential to infertile men and women with disorders of endogenous GnRH secretion. The second mode uses long-acting GnRH agonists administered in a depot delivery to produce a paradoxical desensitization of pituitary gonadotropin secretion which, in turn, results in a complete ablation of the reproductive axis. This biochemical castration induced by GnRH agonist administration is a safe, effective, complete, and reversible method of removing the overlay of gonadal steroids from a variety of diseases which they are known to exacerbate. These diseases include endometriosis and uterine fibroids in women, prostate cancer in men, and precocious puberty in both sexes. This review examines the physiologic and pharmacologic principles underlying the advances produced by these agents, the mechanism of action of GnRH and its analogues at the cellular level, and the individual therapeutic applications to which these analogues have been applied. Because virtually every subspecialty of medicine will be touched by the GnRH analogues, this review provides an overview and background of their use.

  6. Electrical synapses connect a network of gonadotropin releasing hormone neurons in a cichlid fish

    PubMed Central

    Ma, Yunyong; Hu, Caroline K.; Huguenard, John R.; Fernald, Russell D.

    2015-01-01

    Initiating and regulating vertebrate reproduction requires pulsatile release of gonadotropin-releasing hormone (GnRH1) from the hypothalamus. Coordinated GnRH1 release, not simply elevated absolute levels, effects the release of pituitary gonadotropins that drive steroid production in the gonads. However, the mechanisms underlying synchronization of GnRH1 neurons are unknown. Control of synchronicity by gap junctions between GnRH1 neurons has been proposed but not previously found. We recorded simultaneously from pairs of transgenically labeled GnRH1 neurons in adult male Astatotilapia burtoni cichlid fish. We report that GnRH1 neurons are strongly and uniformly interconnected by electrical synapses that can drive spiking in connected cells and can be reversibly blocked by meclofenamic acid. Our results suggest that electrical synapses could promote coordinated spike firing in a cellular assemblage of GnRH1 neurons to produce the pulsatile output necessary for activation of the pituitary and reproduction. PMID:25775522

  7. Pituitary stalk lesion in a 13-year-old female.

    PubMed

    Zilbermint, Mihail; Ramnitz, Mary S; Lodish, Maya B; Kanaka-Gantenbein, Christina; Kattamis, Antonis; Lyssikatos, Charalampos; Patronas, Nicholas J; Quezado, Martha M; Stratakis, Constantine A

    2014-03-01

    Germinomas presenting with a pituitary stalk lesion and panhypopituitarism are rare in children, and their definite diagnosis is challenging. An invasive diagnostic approach, such as a transsphenoidal biopsy, is often required prior to establishing a treatment regimen. A 13-year-old female presented with 1 year of secondary amenorrhea, fatigue, and progressive thirst with polyuria. Laboratory work-up revealed panhypopituitarism (central hypothyroidism, hypogonadotropic hypogonadism, adrenal insufficiency and central diabetes insipidus). α-Fetoprotein and β-human chorionic gonadotropin were not elevated in serum nor in cerebrospinal fluid. The magnetic resonance imaging (MRI) of the pituitary region showed an enhancing infundibular lesion, extending into the hypothalamus, and infiltrating the pituitary gland. A transsphenoidal biopsy of the infundibular lesion confirmed the diagnosis of germinoma (germ-cell tumor). After appropriate hormone replacement therapy, chemotherapy and low-dose radiation therapy, the patient achieved complete resolution of the pituitary stalk lesion on the MRI.

  8. Pituitary stalk lesion in a 13-year-old female

    PubMed Central

    Zilbermint, Mihail; Ramnitz, Mary S.; Lodish, Maya B.; Kanaka-Gantenbein, Christina; Kattamis, Antonis; Lyssikatos, Charalampos; Patronas, Nicholas J.; Quezado, Martha M.

    2016-01-01

    Germinomas presenting with a pituitary stalk lesion and panhypopituitarism are rare in children, and their definite diagnosis is challenging. An invasive diagnostic approach, such as a transsphenoidal biopsy, is often required prior to establishing a treatment regimen. A 13-year-old female presented with 1 year of secondary amenorrhea, fatigue, and progressive thirst with polyuria. Laboratory work-up revealed panhypopituitarism (central hypothyroidism, hypogonadotropic hypogonadism, adrenal insufficiency and central diabetes insipidus). α-Fetoprotein and β-human chorionic gonadotropin were not elevated in serum nor in cerebrospinal fluid. The magnetic resonance imaging (MRI) of the pituitary region showed an enhancing infundibular lesion, extending into the hypothalamus, and infiltrating the pituitary gland. A transsphenoidal biopsy of the infundibular lesion confirmed the diagnosis of germinoma (germ-cell tumor). After appropriate hormone replacement therapy, chemotherapy and low-dose radiation therapy, the patient achieved complete resolution of the pituitary stalk lesion on the MRI. PMID:24129100

  9. Side Effects of Injectable Fertility Drugs (Gonadotropins)

    MedlinePlus

    ... usually are used during fertility treatments such as intrauterine insemination (IUI) or in vitro fertilization (IVF). Injections of gonadotropins ... Gestation. When using injectable gonadotropins alone or with IUI, up to 30% of pregnancies are associated with ...

  10. Epilepsy and reproductive disorders: the role of the gonadotropin-releasing hormone network.

    PubMed

    Fawley, Jessica A; Pouliot, Wendy A; Dudek, F Edward

    2006-05-01

    Individuals with temporal lobe epilepsy have an increased incidence of reproductive dysfunction. The comorbidity may be due to the acute effects of the seizures, the chronic effects of the epilepsy, and/or the use of antiepileptic drugs on the gonadotropin-releasing hormone network and the hypothalamic-pituitary-gonadal axis. This review provides a brief overview of evidence from experimental animal and clinical studies exploring the basis for epilepsy-associated reproductive abnormalities.

  11. Effect of gonadotropin-releasing hormone analogue on thermal nociception in mice.

    PubMed

    Bobyntsev, I I; Sever'yanova, L A; Kryukov, A A

    2006-02-01

    Intraperitoneal treatment with an analogue of gonadotropin-releasing hormone in doses of 0.004-450 microg/kg produced an analgesic effect on male mice in the hot plate test. Castration significantly elevated the nociceptive thresholds. In castrated mice the effects of the test peptide were less pronounced and had an algesic nature. Our results indicate that these effects depend on functional activity of the hypothalamic-pituitary-gonadal axis.

  12. Rapid enlargement of an intracranial germ cell tumor after gonadotropin hormone therapy.

    PubMed

    Sasagawa, Yasuo; Tachibana, Osamu; Nakagawa, Athushi; Nakada, Satoko; Nojima, Takayuki; Koya, Daisuke; Iizuka, Hideaki

    2016-09-01

    We report a case of an intracranial germ cell tumor (iGCT) that showed rapid enlargement after human chorionic gonadotropin (hCG) hormone therapy for pituitary hypogonadism. A 16-year-old boy presented with headache and was diagnosed with a suprasellar tumor. He was initially observed without surgery. Intranasal desmopressin therapy was started for central diabetes insipidus, but there was no change in the tumor size on MRI. The diagnosis of the tumor remained unknown for 4years. Levels of serum gonadotropin hormones (follicle-stimulating and luteinizing hormone) and testosterone progressively decreased, and the patient developed pituitary hypogonadism and complained about his undeveloped beard, lack of underarm hair, and erectile dysfunction. Intramuscular gonadotropin injection (hCG 5000U×2/week) was started at age 20. Eight months after the first gonadotropin injection, the MRI showed tumor growth with vivid enhancement. Craniotomy was performed and the tumor was partially resected. The histological diagnosis was immature teratoma. After surgery, the patient was treated with 5 cycles of chemotherapy with carboplatin and etoposide. He also received radiation therapy of 50Gy (20Gy tumor bed and 30Gy whole ventricles) to the residual tumor, after which the tumor decreased in size. We postulate that iGCT may be at risk of progression during hCG hormone therapy. Thus, careful monitoring is required for a patient with iGCT who receives this therapy.

  13. Insulin Augments Gonadotropin-Releasing Hormone Induction of Translation in LβT2 Cells

    PubMed Central

    Navratil, Amy M.; Song, Hyunjin; Hernandez, Jeniffer B.; Cherrington, Brian D.; Santos, Sharon J.; Low, Janine M.; Do, Minh-Ha T.; Lawson, Mark A.

    2009-01-01

    Summary The integrated signaling of insulin and gonadotropin-releasing hormone in the pituitary gonadotropes may have a profound bearing on reproductive function, although the cross-receptor signaling mechanisms are unclear. We demonstrate that the insulin receptor is constitutively localized to non-caveolar lipid raft microdomains in the pituitary gonadotrope cell line LβT2. The localization to rafts is consistent with similar localization of the GnRH receptor. Insulin receptor phosphorylation occurs in raft domains and activates the downstream signaling targets Insulin Receptor Substrate1 and Akt/Protein Kinase B. Although insulin alone does not strongly activate the extracellular signal-regulated kinase second messenger cascade, co-stimulation potentiates the phosphorylation of the extracellular signal-regulated kinase by gonadotropin-releasing hormone. The co-stimulatory effect of insulin and gonadotropin-releasing hormone is also evident in increased activation of cap-dependent translation. In contrast, co-stimulation attenuates Akt/Protein Kinase B activation. Our results show that both gonadotropin-releasing hormone and insulin are capable of mutually altering their respective regulatory signaling cascades. We suggest that this provides a mechanism to integrate neuropeptide and energy homeostatic signals to modulate reproductive function. PMID:19632296

  14. Hypothalamic-pituitary-gonadal endocrine system in the hagfish.

    PubMed

    Nozaki, Masumi

    2013-12-30

    The hypothalamic-pituitary system is considered to be a seminal event that emerged prior to or during the differentiation of the ancestral agnathans (jawless vertebrates). Hagfishes as one of the only two extant members of the class of agnathans are considered the most primitive vertebrates known, living or extinct. Accordingly, studies on their reproduction are important for understanding the evolution and phylogenetic aspects of the vertebrate reproductive endocrine system. In gnathostomes (jawed vertebrates), the hormones of the hypothalamus and pituitary have been extensively studied and shown to have well-defined roles in the control of reproduction. In hagfish, it was thought that they did not have the same neuroendocrine control of reproduction as gnathostomes, since it was not clear whether the hagfish pituitary gland contained tropic hormones of any kind. This review highlights the recent findings of the hypothalamic-pituitary-gonadal endocrine system in the hagfish. In contrast to gnathostomes that have two gonadotropins (GTH: luteinizing hormone and follicle-stimulating hormone), only one pituitary GTH has been identified in the hagfish. Immunohistochemical and functional studies confirmed that this hagfish GTH was significantly correlated with the developmental stages of the gonads and showed the presence of a steroid (estradiol) feedback system at the hypothalamic-pituitary levels. Moreover, while the identity of hypothalamic gonadotropin-releasing hormone (GnRH) has not been determined, immunoreactive (ir) GnRH has been shown in the hagfish brain including seasonal changes of ir-GnRH corresponding to gonadal reproductive stages. In addition, a hagfish PQRFamide peptide was identified and shown to stimulate the expression of hagfish GTHβ mRNA in the hagfish pituitary. These findings provide evidence that there are neuroendocrine-pituitary hormones that share common structure and functional features compared to later evolved vertebrates.

  15. The hypothalamic-pituitary axis in diabetes mellitus.

    PubMed

    Leroith, D; Shapiro, M; Luboshitsky, R; Spitz, I M

    1980-11-01

    The hormonal response to LHRH and TRH was evaluated in three groups of male diaetics. Five patients were receiving therapy with the hypoglycemic agent glibenclamide, five were on NPH insulin and five were on dietary therapy alone. When compared to controls, the latter two groups had intact gonadotropin responses to LHRH. Despite normal basal gonadotropin levels, however, the group receiving glibenclamide therapy showed significantly exaggerated LH and FSH responses to LHRH. Both basal PRL and TSH levels, as well as the responses to TRH were normal in all three groups. These results indicate that LH, FSH, TSH and PRL secretion is intact in uncomplicated diabetes mellitus. The exaggerated LH and FSH responses to LHRH in the glibenclamide treated subjects are probably related to primary gonadal involvement; alternatively, there may be augmented pituitary gonadotropin secretion in this group.

  16. Pituitary granulomatosis with polyangiitis

    PubMed Central

    Slabu, Hannah; Arnason, Terra

    2013-01-01

    Granulomatosis with polyangiitis (GPA) is a small vessel vasculitis that can affect several organs, most commonly the respiratory tract and kidneys. Pituitary involvement is exceptionally rare. Most case reports of GPA of the pituitary gland have been described in middle-aged women who have concomitant ears, nose and throat involvement. The most frequent manifestation is diabetes insipidus due to a preponderance of posterior pituitary infiltration. The majority of cases sustain permanent damage to the pituitary gland even with remission of the underlying granulomatous disease. Here, the authors describe a case of pituitary GPA involving both the anterior and posterior pituitary glands with permanent residual pituitary insufficiency. PMID:23645699

  17. Pathogenesis of pituitary tumors.

    PubMed

    Yu, Run; Melmed, Shlomo

    2010-01-01

    Pituitary tumors are common and mostly benign neoplasia which cause excess or deficiency of pituitary hormones and compressive damage to adjacent organs. Oncogene activation [e.g. PTTG (pituitary tumor-transforming gene) and HMGA2], tumor suppressor gene inactivation (e.g. MEN1 and PRKAR1A), epigenetic changes (e.g. methylation) and humoral factors (e.g. ectopic production of stimulating hormones) are all possible pituitary tumor initiators; the micro-environment of pituitary tumors including steroid milieu, angiogenesis and abnormal cell adhesion further promote tumor growth. Senescence, a cellular defence mechanism against malignant transformation, may explain the benign nature of at least some pituitary tumors. We suggest that future research on pituitary tumor pathogenesis should incorporate systems approaches, and address regulatory mechanisms for pituitary cell proliferation, development of new animal models of pituitary tumor and isolation of functional human pituitary tumor cell lines. PMID:20541667

  18. Anatomical and functional gonadotrope networks in the teleost pituitary

    PubMed Central

    Golan, Matan; Martin, Agnés O.; Mollard, Patrice; Levavi-Sivan, Berta

    2016-01-01

    Mammalian pituitaries exhibit a high degree of intercellular coordination; this enables them to mount large-scale coordinated responses to various physiological stimuli. This type of communication has not been adequately demonstrated in teleost pituitaries, which exhibit direct hypothalamic innervation and expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in distinct cell types. We found that in two fish species, namely tilapia and zebrafish, LH cells exhibit close cell–cell contacts and form a continuous network throughout the gland. FSH cells were more loosely distributed but maintained some degree of cell–cell contact by virtue of cytoplasmic processes. These anatomical differences also manifest themselves at the functional level as evidenced by the effect of gap-junction uncouplers on gonadotropin release. These substances abolished the LH response to gonadotropin-releasing hormone stimulation but did not affect the FSH response to the same stimuli. Dye transfer between neighboring LH cells provides further evidence for functional coupling. The two gonadotropins were also found to be differently packaged within their corresponding cell types. Our findings highlight the evolutionary origin of pituitary cell networks and demonstrate how the different levels of cell–cell coordination within the LH and FSH cell populations are reflected in their distinct secretion patterns. PMID:27029812

  19. Daily illuminance levels affect pituitary prolactin in male rats.

    PubMed

    Laakso, M L; Porkka-Heiskanen, T; Alila, A; Kajander, S; Stenberg, D; Johansson, G

    1989-04-01

    The 24-h patterns of melatonin, PRL, and gonadotropins in male rats maintained under natural lighting conditions have been found to differ from the patterns in rats kept under artificial lighting. In the present experiments we studied the role of different daily illuminances as a possible causative factor for the variation of the hormonal patterns. Three groups of male rats were kept under artificial lighting conditions (12 h on/12 h off), where the daily illuminance was 550, 110 or 25 lux. After a 7-day adaptation period the pineal content of melatonin, the serum levels of LH, FSH and PRL, and the pituitary content of these hormones were measured by RIAs in samples taken at 10.00, 13.00, 22.00 and 01.00 h. The patterns of pineal melatonin were equal in all three groups. The variation of daily illuminance did not change the serum levels of LH, FSH and PRL or the pituitary content of the gonadotropins. However, the pituitary content of PRL during the light phase was inversely related to the illuminance. The results suggest that the intensity of daily lighting in the studied range does not affect the patterns of melatonin or gonadotropins, but the synthesis of prolactin may be significantly regulated by the daily illuminance level.

  20. Anatomical and functional gonadotrope networks in the teleost pituitary.

    PubMed

    Golan, Matan; Martin, Agnés O; Mollard, Patrice; Levavi-Sivan, Berta

    2016-01-01

    Mammalian pituitaries exhibit a high degree of intercellular coordination; this enables them to mount large-scale coordinated responses to various physiological stimuli. This type of communication has not been adequately demonstrated in teleost pituitaries, which exhibit direct hypothalamic innervation and expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in distinct cell types. We found that in two fish species, namely tilapia and zebrafish, LH cells exhibit close cell-cell contacts and form a continuous network throughout the gland. FSH cells were more loosely distributed but maintained some degree of cell-cell contact by virtue of cytoplasmic processes. These anatomical differences also manifest themselves at the functional level as evidenced by the effect of gap-junction uncouplers on gonadotropin release. These substances abolished the LH response to gonadotropin-releasing hormone stimulation but did not affect the FSH response to the same stimuli. Dye transfer between neighboring LH cells provides further evidence for functional coupling. The two gonadotropins were also found to be differently packaged within their corresponding cell types. Our findings highlight the evolutionary origin of pituitary cell networks and demonstrate how the different levels of cell-cell coordination within the LH and FSH cell populations are reflected in their distinct secretion patterns. PMID:27029812

  1. Gonadotropin excretion and body composition.

    PubMed

    Penny, R; Goldstein, I P; Frasier, S D

    1978-02-01

    Urinary follicle stimulating hormone (FSH) and luteinizing hormone (LH) excretion was correlated with calculated total body water (TBW) and body fat (BF) in 140 normal girls and 142 normal boys, ages 3 to 16 years. In girls, there was a significant increase in gonadotropin excretion at the time of a significant increase in BF as a percent of body weight and decrease in TBW as a percent of body weight. Pubertal changes in body composition were seen in girls at the same chronological age and stage of puberty as increased gonadotropin excretion. Similar findings were observed in boys. Pubertal changes in body composition (an increase in TBW as a percent of body weight and decrease of BF as a percent of body weight) accompanied significantly increased gonadotropin excretion. Both developmental changes were seen at the same chronological age and stage of puberty. Our findings are consistent with the hypothesis that characteristic changes in body composition as well as the other hallmarks of puberty, including menarche in girls, result from increased gonadotropin and gonadal steroid secretion. They do not support the hypothesis that changes of body composition trigger increased hypothalamic function and hormone secretion leading to the subsequent events of puberty. PMID:634687

  2. Evidence that obesity and androgens have independent and opposing effects on gonadotropin production from puberty to maturity.

    PubMed

    Rosenfield, Robert L; Bordini, Brian

    2010-12-10

    Optimal fat mass is necessary for normal gonadotropin levels in adults, and both undernutrition and overnutrition suppress gonadotropins: thus, the gonadotropin response to relative adipose mass is biphasic. Adult obesity is associated with blunted luteinizing hormone (LH) pulse amplitude that is partially attributable to increased LH clearance rate. Testosterone appears to have a biphasic effect on gonadotropin production in females. Moderate elevations of testosterone appear to stimulate LH production at both the hypothalamic and pituitary level, while very high levels of testosterone suppress LH. Thus, obesity per se appears to suppress gonadotropin production, and moderate hyperandrogenemia in women appears to stimulate LH. The ordinary hypergonadotropic hyperandrogenism of obese women appears to be an exception to this model because it is usually due to polycystic ovary syndrome (PCOS), a condition in which intrinsic functional ovarian hyperandrogenism and excess adiposity share a common origin that involves insulin-resistant hyperinsulinemia. LH elevation seems to be secondary to hyperandrogenemia and is absent in the most obese cases. Overweight early pubertal girls have significant blunting of sleep-related LH production, which is the first hormonal change of puberty. The data are compatible with the possibility that excess adiposity may paradoxically subtly suppress hypothalamic-pituitary-gonadal function in early puberty although it is known to contribute to the early onset of puberty. PMID:20816944

  3. [Familial pituitary tumors].

    PubMed

    Yoshimoto, K; Saito, S

    1995-11-01

    Familial pituitary tumors are relatively rare. Most commonly, they occur as a part of multiple endocrine neoplasia type 1 (MEN 1). However, familial pituitary adenomas unrelated MEN 1 (familial pituitary adenomas) are extremely rare. In review of MEN 1 in Japan, 60% of the patients with MEN 1 had pituitary tumors. Only 45 cases of familial pituitary adenomas have been reported from 20 families. In our review of familial pituitary adenomas, 30 (67%) of 45 reported cases are acromegaly or gigantism. This incidence is much higher than 28% in MEN 1 patients with pituitary tumors. Allelic deletions at 11q13 were identified in MEN 1 associated pituitary adenomas and familial pituitary adenomas in two gigantism brothers. PMID:8538028

  4. Gonadotropin (LH and FSH) response after submaximal GnRH stimulation in depressed premenopausal women and healthy controls.

    PubMed

    Amsterdam, J D; Maislin, G; Rosenzweig, M; Halbrecht, U

    1995-01-01

    Although hormonal response abnormalities in depression have been demonstrated in several hypothalamic-pituitary-target organ axes after a variety of neuroendocrine challenge tests, studies of hypothalamic-pituitary-gonadal (HPG) axis function have been inconsistent in their findings. The use of maximal or supramaximal doses of gonadotropin-releasing hormone (GnRH) in early studies (150-600 micrograms) may have masked the presence of more subtle disturbances in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responsiveness in depression. We hypothesized that submaximal doses of GnRH might reveal a more subtle dysregulation in gonadotropin responsiveness in depression, and therefore measured LH and FSH responses after GnRH 10 micrograms and 90 micrograms doses in nine premenopausal depressed women and six healthy controls. There were no statistically significant differences between subject groups for mean basal LH, FSH, and estradiol concentrations, nor for any of the LH and FSH response values after either GnRH stimulation dose. The present observations of an intact HPG axis in depression contrast with findings of disturbances in most other hypothalamic-pituitary axes, and suggest that neuroendocrine dysregulation in depression might not represent a generalized limbic system-hypothalamic-pituitary abnormality, but rather a more restricted lesion sparing the medial preoptic and/or arcuate region of the hypothalamus which regulates gonadotropin secretion.

  5. Gonadotropin-releasing hormone and its receptor in normal and malignant cells.

    PubMed

    Harrison, G S; Wierman, M E; Nett, T M; Glode, L M

    2004-12-01

    Gonadotropin-releasing hormone (GnRH) is the hypothalamic factor that mediates reproductive competence. Intermittent GnRH secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. LH and FSH then stimulate sex steroid hormone synthesis and gametogenesis in the gonads to ensure reproductive competence. The pituitary requires pulsatile stimulation by GnRH to synthesize and release the gonadotropins LH and FSH. Clinically, native GnRH is used in a pump delivery system to create an episodic delivery pattern to restore hormonal defects in patients with hypogonadotropic hypogonadism. Agonists of GnRH are delivered in a continuous mode to turn off reproductive function by inhibiting gonadotropin production, thus lowering sex steroid production, resulting in medical castration. They have been used in endocrine disorders such as precocious puberty, endometriosis and leiomyomata, but are also studied extensively in hormone-dependent malignancies. The detection of GnRH and its receptor in other tissues, including the breast, ovary, endometrium, placenta and prostate suggested that GnRH agonists and antagonists may also have direct actions at peripheral targets. This paper reviews the current data concerning differential control of GnRH and GnRH receptor expression and signaling in the hypothalamic-pituitary axis and extrapituitary tissues. Using these data as a backdrop, we then review the literature about the action of GnRH in cancer cells, the utility of GnRH analogs in various malignancies and then update the research in novel therapies targeted to the GnRH receptor in cancer cells to promote anti-proliferative effects and control of tumor burden.

  6. Pituitary and gonadal responsiveness is enhanced during GnRH-induced puberty.

    PubMed

    Spratt, D I; Crowley, W F

    1988-05-01

    We hypothesized that the hypothalamic gonadotropin-releasing hormone (GnRH) signal that initiates sexual maturation is further amplified at both the pituitary and gonadal levels during puberty. To test this theory, six GnRH-deficient men were monitored during administration of exogenous GnRH at a physiological frequency for greater than or equal to 9 mo. GnRH doses were progressively increased until normal testosterone (T) concentrations and secondary sexual development were achieved. This "optimized" dose of GnRH was then sustained for at least 6 mo to allow maturation of the hypothalamic-pituitary-gonadal axis. The GnRH dose was then progressively decreased to a level that had been unable to stimulate normal T secretion before sexual maturation. Changes in pituitary responsiveness were analyzed in four of the six men by comparing gonadotropin responses to identical doses of GnRH before and after sexual maturation. Mean serum luteinizing hormone and follicle-stimulating hormone levels as well as luteinizing hormone pulse amplitudes were greater after the induction of sexual maturation than before despite identical doses of GnRH. Both pituitary and gonadal responsiveness was then analyzed in the remaining two subjects by choosing periods of evaluation where endogenous gonadotropin levels were matched before and after the period of sexual maturation. Serum T concentrations were greater after sexual maturation than before despite equivalent gonadotropin input to the testes and LH pulse amplitudes. Thus the testicular responsiveness to gonadotropins increased during sexual maturation. After initiation of puberty by GnRH secretion, amplification at both the pituitary and gonadal levels contributes to sexual maturation in the human.

  7. Influence of the hypothalamic-pituitary-adrenal axis on the menstrual cycle and the pituitary responsiveness to estradiol in the female rhesus monkey (Macaca mulatta).

    PubMed

    Hayashi, K T; Moberg, G P

    1990-02-01

    In order to examine the effect of glucocorticoids on the menstrual cycle of rhesus monkeys, cortisol was injected twice daily during the follicular phase. This cortisol treatment did not alter basal gonadotropin secretion but blocked the normal follicular rise of estrogens, the gonadotropin surge and the luteal rise of progesterone, and delayed the onset of the next cycle. In a second study, estradiol benzoate (E2B) was injected on the sixth day following the start of menstrual bleeding either with or without concurrent adrenocorticotropic hormone (ACTH) treatment. E2B injection was able to stimulate surges of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) whether or not the animals had been treated with ACTH. These data suggest that, the action of cortisol, the final mediating step in the hypothalamic-pituitary-adrenal axis, occurs at the level of the gonads versus the pituitary in the rhesus monkey. While the pituitary response to endogenous gonadotropin-releasing hormone or exogenous E2B stimulation appears to remain unaffected, normal folliculogenesis is disrupted, preventing the follicular secretion of estrogens and the subsequent gonadotropin surges. The effects of corticosteroids are temporary, with normal cycling returning when plasma corticosteroids return to basal concentrations, albeit after a delay.

  8. Pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes of rats with mammary gland cancer induced by N-methyl nitrosourea.

    PubMed

    Carrera, M P; Ramírez-Expósito, M J; Valenzuela, M T; García, M J; Mayas, M D; Arias de Saavedra, J M; Sánchez, R; Pérez, M C; Martínez-Martos, J M

    2005-02-01

    Pyrrolidon carboxypeptidase is an omega-peptidase that hydrolyses N-terminal pyroglutamyl residues from biologically active peptides such as gonadotropin-releasing and thyrotrophin-releasing hormones. We previously described a decrease in both rat and human pyrrolidon carboxypeptidase activity with breast cancer, suggesting that gonadotropin-releasing hormone may be an important local intracrine, autocrine and/or paracrine hormonal factor in the pathogenesis of breast cancer while playing a role in the tumoral process. However, the other susceptible substrate of pyrrolidon carboxypeptidase, thyrotrophin-releasing hormone, may also be modified with breast cancer, supporting an association between breast cancer and thyroid disorders. The present work analyses soluble and membrane-bound pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes in N-methyl nitrosourea-induced breast cancer in rats. Our aim was to determine the possible relationship between gonadotropin-releasing hormone and thyrotrophin-releasing hormone regulation through pyrrolidon carboxypeptidase activity. We propose that pyrrolidon carboxypeptidase activity dysregulation at various local and systemic levels may participate in the initiation, promotion and progression of breast cancer induced in rat by N-methyl nitrosourea through the increase in gonadotropin-releasing hormone. Since pyrrolidon carboxypeptidase activity also acts on thyrotrophin-releasing hormone, the dysregulation of this enzyme's activity could indirectly affect hypothalamus-pituitary-thyroid axis function, and thus potentially represent a link between the diseases of thyroid and breast cancer.

  9. The biology of gonadotropin-releasing hormone and its analogs.

    PubMed

    Glode, L M

    1986-01-01

    Gonadotropin-releasing hormone (GnRH) is one of the hormones involved in the complex hypothalamic-pituitary-gonadal axis which regulates the release of testosterone from the testes or estrogen from the ovaries. The development of GnRH analogs has helped elucidate the mechanism of action of the natural hormone, and provided possible new ways to treat hormonally related conditions including hormone-dependent cancers, precocious puberty, and endometriosis. The effectiveness of GnRH agonists in clinical use lies in their ability, with long-term administration, to suppress sex-hormone production. GnRH antagonists may eventually replace agonists because they are able to reduce hormone levels without the initial, temporary rise caused by agonists.

  10. Pulsatile gonadotropin-releasing hormone therapy for ovulatory disorders.

    PubMed

    Santoro, N; Elzahr, D

    1993-09-01

    Pulsatile GnRH remains a physiologic method of inducing ovulation that is effective and safer than other parenteral preparations. Its lower rate of acceptance in the United States stands in curious contrast to its widespread usage in other countries as a second-line (postclomiphene) technique of choice for ovulation induction. In a high-technology era such as ours, women who may benefit from pulsatile GnRH therapy should not be forgotten. By far the most favorable results are obtained in women with primary or secondary hypothalamic amenorrhea. In such women, pregnancy rates appear comparable to those achieved with exogenous gonadotropins with a much lower risk of multiple pregnancy and ovarian hyperstimulation. These positive aspects, combined with the decreased need for clinical monitoring and the increased sense of control imparted to the patient, lead to the conclusion that women with uncomplicated hypothalamic-pituitary disorders are the ideal patient group to consider for therapy. The application of pulsatile GnRH therapy to other groups of women relies on limited data. By all means, women with polycystic ovarian syndrome who have not ovulated or conceived after other forms of treatment should be considered because reasonable pregnancy salvage can be obtained. We have noted a first-cycle successful pregnancy after failure of exogenous gonadotropins, with or without a superimposed GnRH agonist, and even in vitro fertilization with multiple embryo transfers. Before such invasive, high-technology procedures are entertained, it would appear prudent to consider this simple alternative in women with an overactive hypothalamic-pituitary axis, as seen in polycystic ovarian syndrome. Other ovulatory defects also may be amenable to treatment with pulsatile GnRH, but their practical usefulness will await further clinical study.

  11. Aspirin inhibits androgen response to chorionic gonadotropin in humans.

    PubMed

    Conte, D; Romanelli, F; Fillo, S; Guidetti, L; Isidori, A; Franceschi, F; Latini, M; di Luigi, L

    1999-12-01

    Eicosanoids play an important role in the regulation of the hypothalamic-pituitary axis; less clear is their role in testicular steroidogenesis. To evaluate the involvement of cyclooxygenase metabolites, such as prostaglandins, in the regulation of human testicular steroidogenesis, we examined the effects of a prostaglandin-blocker, aspirin, on plasma testosterone, pregnenolone, progesterone, 17OH-progesterone, androstenedione, dehydroepiandrosterone, and 17beta-estradiol response to human chorionic gonadotropin (hCG) in normal male volunteers in a placebo-controlled, single-blinded study. To test the efficacy of aspirin, seminal prostaglandin E(2) levels were also determined. hCG stimulation increased peripheral levels of testosterone, 17OH-progesterone, androstenedione, dehydroepiandrosterone, and 17beta-estradiol, without affecting circulating pregnenolone and progesterone values. Aspirin significantly lowered seminal prostaglandin E(2) levels, whereas it did not modify steroid concentrations not exposed to exogenous hCG. Moreover, the drug significantly reduced the response of testosterone, 17OH-progesterone, androstenedione, and dehydroepiandrosterone to hCG, as assessed by the mean integrated area under the curve, whereas it did not influence 17beta-estradiol response. In conclusion, aspirin treatment inhibits androgen response to chorionic gonadotropin stimulation in normal humans. The action of aspirin is probably mediated via an effective arachidonate cyclooxygenase block.

  12. Luteinizing hormone and human chorionic gonadotropin: distinguishing unique physiologic roles.

    PubMed

    Choi, Janet; Smitz, Johan

    2014-03-01

    Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are integral components of the hypothalamic-pituitary-gonadal axis, which controls sexual maturation and functionality. In the absence of signaling through their shared receptor, fetal sexual differentiation and post-natal development cannot proceed normally. Although they share a high degree of homology, the physiologic roles of these hormones are unique, governed by differences in expression pattern, biopotency and regulation. Whereas LH is a key regulator of gonadal steroidogenesis and ovulation, hCG is predominantly active in pregnancy and fetal development. Emerging evidence has revealed endogenous functions not previously ascribed to hCG, including participation in ovulation and fertilization, implantation, placentation and other activities in support of successful pregnancy. Spontaneous and induced mutations in LH, hCG and their mutual receptor have contributed substantially to our understanding of reproductive development and function. The lack of naturally occurring, functionally significant mutations in the β-subunit of hCG reinforce its putative role in establishment of pregnancy. Rescue of reproductive abnormalities resulting from aberrant gonadotropin signaling is possible in certain clinical contexts, depending on the nature of the underlying defect. By understanding the physiologic roles of LH and hCG in normal and pathologic states, we may better harness their diagnostic, prognostic and therapeutic potential.

  13. Decreased hypothalamic gonadotropin-releasing hormone secretion in male marathon runners.

    PubMed

    MacConnie, S E; Barkan, A; Lampman, R M; Schork, M A; Beitins, I Z

    1986-08-14

    Hypogonadotropic hypogonadism due to a deficiency in hypothalamic gonadotropin-releasing hormone is common in female athletes ("hypothalamic amenorrhea"). It is not known, however, whether a similar phenomenon occurs in male athletes. We investigated the integrity of the hypothalamic-pituitary-gonadal axis in six highly trained male marathon runners (who were running 125 to 200 km per week). The mean (+/- SEM) frequency of spontaneous luteinizing hormone pulses was diminished in the runners, as compared with healthy controls (2.2 +/- 0.48 vs. 3.6 +/- 0.24 pulses per eight hours, P less than 0.05). The amplitude of the pulses was also low in the runners (0.9 +/- 0.24 vs. 1.6 +/- 0.15 mlU per milliliter; P less than 0.05), and the responses of luteinizing hormone to gradually increasing doses of exogenous gonadotropin-releasing hormone were decreased. Plasma testosterone levels were similar in the two groups and increased equally in response to an intramuscular injection of 2000 units of human chorionic gonadotropin. During short-term intense physical exercise (a treadmill run at 72 percent of maximal oxygen consumption for two hours), the plasma gonadotropin levels in the athletes remained stable, but significant elevations in plasma levels of cortisol, prolactin, and testosterone occurred. We conclude that highly trained male athletes, like their female counterparts, may have a deficiency of hypothalamic gonadotropin-releasing hormone. This condition may be caused by the prolonged, repetitive elevations of gonadal steroids and other hormones known to suppress gonadotropin-releasing hormone secretion that are elicited by their daily exercise.

  14. Serum sex hormone and gonadotropin concentrations in premenopausal women with multiple sclerosis.

    PubMed

    Grinsted, L; Heltberg, A; Hagen, C; Djursing, H

    1989-10-01

    Dysfunctions within the hypothalamic-pituitary-gonadal axis occur frequently among women with multiple sclerosis (MS) and may induce menstrual disturbances and subsequent infertility. We have measured serum concentrations of prolactin. gonadotropins and sex hormone binding globulin (SHBG) as well as free and bound oestrogen and androgen levels in 14 women of fertile age with MS. These women all displayed regular cycles without having experienced fertility problems. As controls 14 normal women with regular periods and ideal body weight of 91% (range 80-101) were included. Serum from both groups was sampled during the early follicular phase. The MS-patients had significantly (P less than 0.05) higher concentrations of prolactin, LH, FSH, total and free testosterone (P less than 0.01) and a significantly lower serum concentration of oestrone sulphate (P less than 0.01). The abnormal hormone concentrations were not related to clinical status of the disease. We propose that the increased androgen levels are of ovarian origin as adrenal androgens were normal. The reason for the slight increase of prolactin and the marked increase of gonadotropins in women with MS is speculative. As oestradiol levels, however, were within normal range, we assume that a peripheral resistance to gonadotropins combined with an abnormal central regulation causes the increased pituitary secretion.

  15. Effect of testosterone on the hypothalamic-pituitary-gonadal axis of pinealectomized and pineal-intact male rats.

    PubMed

    Wallen, E P; Turek, F W

    1979-05-15

    Previous studies indicate that steroid hormones alter pineal biochemistry, and it has been suggested that at least part of the negative feedback effect of steroid hormones on pituitary gonadotropin release may be mediated by the pineal gland. In this study, pinealectomy did not alter the inhibitory effect of testosterone on neuroendocine-gonadal activity in the male rat, suggesting that the pineal gland does not mediate the response of the rat hypothalamic-pituitary axis to testosterone.

  16. Pregnancy and pituitary adenomas.

    PubMed

    Glezer, Andrea; Jallad, Raquel S; Machado, Marcio C; Fragoso, Maria C; Bronstein, Marcello D

    2016-09-01

    Infertility is frequent in patients harboring pituitary adenomas. The mechanisms involved include hypogonadism secondary to hormonal hypersecretion (prolactin, growth hormone and cortisol), stalk disconnection and pituitary damage. With the improvement of clinical and surgical treatment, pregnancy in women harboring pituitary adenomas turned into a reality. Pituitary hormonal hyper- and hyposecretion influences pregnancy outcomes, as well as pregnancy can interfere on pituitary tumors, especially in prolactinomas. We review literature about specific follow-up and management in pregnant women harboring prolactinomas, acromegaly, or Cushings disease and the impact of clinical and surgical treatment on each condition. PMID:26977888

  17. Pituitary gonadotrophin responsiveness to synthetic LRF in subjects with normal and abnormal hypothalamic-pituitary-gonadal axis.

    PubMed

    Yen, S S; Rebar, R; Vandenberg, G; Ehara, Y; Siler, T

    1973-12-01

    Pituitary gonadotropin responsiveness to synthetic LRF was studied in normal males, in normal females at different phases of the menstrual cycle, in premenopausal females treated with synthetic estrogen, and in subjects with various abnormalities of the hypothalamic-pituitary-gonadal axis. Iv injection of from 1 to 450 mcg LRF in normal males resulted in an increase of luteinizing hormone (LH) within 2 minutes, with a maximal concentration of LH at a median time of 25 minutes. Maximal follicle stimulating hormone (FSH) levels occurred at a median time of 45 minutes. LH, and to a lesser extent FSH, increased with dose, although a wide variation in quantitative response to the same dose of LRF was seen among patients. In female subjects, the response to LRF varied during different phases of the menstrual cycle. The most sensitive period for pituitary response to LRF for both LH and FSH was just prior to the midcycle surge. Chronic estrogen treatment of premenopausal women enhanced pituitary responsiveness to LRF, with an alteration in both time and magnitude of response. Altered pituitary responsiveness was seen in patients with gonadal dysgenesis, hypogonadotropism, hypogonadotropic hypothalamic amenorrhea, panhypopituitarism, and pituitary tumor.

  18. Gonadotropin-dependent precocious puberty in an 8-year-old boy with leydig cell testicular tumor.

    PubMed

    Santos-Silva, Rita; Bonito-Vítor, Artur; Campos, Miguel; Fontoura, Manuel

    2014-01-01

    Leydig cell testicular tumors are very rare in children. They can present as gonadotropin-independent precocious puberty due to excess androgen secretion. We report the case of an 8-year-old boy with isosexual precocity whose hormonal investigation showed luteinizing hormone-independent testosterone hypersecretion. Although no palpable mass was present, scrotal ultrasound revealed a testicular tumor. Testis-sparing tumor resection was performed and the histopathology analysis showed a Leydig cell tumor. After surgery the testosterone levels remained high and further examination showed gonadotropin-dependent precocious puberty, which is believed to be likely caused by the activation of the hypothalamic-pituitary axis due to a long-term exposition to sex steroids. He is currently being treated with a long-acting gonadotropin-releasing hormone analog and the process of sexual precocity has until now been suppressed.

  19. Neurology of the pituitary.

    PubMed

    Samarasinghe, Shanika; Emanuele, Mary Ann; Mazhari, Alaleh

    2014-01-01

    The anterior pituitary hormones are essential for reproduction, growth, metabolic homeostasis, stress response, and adaptation to changes in the external environment. Each pituitary hormone is secreted in a distinctive pulsatile manner reflecting its regulation by the central nervous system through a complex interaction between hypothalamic neuroendocrine pathways, feedback effects from peripheral target gland hormones, and intrapituitary mechanisms. While the most common cause of a pituitary mass is an adenoma, the differential diagnosis is broad and includes pituitary hyperplasia, lymphocytic hypophysitis, craniopharyngioma among others. Patients with pituitary adenomas can be asymptomatic or present with symptoms due to mass effect, pituitary hormone dysfunction, or both. Prolactinomas represent 40% of pituitary adenomas, the majority of which are microadenomas. Hyperfunction of growth hormone and ACTH are far less common, while TSH-producing tumors are exceedingly rare. Hypopituitarism in patients with pituitary adenomas can be partial or complete. The clinical picture will depend on the type, degree, and rapidity of onset of pituitary hormone deficiency. An MRI specifically focused on the sellar region is the imaging modality of choice to detect pituitary pathology. Management of pituitary tumors ranges from observation of nonfunctioning microadenomas through medical, surgical, and radiotherapeutic approaches dependent on tumor type, function, size, and invasiveness.

  20. Direct evidence of estrogen modulation of pituitary sensitivity to luteinizing hormone-releasing factor during the menstrual cycle.

    PubMed Central

    Wang, C F; Yen, S S

    1975-01-01

    To delineate the role of estradiol in the augmented pituitary gonadotropin responsiveness to synthetic luteinizing hormone releasing factor (LRF) seen during high-estrogen phases of the ovulatory cycles (late follicular and midluteal phases), the anti-estrogenic effect of clomiphene citrate (Clomid) on pituitary response to LRF was evaluated during different phases of the ovulatory cycle. Clomid administration (100 mg/day times 5 days) completely negates the augmented gonadotropin responses to LRF (150 mug) during late follicular and midluteal phases observed during the control studies. Thus, a quantitatively and qualitatively similar pituitary sensitivity to LRF during three distinct phases of the menstrual cycle was induced by Clomid treatment that resembles the LRF responsiveness of themale pituitary. The present study demonstrates the pituitary component of the estrogen-induced changes in the sensitivity to LRF. From this and previous data, we conclude that the increases of estradiol secretion associated with the follicular maturation and corpus luteum formation represent a major component of the feedback signal in the modulation of cyclic gonadotropin release occasioned in a large measure by the augmented pituitary sensitivity to LRF. PMID:1088908

  1. Estrogen bows to a new master: the role of gonadotropins in Alzheimer pathogenesis.

    PubMed

    Webber, Kate M; Casadesus, Gemma; Marlatt, Michael W; Perry, George; Hamlin, Clive R; Atwood, Craig S; Bowen, Richard L; Smith, Mark A

    2005-06-01

    Epidemiological data showing a predisposition of women to develop Alzheimer disease (AD) led many researchers to investigate the role of sex steroids, namely estrogen, in disease pathogenesis. Although there is circumstantial support for the role of estrogen, the unexpected results of the Women's Health Initiative (WHI) Memory Study, which reported an increase in the risk for probable dementia and impaired cognitive performance in postmenopausal women treated with a combination of estrogen and progestin, have raised serious questions regarding the protective effects of estrogen. Although explanations for these surprising results vary greatly, the WHI Memory Study cannot be correctly interpreted without a complete investigation of the effects of the other hormones of the hypothalamic-pituitary-gonadal (HPG) axis on the aging brain. Certain hormones of the HPG axis, namely, the gonadotropins (luteinizing hormone and follicle-stimulating hormone), are not only involved in regulating reproductive function via a complex feedback loop but are also known to cross the blood-brain barrier. We propose that the increase in gonadotropin concentrations, and not the decrease in steroid hormone (e.g., estrogen) production following menopause/andropause, is a potentially primary causative factor for the development of AD. In this review, we examine how the gonadotropins may play a central and determining role in modulating the susceptibility to, and progression of, AD. On this basis, we suggest that the results of the WHI Memory Study are not only predictable but also avoidable by therapeutically targeting the gonadotropins instead of the sex steroids.

  2. Gonadotropin and estrogen responses in freshwater turtle (Chrysemys picta) from Cape Cod, Massachusetts.

    PubMed

    Kitana, Noppadon; Khonsue, Wichase; Won, Seung Jae; Lance, Valentine A; Callard, Ian P

    2006-10-01

    As a result of chemical waste disposal on the Massachusetts Military Reservation, a Superfund site on Cape Cod, MA, contaminated groundwater plumes have formed. These plumes are of concern due to the widespread use of groundwater wells as a drinking water source by the local population. Prior observations on a sentinel species Chrysemys picta field-trapped from ponds on Cape Cod suggested deficits in reproductive processes including lower levels of vitellogenin, estradiol-17beta, oviduct weights, and oocyte numbers in females and lower testicular weight and sperm count in males. Possible loci in the hypothalamic-pituitary-gonadal-liver axis at which xenobiotics may act were determined in turtles trapped from Moody Pond (a test site) and Washburn Pond (a reference site). Specifically, gonadotropin and estrogen responses were assessed using plasma steroids and vitellogenin as markers. Basal vitellogenin levels were significantly lower in Moody Pond females; however, vitellogenin responses to estradiol-17beta were the same in both groups, indicating a normal hepatic response to estrogen. In contrast, estradiol-17beta secretion was not stimulated by gonadotropin in Moody Pond females, compared to Washburn animals. Basal plasma testosterone and the response to gonadotropin in males were similar, although steroid levels in Moody Pond animals were slower to return to baseline after gonadotropin injection. The results suggest that a low-level mixture of xenobiotic contaminants may interfere with the steroid metabolic pathways in turtles exposed to the test site, but not the reference site, environment.

  3. Structural and Functional Divergence of Gonadotropin-Inhibitory Hormone from Jawless Fish to Mammals

    PubMed Central

    Ogawa, Satoshi; Parhar, Ishwar S.

    2014-01-01

    Gonadotropin-inhibitory hormone (GnIH) was discovered as a novel hypothalamic peptide that inhibits gonadotropin release in the quail. The presence of GnIH-homologous peptides and its receptors (GnIHRs) have been demonstrated in various vertebrate species including teleosts, suggesting that the GnIH-GnIHR family is evolutionarily conserved. In avian and mammalian brain, GnIH neurons are localized in the hypothalamic nuclei and their neural projections are widely distributed. GnIH acts on the pituitary and gonadotropin-releasing hormone neurons to inhibit reproductive functions by decreasing gonadotropin release and synthesis. In addition, GnIH-GnIHR signaling is regulated by various factors, such as environmental cues and stress. However, the function of fish GnIH orthologs remains inconclusive because the physiological properties of fish GnIH peptides are debatable. This review summarizes the current research progress in GnIH-GnIHR signaling and their physiological functions in vertebrates with special emphasis on non-mammalian vertebrate species. PMID:25386165

  4. Role of the hypothalamic-pituitary-ovarian axis in puerperal infertility.

    PubMed

    Andreassen, B; Tyson, J E

    1976-06-01

    To gain further insight into the mechanisms of postpartum infertility, plasma gonadotropins, prolactin, estradiol, and progesterone were measured following either iv LHRH or im menopausal gonadotropins (Pergonal) to postpartum women. Plasma estradiol and progesterone rose significantly between 24-72 hours following hMG injection. The response was similar in both nursing and non-nursing women throughout the intermediate and late postpartum study interval. No gonadotropin response was observed following LHRH injection in the early puerperium. Beyond five postpartum weeks, a significantly greater response following LHRH was observed in nursing compared with non-nursing women. A subsequent and significant rise in estradiol correlated with the magnitude of the LHRH-induced increment. Basal prolactin levels in nursing women were significantly greater than in non-nursing women but were unchanged after either hMG or LHRH. We conclude that the postpartum ovary is not refractory to either direct exogenous gonadotropin stimulation or to endogenously released gonadotropins, at least as far as estrogen production is concerned. Furthermore, the difference in the pituitary response to LHRH in nursing and non-nursing women may reflect a difference in the hypothalamic-pituitary axis. Elevated prolactin secretion in response to nursing may be involved in postpartum infertility, but the specific role remaine unclear.

  5. Gonadotropin therapy: a 20th century relic.

    PubMed

    Reindollar, Richard H; Goldman, Marlene B

    2012-04-01

    Gonadotropin therapy has been a cornerstone of infertility therapy for half a century. From the very beginning, its use has been associated with a high rate of multiple births, particularly high order multiples, and ovarian hyperstimulation syndrome. Initially, success rates seemed acceptable when used for superovulation (SO)/IUI therapy. However, as data from RCTs have emerged, reported outcomes suggest that we question the use of injectible gonadotropins. This manuscript examines the studies that have challenged gonadotropin use for SO/IUI and other research that supports reduced doses of gonadotropins for IVF. We examine the challenges for its continued use for SO/IUI and for moving to lower doses worldwide for IVF. We propose a future that views gonadotropins as a relic of the twentieth century. PMID:22463775

  6. Rapid Anti-Inflammatory Effects of Gonadotropin-Releasing Hormone Antagonism in Rheumatoid Arthritis Patients with High Gonadotropin Levels in the AGRA Trial

    PubMed Central

    Kåss, Anita; Hollan, Ivana; Fagerland, Morten Wang; Gulseth, Hans Christian; Torjesen, Peter Abusdal; Førre, Øystein Torleiv

    2015-01-01

    Objectives Gonadotropin-releasing hormone (GnRH) and pituitary gonadotropins, which appear to be proinflammatory, undergo profound secretory changes during events associated with rheumatoid arthritis (RA) onset, flares, or improvement e.g. menopausal transition, postpartum, or pregnancy. Potential anti-inflammatory effects of GnRH-antagonists may be most pronounced in patients with high GnRH and gonadotropin levels. Therefore, we investigated the efficacy and safety of a GnRH-antagonist, cetrorelix, in RA patients with high gonadotropin levels. Methods We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53), i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99). Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1–2; 3mg days 3–5) or placebo, were followed through day 15. Only predefined primary and secondary endpoints were analyzed. Results The primary endpoint, Disease Activity Score of 28-joint counts with C-reactive protein (DAS28-CRP), improved with cetrorelix compared with placebo by day 5 (-1.0 vs. -0.4, P = 0∙010). By day 5, more patients on cetrorelix achieved at least a 20% improvement in the American College of Rheumatology scale (44% vs. 19%, P = 0.049), DAS28-CRP≤3.2 (24% vs. 0%, P = 0.012), and European League against Rheumatism ‘Good-responses’ (19% vs. 0%, P = 0.026). Tumor necrosis factor-α, interleukin-1β, interleukin-10, and CRP decreased with cetrorelix (P = 0.045, P = 0.034, P = 0.020 and P = 0.042 respectively) compared with placebo by day 15. Adverse event rates were similar between groups. Conclusions GnRH-antagonism produced rapid anti-inflammatory effects in RA patients with high gonadotropin levels. GnRH should be investigated further in RA. Trial Registration ClinicalTrials.gov NCT00667758 PMID:26460564

  7. Active immunization of gilts against gonadotropin-releasing hormone: effects on secretion of gonadotropins, reproductive function, and responses to agonists of gonadotropin-releasing hormone.

    PubMed

    Esbenshade, K L; Britt, J H

    1985-10-01

    Sexually mature gilts were actively immunized against gonadotropin-releasing hormone (GnRH) by conjugating GnRH to bovine serum albumin, emulsifying the conjugate in Freund's adjuvant, and giving the emulsion as a primary immunization at Week 0 and as booster immunizations at Weeks 10 and 14. Antibody titers were evident by 2 wk after primary immunization and increased markedly in response to booster immunizations. Active immunization against GnRH caused gonadotropins to decline to nondetectable levels, gonadal steroids to decline to basal levels, and the gilts to become acyclic. Prolactin concentrations in peripheral circulation were unaffected by immunization against GnRH. The endocrine status of the hypothalamic-pituitary-ovarian axis was examined by giving GnRH and two agonists to GnRH and by ovariectomy. An i.v. injection of 100 micrograms GnRH caused release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in control animals, but not in gilts immunized against GnRH. In contrast, administration of 5 micrograms D-(Ala6, des-Gly-NH2(10] ethylamide or 5 micrograms D-(Ser-t-But6, des-Gly-NH2(10] ethylamide resulted in immediate release of LH and FSH in both control and GnRH-immunized gilts. Circulating concentrations of LH and FSH increased after ovariectomy in the controls, but remained at nondetectable levels in gilts immunized against GnRH. Prolactin concentrations did not change in response to ovariectomy. We conclude that cyclic gilts can be actively immunized against GnRH and that this causes cessation of estrous cycles and inhibits secretion of LH, FSH, and gonadal steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Medical hypophysectomy: I. Dose-response using a gonadotropin-releasing hormone antagonist.

    PubMed

    Kenigsberg, D; Littman, B A; Hodgen, G D

    1984-07-01

    The hypothalamic-pituitary-ovarian axis can be "dissected" in a nonsurgical and reversible fashion by the administration of a potent gonadotropin-releasing hormone (GnRH) antagonist. We created a transient, functional lesion at the level of the pituitary gonadotrope by using a potent GnRH antagonist ([ Ac- pClPhe1 , pClDPhe2 , DTrp3 , DArg6 , DAla10 ]-GnRH). In long-term castrate cynomolgus monkeys, doses of 0.05 to 2.0 mg/kg/day intramuscularly were administered for a total of 32 days. At doses up to 0.2 mg/kg/day, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in circulation were only moderately suppressed; these subjects responded to an estradiol challenge by manifesting an LH elevation or surge within 48 hours. At doses of 0.5 to 1.0 mg/kg/day, FSH and LH secretion was suppressed to or below the limits of assay detection within 7 days, remaining in a severely hypogonadotropic state for the remainder of the treatment interval. Using 2 mg/kg/day, estradiol-positive feedback for midcycle-like LH/FSH surges was fully inhibited. This suppression of gonadotropin secretion was rapidly reversible, in that circulating gonadotropin levels had returned to pretreatment castrate levels within 60 days after termination of GnRH antagonist treatments. These findings suggest that potent GnRH antagonists can effectively create a hypogonadotropic milieu without the initial enhancement of gonadotropin secretion that occurs during initiation of GnRH agonist therapy. "Medical hypophysectomy" through GnRH antagonist administration may permit a more direct and controlled approach to gonadal therapies such as ovulation induction.

  9. Failure of ethanol metabolites to alter gonadotropin secretion or luteinizing hormone synthesis in vitro.

    PubMed

    Uddin, S; Kirsteins, L; LaPaglia, N; Emanuele, N V; Lawrence, A M; Kelley, M R; Emanuele, M A

    1995-08-01

    The impact of ethanol on the male reproductive axis are multiple and varied, with both gonadal and control hypothalamic-pituitary pertubations being reported. There appears to be a discrepancy, however, between the in vivo and in vitro effects of ethanol on hypothalamic luteinizing hormones releasing hormone (LHRH) and the pituitary gonadotropins luteinizing hormone (LH) and follicle stimulating hormone (FSH). While in vivo data suggests a decrease in LHRH release after EtOH, in vitro studies find no effect on secretion. Similarly, in vivo acute EtOH profoundly diminishes LH synthesis and secretion, while in vitro impaired release with no alteration in the transcription of beta LH has been found. A potential exploration for these discrept results could be the in vivo metabolism of EtOH into acetaldehyde and acetate, or the subsequent formation of salsolinol, a product of acetate combining with dopamine. To test this possibility, a series of in vitro experiments were conducted exposing dispensed anterior pituitary cells from male rats to different doses of acetaldehyde, acetate or salsolinol for varying amounts of time for which gonadotropin secretion and beta LH mRNA levels were assessed. The results demonstrated no effect of either acetaldehyde or acetate on basal or LHRH stimulated LH release, FSH release or steady-state beta LH mRNA levels. These data suggest that the metabolites of EtOH, which occur in vivo but not in vitro, are not responsible for the discrepant gonadotropin changes reported between the in vivo and in vitro setting. Other potential mechanisms to explain this phenomenon include differences in the molarity of EtOH, hyperprolactinemia and suprapituitary influences including hypothalamic LHRH, catecholamines, excitatory amino acids, substance P and beta endorphin.

  10. Quantitative bioassays for measuring biologically functional gonadotropins based on eel gonadotropic receptors.

    PubMed

    Minegishi, Y; Dirks, R P; de Wijze, D L; Brittijn, S A; Burgerhout, E; Spaink, H P; van den Thillart, G E E J M

    2012-08-01

    Significant declines in eel stocks have been noted in many parts of the world. Because eel aquaculture is dependent on wild-caught juveniles, there is a need to achieve artificial reproduction. Adult eel maturation is currently induced by repeated injections of purified gonadotropin (human chorionic gonadotropin [hCG]) or pituitary extract. Thus the determination of the biological efficacy and quantification of internal levels of gonadotropic hormones is important for optimizing artificial reproduction protocols. To quantify the plasma levels of biologically functional gonadotropic hormones, we developed a bioassay for luteinizing hormone (LH) and follicle-stimulating hormone (FSH) based on the stable expression of receptors in HEK293 cells of the Japanese eel Anguilla japonica LH (ajLHR) and the European eel Anguilla anguilla FSH (aaFSHR), respectively. Such cells also contain a firefly luciferase reporter gene driven by a cAMP-responsive element (CRE-Luc). We found that the obtained stable cells, with ajLHR, responded linearly to a more than 100,000-fold concentration range of hCG diluted in saline. The cells with aaFSHR showed a linear response to a 1000-fold concentration range of salmon pituitary extract mixed with saline. The biological functionality of the LH and FSH bioassays was validated using hCG, human FSH, and pituitary extracts from salmon, carp and eel. Since the toxins in eel plasma damaged the HEK293 cells, the protocol was adapted to selectively inactivate the toxins by heating at 37°C for 24h. This process successfully enabled the monitoring of hormone levels in blood plasma sampled from hCG-injected eels. In this paper, we describe the development of gonadotropin bioassays that will be useful for improving reproduction protocols in eel aquaculture. PMID:22580328

  11. Central and direct regulation of testicular activity by gonadotropin-inhibitory hormone and its receptor.

    PubMed

    Ubuka, Takayoshi; Son, You Lee; Tobari, Yasuko; Narihiro, Misato; Bentley, George E; Kriegsfeld, Lance J; Tsutsui, Kazuyoshi

    2014-01-01

    Gonadotropin-inhibitory hormone (GnIH) was first identified in Japanese quail to be an inhibitor of gonadotropin synthesis and release. GnIH peptides have since been identified in all vertebrates, and all share an LPXRFamide (X = L or Q) motif at their C-termini. The receptor for GnIH is the G protein-coupled receptor 147 (GPR147), which inhibits cAMP signaling. Cell bodies of GnIH neurons are located in the paraventricular nucleus (PVN) in birds and the dorsomedial hypothalamic area (DMH) in most mammals. GnIH neurons in the PVN or DMH project to the median eminence to control anterior pituitary function via GPR147 expressed in gonadotropes. Further, GnIH inhibits gonadotropin-releasing hormone (GnRH)-induced gonadotropin subunit gene transcription by inhibiting the adenylate cyclase/cAMP/PKA-dependent ERK pathway in an immortalized mouse gonadotrope cell line (LβT2 cells). GnIH neurons also project to GnRH neurons that express GPR147 in the preoptic area (POA) in birds and mammals. Accordingly, GnIH can inhibit gonadotropin synthesis and release by decreasing the activity of GnRH neurons as well as by directly inhibiting pituitary gonadotrope activity. GnIH and GPR147 can thus centrally suppress testosterone secretion and spermatogenesis by acting in the hypothalamic-pituitary-gonadal axis. GnIH and GPR147 are also expressed in the testis of birds and mammals, possibly acting in an autocrine/paracrine manner to suppress testosterone secretion and spermatogenesis. GnIH expression is also regulated by melatonin, stress, and social environment in birds and mammals. Accordingly, the GnIH-GPR147 system may play a role in transducing physical and social environmental information to regulate optimal testicular activity in birds and mammals. This review discusses central and direct inhibitory effects of GnIH and GPR147 on testosterone secretion and spermatogenesis in birds and mammals.

  12. Pituitary diseases and bone.

    PubMed

    Mazziotti, Gherardo; Chiavistelli, Silvia; Giustina, Andrea

    2015-03-01

    Pituitary hormones have direct and indirect effects on bone remodeling, and skeletal fragility is a frequent complication of pituitary diseases. Fragility fractures may occur in many patients with prolactinomas, acromegaly, Cushing disease, and hypopituitarism. As in other forms of secondary osteoporosis, pituitary diseases generally affect bone quality more than bone quantity, and fractures may occur even in the presence of normal or low-normal bone mineral density, making difficult the prediction of fractures in these settings. Treatment of excess and defective pituitary hormone generally improves skeletal health, although some patients remain at high risk for fractures, necessitating treatment with bone-active drugs.

  13. General Information about Pituitary Tumors

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  14. Treatment Option Overview (Pituitary Tumors)

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  15. Familial pituitary tumors.

    PubMed

    Alband, Neda; Korbonits, Márta

    2014-01-01

    Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern due to hormone overproduction and/or tumor mass effects. The majority of pituitary adenomas occur sporadically; however, familial cases are increasingly being recognized, such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and familial isolated pituitary adenoma (FIPA). Familial pituitary tumors appear to differ from their sporadic counterparts both in their genetic basis and in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, tumors are more aggressive and affect patients at a younger age, therefore justifying the importance of early diagnosis, while in Carney complex pituitary hyperplasia is common. The genetic alterations responsible for the formation of familial pituitary syndromes include the MEN1 gene, responsible for about 80% of MEN1 cases, the regulatory subunit of the protein kinase A, PRKAR1A, responsible for about 70% of Carney complex cases, and AIP, the gene coding the aryl hydrocarbon receptor interacting protein, responsible for about 20% of FIPA cases. Rarely other genes have also been found responsible for familial pituitary adenoma cases. McCune-Albright syndrome (MAS) also has a genetic origin due to mosaic mutations in the G protein-coupled α subunit coded by the GNAS1 gene. In this chapter, we summarize the genetic and clinical characteristics of these familial pituitary syndromes and MAS. PMID:25248598

  16. Effects of gonadoliberin analogue triptorelin on the pituitary-testicular complex in neonatal rats.

    PubMed

    Dygalo, N N; Shemenkova, T V; Kalinina, T S; Shishkina, G T

    2014-02-01

    Triptorelin, a synthetic analogue of neurohormone gonadoliberin (gonadotropin-releasing hormone, GnRH) administered daily to rats on postnatal days 5-7 suppressed the expression of GnRH receptor in the pituitary gland, but did not change functioning of the pituitary-testicular complex. Administration of triptorelin on postnatal days 12-14 (i.e. during the formation of pulsatile pattern of GnRH secretion and increasing levels of its mRNA receptor in the pituitary gland) had no effect on receptor expression, but increased the levels of luteinizing hormone mRNA in the pituitary gland and the weight of testes. At that time, blood levels of testosterone were lowered, which indicated disturbed pulsatile pattern of GnRH secretion. PMID:24771429

  17. The mechanism responsible for the supraphysiologic gonadotropin surge in GnRH-agonist-treated, GnRH-antagonist-primed females

    PubMed Central

    Taylor, Joelle E.; Miller, Bradley T.; Gray, Karen D.; Scott, Richard T.; Catherino, William H.; Segars, James H.

    2010-01-01

    Objective To elucidate the physiologic mechanism responsible for the supraphysiologic gonadotropin release from the pituitary induced by GnRH-agonist in GnRH-antagonist-primed female rats. Design Controlled experimental intervention. Setting Government research facility. Intervention Forty oophrectomized rats were randomized into 4 groups of 10 and treated with: Group A) control vehicles; Group B) GnRH-a (leuprolide acetate; 1.7μg/kg BID) on day 4; Group C) GnRH-ant (Nal-Lys; 3mg/kg QD) days 1–4; or D) GnRH-ant (Nal-Lys; 3mg/kg QD) days 1–4 and GnRH-a (1.7μg/kg BID) on day 4. Main Outcome Measure(s) Immunohistochemical methods, Northern, and in situ hybridization to quantitate pituitary FSH-β, LH-β and GnRH-R mRNA and receptor protein levels in all treatment groups. Results Treatment with GnRH-ant was associated with increased storage of gonadotropin in the pituitary for FSH-β and LH-β, but mRNA levels were unchanged. GnRH-R mRNA decreased following GnRH-a treatment but remained stable in the GnRH-ant-treated groups. Levels of GnRH-R were decreased following GnRH-ant treatment. Conclusions These data indicate that the in vivo mechanism responsible for the exaggerated release of gonadotropins in the GnRH-ant primed, GnRH-a treated rat was an increase in releasable gonadotropin pools coupled with a reduction in GnRH-R, but receptor function was preserved. PMID:19200975

  18. Cytokines and the hypothalamic-pituitary-adrenal axis.

    PubMed

    Hermus, A R; Sweep, C G

    1990-12-20

    After administration of the cytokines interleukin 1 (IL1), tumor necrosis factor (TNF), interleukin 2 and interleukin 6 to laboratory animals or humans, plasma levels of glucocorticoids are elevated. This effect is mediated by activation of the hypothalamic-pituitary unit. IL1 and TNF inhibit aldosterone production by rat adrenocortical cells in vitro and stimulate renin release by rat renal cortical cells. Administration of IL1 or TNF in rats suppresses hypothalamic-pituitary-thyroid function, whereas IL1 acts at the level of the brain and the gonads to interfere with gonadotropin and sex steroid secretion. During stimulation of the immune system (e.g. during infectious diseases), peculiar alterations in hormone secretion occur (hypercortisolism, hyperreninemic hypoaldosteronism, euthyroid sick syndrome, hypogonadism). The role of cytokines in these alterations remains to be established.

  19. ERK signaling in the pituitary is required for female but not male fertility.

    PubMed

    Bliss, Stuart P; Miller, Andrew; Navratil, Amy M; Xie, Jianjun; McDonough, Sean P; Fisher, Patricia J; Landreth, Gary E; Roberson, Mark S

    2009-07-01

    Males and females require different patterns of pituitary gonadotropin secretion for fertility. The mechanisms underlying these gender-specific profiles of pituitary hormone production are unknown; however, they are fundamental to understanding the sexually dimorphic control of reproductive function at the molecular level. Several studies suggest that ERK1 and -2 are essential modulators of hypothalamic GnRH-mediated regulation of pituitary gonadotropin production and fertility. To test this hypothesis, we generated mice with a pituitary-specific depletion of ERK1 and 2 and examined a range of physiological parameters including fertility. We find that ERK signaling is required in females for ovulation and fertility, whereas male reproductive function is unaffected by this signaling deficiency. The effects of ERK pathway ablation on LH biosynthesis underlie this gender-specific phenotype, and the molecular mechanism involves a requirement for ERK-dependent up-regulation of the transcription factor Egr1, which is necessary for LHbeta expression. Together, these findings represent a significant advance in elucidating the molecular basis of gender-specific regulation of the hypothalamic-pituitary-gonadal axis and sexually dimorphic control of fertility.

  20. The aging male hypothalamic-pituitary-gonadal axis: pulsatility and feedback.

    PubMed

    Veldhuis, Johannes D; Keenan, Daniel M; Liu, Peter Y; Iranmanesh, Ali; Takahashi, Paul Y; Nehra, Ajay X

    2009-02-01

    Aging results in insidious decremental changes in hypothalamic, pituitary and gonadal function. The foregoing three main anatomic loci of control are regulated by intermittent time-delayed signal exchange, principally via gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and testosterone/estradiol (Te/E(2)). A mathematical framework is required to embody these dynamics. The present review highlights integrative adaptations in the aging male hypothalamic-pituitary-gonadal axis, as assessed by recent objective ensemble models of the axis as a whole.

  1. The Aging Male Hypothalamic-Pituitary-Gonadal Axis: pulsatility and feedback

    PubMed Central

    Veldhuis, Johannes D.; Keenan, Daniel M.; Liu, Peter Y.; Iranmanesh, Ali; Takahashi, Paul Y.; Nehra, Ajay X.

    2009-01-01

    Aging results in insidious decremental changes in hypothalamic, pituitary and gonadal function. The foregoing three main anatomic loci of control are regulated by intermittent time-delayed signal exchange, principally via gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and testosterone/estradiol (Te/E2). A mathematical framework is required to embody these dynamics. The present review highlights integrative adaptations in the aging male hypothalamic-pituitary-gonadal axis, as assessed by recent objective ensemble models of the axis as a whole. PMID:18838102

  2. FOXO1 is Regulated by Insulin and IGF1 in Pituitary Gonadotropes

    PubMed Central

    Skarra, Danalea V.; Thackray, Varykina G.

    2015-01-01

    The FOXO1 transcription factor is important for multiple aspects of reproductive function. We previously reported that FOXO1 functions as a repressor of gonadotropin hormone synthesis, but how FOXO1 is regulated in pituitary gonadotropes is unknown. The growth factors, insulin and insulin-like growth factor I (IGF1) function as key regulators of cell proliferation, metabolism and apoptosis in multiple cell types through the PI3K/AKT signaling pathway. In this study, we found that insulin and IGF1 signaling in gonadotropes induced FOXO1 phosphorylation through the PI3K/AKT pathway in immortalized and primary cells, resulting in FOXO1 relocation from the nucleus to the cytoplasm. Furthermore, insulin administration in vivo induced phosphorylation of FOXO1 and AKT in the pituitary. Thus, insulin and IGF1 act as negative regulators of FOXO1 activity and may serve to fine-tune gonadotropin expression. PMID:25676570

  3. [Effect of chronic consumption of alcohol on the hypothalamo-pituitary-testicular axis in the rat].

    PubMed

    Mateos, A; Fermoso, J; Agrasal, C; Martín, I; Paz-Bouza, J; Tresguerres, J A; Esquifino, A I

    1987-03-01

    An experimental model of chronic alcohol abuse is developed, in order to study the hypothalamic-pituitary testicular axis in the rat. For this purpose basal plasma prolactin, gonadotropins, testosterone and estradiol have been measured. Also these hormones were studied after LHRH or hCG stimulation. This experimental model allows us to study the role of alcohol in hypogonadism induction. Chronic alcohol administration resulted in an inconstant decrease in plasma testosterone levels and very diminished response of it to hCG. Along with these modifications, there was an increase in basal plasma estrogen levels, as has been shown in the human. The decrease in plasma LH levels in alcoholic rats together with a normal response to LHRH suggest a toxic role of alcohol at higher levels than the pituitary. The existence of a hyperprolactinemic state under chronic alcohol ingestion is confirmed. The decrease in plasma prolactin levels after LHRH administration suggests that prolactin and gonadotropin secretion are very closely related.

  4. Effect of 1st-trimester loss on restoration of the hypothalamic-pituitary-ovarian axis.

    PubMed

    Elkas, J C; Cunningham, D S

    1995-01-01

    This randomized prospective study was conducted to determine the length of time required for re-establishment of the reproductive axis following a 1st-trimester spontaneous abortion. The spontaneous gonadotropin secretion was significantly depressed during the first menstrual cycle after pregnancy loss, while the estradiol levels had normalized. Provocative testing revealed blunted gonadotropin release in the first menstrual cycle with return to normal during the first menstrual cycle after a spontaneous abortion. Endometrial biopsy specimens were also abnormal during the first menstrual cycle with normal histological characteristics by the second menstrual cycle. Therefore, restoration of the hypothalamic-pituitary- ovarian axis after a 1st-trimester loss is achieved within two menstrual cycles, as determined by return of normal pituitary function.

  5. Suppression of Gonadotropins and Estradiol in Premenopausal Women by Oral Administration of the Nonpeptide Gonadotropin-Releasing Hormone Antagonist Elagolix

    PubMed Central

    Struthers, R. Scott; Nicholls, Andrew J.; Grundy, John; Chen, Takung; Jimenez, Roland; Yen, Samuel S. C.; Bozigian, Haig P.

    2009-01-01

    Context: Parenteral administration of peptide GnRH analogs is widely employed for treatment of endometriosis and fibroids and in assisted-reproductive therapy protocols. Elagolix is a novel, orally available nonpeptide GnRH antagonist. Objective: Our objective was to evaluate the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single-dose and 7-d elagolix administration to healthy premenopausal women. Design: This was a first-in-human, double-blind, placebo-controlled, single- and multiple-dose study with sequential dose escalation. Participants: Fifty-five healthy, regularly cycling premenopausal women participated. Interventions: Subjects were administered a single oral dose of 25–400 mg or placebo. In a second arm of the study, subjects received placebo or 50, 100, or 200 mg once daily or 100 mg twice daily for 7 d. Treatment was initiated on d 7 (±1) after onset of menses. Main Outcome Measures: Safety, tolerability, pharmacokinetics, and serum LH, FSH, and estradiol concentrations were assessed. Results: Elagolix was well tolerated and rapidly bioavailable after oral administration. Serum gonadotropins declined rapidly. Estradiol was suppressed by 24 h in subjects receiving at least 50 mg/d. Daily (50–200 mg) or twice-daily (100 mg) administration for 7 d maintained low estradiol levels (17 ± 3 to 68 ± 46 pg/ml) in most subjects during late follicular phase. Effects of the compound were rapidly reversed after discontinuation. Conclusions: Oral administration of a nonpeptide GnRH antagonist, elagolix, suppressed the reproductive endocrine axis in healthy premenopausal women. These results suggest that elagolix may enable dose-related pituitary and gonadal suppression in premenopausal women as part of treatment strategies for reproductive hormone-dependent disease states. PMID:19033369

  6. Blood, pituitary, and brain renin-angiotensin systems and regulation of secretion of anterior pituitary gland.

    PubMed

    Ganong, W F

    1993-07-01

    In addition to increasing blood pressure, stimulating aldosterone and vasopressin secretion, and increasing water intake, angiotensin II affects the secretion of anterior pituitary hormones. Some of these effects are direct. There are angiotensin II receptors on lactotropes and corticotropes in rats, and there may be receptors on thyrotropes and other secretory cells. Circulating angiotensin II reaches these receptors, but angiotensin II is almost certainly generated locally by the pituitary renin-angiotensin system as well. There are also indirect effects produced by the effects of brain angiotensin II on the secretion of hypophyseotropic hormones. In the anterior pituitary of the rat, the gonadotropes contain renin, angiotensin II, and some angiotensin-converting enzyme. There is debate about whether these cells also contain small amounts of angiotensinogen, but most of the angiotensinogen is produced by a separate population of cells and appears to pass in a paracrine fashion to the gonadotropes. An analogous situation exists in the brain. Neurons contain angiotensin II and probably renin, but most angiotensin-converting enzyme is located elsewhere and angiotensinogen is primarily if not solely produced by astrocytes. Angiotensin II causes secretion of prolactin and adrenocorticotropic hormone (ACTH) when added to pituitary cells in vitro. Paracrine regulation of prolactin secretion by angiotensin II from the gonadotropes may occur in vitro under certain circumstances, but the effects of peripheral angiotensin II on ACTH secretion appear to be mediated via the brain and corticotropin-releasing hormone (CRH). In the brain, there is good evidence that locally generated angiotensin II causes release of norepinephrine that in turn stimulates gonadotropin-releasing hormone-secreting neurons, increasing circulating luteinizing hormone. In addition, there is evidence that angiotensin II acts in the arcuate nuclei to increase the secretion of dopamine into the portal

  7. Distribution and regulation by oestrogen of fully processed and variant transcripts of gonadotropin releasing hormone I and gonadotropin releasing hormone receptor mRNAs in the male chicken.

    PubMed

    Sun, Y M; Dunn, I C; Baines, E; Talbot, R T; Illing, N; Millar, R P; Sharp, P J

    2001-01-01

    The aim of this study was to increase understanding of the occurrence and regulation of chicken gonadotropin releasing hormone I (cGnRH I) and chicken gonadotropin releasing hormone receptor (cGnRH-R) mRNA variants in the hypothalamic-pituitary-testicular axis (HPTA). The study was carried out in the cockerel. Fully processed cGnRH I mRNA (cGnRH Ia) and a variant transcript (cGnRH Ib) with a retained intron 1 were observed in the preoptic/anterior hypothalamus (POA), the basal hypothalamus, anterior pituitary gland, and testes. Fully processed cGnRH-R mRNA (cGnRH-Ra) and a variant transcript (cGnRH-Rb) with a deletion were detected in the same tissues. In juvenile cockerels, concentrations of cGnRH Ia and b in the POA increased after castration, and this was prevented by oestrogen treatment. In the anterior pituitary gland, the concentration of cGnRH-Ra increased after castration and this was reversed by oestrogen treatment. In intact adult cockerels, oestrogen treatment depressed plasma luteinizing hormone but did not affect concentrations of cGnRH I and cGnRH-R mRNAs in the POA, basal hypothalamus, and anterior pituitary gland, suggesting that locally produced oestrogen, by aromatization, may exert maximal suppression on cGnRH I and GnRH-R mRNAs. In intact adult cockerels, the concentrations of cGnRH Ia and b in the testis, but not cGnRH-Ra and b, were depressed by oestrogen treatment. It was concluded that fully processed and variant cGnRH I and cGnRH-R mRNAs occur in all components of the HPTA. Oestrogen appears to play a role in the regulation of cGnRH Ia and b in the POA and testes, and of cGnRH-Ra in the POA and anterior pituitary gland.

  8. Gonadotropin determinations in timed 3-hour urine collections during the menstrual cycle and LHRH testing.

    PubMed

    Beitins, I Z; O'loughlin, K; Ostrea, T; Mcarthur, J W

    1976-07-01

    Gonadotropin determinations in timed 3-hour urine collections during the menstrual cycle and luteinizing hormone-releasing hormone (LHRH) testing are reported. No marked temporal trend was seen when urine aliquots were collected every 3 hours throughout 2 24-hour periods in 1 mature woman. A good correlation (p less than .001) was seen between serum LH and follicle stimulation hormone (FSH) concentrations and the quantity ovulatory menstrual cycles in 2 women. A good correlation (p less than .001) was also seen between the quantity of the gonadotropins in timed 3-hour urine collections and serum LH and FSH concentrations before and during the LHRH test in 51 normal men, women, and children and in patients with hypothalamic-pituitary-gonadal axis disorders. The "response area" for serum LH and FSH also correlated well (p less than .001) with the LH and FSH in the urine collected. It is concluded that the timed 3-hour urine collection for gonadotropin estimation provides a simple, accurate method for the integration of fluctuating serum concentrations of LH and FSH during such instances of physiologic variability as the menstrual cycle and LHRH stimulation tests.

  9. Control of puberty onset and fertility by gonadotropin-releasing hormone neurons.

    PubMed

    Herbison, Allan E

    2016-08-01

    The gonadotropin-releasing hormone (GnRH) neuronal network generates pulse and surge modes of gonadotropin secretion critical for puberty and fertility. The arcuate nucleus kisspeptin neurons that innervate the projections of GnRH neurons in and around their neurosecretory zone are key components of the pulse generator in all mammals. By contrast, kisspeptin neurons located in the preoptic area project to GnRH neuron cell bodies and proximal dendrites and are involved in surge generation in female rodents (and possibly other species). The hypothalamic-pituitary-gonadal axis develops embryonically but, apart from short periods of activation immediately after birth, remains suppressed through a combination of gonadal and non-gonadal mechanisms. At puberty onset, the pulse generator reactivates, probably owing to progressive stimulatory influences on GnRH neurons from glial and neurotransmitter signalling, and the re-emergence of stimulatory arcuate kisspeptin input. In females, the development of pulsatile gonadotropin secretion enables final maturation of the surge generator that ultimately triggers the first ovulation. Representation of the GnRH neuronal network as a series of interlocking functional modules could help conceptualization of its functioning in different species. Insights into pulse and surge generation are expected to aid development of therapeutic strategies ameliorating pubertal disorders and infertility in the clinic.

  10. Gonadotropin determinations in times 3-hour urine collections during the menstrual cycle and LHRH testing.

    PubMed

    Beitins, I Z; O'Loughlin, K; Ostrea, T; McArthur, J W

    1976-07-01

    The usefulness of timed 3-hour urine collections as a substitute for serum gonadotropin (LH and FSH) determinations during the menstrual cycle and during LHRH testing was examined. The timing of the 3-hour urine collection is not important in mature individuals, since no significant temporal trend was found when aliquots were collected every 3 hours throughout two 24-hour periods in one mature woman. Good correlation was found between serum LH and FSH concentrations and the quantity of LH and FSH in timed 3-hour urine specimens throughout normal, ovulatory menstrual cycles in two women. Studies before and during 51 LHRH stimulation tests in normal men, children, and women during different phases of the menstrual cycle and in patients with a variety of hypothalamic-pituitary-gonadal axis disorders were performed. There was good correlation between the quantity of the gonadotropins in time 3-hour urine collections and the mean serum LH and FSH concentrations before and during the LHRH test. The "response area" for serum LH and FSH also correlated well with the amounts of LH and FSH in the urine collected during this period. Therefore, the timed 3-hour urine collection for gonadotropin estimation provides a simple, accurate method for the integration of fluctuating serum concentrations of LH and FSH during such instances of physiologic variability as the menstrual cycle and LHRH stimulation tests.

  11. Beyond estrogen: targeting gonadotropin hormones in the treatment of Alzheimer's disease.

    PubMed

    Casadesus, Gemma; Zhu, Xiongwei; Atwood, Craig S; Webber, Kate M; Perry, George; Bowen, Richard L; Smith, Mark A

    2004-08-01

    Based on epidemiological and observational studies, estrogen and hormone-replacement therapy were until recently viewed as major factors in the prevention of Alzheimer's disease (AD). However, a recent randomized clinical trial revealed that hormone replacement therapy using estrogen plus progestin may actually exacerbate the incidence of dementia when administered to elderly women. These contradictory reports have cast grave doubt on the role of estrogen in disease pathogenesis and led us to consider an alternate hypothesis that would be consistent with both observations. Specifically, we suspect that hormones of the hypothalamic pituitary gonadal axis such as gonadotropins, that are regulated by estrogen (or in males by testosterone), are involved in the pathogenesis of Alzheimer's disease. One such gonadotropin, luteinizing hormone (LH), is significantly elevated in both the sera and brain tissue of patients with AD and leads to an increased production of amyloid-beta. Importantly, a key role in disease pathogenesis is further supported by the fact that the distribution of neuronal receptors for LH parallels those populations of neurons that degenerate during the course of the disease. That gonadotropins, not estrogen nor testosterone, mediate disease pathogenesis has led to a paradigm shift, not only for the treatment of AD but a wide variety of other age-related diseases. Therefore, the effects of agents that abolish LH, such as leuprolide acetate, which are currently being evaluated in Phase II clinical trials for the treatment of AD, are eagerly anticipated.

  12. Allopregnanolone, a GABAA receptor agonist, decreases gonadotropin levels in women. A preliminary study.

    PubMed

    Timby, Erika; Hedström, Helena; Bäckström, Torbjörn; Sundström-Poromaa, Inger; Nyberg, Sigrid; Bixo, Marie

    2011-12-01

    Animal studies suggest regulatory effects on the hypothalamic-pituitary-gonad axis by allopregnanolone, an endogenous gamma-aminobutyric acid A (GABA(A)) receptor agonist. Elevated levels of allopregnanolone in women with hypothalamic amenorrhea have been seen. Isoallopregnanolone is an isomer to allopregnanolone, but without GABA(A) receptor effects. The purpose of this study was to investigate effects of allopregnanolone and isoallopregnanolone on gonadotropin levels in healthy women of fertile age. Ten women were given allopregnanolone and five women isoallopregnanolone intravenously in follicular phase. Repeated blood samples were drawn during the test day. Main outcomes were changes in serum levels of follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, and progesterone. Serum-FSH decreased between 5 and 105 min after the allopregnanolone injection (F(16,144)=2.18, p=0.008). Serum-LH was reduced between 5 and 35 min following the allopregnanolone injection (F(16,144)=2.63, p=0.001). Serum-oestradiol and -progesterone were not significantly changed after allopregnanolone injections. No effect on gonadotropin levels were seen after administration of isoallopregnanolone. Allopregnanolone reduces FSH and LH levels in women and the effect might be mediated via a specific GABA(A) receptor activation since isoallopregnanolone lacked this effect. Although the number of women was small, the results suggest a regulatory mechanism on the hypothalamic-pituitary-gonadal axis by allopregnanolon.

  13. SAH pituitary adrenal dysfunction.

    PubMed

    Vespa, P

    2011-09-01

    Disruption of the hypothalamic-pituitary-adrenal axis may occur after aneurysmal subarachnoid hemorrhage, resulting in hypopituitarism. An electronic literature search was conducted to identify articles with English-language abstracts published between 1980 and March 2011 that addressed hypothalamic-pituitary-adrenal axis insufficiency and hormone replacement. A total of 18 observational and prospective, randomized studies were selected for this review. Limited data are available evaluating pituitary effects during the acute stage after subarachnoid hemorrhage, with inconsistent results reported. Overall, acutely after subarachnoid hemorrhage, cortisol levels may initially be supranormal, decreasing toward normal levels over time. During the months to years after subarachnoid hemorrhage, pituitary deficiency may occur in up to one in three patients. Limited data suggest modest outcome benefits with fludrocortisone and no benefit or harm from corticosteroids. PMID:21800209

  14. Pituitary Tumors: Condition Information

    MedlinePlus

    ... stress. Growth hormone helps control body growth and metabolism. Thyroid-stimulating hormone is involved in growth, body temperature, and heart rate. Nonfunctioning pituitary tumors (also called nonsecretory tumors) do ...

  15. Management of pituitary tumors.

    PubMed

    Post, K D; Muraszko, K

    1986-11-01

    Pituitary adenomas represent the only true adenomas of the cranial cavity. In 1000 asymptomatic pituitary glands examined at autopsy, there was a 22.4 per cent incidence of undetected microadenomas. Advances in diagnostic endocrinology, in radiologic imaging, and in surgical and medical treatments have brought many more patients to the attention of the authors. Over the last 10 years, their treatment approaches have evolved to those presented in this article.

  16. Emerging functions of gonadotropin-releasing hormone II in mammalian physiology and behaviour.

    PubMed

    Kauffman, A S

    2004-09-01

    Gonadotropin-releasing hormone (GnRH) is the central neuroendocrine regulator of the hypothalamic-pituitary-gonadal axis. Multiple structural variants of GnRH are present in vertebrates. The first isoform isolated in the mammalian brain (GnRH I) was shown to regulate the release of pituitary gonadotropins. Recently, a second form has been discovered in mammals (GnRH II), both in the brain and periphery. Although it is unlikely to be a primary regulator of gonadotropin release, the highly conserved GnRH II variant appears to have a wide array of physiological functions. In the periphery, GnRH I and II have similar roles in regulating cell proliferation and mediating hormonal secretion from the ovary and placenta in an autocrine/paracrine manner. In the brain, GnRH I and II apparently modulate mammalian reproductive behaviours in different but complementary ways: GnRH I stimulates luteinizing hormone/follicle-stimulating hormone secretion (and thus gonadal steroids) and promotes sexual behaviour in ad libitum fed animals. By contrast, GnRH II acts as a permissive regulator of female reproductive behaviour based on energy status, as well as a modifier of short-term food intake. GnRH II has also been implicated in the regulation of calcium and potassium channels in nervous systems of amphibians, functions which may also be present in mammals. Increasing evidence suggests that the effects of GnRH II in both the periphery and brain may be mediated by GnRH receptor subtypes distinct from the type-1 GnRH receptor. It is likely that this evolutionarily conserved peptide has been co-opted over evolutionary time to possess multiple regulatory functions in a broad range of biological aspects, including, but not limited to, reproduction. Here, the proposed actions of both neural and peripheral GnRH II in affecting physiology and behaviour are summarized, and an outline of critical directions for future research is proposed.

  17. RNA Interference of Gonadotropin-Inhibitory Hormone Gene Induces Arousal in Songbirds

    PubMed Central

    Ubuka, Takayoshi; Mukai, Motoko; Wolfe, Jordan; Beverly, Ryan; Clegg, Sarah; Wang, Ariel; Hsia, Serena; Li, Molly; Krause, Jesse S.; Mizuno, Takanobu; Fukuda, Yujiro; Tsutsui, Kazuyoshi; Bentley, George E.; Wingfield, John C.

    2012-01-01

    Gonadotropin-inhibitory hormone (GnIH) was originally identified in quail as a hypothalamic neuropeptide inhibitor of pituitary gonadotropin synthesis and release. However, GnIH neuronal fibers do not only terminate in the median eminence to control anterior pituitary function but also extend widely in the brain, suggesting it has multiple roles in the regulation of behavior. To identify the role of GnIH neurons in the regulation of behavior, we investigated the effect of RNA interference (RNAi) of the GnIH gene on the behavior of white-crowned sparrows, a highly social songbird species. Administration of small interfering RNA against GnIH precursor mRNA into the third ventricle of male and female birds reduced resting time, spontaneous production of complex vocalizations, and stimulated brief agonistic vocalizations. GnIH RNAi further enhanced song production of short duration in male birds when they were challenged by playbacks of novel male songs. These behaviors resembled those of breeding birds during territorial defense. The overall results suggest that GnIH gene silencing induces arousal. In addition, the activities of male and female birds were negatively correlated with GnIH mRNA expression in the paraventricular nucleus. Density of GnIH neuronal fibers in the ventral tegmental area was decreased by GnIH RNAi treatment in female birds, and the number of gonadotropin-releasing hormone neurons that received close appositions of GnIH neuronal fiber terminals was negatively correlated with the activity of male birds. In summary, GnIH may decrease arousal level resulting in the inhibition of specific motivated behavior such as in reproductive contexts. PMID:22279571

  18. Approaches to define the role of SF-1 at different levels of the hypothalamic-pituitary-steroidogenic organ axis.

    PubMed

    Bakke, M; Zhao, L; Parker, K L

    2001-06-20

    Targeted gene disruption has produced knockout mice lacking the orphan nuclear receptor steroidogenic factor 1 (SF-1). These SF-1 knockout mice lacked adrenal glands and gonads, resulting in adrenocortical insufficiency and sex reversal of their internal and external genitalia. They also had impaired expression of pituitary gonadotropins and agenesis of the ventromedial hypothalamic nucleus (VMH), confirming roles of SF-1 at multiple levels of the hypothalamic-pituitary-steroidogenic tissue axis. Using the Cre-loxP system, we now have generated mice in which SF-1 is inactivated selectively in the anterior pituitary. These pituitary-specific SF-1 knockout mice were sterile and failed to exhibit sexual maturation. Histologically, their gonads were markedly hypoplastic, weighing only approximately 5% of the gonads of wild-type mice. Consistent with an important role of SF-1 in gonadotropes, there were no cells in the pituitary gland that expressed either follicle-stimulating hormone (FSH) or luteinizing hormone (LH). These pituitary-specific SF-1 knockout mice are a novel genetic model of hypogonadotropic hypogonadism and establish essential roles of SF-1 in gonadotropin expression.

  19. Social regulation of the brain-pituitary-gonadal axis.

    PubMed

    Francis, R C; Soma, K; Fernald, R D

    1993-08-15

    Reproduction in vertebrates is regulated by the hypothalamic-pituitary-gonadal axis via neural and hormonal feedback. This axis is also subject to exogenous influences, particularly social signals. In the African cichlid fish Haplochromis burtoni, gonadal development in males is socially regulated. A small fraction of the males, which are brightly colored, maintain territories and aggressively dominate inconspicuously colored nonterritorial males. Here we show through manipulation of the social and endocrine environment that changes in social status and gonadal state are accompanied by soma size changes in a population of gonadotropin-releasing hormone-containing neurons in the ventral forebrain. In territorial males, these cells are significantly larger than in nonterritorial males. When an animal switches from being territorial to nonterritorial through a change in social situation, these cells shrink; in animals that change from nonterritorial to territorial status, the cells enlarge. These gonadotropin-releasing hormone-containing cells project to the pituitary and are ultimately responsible for regulating gonadal growth. This mechanism of socially induced cell size change provides the potential for relatively quick adaptive changes in the neuron-endocrine system without nerve cell addition or death. Since the structure of this regulatory axis is conserved among all vertebrates, other species with socially modulated reproductive physiology may exhibit a similar form of physiological regulation.

  20. High prevalence rate of pituitary incidentaloma: is it associated with the age-related decline of the sex hormones levels?

    PubMed

    Kastelan, Darko; Korsic, Mirko

    2007-01-01

    Incidental pituitary adenoma is the common finding during brain imaging. According to multistep model of pituitary tumourigenesis genetic alterations provide the initiating event that transforms cells while hormones play a role in promoting cell proliferation. Development of pituitary adenoma in a case of excessive hypophysiotrophic hormones production or reduced feedback suppression by target gland hormones emphasizes the importance of hormonal stimulation in pituitary tumourigenesis. Pituitary hyperplasia has been reported in pregnancy, hypothyroidism and conditions such as CRH or GHRH hypersecretion. Moreover, recent study reported one case of gonadotroph macroadenoma and two cases of gonadotroph cells hyperplasia in patients with Klinefelter syndrome probably due to protracted stimulation of gonadotroph cells because of lack of androgen feedback. Significant changes of the hypothalamic-pituitary-gonadal axis occurred with aging. In females, after menopause, estradiol level decreases by 35-fold and estrone level by 20-fold that results in increased gonadotropins levels. Similarly, FSH, but not LH, level is increased with advancing age in men, too, although the age-related difference in the level is less in comparison with women. Regarding these data, we hypothesised that high prevalence rate of pituitary incidentaloma in the elderly is associated with age-related decline in sex hormones levels and subsequent lack of feedback suppression leading to permanent gonadotrophs stimulation which is the crucial step in the pituitary tumour development. According to previously mentioned multistep model of pituitary tumourigenesis, incidentaloma will develop only in persons with already present intrinsic pituitary cell defects. However, further studies have to answer the questions of whether the incidence of pituitary tumours is more frequent in elderly, whether women with late onset menopause or those taking long-term hormone replacement therapy have lower rate of

  1. Separation of gonadotropic fractions with different species specificities from tuna pituitaries

    SciTech Connect

    Ando, H.; Ishii, S.

    1988-05-01

    Eight different gonadotropic glycoprotein fractions were separated from the acetone-dried powder of yellow fin tuna pituitary glands by successive chromatographies on Superose 12 for gel filtration and Mono Q for anion exchange using the Pharmacia fast protein liquid chromatography system. This was preceded by preliminary separations using an ammonium sulfate precipitation method and affinity chromatography on concanavalin A-Sepharose. For biological characterization, we employed two radioreceptor assay systems, one using goby testis plasma membranes and silver carp GTH as the receptor and radioligand, respectively, and the other using testis plasma membranes of the yellow fin tuna and gonadotropin of the same species, respectively. We also employed two testicular cyclic AMP accumulation bioassay methods in vitro, one with the goby testis and the other with the mackerel testis. The least acidic fraction after Mono Q was further separated into four subfractions by rechromatography with Mono Q. They were strongly active in the tuna and mackerel assays but almost inactive in the goby assays. They were referred to as tuna-type tuna gonadotropin. In contrast, the most acidic fraction obtained after the first Mono Q was active in the goby assays but almost inactive in the tuna and mackerel assays. It was referred to as goby-type tuna gonadotropin. The intermediate fractions were active on both assays and are considered to be mixtures of tuna-type and goby-type gonadotropins. The reason for the presence of gonadotropin inactive to homologous species is discussed from the evolutionary viewpoint.

  2. Do androgens directly regulate gonadotropin secretion in the polycystic ovary syndrome?

    PubMed

    Dunaif, A

    1986-07-01

    This study was designed to investigate whether androgens directly, independent of their aromatization to estrogens, disrupt gonadotropin secretion in hyperandrogenic women with the polycystic ovary syndrome (PCO). Pulsatile gonadotropin release and gonadotroph sensitivity to GnRH were determined on consecutive study days basally and during a primed continuous infusion of testosterone (T; n = 4; 100 micrograms/h; twice the mean production rate of T in PCO) or dihydrotestosterone (DHT; n = 5; 50 micrograms/h). To determine if the gonadotropin secretory changes during T infusion were secondary to spontaneous variation, four patients had two consecutive basal studies, and all patients received DHT on the third study day. T infusion that increased mean plasma T levels from 76 +/- 12 (+/- SE) to 315 +/- 28 ng/dl produced no significant changes in the amount or pattern of LH release or in LH sensitivity to GnRH. Mean plasma FSH levels decreased slightly but significantly during T infusion (basal, 242 +/- 29 vs. T 226 +/- 30 ng/ml LER-907; P less than 0.05 by two-tailed paired t test), but the pulsatile pattern of FSH release and FSH sensitivity to GnRH did not change. DHT infusion increased plasma DHT levels from 17 +/- 3 to 244 +/- 31 ng/dl, but did not alter the mean levels, pulsatile patterns, or sensitivity to GnRH of LH or FSH. These data suggest that androgens do not directly alter gonadotropin release in PCO. Thus, regulation of the hypothalamic-pituitary axis in women with PCO is different from that in men despite chronic exposure to hyperandrogenemia.

  3. Effect of oral contraceptives on the rat brain and pituitary beta-endorphin.

    PubMed

    Tejwani, G A; Vaswani, K K; Barbacci, J C; Richard, C W; Bianchine, J R

    1983-01-01

    The purpose of this study was to investigate the effect of oral administration of progesterone (15 micrograms norethindrone, NE) in presence and absence of estradiol (1 microgram ethinyl estradiol, EE2) on the CNS levels of beta-endorphin like immunoreactivity (beta-EI) in female rats. In acute study (5 days), NE alone did not change beta-EI significantly in pituitary. NE and EE2 together decreased beta-EI by 37% (47% at 10X dose). In chronic study (7 weeks), 2NE had no significant effect on pituitary beta-EI, however, NE and EE2 together at 10X dose decreased it by 14%. In the hypothalamus, NE alone or in presence of EE2 had no significant effect on beta-EI, but 10X dose of NE+ EE2 caused 50 and 76% decrease in beta-EI in acute and chronic study. Striatum was the only tissue where NE alone caused a decrease of 82% in beta-EI when given acutely and 52% when given chronically. EE2 had some protective effect on this decrease since when given together (NE+EE2) the decrease in beta-EI was 21% in acute and 43% in chronic study. Thus our results, along with other studies on the regulation of gonadotropin levels by opioids, suggest that oral contraceptives alter the level of beta-EI and in turn may regulate the release of gonadotropins. Morphine and endogenous opioids have been shown to decrease gonadotropin secretion in various species including humans, apparently by suppressing the release of LH-RH from the hypothalamus (1-5). The opiate antagonist naloxone not only causes up to 10-fold increase in the secretion of gonadotropins (1,3, 6-9) but also opposes the negative feedback effect of steroids on the hypothalamic-pituitary-gonadotropin axis (8), suggesting a regulatory interaction between the endogenous opioids, gonadotropins and gonadal steroids. Like ACTH, the secretion of beta-endorphin is inhibited by glucocorticoids (10). Naloxone induced release of LH is facilitated by estradiol in humans (11) suggesting an antagonistic effect of estradiol on the endogenous

  4. Orchidectomy selectively increases follicle-stimulating hormone secretion in gonadotropin-releasing hormone antagonist-treated male rats.

    PubMed

    Tena-Sempere, M; Pinilla, L; Aguilar, E

    1995-03-01

    The pituitary component of the feedback mechanisms exerted by testicular factors on gonadotropin secretion was analyzed in adult male rats treated with a potent gonadotropin-releasing hormone (GnRH) antagonist. In order to discriminate between androgens and testicular peptides, groups of males were orchidectomized (to eliminate androgens and non-androgenic testicular factors) or injected with ethylene dimethane sulfonate (EDS), a selective toxin for Leydig cells (to eliminate selectively androgens) and treated for 15 days with vehicle or the GnRH antagonist Ac-D-pClPhe-D-pClPhe-D-Trp-Ser-Tyr-D-Arg-Leu-Arg-Pro-D-Ala-+ ++NH2CH3COOH (Org.30276, 5 mg/kg/72 hours). Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured 7 and 14 days after the beginning of treatment. We found that: in males treated with GnRH antagonist, orchidectomy or EDS treatment did not induce any increase in LH secretion; and orchidectomy, but not EDS treatment, increased FSH secretion in GnRH-treated males. The present results show that negative feedback of testicular factors on LH secretion is mediated completely through changes in GnRH actions. In contrast, a part of the inhibitory action of the testis on FSH secretion is exerted directly at the pituitary level. It can be hypothesized that non-Leydig cell testicular factor(s) inputs at different levels of the hypothalamic-pituitary axis in controlling LH and FSH secretion.

  5. Regulation of gonadotropin gene expression by Müllerian inhibiting substance

    PubMed Central

    Bédécarrats, Grégoy Y.; O'Neill, Francis H.; Norwitz, Errol R.; Kaiser, Ursula B.; Teixeira, Jose

    2003-01-01

    In addition to its role in causing Müllerian duct regression, Müllerian inhibiting substance (MIS) is implicated in the regulation of steroidogenesis, breast and prostate growth, and ovarian follicle recruitment, all of which are processes controlled or influenced by the hypothalamic–pituitary–gonadal axis. Whereas the direct effect of MIS on gonadal, prostate, and breast cells is under investigation, the ability of MIS to modulate pituitary function, thereby affecting those tissues indirectly, has not yet been studied. Using LβT2 cells, a murine gonadotrope-derived cell line, we have evaluated the effects of MIS on the expression of the gonadotropin genes. We show that both LβT2 cells and adult rat pituitaries express MIS type II receptor (MISRII) mRNA. Within 2 h, follicle-stimulating hormone β subunit (FSHβ) mRNA levels are significantly induced by addition of MIS to LβT2 cells and remain elevated through 8 h of treatment. Transcriptional activation of both the FSHβ and luteinizing hormone β subunit (LHβ) gene promoters was observed by MIS, which enhances the effect of gonadotropin-releasing hormone (GnRH) agonist on the FSHβ gene promoter and synergizes with the GnRH agonist to stimulate LHβ gene promoter activity. Addition of MIS to LβT2 cells stimulates the activity of the rat LHβ gene promoter with as little as 1 μg/ml and in a dose-dependent manner. These studies report both MISRII expression in rat pituitary cells and a gonadotrope-derived cell line and MIS-mediated activation of LHβ and FSHβ gene expression, and suggest that MIS may modulate the hypothalamic–pituitary–gonadal axis at more than one level. PMID:12878721

  6. Neuroendocrine disorders: pituitary imaging.

    PubMed

    Faje, Alexander; Tritos, Nicholas A; Swearingen, Brooke; Klibanski, Anne

    2016-01-01

    Significant advances in pituitary imaging have taken place in the past several decades, including the introduction of magnetic resonance imaging (MRI). This imaging modality has vastly improved our ability to detect and characterize sellar masses and more accurately characterize the extent and spread of lesions in and around the sella. Intraoperative MRI may help improve the completeness of resection of sellar masses. Other imaging modalities, including magnetic resonance angiography, computed tomography (CT), and CT angiography, have an important role in specific cases. Interventional methods, including bilateral inferior petrosal sinus sampling, may establish the pituitary origin of corticotropin (ACTH) excess in patients with ACTH-dependent Cushing's syndrome. Pituitary imaging should be obtained in patients with pituitary hormone excess, hypopituitarism, or mass effect in the sella. Despite rapid advances in pituitary imaging, there are several diagnostic challenges remaining. Future research may help improve the radiographic detection of small sellar lesions, such as ACTH-secreting adenomas causing Cushing's disease, accurately characterize the type and extent of sellar pathologies, and provide prognostic information regarding their growth potential. PMID:27430447

  7. Role of prolactin in the regulation of sensitivity of the hypothalamic-pituitary system to steroid feedback.

    PubMed

    Bartke, A; Matt, K S; Steger, R W; Clayton, R N; Chandrashekar, V; Smith, M S

    1987-01-01

    During sexual maturation, pituitary gonadotropins stimulate the gonads to produce increasing amounts of biologically active steroids and yet gonadotropin release does not become suppressed until concentrations of sex hormones, LH and FSH, in peripheral circulation stabilizes at a higher adult level. There is a substantial amount of evidence that in many mammals, this transition from prepubertal to adult level of activity of the pituitary-gonadal axis is associated with a reduction in the sensitivity of the hypothalamic-adenohypophyseal system to negative feedback of gonadal steroids. In the female, these changes are accompanied by the appearance of positive estrogen feedback on gonadotropin release. In seasonal breeders, annual transitions between the periods of gonadal activity and quiescence are associated with corresponding shifts in the sensitivity to steroid feedback. Peripheral levels of pituitary prolactin (PRL) typically increase during sexual maturation and exhibit large seasonal fluctuations in response to changes in photoperiod and ambient temperature. We propose that PRL is one of the factors which regulate the sensitivity of gonadotropin release to gonadal steroid feedback. In hyperprolactinemic women, responsiveness to negative estrogen feedback increases, while LH response to positive estrogen feedback is reduced or absent. In hyperprolactinemic men, both LH and testosterone levels are reduced, implying increased sensitivity of LH release to negative testosterone feedback. In the male rat, both physiological amounts of PRL and experimentally-induced hyperprolactinemia increase the ability of exogenous testosterone to suppress LH and FSH release. Different regulatory mechanisms appear to operate in the seasonally breeding male golden hamster, in which short photoperiod causes concomitant suppression of PRL, LH, FSH and testosterone release. In this species, pharmacologic suppression of PRL release leads to increased responsiveness of plasma

  8. Restoration of Dioxin-Induced Damage to Fetal Steroidogenesis and Gonadotropin Formation by Maternal Co-Treatment with α-Lipoic Acid

    PubMed Central

    Koga, Takayuki; Ishida, Takumi; Takeda, Tomoki; Ishii, Yuji; Uchi, Hiroshi; Tsukimori, Kiyomi; Yamamoto, Midori; Himeno, Masaru; Furue, Masutaka; Yamada, Hideyuki

    2012-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an endocrine disruptor, causes reproductive and developmental toxic effects in pups following maternal exposure in a number of animal models. Our previous studies have demonstrated that TCDD imprints sexual immaturity by suppressing the expression of fetal pituitary gonadotropins, the regulators of gonadal steroidogenesis. In the present study, we discovered that all TCDD-produced damage to fetal production of pituitary gonadotropins as well as testicular steroidogenesis can be repaired by co-treating pregnant rats with α-lipoic acid (LA), an obligate co-factor for intermediary metabolism including energy production. While LA also acts as an anti-oxidant, other anti-oxidants; i.e., ascorbic acid, butylated hydroxyanisole and edaravone, failed to exhibit any beneficial effects. Neither wasting syndrome nor CYP1A1 induction in the fetal brain caused through the activation of aryl hydrocarbon receptor (AhR) could be attenuated by LA. These lines of evidence suggest that oxidative stress makes only a minor contribution to the TCDD-induced disorder of fetal steroidogenesis, and LA has a restorative effect by targeting on mechanism(s) other than AhR activation. Following a metabolomic analysis, it was found that TCDD caused a more marked change in the hypothalamus, a pituitary regulator, than in the pituitary itself. Although the components of the tricarboxylic acid cycle and the ATP content of the fetal hypothalamus were significantly changed by TCDD, all these changes were again rectified by exogenous LA. We also provided evidence that the fetal hypothalamic content of endogenous LA is significantly reduced following maternal exposure to TCDD. Thus, the data obtained strongly suggest that TCDD reduces the expression of fetal pituitary gonadotropins to imprint sexual immaturity or disturb development by suppressing the level of LA, one of the key players serving energy production. PMID:22911699

  9. Treatment Options for Pituitary Tumors

    MedlinePlus

    ... brain, including the sella (the bone at the base of the skull , where the pituitary gland sits). ... sphenoid bone (a butterfly-shaped bone at the base of the skull ) to reach the pituitary gland . ...

  10. Time-of-day-dependent changes in GnRH1 neuronal activities and gonadotropin mRNA expression in a daily spawning fish, medaka.

    PubMed

    Karigo, Tomomi; Kanda, Shinji; Takahashi, Akiko; Abe, Hideki; Okubo, Kataaki; Oka, Yoshitaka

    2012-07-01

    GnRH neurons in the preoptic area and hypothalamus control the secretion of GnRH and form the final common pathway for hypothalamic-pituitary-gonadal axis regulation in vertebrates. Temporal regulation of reproduction by coordinating endogenous physiological conditions and behaviors is important for successful reproduction. Here, we examined the temporal regulation of reproduction by measuring time-of-day-dependent changes in the electrical activity of GnRH1 neurons and in levels of expression of pituitary gonadotropin mRNA using a daily spawning teleost, medaka (Oryzias latipes). First, we performed on-cell patch-clamp recordings from GnRH1 neurons that directly project to the pituitary, using gnrh1-green fluorescent protein transgenic medaka. The spontaneous firing activity of GnRH1 neurons showed time-of-day-dependent changes: overall, the firing activity in the afternoon was higher than in the morning. Next, we examined the daily changes in the pituitary gonadotropin transcription level. The expression levels of lhb and fshb mRNA also showed changes related to time of day, peaking during the lights-off period. Finally, we analyzed effects of GnRH on the pituitary. We demonstrated that incubation of isolated pituitary with GnRH increases lhb mRNA transcription several hours after GnRH stimulation, unlike the well-known immediate LH releasing effect of GnRH. From these results, we propose a working hypothesis concerning the temporal regulation of the ovulatory cycle in the brain and pituitary of female medaka.

  11. 21 CFR 556.304 - Gonadotropin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.304 Gonadotropin. (a) Acceptable daily intake (ADI). The ADI...

  12. 21 CFR 556.304 - Gonadotropin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.304 Gonadotropin. (a) Acceptable daily intake (ADI). The ADI...

  13. Adrenocorticotropic Hormone Suppresses Gonadotropin-Stimulated Estradiol Release from Zebrafish Ovarian Follicles

    PubMed Central

    Alsop, Derek; Ings, Jennifer S.; Vijayan, Mathilakath M.

    2009-01-01

    While stress is known to impact reproductive performance, the pathways involved are not entirely understood. Corticosteroid effects on the functioning of the hypothalamus-pituitary-gonadal axis are thought to be a key aspect of stress-mediated reproductive dysfunction. A vital component of the stress response is the pituitary secretion of adrenocorticotropic hormone (ACTH), which binds to the melanocortin 2 receptor (MC2R) in the adrenal glands and activates cortisol biosynthesis. We recently reported MC2R mRNA abundance in fish gonads leading to the hypothesis that ACTH may be directly involved in gonadal steroid modulation. Using zebrafish (Danio rerio) ovarian follicles, we tested the hypothesis that acute ACTH stimulation modulates cortisol and estradiol (E2) secretion. ACTH neither affected cortisol nor unstimulated E2 release from ovarian follicles. However, ACTH suppressed human chorionic gonadotropin (hCG)-stimulated E2 secretion in a dose-related manner, with a maximum decrease of 62% observed at 1 I.U. ACTH mL−1. This effect of ACTH on E2 release was not observed in the presence of either 8-bromo-cAMP or forskolin, suggesting that the mechanism(s) involved in steroid attenuation was upstream of adenylyl cyclase activation. Overall, our results suggest that a stress-induced rise in plasma ACTH levels may initiate a rapid down-regulation of acute stimulated E2 biosynthesis in the zebrafish ovary, underscoring a novel physiological role for this pituitary peptide in modulating reproductive activity. PMID:19649243

  14. Molecular Characterization of Three Gonadotropin Subunits and Their Expression Patterns during Ovarian Maturation in Cynoglossus semilaevis

    PubMed Central

    Shi, Bao; Liu, Xuezhou; Xu, Yongjiang; Wang, Shanshan

    2015-01-01

    The endocrine regulation of reproduction in a multiple spawning flatfish with an ovary of asynchronous development remains largely unknown. The objectives of this study were to monitor changes in mRNA expression patterns of three gonadotropin hormone (GTH) subunits (FSHβ, LHβ and CGα) and plasma GTH levels during ovarian maturation of half-smooth tongue sole Cynoglossus semilaevis. Cloning and sequence analysis revealed that the cDNAs of FSHβ, LHβ and CGα were 541, 670 and 685 bp in length, and encode for peptides of 130, 158 and 127 amino acids, respectively. The number of cysteine residues and potential N-linked glycosylation sites of the flatfish GTHs were conserved among teleosts. However, the primary structure of GTHs in Pleuronectiformes appeared to be highly divergent. The FSHβ transcriptional level in the pituitary remained high during the vitellogenic stage while plasma levels of FSH peaked and oocyte development was stimulated. The LHβ expression in the pituitary and ovary reached the maximum level during oocyte maturation stages when the plasma levels of LH peaked. The brain GTHs were expressed at the different ovarian stages. These results suggested that FSH and LH may simultaneously regulate ovarian development and maturation through the brain-pituitary-ovary axis endocrine system in tongue sole. PMID:25633101

  15. Causes of hypogonadotropic hypogonadism predict response to gonadotropin substitution in adults.

    PubMed

    Rohayem, J; Sinthofen, N; Nieschlag, E; Kliesch, S; Zitzmann, M

    2016-01-01

    Germ cell and Sertoli cell proliferation and maturation in human testes occur in three main waves, during the late fetal and early neonatal period and at early puberty. They are triggered by periods of increased activity of the hypothalamic-pituitary-gonadal (HPG) axis. In hypogonadotropic hypogonadism (HH), these processes are variably disturbed. The objective of this study was to explore whether success of gonadotropin replacement in HH men is predictable by the origin of HH, indicating time of onset and severity of GnRH/gonadotropin deficiency. The data of 51 adult HH patients who had undergone one cycle of hCG/FSH treatment were reviewed. Five groups were established, according to the underlying HH origin. Therapeutic success by final bi-testicular volumes (BTVs) final sperm concentrations (SC) and conception rates were compared and related to baseline parameters, indicative of the degree of HPG-axis disruption. Overall, BTVs rose from 13 ± 15 to 27 ± 15 mL, spermatogenesis was induced in 98%, with mean SCs of 15 ± 30 mill/mL, spontaneous pregnancies in 37% and additional 18% via intracytoplasmic sperm injection. Kallmann syndrome patients had the poorest responses (BTV: 16.9 ± 10 mL; SC: 3.5 ± 5.6 mill/mL), followed by patients with congenital/infancy-acquired multiple pituitary hormone deficiencies (MPHD) and patients with HH+absent puberty (BTV: 21 ± 14/24 ± 9 mL; SC: 5.5 ± 6.5/ 14.5 ± 23.8 mill/mL). HH men with pubertal arrest and with post-pubertally acquired MPHD had the best results (BTV: 36 ± 14/38 ± 16 mL; SC: 25.4 ± 34.2/29.9 ± 50.5 mill/mL). Earlier conception after 20.3 ± 11.5 months (vs. 43.1 ± 43.8; p = 0.047) of gonadotropin treatment with higher pregnancy rates (62% vs. 42%) was achieved in the two post-pubertally acquired HH subgroups, compared to the three pre-pubertally acquired. Therapeutic success was higher in patients without previously undescended testes, with higher baseline BTVs (pre- vs. post-pubertal HH: 5 ± 4 mL vs

  16. Review: regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH) synthesis and release in photoperiodic animals

    PubMed Central

    Tsutsui, Kazuyoshi; Ubuka, Takayoshi; Bentley, George E.; Kriegsfeld, Lance J.

    2013-01-01

    Gonadotropin-inhibitory hormone (GnIH) is a novel hypothalamic neuropeptide that was discovered in quail as an inhibitory factor for gonadotropin release. GnIH inhibits gonadotropin synthesis and release in birds through actions on gonadotropin-releasing hormone (GnRH) neurons and gonadotropes, mediated via the GnIH receptor (GnIH-R), GPR147. Subsequently, GnIH was identified in mammals and other vertebrates. As in birds, mammalian GnIH inhibits gonadotropin secretion, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal (HPG) axis across species. Identification of the regulatory mechanisms governing GnIH expression and release is important in understanding the physiological role of the GnIH system. A nocturnal hormone, melatonin, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail, a photoperiodic bird. Recently, a similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH was shown in hamsters and sheep, photoperiodic mammals. These results in photoperiodic animals demonstrate that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Recent findings indicate that GnIH may be a mediator of stress-induced reproductive disruption in birds and mammals, pointing to a broad role for this neuropeptide in assessing physiological state and modifying reproductive effort accordingly. This paper summarizes the advances made in our knowledge regarding the regulation of GnIH synthesis and release in photoperiodic birds and mammals. This paper also discusses the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin, and glucocorticoids, to control avian and mammalian reproduction. PMID:23596387

  17. Review: regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH) synthesis and release in photoperiodic animals.

    PubMed

    Tsutsui, Kazuyoshi; Ubuka, Takayoshi; Bentley, George E; Kriegsfeld, Lance J

    2013-01-01

    Gonadotropin-inhibitory hormone (GnIH) is a novel hypothalamic neuropeptide that was discovered in quail as an inhibitory factor for gonadotropin release. GnIH inhibits gonadotropin synthesis and release in birds through actions on gonadotropin-releasing hormone (GnRH) neurons and gonadotropes, mediated via the GnIH receptor (GnIH-R), GPR147. Subsequently, GnIH was identified in mammals and other vertebrates. As in birds, mammalian GnIH inhibits gonadotropin secretion, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal (HPG) axis across species. Identification of the regulatory mechanisms governing GnIH expression and release is important in understanding the physiological role of the GnIH system. A nocturnal hormone, melatonin, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail, a photoperiodic bird. Recently, a similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH was shown in hamsters and sheep, photoperiodic mammals. These results in photoperiodic animals demonstrate that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Recent findings indicate that GnIH may be a mediator of stress-induced reproductive disruption in birds and mammals, pointing to a broad role for this neuropeptide in assessing physiological state and modifying reproductive effort accordingly. This paper summarizes the advances made in our knowledge regarding the regulation of GnIH synthesis and release in photoperiodic birds and mammals. This paper also discusses the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin, and glucocorticoids, to control avian and mammalian reproduction.

  18. Sexually dimorphic expression of pituitary glycoprotein hormones in a sex-changing fish (Pseudolabrus sieboldi).

    PubMed

    Ohta, Kohei; Mine, Takayuki; Yamaguchi, Akihiko; Matsuyama, Michiya

    2008-11-01

    It is widely accepted that the hypothalamic-pituitary-gonadal axis is involved in gonadal sex change in socially controlled sex-changing fish. However, the specific secretion profiles of pituitary gonadotropins (GtHs) in this type of fish are not known. To address this fundamental question, we demonstrated that the diurnal secretion patterns of GtHs differ distinctly between males and females in a socially controlled sex-changing fish. We analyzed the pituitary mRNA levels of glycoprotein hormone subunits (i.e., the common alpha-subunit and specific beta-subunits follicle-stimulating hormone beta, luteinizing hormone beta, and thyroid-stimulating hormone beta) in the wrasse Pseudolabrus sieboldi, which is a model fish that exhibits accurate diurnal rhythms of gametogenesis in both males and females. Northern blots clearly showed that each subunit gene exhibits a diurnal rhythm of expression in the pituitary and that the expression patterns differ distinctly between the sexes. Our results suggest that oogenesis and spermatogenesis in this hermaphroditic fish are regulated differentially through the distinct secretion patterns of pituitary glycoprotein hormones. This study also provides direct evidence of the sexual plasticity of pituitary GtH secretion in a socially controlled sex-changing fish.

  19. Effects of zinc deficiency upon pituitary function in sexually mature and immature male rats.

    PubMed

    Root, A W; Duckett, G; Sweetland, M; Reiter, E O

    1979-06-01

    Serum pituitary levels of growth hormone (GH), thyrotropin (TSH), prolactin (PRL), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured in sexually mature (adult) and sexually immature (juvenile) male rats who had been deprived of dietary zinc for 15 and 7 weeks, respectively. When compared to pair-fed control rats receiving a zinc supplemented diet, both the adult and juvenile zinc deficient rats had significantly lower body weights, tail lengths and ventral prostate weights. The testes of the sexually immature rats were also smaller than those of the pair-fed animals. In sexually mature, zinc deficient rats serum concentrations of GH and testosterone were significantly lower and serum LH levels significantly higher than in ad libitum fed control rats. Pituitary and hypothalamic levels of other hormones did not differ from values recorded in control animals. In sexually immature zinc deficient rats serum concentrations of GH were also significantly depressed; pituitary content and concentration of LH and pituitary and serum levels of FSH were significantly increased over control values. No discernible effects of zinc deficiency upon hyplthalamic content of LH-releasing hormone or serum concentrations of PRL or TSH were recorded in juvenile rats. Zinc deficiency has minimal effects upon the hypothalamic-pituitary axis of sexually mature rats. In sexually immature males, zinc deprivation leads to impairment of gonadal growth and increased synthesis and/or secretion of the pituitary gonadotropins.

  20. Advances in understanding pituitary tumors

    PubMed Central

    Renner, Ulrich; Karl Stalla, Günter

    2014-01-01

    Pituitary tumors are common in the general population. Since neuroimaging techniques have improved, pituitary tumors are more often diagnosed incidentally. About 16.7% of the general population show changes in the pituitary gland. Predominantly, pituitary tumors are benign pituitary adenomas. Pituitary carcinomas or aggressive pituitary tumors are extremely rare. They might develop from benign adenomas. New genetic and epigenetic abnormalities help us to understand pituitary tumorigenesis and might lead to therapeutical targeting drugs in the future. Macroadenomas (>1 cm) can lead to visual field disturbances, compression of cranial nerves, hypopituitarism, and infiltration of the cavernous sinuses. The functional status of the pituitary tumor is important. About half to one third of all pituitary tumors are non-functioning pituitary adenomas. The other pituitary tumors show a specific pattern of hormone secretion. About 25% to 41% of all pituitary tumors are prolactinomas, acromegaly with production of growth hormone represents 10% to 15% of adenomas, Cushing's disease with production of adrenocorticotropic hormone accounts for 10%, and other hormonal characteristics are less common. Transsphenoidal resection and total adenomectomy are desirable. Radiosurgery has enriched the surgical treatment options. Surgical treatment is the intervention of choice except for prolactinomas, where pharmaceutical treatment is recommended. Pharmaceutical treatment consists of dopamine agonists such as cabergoline and somatostatin analogues that include octreotide and pasireotide; retinoic acid is of theoretical interest while peroxisome proliferator-activated receptor-gamma-ligands are not clinically useful. In acromegaly, pegvisomant is a further treatment option. Temozolomide should be considered in aggressive pituitary tumors. In general, pharmaceutical options developed recently have extended the repertoire of treatment possibilities of pituitary tumors. PMID:24592317

  1. Pituitary Disorders and Osteoporosis

    PubMed Central

    Jawiarczyk-Przybyłowska, Aleksandra

    2015-01-01

    Various hormonal disorders can influence bone metabolism and cause secondary osteoporosis. The consequence of this is a significant increase of fracture risk. Among pituitary disorders such effects are observed in patients with Cushing's disease, hyperprolactinemia, acromegaly, and hypopituitarism. Severe osteoporosis is the result of the coexistence of some of these disorders and hypogonadism at the same time, which is quite often. PMID:25873948

  2. Mortality and pituitary disease.

    PubMed

    Stewart, Paul M; Sherlock, Mark

    2012-04-01

    Outcome data from large series confirm increased mortality of patients with pituitary tumours, predominantly due to vascular disease. Control of cortisol secretion and growth hormone (GH) hypersecretion (together with cardiovascular risk factor reduction) is key in the normalisation of mortality rates in patients with Cushing's disease and acromegaly, respectively, though some excess mortality may persist even in "cured" patients.

  3. Pituitary cells in space

    NASA Astrophysics Data System (ADS)

    Hymer, W. C.; Shellenberger, K.; Grindeland, R.

    1994-08-01

    Cells of the mammalian pituitary gland synthesize and secrete several protein hormones which regulate a number of organ systems throughout the body. These include the musculoskeletal, immune, vascular and endocrine systems. Since changes occur in these tissues as a result of spaceflight, and since pituitary growth hormone (GH) and prolactin (PRL) play a role in the control of these systems on earth, we have focused attention over the last 10 years on GH and PRL cell function during and after spaceflight. The cumulative results of 4 spaceflight missions and several mimicked microgravity (μG) experiments establish 1) that production and release of biologically active GH and PRL is repeatedly and significantly attenuated (usually > 50%) and 2) that changes in cell morphology also occur. In this paper we describe our results within the framework of methodologies and approaches frequently used to study pituitary cell function on earth. In so doing we hope to develop future flight experiments aimed at uncovering possible μG ``sensing systems'' within the pituitary cell.

  4. Pituitary cells in space

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Shellenberger, K.; Grindeland, R.

    1994-01-01

    Cells of the mammalian pituitary gland synthesize and secrete several protein hormones which regulate a number of organ systems throughout the body. These include the musculoskeletal, immune, vascular and endocrine systems. Since changes occur in these tissues as a result of spaceflight, and since pituitary growth hormone (GH) and prolactin (PRL) play a role in the control of these systems on earth, we have focused attention over the last 10 years on GH and PRL cell function during and after spaceflight. The cumulative results of 4 spaceflight missions and several mimicked microgravity experiments establish 1) that production and release of biologically active GH and PRL is repeatedly and significantly attenuated (usually >50%) and 2) that changes in cell morphology also occur. In this paper we describe our results within the framework of methodologies and approaches frequently used to study pituitary cell function on earth. In so doing we hope to develop future flight experiments aimed at uncovering possible microgravity 'sensing systems' within the pituitary cell.

  5. Hypothalamic-pituitary abscess

    PubMed Central

    Mohr, P. D.

    1975-01-01

    A case of hypothalamic-pituitary abscess is described, and previous case reports discussed. The clinical picture is one of hypopituitarism, a fluctuating clinical course with attacks of meningism, and a background of sphenoid sinusitis. ImagesFig. 1 PMID:1187501

  6. Pituitary adenoma: a radiotherapeutic perspective.

    PubMed

    Platta, Christopher S; Mackay, Christopher; Welsh, James S

    2010-08-01

    Pituitary adenomas comprise approximately 10% to 20% of all central nervous system neoplasms whereas autopsy series have suggested that the incidence of pituitary adenoma in the general population may approach 25%. Several treatment modalities are used in the treatment of pituitary adenomas, including observation, surgery, medical intervention, and radiotherapy. The treatment modality employed depends greatly on the type of pituitary adenoma and presenting symptoms. This review will discuss the biology of pituitary adenomas and the current management principles for the treatment of prolactinomas, Cushing disease, acromegaly, and nonsecretory adenomas, with an emphasis on the published radiotherapeutic literature.

  7. Tests of the hypothalamic-pituitary-ovarian axis.

    PubMed

    Shaw, R W

    1976-12-01

    The availability of RIA to measure the pituitary gonadotropins and ovarian sex steroids has greatly helped in the development of tests of hypothalamic-pituitary-ovarian function. The use of estimates of basal gonadotrophin and sex steroid hormones together with dynamic tests such as the LH-RH test, oestrogen provocation test, clomiphene tests and exogenous gonadotrophins can now test the integrity and functional capacity of each of the components of the HPO axis. Figure 4 demonstrates how these tests can be used in a logical sequence to investigate patients with a disorder of the HPO axis after having first excluded any other endocrine abnormality. Screening of serum for elevated levels of gonadotrophins, prolactin and progesterone is an important initial step. Interpretation of the oestrogen provocation and clomiphene tests requires a normally functioning pituitary gland and hence the response to an LH-RH test also plays a ket role. The flow chart also demonstrates the points at which specific ovulation induction treatment can be instituted and should be useful in saving patient and doctor investigative time. Using these types of tests it should be possible to reclassify disorders of the HPO axis on the basis of their underlying pathology.

  8. Ghrelin role in hypothalamus-pituitary-ovarian axis.

    PubMed

    Rak-Mardyla, A

    2013-12-01

    Based on the available data, it was shown that ghrelin is involved in a series of physiological processes such as regulation of food intake, body weight, and cardiovascular or immune function. Recent studies have shown that ghrelin also plays an important role in the regulation of female reproduction. Information exists that its functional receptor, GHSR type 1a (GHS-R1a), is expressed in the hypothalamic-pituitary-ovarian axis. Ghrelin is synthesized locally in the hypothalamus, pituitary and ovaries of many species and has autocrine and/or paracrine effects. Most research indicates that ghrelin has inhibitory effect on gonadotropin secretion. Ghrelin also participates in the direct regulation of different ovarian functions such as steroid secretion, cell proliferation and apoptosis; these functions appear to be species-specific. Moreover, the importance of GHS-R1a or MAPK/IP3 pathway activation in ghrelin action in the ovary has been described. The article summarizes results of a series of recent studies on the effect of ghrelin on the hypothalamic-pituitary-ovarian axis, as well as on ovarian physiology with an indication that ghrelin via its biological functions such as energy metabolism and food intake could also be a key signal between animal energy status and control of ovarian function.

  9. Aberrant hypothalamic-pituitary-ovarian axis in the Watanabe heritable hyperlipidemic rabbit.

    PubMed

    Robins, E D; Nelson, L M; Hoeg, J M

    1994-01-01

    The WHHL rabbit has a defective low density lipoprotein receptor and is a model for familial hypercholesterolemia. WHHL rabbits are less fecund than NZW rabbits, the strain into which the defect has been inbred. This lower fecundity could be related to impaired ovarian steroidogenesis due to reduced intracellular availability of cholesterol. Here we compare the WHHL and NZW rabbits with regard to oocyte morphology and fertilization rates after stimulation with equine chorionic gonadotropin. We also compare hypothalamic-pituitary-ovarian axis function by measuring baseline and gonadotropin releasing hormone-stimulated plasma estradiol, progesterone, and gonadotropin levels, both before and after simvastatin inhibition of de novo cholesterol synthesis. WHHL rabbit oocytes remained encased in cumulus and had a lowered fertilization rate (9/50 vs. 83/87, P < 0.05). WHHL rabbits had lower baseline estradiol levels (7.1 +/- 0.72 vs. 10.2 +/- 0.94, P < 0.05) and had higher baseline follicle stimulating hormone (P < 0.05) and luteinizing hormone (P < 0.05) levels. Simvastatin lowered luteal progesterone concentrations only in WHHL rabbits (P < 0.05). We conclude that the hypothalamic-pituitary-ovarian axis in WHHL rabbits is abnormal. The reduced availability of intracellular cholesterol for progesterone synthesis by inhibition of de novo cholesterol biosynthesis leads to a significant reduction in plasma progesterone concentrations in the WHHL. These findings have implications for women with familial hypercholesterolemia, particularly regarding treatment with inhibitors of de novo cholesterol synthesis.

  10. Evidence that estrogen regulation of testosterone secretion in adult rams is mediated by both indirect (gonadotropin dependent) and direct (gonadotropin independent) means.

    PubMed

    Sanford, L M

    1985-01-01

    Involvement of endogenous estrogen in the regulation of gonadotropin and testosterone secretion was investigated in adult rams. Groups of four rams were either passively immunized against estradiol or treated with the antiestrogen tamoxifen for 2 weeks during the breeding season (October). Circulating testosterone levels in immunized rams increased eight-fold to supraphysiologic values as episodic elevations and baseline levels increased in magnitude; only moderate increases in LH peak frequency and magnitude occurred, and prolactin fell to undetectable levels. Tamoxifen treatment was not associated with changes in mean hormone levels, although there was a tendency toward reductions in the magnitude of episodic LH and testosterone secretion. When rams were challenged with exogenous GnRH and LH, a greater testicular endocrine response was observed in the immunized rams and the pituitary endocrine response was delayed in the tamoxifen-treated rams. Results indicate that in the ram 1) circulating levels of estradiol provide negative feedback signals of different intensities to the testis and the hypothalamic-pituitary axis and 2) tamoxifen exerts a mild estrogenic effect when administered at the dose of 25 mg/day.

  11. Gonadotropins in the Russian Sturgeon: Their Role in Steroid Secretion and the Effect of Hormonal Treatment on Their Secretion.

    PubMed

    Yom-Din, Svetlana; Hollander-Cohen, Lian; Aizen, Joseph; Boehm, Benjamin; Shpilman, Michal; Golan, Matan; Hurvitz, Avshalom; Degani, Gad; Levavi-Sivan, Berta

    2016-01-01

    In the reproduction process of male and female fish, pituitary derived gonadotropins (GTHs) play a key role. To be able to specifically investigate certain functions of Luteinizing (LH) and Follicle stimulating hormone (FSH) in Russian sturgeon (Acipenser gueldenstaedtii; st), we produced recombinant variants of the hormones using the yeast Pichia pastoris as a protein production system. We accomplished to create in vitro biologically active heterodimeric glycoproteins consisting of two associated α- and β-subunits in sufficient quantities. Three dimensional modelling of both GTHs was conducted in order to study the differences between the two GTHs. Antibodies were produced against the unique β-subunit of each of the GTHs, in order to be used for immunohistochemical analysis and to develop an ELISA for blood and pituitary hormone quantification. This detection technique revealed the specific localization of the LH and FSH cells in the sturgeon pituitary and pointed out that both cell types are present in substantially higher numbers in mature males and females, compared to immature fish. With the newly attained option to prevent cross-contamination when investigating on the effects of GTH administration, we compared the steroidogeneic response (estradiol and 11-Keto testosterone (11-KT) in female and males, respectively) of recombinant stLH, stFSH, and carp pituitary extract in male and female sturgeon gonads at different developmental stages. Finally, we injected commercially available gonadotropin releasing hormones analog (GnRH) to mature females, and found a moderate effect on the development of ovarian follicles. Application of only testosterone (T) resulted in a significant increase in circulating levels of 11-KT whereas the combination of GnRH + T did not affect steroid levels at all. The response pattern for estradiol demonstrated a similar situation. FSH levels showed significant increases when GnRH + T was administered, while no changes were present in

  12. Gonadotropins in the Russian Sturgeon: Their Role in Steroid Secretion and the Effect of Hormonal Treatment on Their Secretion

    PubMed Central

    Yom-Din, Svetlana; Hollander-Cohen, Lian; Aizen, Joseph; Boehm, Benjamin; Shpilman, Michal; Golan, Matan; Hurvitz, Avshalom; Degani, Gad; Levavi-Sivan, Berta

    2016-01-01

    In the reproduction process of male and female fish, pituitary derived gonadotropins (GTHs) play a key role. To be able to specifically investigate certain functions of Luteinizing (LH) and Follicle stimulating hormone (FSH) in Russian sturgeon (Acipenser gueldenstaedtii; st), we produced recombinant variants of the hormones using the yeast Pichia pastoris as a protein production system. We accomplished to create in vitro biologically active heterodimeric glycoproteins consisting of two associated α- and β-subunits in sufficient quantities. Three dimensional modelling of both GTHs was conducted in order to study the differences between the two GTHs. Antibodies were produced against the unique β-subunit of each of the GTHs, in order to be used for immunohistochemical analysis and to develop an ELISA for blood and pituitary hormone quantification. This detection technique revealed the specific localization of the LH and FSH cells in the sturgeon pituitary and pointed out that both cell types are present in substantially higher numbers in mature males and females, compared to immature fish. With the newly attained option to prevent cross-contamination when investigating on the effects of GTH administration, we compared the steroidogeneic response (estradiol and 11-Keto testosterone (11-KT) in female and males, respectively) of recombinant stLH, stFSH, and carp pituitary extract in male and female sturgeon gonads at different developmental stages. Finally, we injected commercially available gonadotropin releasing hormones analog (GnRH) to mature females, and found a moderate effect on the development of ovarian follicles. Application of only testosterone (T) resulted in a significant increase in circulating levels of 11-KT whereas the combination of GnRH + T did not affect steroid levels at all. The response pattern for estradiol demonstrated a similar situation. FSH levels showed significant increases when GnRH + T was administered, while no changes were present in

  13. Gonadotropins in the Russian Sturgeon: Their Role in Steroid Secretion and the Effect of Hormonal Treatment on Their Secretion.

    PubMed

    Yom-Din, Svetlana; Hollander-Cohen, Lian; Aizen, Joseph; Boehm, Benjamin; Shpilman, Michal; Golan, Matan; Hurvitz, Avshalom; Degani, Gad; Levavi-Sivan, Berta

    2016-01-01

    In the reproduction process of male and female fish, pituitary derived gonadotropins (GTHs) play a key role. To be able to specifically investigate certain functions of Luteinizing (LH) and Follicle stimulating hormone (FSH) in Russian sturgeon (Acipenser gueldenstaedtii; st), we produced recombinant variants of the hormones using the yeast Pichia pastoris as a protein production system. We accomplished to create in vitro biologically active heterodimeric glycoproteins consisting of two associated α- and β-subunits in sufficient quantities. Three dimensional modelling of both GTHs was conducted in order to study the differences between the two GTHs. Antibodies were produced against the unique β-subunit of each of the GTHs, in order to be used for immunohistochemical analysis and to develop an ELISA for blood and pituitary hormone quantification. This detection technique revealed the specific localization of the LH and FSH cells in the sturgeon pituitary and pointed out that both cell types are present in substantially higher numbers in mature males and females, compared to immature fish. With the newly attained option to prevent cross-contamination when investigating on the effects of GTH administration, we compared the steroidogeneic response (estradiol and 11-Keto testosterone (11-KT) in female and males, respectively) of recombinant stLH, stFSH, and carp pituitary extract in male and female sturgeon gonads at different developmental stages. Finally, we injected commercially available gonadotropin releasing hormones analog (GnRH) to mature females, and found a moderate effect on the development of ovarian follicles. Application of only testosterone (T) resulted in a significant increase in circulating levels of 11-KT whereas the combination of GnRH + T did not affect steroid levels at all. The response pattern for estradiol demonstrated a similar situation. FSH levels showed significant increases when GnRH + T was administered, while no changes were present in

  14. Intraovarian expression of GnRH-1 and gonadotropin mRNA and protein levels in Siberian hamsters during the estrus cycle and photoperiod induced regression/recrudescence.

    PubMed

    Shahed, Asha; Young, Kelly A

    2011-01-15

    The hypothalamic-pituitary-gonadal (HPG) axis is the key reproductive regulator in vertebrates. While gonadotropin releasing hormone (GnRH), follicle stimulating (FSH), and luteinizing (LH) hormones are primarily produced in the hypothalamus and pituitary, they can be synthesized in the gonads, suggesting an intraovarian GnRH-gonadotropin axis. Because these hormones are critical for follicle maturation and steroidogenesis, we hypothesized that this intraovarian axis may be important in photoperiod-induced ovarian regression/recrudescence in seasonal breeders. Thus, we investigated GnRH-1 and gonadotropin mRNA and protein expression in Siberian hamster ovaries during (1) the estrous cycle; where ovaries from cycling long day hamsters (LD;16L:8D) were collected at proestrus, estrus, diestrus I, and diestrus II and (2) during photoperiod induced regression/recrudescence; where ovaries were collected from hamsters exposed to 14 weeks of LD, short days (SD;8L:16D), or 8 weeks post-transfer to LD after 14 weeks SD (PT). GnRH-1, LHβ, FSHβ, and common α subunit mRNA expression was observed in cycling ovaries. GnRH-1 expression peaked at diestrus I compared to other stages (p < 0.05). FSHβ and LHβ mRNA levels peaked at proestrus and diestrus I (p < 0.05), with no change in the α subunit across the cycle (p > 0.05). SD exposure decreased ovarian mass and plasma estradiol concentrations (p<0.05) and increased GnRH-1, LHβ, FSHβ, and α subunit mRNA expression as compared to LD and, except for LH, compared to PT (p < 0.05). GnRH and gonadotropin protein was also dynamically expressed across the estrous cycle and photoperiod exposure. The presence of cycling intraovarian GnRH-1 and gonadotropin mRNA suggests that these hormones may be locally involved in ovarian maintenance during SD regression and/or could potentially serve to prime ovaries for rapid recrudescence.

  15. Decreased plasma gonadotropin and testosterone levels in arthritic rats: are corticosteroids involved?

    PubMed

    Rivier, C

    1995-05-01

    Infectious and inflammatory diseases are often accompanied by abnormal reproductive functions, and the present working hypothesis is that proteins (called cytokines or interleukins, ILs) released by activated immune cells are at least in part responsible for these neuroendocrine changes. In order to test this hypothesis, we need paradigms of immune pathologies in which concentrations of cytokines are increased, and those of hormones of the hypothalamic-pituitary-gonadal (HPG) axis are blunted. We chose a rodent model of arthritis, adjuvant-induced arthritis (AIA), in which rats show elevated plasma IL-6 and decreased testosterone (T) concentrations. We describe here the first phase of our studies, in which we determined whether gonadotropin release was also altered, whether this change was responsible for the low T levels, and whether elevated corticosterone participated in the decreased activity of the HPG axis.AIA is induced by the intramuscular injection ofMycobacterium butyricum (MBB) into the tail base of the rat, with swelling of the limbs occurring 11-12 days later. We observed significant decreases in LH and FSH secretion of castrated AIA male rats, suggesting that altered gonadotropin output was independent of the gonads. The absence of significant alterations in GnRH gene expression in the hypothalamus of AIA rats, as well as only modest declines in pituitary responsiveness to GnRH, indicate that these mechanisms are not primarily responsible for the blunted gonadotropin concentrations. Intact AIA rats exhibited a dramatic decline in T levels, but no concimitant rise in LH concentrations. The observation that gonadotropin secretion does not increase despite significantly reduced T levels suggests the presence of an unidentified defect within the GnRH neuronal circuitry that prevents the gonadotrophs to respond to decreased steroid feedback. Testicular responsiveness to hCG was significantly blunted in AIA rats, and this decrease was not reversed by acute

  16. Gonadotropin-releasing hormone receptor system: modulatory role in aging and neurodegeneration.

    PubMed

    Wang, Liyun; Chadwick, Wayne; Park, Sung-Soo; Zhou, Yu; Silver, Nathan; Martin, Bronwen; Maudsley, Stuart

    2010-11-01

    Receptors for hormones of the hypothalamic-pituitary-gonadal axis are expressed throughout the brain. Age-related decline in gonadal reproductive hormones cause imbalances of this axis and many hormones in this axis have been functionally linked to neurodegenerative pathophysiology. Gonadotropin-releasing hormone (GnRH) plays a vital role in both central and peripheral reproductive regulation. GnRH has historically been known as a pituitary hormone; however, in the past few years, interest has been raised in GnRH actions at non-pituitary peripheral targets. GnRH ligands and receptors are found throughout the brain where they may act to control multiple higher functions such as learning and memory function and feeding behavior. The actions of GnRH in mammals are mediated by the activation of a unique rhodopsin-like G protein-coupled receptor that does not possess a cytoplasmic carboxyl terminal sequence. Activation of this receptor appears to mediate a wide variety of signaling mechanisms that show diversity in different tissues. Epidemiological support for a role of GnRH in central functions is evidenced by a reduction in neurodegenerative disease after GnRH agonist therapy. It has previously been considered that these effects were not via direct GnRH action in the brain, however recent data has pointed to a direct central action of these ligands outside the pituitary. We have therefore summarized the evidence supporting a central direct role of GnRH ligands and receptors in controlling central nervous physiology and pathophysiology.

  17. Gonadotropin-releasing hormone: gene evolution, expression, and regulation.

    PubMed

    Belsham, Denise D; Lovejoy, David A

    2005-01-01

    The gonadotropin-releasing hormone (GnRH) gene is a superb example of the diverse regulation that is required to maintain the function of an evolutionarily conserved and fundamental gene. Because reproductive capacity is critical to the survival of the species, physiological homeostasis dictates optimal conditions for reproductive success, and any perturbation from this balance may affect GnRH expression. These disturbances may include alterations in signals dictated by stress, nutritional imbalance, body weight, and neurological problems; therefore, changes in other neuroendocrine systems may directly influence the hypothalamic-pituitary-gonadal axis through direct regulation of GnRH. Thus, to maintain optimal reproductive capacity, the regulation of the GnRH gene is tightly constrained by a number of diverse signaling pathways and neuromodulators. In this review, we summarize what is currently known of GnRH gene structure, the location and function of the two isoforms of the GnRH gene, some of the many hormones and neuromodulators found to affect GnRH expression, and the molecular mechanisms responsible for the regulation of the GnRH gene. We also discuss the latest models used to study the transcriptional regulation of the GnRH gene, from cell models to evolving in vivo technologies. Although we have come a long way in the last two decades toward uncovering the intricacies behind the control of the GnRH neuron, there remain vast distances to cover before direct therapeutic manipulation of the GnRH gene to control reproductive competence is possible.

  18. Sociosexual stimuli and gonadotropin-releasing hormone/luteinizing hormone secretion in sheep and goats.

    PubMed

    Hawken, P A R; Martin, G B

    2012-08-01

    Sociosexual stimuli have a profound effect on the physiology of all species. Sheep and goats provide an ideal model to study the impact of sociosexual stimuli on the hypothalamic-pituitary-gonadal axis because we can use the robust changes in the pulsatile secretion of luteinizing hormone as a bioassay of gonadotropin-releasing hormone secretion. We can also correlate these changes with neural activity using the immediate early gene c-fos and in real time using changes in electrical activity in the mediobasal hypothalamus of female goats. In this review, we will update our current understanding of the proven and potential mechanisms and mode of action of the male effect in sheep and goats and then briefly compare our understanding of sociosexual stimuli in ungulate species with the "traditional" definition of a pheromone.

  19. Gonadotropin-releasing hormone agonists in the treatment of girls with central precocious puberty.

    PubMed

    Breyer, P; Haider, A; Pescovitz, O H

    1993-09-01

    The onset of puberty before the age of 8 years in a girl is considered precocious. A child who presents with premature sexual development requires a thorough history, physical examination, and appropriate laboratory evaluation. Making the correct diagnosis is crucial to the selection of the appropriate form of therapy and management. Generally, CPP is the result of premature activation of the hypothalamic-pituitary-gonadal axis and can be successfully managed with long-acting GnRH agonists. In addition, GnRH analogue therapy has been shown to be safe, effective, and reversible. Treatment has resulted in a delay in the progression of secondary sexual development, normalization of the growth velocity, slowing of the rate of bone maturation, and an increase in the predicted final adult height. The GnRH agonists are ineffective in the therapy of gonadotropin-independent precocious puberty.

  20. Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis.

    PubMed

    Ubuka, Takayoshi; Morgan, Kevin; Pawson, Adam J; Osugi, Tomohiro; Chowdhury, Vishwajit S; Minakata, Hiroyuki; Tsutsui, Kazuyoshi; Millar, Robert P; Bentley, George E

    2009-01-01

    The existence of a hypothalamic gonadotropin-inhibiting system has been elusive. A neuropeptide named gonadotropin-inhibitory hormone (GnIH, SIKPSAYLPLRF-NH(2)) which directly inhibits gonadotropin synthesis and release from the pituitary was recently identified in quail hypothalamus. Here we identify GnIH homologs in the human hypothalamus and characterize their distribution and biological activity. GnIH homologs were isolated from the human hypothalamus by immunoaffinity purification, and then identified as MPHSFANLPLRF-NH(2) (human RFRP-1) and VPNLPQRF-NH(2) (human RFRP-3) by mass spectrometry. Immunocytochemistry revealed GnIH-immunoreactive neuronal cell bodies in the dorsomedial region of the hypothalamus with axonal projections to GnRH neurons in the preoptic area as well as to the median eminence. RT-PCR and subsequent DNA sequencing of the PCR products identified human GnIH receptor (GPR147) mRNA expression in the hypothalamus as well as in the pituitary. In situ hybridization further identified the expression of GPR147 mRNA in luteinizing hormone producing cells (gonadotropes). Human RFRP-3 has recently been shown to be a potent inhibitor of gonadotropin secretion in cultured sheep pituitary cells by inhibiting Ca(2+) mobilization. It also directly modulates GnRH neuron firing. The identification of two forms of GnIH (RFRP-1 and RFRP-3) in the human hypothalamus which targets human GnRH neurons and gonadotropes and potently inhibit gonadotropin in sheep models provides a new paradigm for the regulation of hypothalamic-pituitary-gonadal axis in man and a novel means for manipulating reproductive functions.

  1. Molecular Mechanisms Underlying Pituitary Pathogenesis.

    PubMed

    Sapochnik, Melanie; Nieto, Leandro Eduardo; Fuertes, Mariana; Arzt, Eduardo

    2016-04-01

    During the last years, progress has been made on the identification of mechanisms involved in anterior pituitary cell transformation and tumorigenesis. Oncogene activation, tumor suppressor gene inactivation, epigenetic changes, and microRNAs deregulation contribute to the initiation of pituitary tumors. Despite the high prevalence of pituitary adenomas, they are mostly benign, indicating that intrinsic mechanisms may regulate pituitary cell expansion. Senescence is characterized by an irreversible cell cycle arrest and represents an important protective mechanism against malignancy. Pituitary tumor transforming gene (PTTG) is an oncogene involved in early stages of pituitary tumor development, and also triggers a senescence response by activating DNA-damage signaling pathway. Cytokines, as well as many other factors, play an important role in pituitary physiology, affecting not only cell proliferation but also hormone secretion. Special interest is focused on interleukin-6 (IL-6) because its dual function of stimulating pituitary tumor cell growth but inhibiting normal pituitary cells proliferation. It has been demonstrated that IL-6 has a key role in promoting and maintenance of the senescence program in tumors. Senescence, triggered by PTTG activation and mediated by IL-6, may be a mechanism for explaining the benign nature of pituitary tumors.

  2. Gonadotropin and kisspeptin gene expression, but not GnRH, are impaired in cFOS deficient mice.

    PubMed

    Xie, Changchuan; Jonak, Carrie R; Kauffman, Alexander S; Coss, Djurdjica

    2015-08-15

    cFOS is a pleiotropic transcription factor, which binds to the AP1 site in the promoter of target genes. In the pituitary gonadotropes, cFOS mediates induction of FSHβ and GnRH receptor genes. Herein, we analyzed reproductive function in the cFOS-deficient mice to determine its role in vivo. In the pituitary cFOS is necessary for gonadotropin subunit expression, while TSHβ is unaffected. Additionally, cFOS null animals have the same sex-steroid levels, although gametogenesis is impeded. In the brain, cFOS is not necessary for GnRH neuronal migration, axon targeting, cell number, or mRNA levels. Conversely, cFOS nulls, particularly females, have decreased Kiss1 neuron numbers and lower Kiss1 mRNA levels. Collectively, our novel findings suggest that cFOS plays a cell-specific role at multiple levels of the hypothalamic-pituitary-gonadal axis, affecting gonadotropes but not thyrotropes in the pituitary, and kisspeptin neurons but not GnRH neurons in the hypothalamus, thereby contributing to the overall control of reproduction.

  3. Imaging of pituitary pathology.

    PubMed

    Buchfelder, Michael; Schlaffer, Sven

    2014-01-01

    Modern imaging techniques play a vital role in the diagnosis, surveillance, and treatment monitoring of patients with pituitary disease. For its high soft tissue contrast, magnetic resonance (MR) imaging provides detailed information about the localization and extent of a lesion. It is thus, to date, the most important imaging technique for documenting or ruling out structural lesions. It is usually the first and only imaging procedure to be employed in pituitary pathology. While large pituitary adenomas are reliably depicted in standard T1-weighted sequences, small microadenomas, such as in Cushing's disease, may only become visible if repeat studies, sophisticated techniques and high-field scanners are employed. For monitoring treatment effects after surgical procedures, drug applications, or irradiation, follow-up studies with identical parameters should be employed, preferably at the same investigation site. Some space is devoted to intraoperative imaging, which not only allows assessment of how radical tumor resection needs to be during pituitary tumor surgery, but also provides extremely accurate structural data for neuronavigation. Less frequent lesions, such as craniopharyngiomas, meningiomas, germ cell tumors, gliomas, skull base tumors, hypothalamic hamartomas, vascular malformations, inflammatory and developmental lesions and other, even less frequent pathologies should be considered in the differential diagnosis. The particular strength of computed tomography (CT) is the direct depiction of calcification, a weakness of MRI, and the high resolution of bone structures at the skull base. This chapter presents the characteristics of both frequent and less commonly encountered tumoral lesions, with an emphasis on computed tomography and magnetic resonance imaging. PMID:25248586

  4. Three gonadotropin-releasing hormone genes in one organism suggest novel roles for an ancient peptide.

    PubMed Central

    White, S A; Kasten, T L; Bond, C T; Adelman, J P; Fernald, R D

    1995-01-01

    Gonadotropin-releasing hormone (GnRH) is known and named for its essential role in vertebrate reproduction. Release of this decapeptide from neurons in the hypothalamus controls pituitary gonadotropin levels which, in turn, regulate gonadal state. The importance of GnRH is underscored by its widespread expression and conservation across vertebrate taxa: five amino acids are invariant in all nine known forms, whereas two others show only conservative changes. In most eutherian mammals, only one form, expressed in the hypothalamus, is thought to exist, although in a recent report, antibody staining in developing primates suggests an additional form. In contrast, multiple GnRH forms and expression loci have been reported in many non-mammalian vertebrates. However, evidence based on immunological discrimination does not always agree with analysis of gene expression, since GnRH forms encoded by different genes may not be reliably distinguished by antibodies. Here we report the expression of three distinct GnRH genes in a teleost fish brain, including the sequence encoding a novel GnRH preprohormone. Using in situ hybridization, we show that this form is found only in neurons that project to the pituitary and exhibit changes in soma size depending on social and reproductive state. The other two GnRH genes are expressed in other, distinct cell populations. All three genes share the motif of encoding a polypeptide consisting of GnRH and a GnRH-associated peptide. Whereas the GnRH moiety is highly conserved, the GnRH-associated peptides are not, reflecting differential selective pressure on different parts of the gene. GnRH forms expressed in nonhypothalamic regions may serve to coordinate reproductive activities of the animal. Images Fig. 3 PMID:7667296

  5. Estrogen receptor-β in the gonadotropin-releasing hormone neuron.

    PubMed

    Wolfe, Andrew; Wu, Sheng

    2012-01-01

    Estrogen regulation of gonadotropin-releasing hormone (GnRH) neuronal activity plays a crucial role in homeostatic regulation of the hypothalamic-pituitary-gonadal axis. Estrogen also coordinates a complex series of physiological changes culminating with a surge of gonadotropin secretion that triggers ovulation of a developed follicle from the ovary. The coordinated functions of estrogen ensure that the female will elaborate appropriate reproductive behaviors ultimately designed to deliver sperm to the oocyte and to provide a receptive uterine environment for the fertilized embryo. Although the effects of estrogen on GnRH neuronal function have long been proposed to be indirect due to the presumed lack of estrogen receptors in GnRH neurons, the identification of alternative estrogen signaling pathways, including estrogen receptor (ER)β and membrane ERs such as GPR30, has put the focus back on estrogen's effect at the level of the GnRH neuron itself. One candidate to mediate the effects of estrogen is the β isoform of the estrogen receptor. We review the evidence for a role for ERβ-mediated regulation of GnRH neuronal function.

  6. Familial pituitary adenomas.

    PubMed

    Vandeva, S; Vasilev, V; Vroonen, L; Naves, L; Jaffrain-Rea, M-L; Daly, A F; Zacharieva, S; Beckers, A

    2010-12-01

    Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern because of hormonal overproduction or compression symptoms of adjacent structures. Most arise in a sporadic setting with a small percentage developing as a part of familial syndromes such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and the recently described familial isolated pituitary adenomas (FIPA) and MEN-4. While the genetic alterations responsible for the formation of sporadic adenomas remain largely unknown, considerable advances have been made in defining culprit genes in these familial syndromes. Mutations in MEN1 and PRKAR1A genes are found in the majority of MEN1 and CNC patients, respectively. About 15% of FIPA kindreds present with mutations of the aryl hydrocarbon receptor-interacting protein (AIP) gene. Mutations in the CDKN1B gene, encoding p27(Kip)¹ were identified in MEN4 cases. Familial tumours appear to differ from their sporadic counterparts not only in genetic basis but also in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, they are more aggressive and affect patients at younger age, therefore justifying the importance of early diagnosis. In this review, we summarize the genetic and clinical characteristics of these familial pituitary adenomas. PMID:20961530

  7. Evaluation of gonadotropin responses to synthetic gonadotropin-releasing hormone in girls with idiopathic hypopituitarism.

    PubMed

    Foster, C M; Hopwood, N J; Beitins, I Z; Mendes, T M; Kletter, G B; Kelch, R P

    1992-10-01

    We hypothesized that prepubertal girls with gonadotropin deficiency would produce less follicle-stimulating hormone (FSH) in response to synthetic gonadotropin-releasing hormone (GnRH) than would gonadotropin-sufficient children. To test this hypothesis, we performed 103 GnRH tests serially in 21 children who had idiopathic hypopituitarism with growth hormone deficiency. We tried to predict whether puberty would occur in the 17 girls with bone ages of 8 years or less. Of these 17 girls, 4 failed to have spontaneous secondary sexual characteristics by age 16 1/2 years, and 12 had spontaneous complete pubertal development. One girl had incomplete pubertal maturation with partial gonadotropin deficiency; her results were combined with those of the girls who had no spontaneous pubertal development. With increasing bone age, the girls with complete pubertal development had a decrease in the increment of FSH released in response to GnRH, although basal gonadotropin concentrations did not change. For GnRH tests performed at bone ages of 8 years or less, basal luteinizing hormone (LH) values did not differ between girls with complete puberty and those with absent or incomplete puberty. However, basal FSH and the incremental response of LH and FSH to GnRH were greater in those with complete puberty. Only two girls with prepubertal bone ages at the time of testing, who subsequently had complete puberty, had incremental FSH responses to GnRH that were less than 5 IU/L. Individual incremental LH responses to GnRH did not discriminate well between groups. None of the girls with adrenocorticotropic hormone deficiency, either originally or subsequently, had spontaneous puberty, but 4 of 12 girls with thyrotropin deficiency, either originally or subsequently, had complete puberty. We conclude that a significant increase in GnRH-stimulated FSH suggests that spontaneous pubertal development will occur in girls with idiopathic hypopituitarism. However, a low FSH response to GnRH may

  8. Marked suppression of gonadotropins and testosterone by an antagonist analog of gonadotropin-releasing hormone in men.

    PubMed

    Salameh, W; Bhasin, S; Steiner, B; McAdams, L A; Peterson, M; Swerdloff, R

    1991-01-01

    To study the dose response characteristics of a gonadotropin-releasing hormone (GnRH) antagonist ([Ac-D2-Nal1,D4-Cl-Phe2,D3-Pal3,Arg5,dGlu6 (AA), d-Ala10] GnRH; Nal-Glu), 1.5 or 5.0 mg of Nal-Glu were administered to two groups of five normal men by daily subcutaneous injection for 21 days. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) were determined on multiple occasions before, during, and after the antagonist treatment. Five milligrams Nal-Glu markedly suppressed mean serum immunoreactive LH to a mean of 1.5 +/- 0.4 IU/L (+/- SEM), immunoreactive FSH to the limit of assay detection (1 IU/L), and lowered basal mean serum T to castrate range (less than 2 nmol/L). Serum bioactive LH levels also showed a marked decrease in the 5.0-mg group similar to that seen in immunoreactive LH levels. Amplitude of immunoreactive LH pulses was markedly reduced in the 5.0-mg group on day 21. A 1.5-mg dose of Nal-Glu transiently suppressed serum immunoreactive LH levels on day 1. There was a subsequent escape on the rest of the days sampled. Serum immunoreactive FSH levels were not significantly changed over the 21-day treatment period. Serum T levels were transiently suppressed only on day 1 paralleling immunoreactive LH suppression. No adverse systemic side effects occurred. Thus, the 5.0-mg dose of this GnRH antagonist provides a pharmacological means of markedly suppressing the hypothalamic-pituitary-gonadal axis and, therefore, has potential as a male contraceptive.

  9. Evidence for a defect in pituitary secretion of luteinizing hormone in chronic alcoholic men.

    PubMed

    Van Thiel, D H; Lester, R; Vaitukaitis, J

    1978-09-01

    To characterize the defect in the hypothalamic-pituitary-gonadal axis of alcoholic men, acute and chronic LRF responses were evaluated in 22 chronic alcoholic men with varying degrees of biochemically and histologically confirmed liver disease. In addition, acute LRF responses in 14 normal men, before and at the end of 72 h of administration of 2 ml/kg/day 95% ethanol, were evaluated. The alcoholics hd significantly reduced basal testosterone and elevated gonadotropin levels (both FSH and LH) compared to the normal volunteers (P less than 0.02). Serum concentrations of estradiol and PRL did not differ between alcoholics and normal volunteers. A 100-micrograms bolus of LRF resulted in a 3-fold increase of LH in alcoholic men as compared to a 6-fold increase of serum LH in normal volunteers. No significant difference in the LRF-induced FSH responses was observed. When the response of normal volunteers to LRF before and after ethanol administration was evaluated, basal levels of both gonadotropins were increased after alcohol administration and a reduced LRF-induced LH response was observed. Based upon these results, we conclude that: 1) the central hypothalamic-pituitary defect known to exist for LH secretion is in part due to inadequate pituitary secretion and 2) acute alcohol ingestion in normal men suppresses the LRF-induced LH but not the FSH response.

  10. Enhanced activity of the pituitary-gonadal axis in premature human infants.

    PubMed

    Tapanainen, J; Koivisto, M; Vihko, R; Huhtaniemi, I

    1981-02-01

    The postnatal pituitary-gonadal function of fullterm and premature boys and girls (mean gestational age, 40 and 32 weeks, respectively) was studied by measurements of serum FSH, LH, PRL, and testosterone (T) between 0-25 weeks of postnatal age. During the first 10 postnatal weeks, serum FSH in premature girls reached 10-20 times higher levels than in fullterm girls (mean at 1-5 weeks, 63 and 3.9 mIU/ml, respectively; P < 1.001). During the same time, serum LH levels were 3-4 times higher in premature (12-17 mIU/ml) than in fullterm girls (3.8-4.7 mIU/ml; P < 0.01). In contrast, no difference in serum gonadotropin levels were observed between premature and fullterm boys. Serum T in premature boys (mean, 2.95 ng/ml) reached a significantly higher level (P < 0.01) than in fullterm boys (1.45 ng/ml) from 11-15 weeks of age. The results emphasize the importance of the last weeks of gestation for the functional maturation of the fetal hypothalamic-pituitary-gonadal axis. Interruption of this maturational process by premature birth results in enhanced pituitary gonadotropin production in girls and increased testicular T production in boys.

  11. The Regulation and Function of Fibroblast Growth Factor 8 and Its Function during Gonadotropin-Releasing Hormone Neuron Development.

    PubMed

    Chung, Wilson C J; Linscott, Megan L; Rodriguez, Karla M; Stewart, Courtney E

    2016-01-01

    Over the last few years, numerous studies solidified the hypothesis that fibroblast growth factor (FGF) signaling regulates neuroendocrine progenitor cell proliferation, fate specification, and cell survival and, therefore, is critical for the regulation and maintenance of homeostasis of the body. One important example that underscores the involvement of FGF signaling during neuroendocrine cell development is gonadotropin-releasing hormone (GnRH) neuron ontogenesis. Indeed, transgenic mice with reduced olfactory placode (OP) Fgf8 expression do not have GnRH neurons. This observation indicates the requirement of FGF8 signaling for the emergence of the GnRH neuronal system in the embryonic OP, the putative birth place of GnRH neurons. Mammalian reproductive success depends on the presence of GnRH neurons to stimulate gonadotropin secretion from the anterior pituitary, which activates gonadal steroidogenesis and gametogenesis. Together, these observations are critical for understanding the function of GnRH neurons and their control of the hypothalamus-pituitary-gonadal (HPG) axis to maintain fertility. Taken together, these studies illustrate that GnRH neuron emergence and hence HPG function is vulnerable to genomic and molecular signals that abnormally modify Fgf8 expression in the developing mouse OP. In this short review, we focus on research that is aimed at unraveling how androgen, all-trans retinoic acid, and how epigenetic factors modify control mouse OP Fgf8 transcription in the context of GnRH neuronal development and mammalian reproductive success. PMID:27656162

  12. Emergence of an Ancestral Glycoprotein Hormone in the Pituitary of the Sea Lamprey, a Basal Vertebrate.

    PubMed

    Sower, Stacia A; Decatur, Wayne A; Hausken, Krist N; Marquis, Timothy J; Barton, Shannon L; Gargan, James; Freamat, Mihael; Wilmot, Michael; Hollander, Lian; Hall, Jeffrey A; Nozaki, Masumi; Shpilman, Michal; Levavi-Sivan, Berta

    2015-08-01

    The gnathostome (jawed vertebrates) classical pituitary glycoprotein hormones, FSH, LH, and TSH, consist of a common α-subunit (GpA1) and unique β-subunits (Gpβ1, -2, and -3), whereas a recently identified pituitary glycoprotein hormone, thyrostimulin, consists of GpA2 and GpB5. This paper reports the identification, expression, and function of an ancestral, nonclassical, pituitary heterodimeric glycoprotein hormone (GpH) consisting of the thyrostimulin A2 subunit with the classical β-subunit in the sea lamprey, Petromyzon marinus, a jawless basal vertebrate. Lamprey (l) GpA2, and lGpHβ were shown to form a heterodimer by coimmunoprecipitation of lGpA2 with FLAG-tagged lGpHβ after the overexpression in transiently transfected COS7 cells using a bipromoter vector. Dual-label fluorescent in situ hybridization and immunohistochemistry showed the coexpression of individual subunits in the proximal pars distalis of the pituitary. GnRH-III (1μΜ) significantly increased the expression of lGpHβ and lGpA2 in in vitro pituitary culture. Recombinant lamprey GpH was constructed by tethering the N terminal of lGpA2 to the C terminal of lGpHβ with a linker region composed of six histidine residues followed by three glycine-serine repeats. This recombinant lamprey GpH activated the lamprey glycoprotein hormone receptor I as measured by increased cAMP/luciferase activity. These data are the first to demonstrate a functional, unique glycoprotein heterodimer that is not found in any other vertebrate. These data suggest an intermediate stage of the structure-function of the gonadotropin/thyroid-stimulating hormone in a basal vertebrate, leading to the emergence of the highly specialized gonadotropin hormones and thyroid stimulating hormones in gnathostomes.

  13. Hypothalamic-pituitary-gonadal dysfunction in men using cimetidine.

    PubMed

    Van Thiel, D H; Gavaler, J S; Smith, W I; Paul, G

    1979-05-01

    We studied the effect of cimetidine therapy (1200 mg per day by mouth for nine weeks) on the hypothalamic-pituitary-gonadal axis of seven men. There was a 43 per cent mean reduction in sperm count after therapy. The luteinizing hormone response to luteinizing hormone releasing factor was also reduced, and a statistically significnat rise in plasma testosterone occurred, although it was less than that before therapy. Gonadotropin responses to provocative clomiphene stimulation were inadequate when compared with those of controls. Cimetidine did not affect the responses of thyroid-stimulating hormone, prolactin, growth hormone and thyroxine to thyrotropin releasing factor. Caution is advisable in administration of cimetidine for prolonged periods to young men.

  14. Hypothalamic-pituitary-gonadotropic function in girls with premature thelarche.

    PubMed

    Pasquino, A M; Piccolo, F; Scalamandre, A; Malvaso, M; Ortolani, R; Boscherini, B

    1980-12-01

    Hypothalamic-pituitary-gonadotropic activity was investigated in 9 girls with premature thelarche, and compared with that in 9 healthy girls and 6 girls with true precocious puberty. The gonadotropin stimulation test with luteinising hormone-releasing hormone was used. Girls with premature thelarche showed luteinising hormone response resembling that of normal girls, and follicle-stimulating hormone (FSH) response quite similar to that of girls with precocious puberty. This suggests that in premature thelarche there is a partial activation of the diencephalic-hypophyseal-gonadal axis, which affects FSH only. Premature thelarche therefore, should be considered as one of the disorders due to altered sensitivity of the hypothalamic receptors which regulate sex maturation.

  15. Optimisation of an oviposition protocol employing human chorionic and pregnant mare serum gonadotropins in the Barred Frog Mixophyes fasciolatus (Myobatrachidae)

    PubMed Central

    2012-01-01

    Background Protocols for the hormonal induction of ovulation and oviposition are essential tools for managing threatened amphibians with assisted reproduction, but responses vary greatly between species and even broad taxon groups. Consequently, it is necessary to assess effectiveness of such protocols in representative species when new taxa become targets for induction. The threatened genus Mixophyes (family Myobatrachidae) has amongst the highest proportion of endangered species of all the Australian amphibians. This study developed and optimised the induction of oviposition in a non-threatened member of this taxon, the great barred frog (Mixophyes fasciolatus). Methods Gravid female M. fasciolatus were induced to oviposit on one or more occasions by administration of human chorionic gonadotropin (hCG) with or without priming with pregnant mare serum gonadotropin (PMSG). Treatments involved variations in hormone doses and combinations (administered via injection into the dorsal lymph sacs), and timing of administration. Pituitary homogenates from an unrelated bufonid species (Rhinella marina) were also examined with hCG. Results When injected alone, hCG (900 to 1400 IU) induced oviposition. However, priming with two time dependent doses of PMSG (50 IU, 25 IU) increased responses, with lower doses of hCG (200 IU). Priming increased response rates in females from around 30% (hCG alone) to more than 50% (p = 0.035), and up to 67%. Increasing the interval between the first PMSG dose and first hCG dose from 3 to 6 days also produced significant improvement (p<0.001). Heterologous pituitary extracts administered with hCG were no more effective than hCG alone (p = 0.628). Conclusions This study found that M. fasciolatus is amongst the few amphibian species (including Xenopus (Silurana) and some bufonids) that respond well to the induction of ovulation utilising mammalian gonadotropins (hCG). The optimal protocol for M. fasciolatus involved two priming doses of

  16. Adaptive interactions between cytokines and the hypothalamic-pituitary-gonadal axis.

    PubMed

    Cannon, J G

    1998-09-29

    Circulating and tissue concentrations of pyrogenic cytokines, especially interleukin (IL)-1 beta, vary temporally through the menstrual cycle and pregnancy. The secretion of these cytokines in vitro by isolated human mononuclear cells is significantly influenced by exogenous gonadal steroids and gonadotropins. Reciprocally, cytokines influence gonadotropin secretion by the pituitary and steroidogenesis by the ovaries and testes. Several hypotheses have been advanced regarding the adaptive value of these interrelationships. Cytokine-induced synthesis of proteolytic enzymes and extracellular matrix proteins may be important for the tissue remodeling necessary for ovulation, implantation, and delivery. Tolerance of the fetal allograft may require downregulation of cytotoxic effector cells and reciprocal upregulation of humoral and nonspecific host defenses. The inhibitory influence of IL-1 beta on the luteinizing hormone surge may prevent inopportune conception, and the abortive influences of tumor necrosis factor-alpha and gamma interferon may terminate pregnancy during periods of infection.

  17. Participation of endogenous opiates in regulation of the hypothalamic-pituitary-testicular axis in normal men.

    PubMed

    Delitala, G; Giusti, M; Mazzocchi, G; Granziera, L; Tarditi, W; Giordano, G

    1983-12-01

    To assess the influence of endogenous opioids on human gonadotropin secretion, integrated concentrations of gonadotropins during 24-h naloxone infusion (2.08 mg/h) were examined in a group of six normal men. Naloxone significantly stimulated LH secretion in all subjects, whereas serum FSH levels were similar during both saline and naloxone infusion. Serum testosterone, dihydrotestosterone, and 17 alpha-hydroxyprogesterone levels increased during the infusion of naloxone, but the delta 4-androstenedione concentration was not modified. The frequency and amplitude of LH secretory episodes were clearly increased when an equal amount of the drug was given and LH concentrations were measured every 15 min for 6 h. The results suggest the endogenous opioids inhibit the hypothalamic-pituitary-gonadal axis in normal men.

  18. Hypothalamic-pituitary gonadal axis in boys with primary hypothyroidism and macroorchidism.

    PubMed

    Castro-Magaña, M; Angulo, M; Cañas, A; Sharp, A; Fuentes, B

    1988-03-01

    Nine of 15 boys with severe long-standing primary hypothyroidism were found to have macroorchidism. All 15 patients had elevated thyroid-stimulating hormone levels. However, only those patients with testicular enlargement had striking elevations of serum prolactin and gonadotropin values. The response to gonadotropin-releasing hormone in our patients was blunted, in contradistinction to that of children with true precocious puberty. In spite of the elevated levels of luteinizing hormone, the serum testosterone levels were in the prepubertal range, explaining the lack of peripheral manifestations of androgenic effect. Improvement of testosterone secretion followed decreasing prolactin levels with bromocriptine administration, suggesting an inhibitory effect of prolactin on luteinizing hormone action at the Leydig cell. We conclude that testicular enlargement is the result of continuous follicle-stimulating hormone stimulation and that the term "true precocious puberty" is not appropriate in children with hypothyroidism and macroorchidism unless the hypothalamic-pituitary gonadal axis is shown to be at the pubertal stage.

  19. Gene Therapy for Pituitary Tumors

    PubMed Central

    Seilicovich, Adriana; Pisera, Daniel; Sciascia, Sandra A.; Candolfi, Marianela; Puntel, Mariana; Xiong, Weidong; Jaita, Gabriela; Castro, Maria G.

    2009-01-01

    Pituitary tumors are the most common primary intracranial neoplasms. Although most pituitary tumors are considered typically benign, others can cause severe and progressive disease. The principal aims of pituitary tumor treatment are the elimination or reduction of the tumor mass, normalization of hormone secretion and preservation of remaining pituitary function. In spite of major advances in the therapy of pituitary tumors, for some of the most difficult tumors, current therapies that include medical, surgical and radiotherapeutic methods are often unsatisfactory and there is a need to develop new treatment strategies. Gene therapy, which uses nucleic acids as drugs, has emerged as an attractive therapeutic option for the treatment of pituitary tumors that do not respond to classical treatment strategies if the patients become intolerant to the therapy. The development of animal models for pituitary tumors and hormone hypersecretion has proven to be critical for the implementation of novel treatment strategies and gene therapy approaches. Preclinical trials using several gene therapy approaches for the treatment of anterior pituitary diseases have been successfully implemented. Several issues need to be addressed before clinical implementation becomes a reality, including the development of more effective and safer viral vectors, uncovering novel therapeutic targets and development of targeted expression of therapeutic transgenes. With the development of efficient gene delivery vectors allowing long-term transgene expression with minimal toxicity, gene therapy will become one of the most promising approaches for treating pituitary adenomas. PMID:16457646

  20. The hypothalamic-pituitary axis in men and women with chronic kidney disease.

    PubMed

    Holley, Jean L

    2004-10-01

    Although the precise abnormalities that lead to failure of the hypothalamic-pituitary-gonadal axis in men and women with chronic kidney disease (CKD) and end-stage renal disease (ESRD) remains undefined, evidence exists for defects in both the hypothalamus and the pituitary. The lack of appropriate cyclic release of gonadotropin-releasing hormone (GnRH) by the hypothalamus leads to loss of normal pulsatile luteinizing hormone (LH) release by the pituitary, which results in impaired ovulation in women and reduced testosterone and sperm production in men. The cause of impaired cyclic release of GnRH is unclear, but hyperprolactinemia, elevated endorphins, and high levels of GnRH and LH caused by reduced clearance may contribute. Perturbations of the hypothalamic-pituitary-gonadaotropin axis in CKD lead to high rates of infertility, dysfunctional uterine bleeding, and impaired puberty in children. Only through additional study of the complex effects of CKD on the hypothalamic-pituitary-gonadal axis will the precise abnormalities in hormonal control of reproduction be explained.

  1. Dissecting the Roles of Gonadotropin-Inhibitory Hormone in Mammals: Studies Using Pharmacological Tools and Genetically Modified Mouse Models.

    PubMed

    Leon, Silvia; Tena-Sempere, Manuel

    2015-01-01

    Reproduction is essential for perpetuation of the species and, hence, is controlled by a sophisticated network of regulatory factors of central and peripheral origin that integrate at the hypothalamic-pituitary-gonadal (HPG) axis. Among the central regulators of reproduction, kisspeptins, as major stimulatory drivers of gonadotropin-releasing hormone (GnRH) neurosecretion, have drawn considerable interest in the last decade. However, the dynamic, if not cyclic (in the female), nature of reproductive function and the potency of kisspeptins and other stimulatory signals of the HPG axis make tenable the existence of counterbalance inhibitory mechanisms, which may keep stimulation at check and would allow adaptation of reproductive maturation and function to different endogenous and environmental conditions. In this context, discovery of the gonadotropin-inhibitory hormone (GnIH) in birds, and its mammalian homolog, RFRP, opened up the exciting possibility that this inhibitory signal might operate centrally to suppress, directly or indirectly, GnRH/gonadotropin secretion, thus reciprocally cooperating with other stimulatory inputs in the dynamic regulation of the reproductive hypothalamic-pituitary unit. After more than 15 years of active research, the role of GnIH/RFRP in the control of the HPG axis has been documented in different species. Yet, important aspects of the physiology of this system, especially regarding its relative importance and actual roles in the control of key facets of reproductive function, remain controversial. In the present work, we aim to provide a critical review of recent developments in this area, with special attention to studies in rodent models, using pharmacological tools and functional genomics. In doing so, we intend to endow the reader with an updated view of what is known (and what is not known) about the physiological role of GnIH/RFRP signaling in the control of mammalian reproduction.

  2. The interaction of castration and photoperiod in the regulation of hypophyseal and serum gonadotropin levels in male golden hamsters.

    PubMed

    Turek, F W; Elliott, J A; Alvis, J D; Menaker, M

    1975-04-01

    Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in intact and castrate adult male hamsters maintained on photostimulatory (LD 14:10) and non-photostimulatory (LD 6:18) light:dark cycles to assess the interaction of photic stimuli and gonadal hormones on pituitary gonadotropin release. Immunoreactive serum LH and FSH levels increased 1.6- and 8-fold respectively, within 3 days after photostimulated hamsters were castrated. In contrast, castration failed to alter serum LH concentration and had only a slight, if any, effect on FSH concentration in hamsters exposed to nonstimulatory photoperiods that induced testicular atrophy. In a second experiment, male hamsters previously maintained on LD 14:10 were castrated, transferred with intact animals to LD 6:18, and killed periodically over 60 days. In intact animals, pituitary content and serum levels of LH and FSH declined substantially during exposure to the non-stimulatory LD 6:18 cycle. In castrated animals, serum LH and FSH levels which had increased 2- and 8-fold in response to the castration eventually declined to about the levels found in the intact initial control animals. In contrast to serum gonadotropins, the increased hypophyseal content of LH and FSH following castration was not reduced during exposure to LD 6:18. Exposure to nonstimulatory photoperiods does not alter the increased hypophyseal LH and FSH content observed after castration. However, our results indicate that exposure to short days renders the hypothalamic-hypophyseal neuroendocrine system governing gonadotropin release relatively insensitive to gonadal steroid hormone feedback. PMID:1120474

  3. Anti-Müllerian hormone: a new actor of sexual dimorphism in pituitary gonadotrope activity before puberty

    PubMed Central

    Garrel, Ghislaine; Racine, Chrystèle; L’Hôte, David; Denoyelle, Chantal; Guigon, Céline J.; di Clemente, Nathalie; Cohen-Tannoudji, Joëlle

    2016-01-01

    Anti-Müllerian hormone (AMH) contributes to male sexual differentiation and acts on gonads of both sexes. Identification of AMH receptivity in both pituitary and brain has led to the intriguing idea that AMH participates to the hypothalamic-pituitary control of reproduction, however in vivo experimental evidence is still lacking. We show that AMH stimulates secretion and pituitary gene expression of the gonadotropin FSH in vivo in rats. AMH action is sex-dependent, being restricted to females and occurring before puberty. Accordingly, we report higher levels of pituitary AMH receptor transcripts in immature females. We show that AMH is functionally coupled to the Smad pathway in LβT2 gonadotrope cells and dose-dependently increases Fshb transcript levels. Furthermore, AMH was shown to establish complex interrelations with canonical FSH regulators as it cooperates with activin to induce Fshb expression whereas it reduces BMP2 action. We report that GnRH interferes with AMH by decreasing AMH receptivity in vivo in females. Moreover, AMH specifically regulates FSH and not LH, indicating that AMH is a factor contributing to the differential regulation of gonadotropins. Overall, our study uncovers a new role for AMH in regulating gonadotrope function and suggests that AMH participates in the postnatal elevation of FSH secretion in females. PMID:27030385

  4. Atrazine disrupts the hypothalamic control of pituitary-ovarian function.

    PubMed

    Cooper, R L; Stoker, T E; Tyrey, L; Goldman, J M; McElroy, W K

    2000-02-01

    The chloro-S-triazine herbicides (i.e., atrazine, simazine, cyanazine) constitute the largest group of herbicides sold in the United States. Despite their extensive usage, relatively little is known about the possible human-health effects and mechanism(s) of action of these compounds. Previous studies in our laboratory have shown that the chlorotriazines disrupt the hormonal control of ovarian cycles. Results from these studies led us to hypothesize that these herbicides disrupt endocrine function primarily through their action on the central nervous system. To evaluate this hypothesis, we examined the estrogen-induced surges of luteinizing hormone (LH) and prolactin in ovariectomized Sprague-Dawley (SD) and Long-Evans hooded (LE) rats treated with atrazine (50-300 mg/kg/day, by gavage) for 1, 3, or 21 days. One dose of atrazine (300 mg/kg) suppressed the LH and prolactin surge in ovariectomized LE, but not SD female rats. Atrazine (300 mg/kg) administered to intact LE females on the day of vaginal proestrus was without effect on ovulation but did induce a pseudopregnancy in 7 of 9 females. Three daily doses of atrazine suppressed the estrogen-induced LH and prolactin surges in ovariectomized LE females in a dose-dependent manner, but this same treatment was without effect on serum LH and prolactin in SD females. The estrogen-induced surges of both pituitary hormones were suppressed by atrazine (75-300 mg/kg/day) in a dose-dependent manner in females of both strains evaluated after 21 days of treatment. Three experiments were then performed to determine whether the brain, pituitary, or both organs were the target sites for the chlorotriazines. These included examination of the ability of (1) the pituitary lactotrophs to secrete prolactin, using hypophyosectomized females bearing pituitary autotransplants (ectopic pituitaries); (2) the synthetic gonadotropin-releasing hormone (GnRH) to induce LH secretion in females treated with high concentrations of atrazine for 3

  5. Intrasellar pituitary mucocele: diagnostic dilemma.

    PubMed

    Tang, Ing Ping; Chai, Chun Kian; Kumar, Gnana; Prepageran, Narayanan; Waran, Vicknes

    2014-06-01

    Isolated intrasellar pituitary mucocele following transsphenoidal sinus surgery is extremely rare. The clinical features resemble a pituitary tumor, therefore careful radiological interpretation is crucial to reach the correct diagnosis. We report a case of intrasellar mucocele who had transsphenoidal sinus surgery performed 15 years prior.

  6. Acromegaloidism Associated with Pituitary Incidentaloma.

    PubMed

    Narendra, B S; Dharmalingam, M; Kalra, P

    2015-06-01

    Acromegaloidism with pituitary microadenoma has not been previously reported. We present a case of a 28-year old male with typical features of acromegaly for 11 years.with a pituitary tumor. He had characteristic acromegaloid facial features, clubbing of hands and feet, enlargement of fingers and toes. The natural history of the disease is reviewed and the differential diagnosis is discussed. PMID:26710410

  7. Effects of ethanol on superovulation in the immature rat following pregnant mare's serum gonadotropin (PMSG) or PMSG and human chorionic gonadotropin treatment.

    PubMed

    Bo, W J; Krueger, W A; Rudeen, P K

    1983-05-01

    We sought to determine whether superovulation could occur in immature rats on a 5% ethanol diet and treated with pregnant mare's serum gonadotropin (PMSG) alone or with human chorionic gonadotropin (hCG). Holtzman female rats were divided into five groups at 20 days of age. Six rats (Group I) were killed at that age. Ten rats (Group II) were placed on an ad libitum laboratory chow diet and killed on Day 33. Twenty-four rats (Group III) were placed on an ad libitum laboratory chow diet. Twenty-four rats (Group IV) were placed on 5% ethanol liquid diet, while 24 rats in Group V were pair-fed with the animals in Group IV. At 30 days of age, 12 rats from each Group, III, IV, and V, received 25 IU of PMSG s.c. and were killed 74-76 h later. The remaining 12 rats from each Group, III, IV and V, received 25 IU of PMSG and 54-56 h later received 10 IU of hCG and were killed 20 h later. Ovulation occurred in all the rats of Groups III and V that received PMSG alone or with hCG. In the ethanol-treated rats that received PMSG alone, 75% ovulated, while 92% ovulated that received PMSG and hCG. The number of ova shed in the ethanol-PMSG-treated rats was significantly less than in the ethanol-PMSG-hCG-treated animals and in the controls. The uterine weights and morphology of the animals in Group IV were similar to those in Groups III and V. The study indicates that ethanol does not have a direct gonadotoxic effect on the ovary but indicates that ethanol has an effect on the hypothalamus and/or the pituitary, thereby disrupting the synthesis and/or release of luteinizing hormone releasing hormone (LHRH) or luteinizing hormone (LH). PMID:6860748

  8. Effects of gonadotropin inhibitory hormone or gonadotropin-releasing hormone on reproduction-related genes in the protandrous cinnamon clownfish, Amphiprion melanopus.

    PubMed

    Choi, Young Jae; Kim, Na Na; Habibi, Hamid R; Choi, Cheol Young

    2016-09-01

    Hypothalamic peptide neurohormones such as gonadotropin-releasing hormones (GnRHs) and gonadotropin-inhibitory hormone (GnIH) play pivotal roles in the control of reproduction and gonadal maturation in teleost fish. To study the effects of GnIH on fish reproduction, we investigated the influence of seabream GnRH (sbGnRH) and GnIH (both alone and in combination) on levels of reproductive genes (GnIH, GnIH-receptor [GnIH-R], melatonin receptor [MT3], sbGnRH, and gonadotropic hormones [GTHs]) during different stages of gonadal maturation in male, female, and immature cinnamon clownfish, Amphiprion melanopus. The results showed that the expression levels of GnIH, GnIH-R, and MT3 genes increased after the GnIH injection, but decreased after the sbGnRH injection. In addition, these gene expression levels gradually lowered after GnIH3 and sbGnRH combination treatment, as compared to the MT3 mRNA levels of GnIH treatment alone. However, the expression levels of the HPG (hypothalamus-pituitary-gonad) axis genes (sbGnRH and GTHs) decreased after the GnIH injection, but increased after the sbGnRH injection. In all cinnamon clownfish groups, HPG axis gene mRNA levels gradually decreased after mixed GnIH3 and sbGnRH treatment, compared to GnIH treatment alone. The present study provides novel information on the effects of GnIH and strongly supports the hypothesis that GnIH plays an important role in the negative regulation of the HPG axis in the protandrous cinnamon clownfish. PMID:27288637

  9. Castration differentially regulates nitric oxide synthase in the hypothalamus and pituitary.

    PubMed

    Shi, Q; LaPaglia, N; Emanuele, N V; Emanuele, M A

    1998-02-01

    Mammalian reproductive function is under control of the integrated hypothalamic-pituitary-gonadal (HPG) axis. Castration in male rats has been utilized as an effective tool to investigate hormonal interactions in the mammalian HPG axis. Recently, nitric oxide (NO) has been suggested to play a role in HPG hormonal regulation. In order to gain further insight into the function of the NO-NOS system in reproductive neuroendocrine control, particularly in the gonadal feedback regulation of the hypothalamic-pituitary unit, we examined steady state levels of nNOS mRNA, nNOS protein, and the important physiological index, NOS enzyme activity, of the intrinsic NOergic system in both hypothalamus and pituitary in castrated male rats and their sham-operated counterparts one week after surgery. In the pituitary, we found a significant four-fold increase in nNOS mRNA, p < 0.0003 compared to sham. Castration also resulted in a four-fold rise in pituitary nNOS protein, p < 0.02 compared to sham. Pituitary NOS enzyme activity was stimulated 2 fold, p < 0.003 after castration. In the hypothalamus, conversely, we observed no significant castration-modulated difference in either nNOS mRNA, nNOS protein or NOS enzyme activity. Thus, it appears that the hypothalamic NO-NOS system is either not required for hypothalamic adaptations to castration, although important in the release of LHRH under normal physiological conditions, or alternatively, the hypothalamus may become more sensitive to the effects of NO in the castrated state. In the pituitary, NO may attenuate the gonadotropin response to castration as a local balancing mediator.

  10. Gonadotropin-associated psychosis in perimenstrual behavior disorder.

    PubMed

    Constant, M; Abrams, C A; Chasalow, F I

    1993-01-01

    Sexually provocative and violent behavior have been reported as a result of excess androgens. We now report a temporal relationship between increased gonadotropin levels and behavioral changes in two adolescent girls who presented with a history of aggressive and bizarre sexual behavior coincident with the onset of menarche. We evaluated the possibility of a cyclical hormonal cause with daily measurements of gonadotropins, androgens and estradiol levels and correlated the results with periodic reports on the girls' behavior. We concluded that a correlation exists between periods of extremely violent and sexually provocative behavior and peaks of gonadotropin hormone secretion, even though androgen levels were normal. Treatment with medroxyprogesterone acetate (Depo-Provera) in one case and with leuprolide acetate (Lupron-Depot) in the other suppressed gonadotropin levels, and behavior improved markedly. Thus, the behavioral changes (or psychosis) seen in these girls might have been induced by increased levels of gonadotropins.

  11. Gonadotropin surge-inhibiting/attenuating factors: a review of current evidence, potential applications, and future directions for research.

    PubMed

    Vega, Mario G; Zarek, Shvetha M; Bhagwat, Medha; Segars, James H

    2015-01-01

    Animal studies in the 1980s suggested the existence of an ovarian hormone, termed gonadotropin surge-inhibiting/attenuating factor (GnSIF/AF), that modulates pituitary secretion of luteinizing hormone (LH). Given the importance of identifying regulatory factors of the hypothalamic-pituitary-ovarian axis and the accumulating data suggesting its existence, we conducted a comprehensive literature search using PubMed, Web of Science, Scopus, and Embase to identify articles related to GnSIF/AF. The search generated 161 publications, of which 97 were included in this study. Several attempts have been made to identify and characterize this hormone and several candidates have been identified, but the protein sequences of these putative GnSIF/AF factors differ widely from one study to another. In addition, while the RF-amide RFRP-3 is known foremost as a neuropeptide, some research supports an ovarian origin for this non-steroidal hormone, thereby suggesting a role for RFRP-3 either as a co-modulator of GnSIF/AF or as a gonadotropin-inhibiting factor in the hypothalamus (GnIH). Discovery of the KNDy neurons that modulate GnRH secretion, on the other hand, further encourages the search for substance(s) that modulate their activity and that indirectly affect LH secretion and the hypothalamic-pituitary-ovarian axis. While it has remained an elusive hormone, GnSIF/AF holds many potential applications for contraception, in vitro fertilization, and/or cancer as well as for understanding polycystic ovary syndrome, metabolic diseases, and/or pubertal development. In this review, we rigorously examine the available evidence regarding the existence of GnSIF/AF, previous attempts at its identification, limitations to its discovery, future directions of research, and potential clinical applications.

  12. Molecular cloning and tissue-specific expression of a gonadotropin-releasing hormone receptor in the Japanese eel.

    PubMed

    Okubo, K; Suetake, H; Usami, T; Aida, K

    2000-08-01

    Gonadotropin-releasing hormone (GnRH) is a key regulatory neuropeptide involved in the control of reproduction in vertebrates. In the Japanese eel, one of the most primitive teleost species, two molecular forms of GnRH, mammalian-type GnRH and chicken-II-type GnRH (cGnRH-II), have been identified. This study has isolated a full-length cDNA for a GnRH receptor from the pituitary of the eel. The 3233-bp cDNA encodes a 380-amino acid protein which contains seven hydrophobic transmembrane domains and N- and C-terminal regions. The exon/intron organization of the open reading frame of the eel GnRH receptor gene was also determined. The open reading frame consists of three exons and two introns. The exon-intron splice site is similar to that of the GnRH receptor genes of mammals reported so far. Expression of the eel GnRH receptor was detected in various parts of the brain, pituitary, eye, olfactory epithelium, and testis. This result suggests that GnRH has local functions in these tissues in addition to its actions on gonadotropin synthesis and release in the pituitary. This tissue-specific expression pattern is similar to that of the eel cGnRH-II. Furthermore, the present eel receptor shows very high amino acid identity with the catfish and goldfish GnRH receptors, which are highly selective for the cGnRH-II. These results suggest that the cGnRH-II acts through binding to the present receptor in the eel.

  13. Imaging of pediatric pituitary endocrinopathies

    PubMed Central

    Chaudhary, Vikas; Bano, Shahina

    2012-01-01

    Accurate investigation of the hypothalamic-pituitary area is required in pediatric patients for diagnosis of endocrine-related disorders. These disorders include hypopituitarism, growth failure, diencephalic syndrome, delayed puberty, precocious puberty, diabetes insipidus, syndrome of inappropriate antidiuretic hormone (SIADH) secretion, and hyperpituitarism. Magnetic resonance imaging (MRI) is the modality of choice to visualize hypothalamic-pituitary axis and associated endocrinopathies. Neuroimaging can be normal or disclose abnormalities related to pituitary-hypothalamic axis like (i) congenital and developmental malformations; (ii) tumors; (iii) cystic lesions; and (iv) infectious and inflammatory conditions. Classical midline anomalies like septo-optic dysplasias or corpus callosum agenesis are commonly associated with pituitary endocrinopathies and also need careful evaluation. In this radiological review, we will discuss neuroendocrine disorders related to hypothalamic pituitary-axis. PMID:23087850

  14. Pituitary autoimmunity: 30 years later

    PubMed Central

    Caturegli, Patrizio; Lupi, Isabella; Landek-Salgado, Melissa; Kimura, Hiroaki; Rose, Noel R.

    2012-01-01

    Pituitary autoimmunity encompasses a spectrum of conditions ranging from histologically proven forms of lymphocytic hypophysitis to the presence of pituitary antibodies in apparently healthy subjects. Hypophysitis is a rare but increasingly recognized disorder that typically presents as a mass in the sella turcica. It mimics clinically and radiologically other non-secreting sellar masses, such as the more common pituitary adenoma. Hypophysitis shows a striking temporal association with pregnancy, and it has been recently described during immunotherapies that block CTLA-4. Several candidate pituitary autoantigens have been described in the last decade, although none has proven useful as a diagnostic tool. This review summarizes the advances made in the field since the publication of the first review on pituitary autoimmunity, and the challenges that await clarification. PMID:18774118

  15. The Pituitary in Gigantism.

    PubMed

    Scheithauer, Bernd W.; Kovacs, Kalman T.; Stefaneanu, Lucia; Horvath, Eva; Kane, Laurie A.; Young, William F.; Lloyd, Ricardo V.; Randall, Raymond V.; Davis, Dudley H.

    1995-01-01

    To compare the pituitary pathology of gigantism to that of acromegaly, 19 surgically resected lesions were studied from 10 males and 9 females, ages 13-49 (mean, 19 yr) with excessive height (>/=95th percentile), onset of disease prior to puberty, elevated growth hormone (GH) levels despite glucose suppression, and a pathologically confirmed GH-producing pituitary mass. One patient had MEN-I. The lesions included 18 adenomas and 1 case of pure hyperplasia. The median, mean, and range of serum GH and prolactin (PRL) levels were 64, 235, 5-1000 ng/mL and 47, 146, 29-770 ng/mL, respectively. Of the 8 adenoma specimens accompanied by nontumoral pituitary (i.e., tissue wherein the presence of hyperplasia was assessable), 3 (37%) demonstrated both. Of the 18 tumors, 78% were macroadenomas and 22% were grossly invasive; their immunophenotypes included GH (5%), GH and PRL (19%), and GHPRL and a glycoprotein hormone, usually TSH and/or a-subunit (76%). Of the 10 adenoma-containing lesions subject to electron microscopy (EM), 2 consisted of GH cells alone; 2 of mammosomatotroph (MS) cells alone; 1 of GH and MS cells; 1 of GH and PRL cells; 2 of GH, PRL, and MS cells; 1 of GH, PRL, and glycoprotein cells; and 1 was a subtype 3 adenoma. Ultrastructurally, GH cells and/or MS cells predominated in these lesions. Immuno-EM of one CH and PRL cell and of one GH-PR-MS tumor showed GH and PRL to be present not only in single cells but within the same granules. Nine of 12 adenoma-associated lesions subject to combined in situ hybridization (ISH) and immunostaining showed double labeling for PRL (or GH) mRNA and for GH (or PRL), respectively, features indicating MS differentiation. In the 4 lesions exhibiting hyperplasia, either alone (1) or in association with adenoma (3), EM showed MS cells in 3, and immuno-EM as well as combined immunohistochemistry and ISH showed double labeling for GH and PRL in both of the 2 cases studied. In summary, although in terms of their tinctorial

  16. Hypothalamic-pituitary-gonadal function in anorexia nervosa and bulimia.

    PubMed

    Devlin, M J; Walsh, B T; Katz, J L; Roose, S P; Linkie, D M; Wright, L; Vande Wiele, R; Glassman, A H

    1989-04-01

    Patients with anorexia nervosa (AN) exhibit neuroendocrine abnormalities that may result solely from emaciation or may reflect defective endocrine mechanisms which are intrinsic to disordered eating even in the absence of starvation. To distinguish these possibilities, we have studied indices of hypothalamic-pituitary-gonadal (HPG) function in 9 patients with AN, 12 normal weight patients with bulimia and recent or current oligomenorrhea, and 8 normal weight controls. Measurement of 24-hour luteinizing hormone (LH) secretion with 30-min sampling revealed significantly fewer LH secretory spikes and a trend toward lower mean 24-hour LH levels in both bulimic and anorectic patients than in controls. Stimulation with gonadotropin releasing hormone produced elevated LH responses in the bulimic group and blunted LH responses in the anorectic group. Stimulation with estradiol revealed diminished LH augmentative responses and a trend toward diminished follicle stimulating hormone augmentative responses among bulimic as well as AN patients compared to controls. In each instance, the bulimic group tended to show within-group heterogeneity, with some individuals falling within the AN range. These findings suggest that HPG axis abnormalities in eating disordered patients cannot entirely be attributed to emaciation and that factors other than subnormal weight contribute to disturbed hypothalamic-pituitary functioning in these patients.

  17. Hypothalamic-pituitary-testicular axis in patients with hyperthyroidism.

    PubMed

    Röjdmark, S; Berg, A; Kallner, G

    1988-01-01

    To test whether chronic thyroid hormone excess influences the hypothalamic-pituitary-testicular axis, 8 hyperthyroid men were given two identical intravenous GnRH tests. The first test was performed before any treatment had been instituted, the second 6-13 months later, when medical treatment had made the patients euthyroid. Although basal serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T) levels were of similar magnitudes before and after the medical treatment, LH and FSH responsiveness to gonadotropin-releasing hormone (GnRH), as reflected by the hormone incremental areas (U/l X min), were significantly larger in the thyrotoxic state compared with the euthyroid state (LH incremental areas: 3,999 +/- 665 vs. 2,640 +/- 430, p less than 0.02; FSH incremental areas: 825 +/- 193 vs. 542 +/- 98, p less than 0.05). Furthermore, serum T increased significantly in response to GnRH when the patients were hyperthyroid (T incremental area: 162 +/- 51, p less than 0.02), but failed to do so when they were euthyroid (T incremental area: 92 +/- 53, NS). These results imply that chronic thyroid hormone excess makes the pituitary gonadotrophs 'hypersensitive' to exogenous GnRH. This may in turn explain why human Leydig cells respond more powerful to exogenous GnRH in thyrotoxic patients than in euthyroid subjects.

  18. Modeling the brain-pituitary-gonad axis in salmon

    SciTech Connect

    Kim, Jonghan; Hayton, William L.; Schultz, Irv R.

    2006-08-24

    To better understand the complexity of the brain-pituitary-gonad axis (BPG) in fish, we developed a biologically based pharmacodynamic model capable of accurately predicting the normal functioning of the BPG axis in salmon. This first-generation model consisted of a set of 13 equations whose formulation was guided by published values for plasma concentrations of pituitary- (FSH, LH) and ovary- (estradiol, 17a,20b-dihydroxy-4-pregnene-3-one) derived hormones measured in Coho salmon over an annual spawning period. In addition, the model incorporated pertinent features of previously published mammalian models and indirect response pharmacodynamic models. Model-based equations include a description of gonadotropin releasing hormone (GnRH) synthesis and release from the hypothalamus, which is controlled by environmental variables such as photoperiod and water temperature. GnRH stimulated the biosynthesis of mRNA for FSH and LH, which were also influenced by estradiol concentration in plasma. The level of estradiol in the plasma was regulated by the oocytes, which moved along a maturation progression. Estradiol was synthesized at a basal rate and as oocytes matured, stimulation of its biosynthesis occurred. The BPG model can be integrated with toxico-genomic, -proteomic data, allowing linkage between molecular based biomarkers and reproduction in fish.

  19. Serum estradiol but not gonadotropin levels decrease acutely after insulin-induced hypoglycemia in cycling women.

    PubMed

    Bing-You, R G; Spratt, D I

    1992-10-01

    Although corticotropin-releasing hormone (CRH) acutely suppresses gonadotropin-releasing hormone (GnRH) secretion in animal models, its effect on the hypothalamic-pituitary-gonadal axis in humans is not well defined. To further evaluate the acute effects of adrenal axis activation on the hypothalamic-pituitary-gonadal axis in humans, we employed a model of insulin-induced hypoglycemia to stimulate endogenous CRH secretion in eight cycling women. Serum samples were obtained immediately before and 15, 30, 45, 60, 75, 90, and 120 min following iv insulin (0.15 U/kg) or saline injection. To ensure that the degree of hypothalamic-pituitary-adrenal activation in our subjects was similar to that observed in severely ill patients with hypogonadotropism, serum cortisol (F) levels were also measured in a group of acutely ill patients selected to have hypogonadotropism. All women experienced symptomatic hypoglycemia after insulin injection. Differences between serum F levels in hypoglycemic vs. control sessions were evident at 30 min (P < 0.01) and maximum at 120 min (P < 0.0001) after insulin injection. Serum estradiol levels were significantly lower following hypoglycemia than during control sessions (P < 0.001). In contrast, serum LH and FSH levels were not significantly different between control and hypoglycemic sessions. Peak serum F levels in these hypoglycemic women were similar to F levels in critically ill patients with hypogonadotropism. These results demonstrate that stress and/or hypoglycemia can acutely decrease circulating estradiol levels. In addition, these data suggest that endogenous CRH does not play a major role in acute suppression of GnRH (over 2 h) in humans. Further studies are required to identify longer term effects of CRH on GnRH secretion which may be present in hypothalamic amenorrhea or hypogonadotropic hypogonadism of critical illness.

  20. Functional relationships of the hypothalamic-pituitary-testicular system in Graves' disease.

    PubMed

    Földes, J; Bános, C; Fehér, T; Bodrogi, L; Szalay, F; Borvendég, J; Csillag, J; Takó, J

    1982-01-01

    An increased secretion of gonadotropic hormone was found in hyperthyroid males despite the high basal serum total testosterone and oestradiol levels. This suggests that hyperthyroidism affects the responsiveness of the hypothalamic-pituitary axis to sexual steroid hormones. While in the hyperthyroid patients the elevation of the serum testosterone level in response to chorionic gonadotropin was lower than normally, the LH and FSH responses to LRH were increased. The results indicate that male hyperthyroidism is associated with a loss of responsiveness of the Leydig-cells to adequate stimuli, to which the pituitary reacts by a compensatory increase in its LH-secretion and by an increased reactivity to LRH. It is suggested that in addition to the direct effect of the increased thyroid hormone levels, a secondary elevation of the oestradiol concentration plays a major part in the alterations in question.

  1. Pituitary responsiveness to LRF in castrated male hamsters exposed to different photoperiodic conditions.

    PubMed

    Turek, F W; Alvis, J D; Menaker, M

    1977-01-01

    The effect of various doses of LRF on pituitary LH and FSH release was examined in castrated adult male hamsters with different photoperiodic histories. Gonadotropin (Gn) release in response to LRF was independent of whether the animals had been exposed to a photostimulatory (LD 14:10) or a nonstimulatory (LD 6:18) light cycle for 60 days following castration. The lowest dose that caused a significant increase in serum Gns was 10 ng LRF/100 g b.w. for LH and 50 ng LRF/100 g b.w. for FSH. These results indicate that photoperiod, which is well known to exert major effects on the reproductive system of the golden hamster, does not do so by directly altering the responsiveness of the pituitary gland to hypothalamic Gn-releasing factor. PMID:345144

  2. Endometrioid endometrial carcinoma indirectly caused by pituitary prolactinoma: a case report.

    PubMed

    Nishino, Kimihiro; Niwa, Yuri; Mizutani, Teruyuki; Shimizu, Ken; Hayashi, Kazumasa; Chaya, Jyunya; Kato, Noriko; Yamamuro, Osamu

    2013-01-01

    We present the case of a 44-year-old nulliparous woman who experienced irregular menstrual cycles for about 10 years and developed both pituitary prolactinoma and endometrioid endometrial carcinoma. In premenopausal women, hyperprolactinemia causes hypogonadism by inhibiting secretion of gonadotropin-releasing hormone and thus suppressing luteinizing hormone levels, which can cause menstrual disorders ranging from amenorrhea, oligomenorrhea and chronic anovulatory cycle to short luteal phase of the menstrual cycle. A chronic anovulatory menstrual cycle is the most common cause of long-term exposure of the endometrium to endogenous estrogen without adequate opposition from progestins, which can lead to endometrioid endometrial carcinoma. In this case, pituitary prolactinoma may have caused the chronic anovulatory cycle and indirectly led to the endometrioid endometrial carcinoma. In patients for whom the cause of irregular menstruation and chronic anovulatory cycle is suspected to be hyperprolactinemia, explorations of both the hypophysis and endometrium are essential.

  3. Presentation of a functional pituitary adenoma as a significant decrease in prostate-specific antigen level in a patient followed for prostate cancer.

    PubMed

    Grotas, Aaron B; Nagler, Harris M

    2006-12-01

    The stimulatory role of testosterone in the production and release of prostate-specific antigen (PSA) has been well characterized. Testosterone production by the testes is dependent on a functional hypothalamic-pituitary-gonadal axis. High prolactin levels have been shown to disrupt this axis, resulting in decreases in gonadotropins and testosterone levels. We report a patient with prostate cancer and elevated PSA levels followed with "watchful waiting" for several years who experienced a precipitous decrease in PSA level over a 3 month period. The patient was found to have an asymptomatic prolactin-secreting pituitary macroadenoma.

  4. Electrotonic Coupling in the Pituitary Supports the Hypothalamic-Pituitary-Gonadal Axis in a Sex Specific Manner.

    PubMed

    Göngrich, Christina; García-González, Diego; Le Magueresse, Corentin; Roth, Lena C; Watanabe, Yasuhito; Burks, Deborah J; Grinevich, Valery; Monyer, Hannah

    2016-01-01

    Gap junctions are present in many cell types throughout the animal kingdom and allow fast intercellular electrical and chemical communication between neighboring cells. Connexin-36 (Cx36), the major neuronal gap junction protein, synchronizes cellular activity in the brain, but also in other organs. Here we identify a sex-specific role for Cx36 within the hypothalamic-pituitary-gonadal (HPG) axis at the level of the anterior pituitary gland (AP). We show that Cx36 is expressed in gonadotropes of the AP sustaining their synchronous activity. Cx36 ablation affects the entire downstream HPG axis in females, but not in males. We demonstrate that Cx36-mediated coupling between gonadotropes in the AP supports gonadotropin-releasing hormone-induced secretion of luteinizing hormone. Furthermore, we provide evidence for negative feedback regulation of Cx36 expression in the AP by estradiol. We thus, conclude that hormonally-controlled plasticity of gap junction communication at the level of the AP constitutes an additional mechanism affecting female reproduction.

  5. Electrotonic Coupling in the Pituitary Supports the Hypothalamic-Pituitary-Gonadal Axis in a Sex Specific Manner

    PubMed Central

    Göngrich, Christina; García-González, Diego; Le Magueresse, Corentin; Roth, Lena C.; Watanabe, Yasuhito; Burks, Deborah J.; Grinevich, Valery; Monyer, Hannah

    2016-01-01

    Gap junctions are present in many cell types throughout the animal kingdom and allow fast intercellular electrical and chemical communication between neighboring cells. Connexin-36 (Cx36), the major neuronal gap junction protein, synchronizes cellular activity in the brain, but also in other organs. Here we identify a sex-specific role for Cx36 within the hypothalamic-pituitary-gonadal (HPG) axis at the level of the anterior pituitary gland (AP). We show that Cx36 is expressed in gonadotropes of the AP sustaining their synchronous activity. Cx36 ablation affects the entire downstream HPG axis in females, but not in males. We demonstrate that Cx36-mediated coupling between gonadotropes in the AP supports gonadotropin-releasing hormone-induced secretion of luteinizing hormone. Furthermore, we provide evidence for negative feedback regulation of Cx36 expression in the AP by estradiol. We thus, conclude that hormonally-controlled plasticity of gap junction communication at the level of the AP constitutes an additional mechanism affecting female reproduction. PMID:27587994

  6. Electrotonic Coupling in the Pituitary Supports the Hypothalamic-Pituitary-Gonadal Axis in a Sex Specific Manner.

    PubMed

    Göngrich, Christina; García-González, Diego; Le Magueresse, Corentin; Roth, Lena C; Watanabe, Yasuhito; Burks, Deborah J; Grinevich, Valery; Monyer, Hannah

    2016-01-01

    Gap junctions are present in many cell types throughout the animal kingdom and allow fast intercellular electrical and chemical communication between neighboring cells. Connexin-36 (Cx36), the major neuronal gap junction protein, synchronizes cellular activity in the brain, but also in other organs. Here we identify a sex-specific role for Cx36 within the hypothalamic-pituitary-gonadal (HPG) axis at the level of the anterior pituitary gland (AP). We show that Cx36 is expressed in gonadotropes of the AP sustaining their synchronous activity. Cx36 ablation affects the entire downstream HPG axis in females, but not in males. We demonstrate that Cx36-mediated coupling between gonadotropes in the AP supports gonadotropin-releasing hormone-induced secretion of luteinizing hormone. Furthermore, we provide evidence for negative feedback regulation of Cx36 expression in the AP by estradiol. We thus, conclude that hormonally-controlled plasticity of gap junction communication at the level of the AP constitutes an additional mechanism affecting female reproduction. PMID:27587994

  7. Heart in pituitary diseases.

    PubMed

    Hradec, J; Marek, J; Král, J; Simper, D; Spácil, J

    1992-01-01

    Of hormones secreted by the pituitary, a direct effect on cardiac metabolism and function is exerted only by growth hormone (GH). Its chronic overproduction in adulthood leads to acromegaly. The main cardiovascular manifestations of acromegaly are hypertension and cardiac hypertrophy. The paper summarizes the results of clinical research into the "acromegalic heart" in an internationally unique group of 78 patients with acromegaly on long-term follow-up. Both clinical findings and experimental data available in the literature indicate that cardiac hypertrophy is due to a direct effect of GH on the myocardium. Hypertension occurs in 50% of patients, has the nature of volume hypertension and exerts only an additive effect on the development of left ventricular hypertrophy. Once GH overproduction has been eliminated, cardiac hypertrophy and hypertension can be reversed to a certain stage, a finding highlighting the necessity of instituting treatment of acromegaly as early and as vigorous as possible. PMID:1304450

  8. Effects of discrete medial preoptic hypothalamic lesions on the androgen gonadotropin feedback system in the male rat.

    PubMed

    Bravo, C; Fernández-Galaz, C; Rodríguez, P; Alvarez-Sanz, C; Tejero, A; Vaticón, M D

    1987-06-01

    The effect of discrete lesions of the Anterior Medial Preoptic Area of the Hypothalamus (MPOA) in the control of pituitary gonadotropins in the adult male Wistar rat has been studied. Electrolytic lesions were made by passing an anodal current through tungsten electrodes. Electrodes were oriented stereotaxically into the MPOA and lesion placement was histologically checked. In sham controls, electrodes were lowered into the MPOA but no current was applied. Serum LH and FSH were measured by RIA. MPOA lesioned animals showed significantly lower plasma LH (p less than 0.01) in comparison to sham lesioned group. Plasma FSH remained unaltered. To test whether these results were related to an alteration in the negative feedback system, the response to administration of Testosterone Propionate (TP) and the secretion patterns of LH and FSH after castration were analyzed. Administration of TP revealed similar LH and FSH 24 and 48 h decrements and the pattern of LH and FSH secretion after gonadectomy was not significantly different in lesioned and sham lesioned animals. Responsiveness to exogenous LHRH was not impaired by MPOA lesions. The results suggest that neural elements within the MPOA are functionally related to pituitary LH secretion in the male rat. The LH control alteration in lesioned animals is not associated with modifications in negative feedback of androgens and pituitary sensitivity to LHRH remains unaltered.

  9. Male sexual development in the monkey. II. Cross-sectional analysis of pulsatile hypothalamic-pituitary secretion in castrated males.

    PubMed

    Bercu, B B; Lee, B C; Spiliotis, B E; Pineda, J L; Denman, D W; Hoffman, H J; Brown, T J

    1983-06-01

    Pulsatile secretion of serum gonadotropins was studied in 16 castrated monkeys from 4 weeks of age through adult life. Animals were castrated at various ages from birth through adult life. Although some studies of the gonadotropin-secretory patterns were longitudinal in nature, most comparisons were cross-sectional. On the basis of our observations, we have arbitrarily grouped the animals into 4 developmental ages: postnatal (less than 7 months), prepubertal or juvenile (7-27 months), pubertal (28-59 months), and adult (greater than or equal to 60 months). In carrying out these studies, blood was withdrawn at 15-min intervals over 24 h without anesthesia using a mobile vest and tether assembly to support an indwelling catheter. GnRH challenge tests were done on 1 or more occasions on all animals. Plasma samples were analyzed for concentrations of FSH and LH by established RIAs and an in vitro bioassay for LH. During the frequent sampling period (24 h for all except postnatal animals), the amplitude of gonadotropin pulses was greatest in adult animals followed by postnatal and pubertal monkeys. During pubertal development, there was a marked increase in the magnitude of gonadotropin pulses, and remarkedly, there was a substantial increase in the LH bioassay: RIA (greater than 5:1) by adult life. GnRH challenge tests of gonadotropins correlated with these observations. Time series analysis was applied to the data for objective statistical characterization of cyclic patterns. Our findings can be summarized: 1) during pubertal maturation there is a change in amplitude but not frequency of gonadotropin pulses, 2) pubertal development of the hypothalamic-pituitary axis advances in the absence of gonadal feedback, and 3) there is a significant increase in the LH bioassay: RIA during pubertal development. We conclude that the castrate monkey is a valuable adjunct to direct clinical investigations of the mechanisms controlling human sexual development.

  10. Effect of cranial irradiation on hypothalamus and pituitary functions.

    PubMed

    Huang, T S; Huang, L S; Tung, C C; Lee, S H; Chen, F W; Huang, S C; Hsieh, T

    1989-07-01

    Hypopituitarism can occur after cranial irradiation for tumors distant from the pituitary gland. Recent studies have suggested that this is hypothalamic in origin. Hypothalamic and pituitary functions were studied in 11 patients, 4 men and 7 women, 4.5 years or more after radiotherapy for nasopharyngeal carcinomas. The estimated average total dose was 5000 cGys for the hypothalamus and pituitary gland. Except for 2 women with amenorrhea and 4 men with impotency, the patients did not have evident endocrine deficiency. Baseline hormone profiles revealed normal T4, T3 and cortisol levels, 6 with elevated prolactin, 3 with reduced testosterone and 3 with slightly elevated basal TSH. The four menopausal women had impaired gonadotropin response to LHRH (100 micrograms, i.v.). Four (1 menstruating, 1 amenorrheic, 2 menopausal) women did not reach peak FSH response 4 hours after LHRH injection. The other amenorrheic woman had minimal FSH and LH response to LHRH which persisted even after 8 days of pulsatile infusion of LHRH (1 microgram/90min). TSH response to TRH (400 micrograms, i.v.) was delayed in 7 patients. GH response to human GRH (1 microgram/kg, i.v.) was impaired in 6 patients (maximal GH less than 5 mU/l). ACTH response to ovine CRH (1 microgram/kg, i.v.) was impaired in 3 patients (less than 50% elevation from baseline). Three patients who had normal GRH tests had impaired GH response to insulin hypoglycemia. Six patients had an empty sella on CT scan. From this study the following conclusions are drawn: (1) Among the four axes, GH is the most vulnerable. (2) The insulin tolerance test is still the best single test for evaluation of hypothalamic function.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Gonadotropin-I and -II subunit gene expression of male striped bass (Morone saxatilis) after gonadotropin-releasing hormone analogue injection: quantitation using an optimized ribonuclease protection assay.

    PubMed

    Hassin, S; Gothilf, Y; Blaise, O; Zohar, Y

    1998-05-01

    In fish, both gonadotropin (GtH)-I and -II are involved in the spermatogenic process, but the differential regulation of these hormones by GnRH is still poorly understood. To gain further insight into the GnRH regulation of GtH-I and -II gene expression in the male striped bass, we have developed and optimized a ribonuclease protection assay for the simultaneous measurement of all GtH subunit mRNAs in a single pituitary gland. The RNA extraction protocol enables the determination of GtH protein content in the same sample, thus enhancing the power of the method. Maturing striped bass males were injected intramuscularly with [D-Ala6,Pro9Net]-LHRH (GnRHa) and sampled at 6 and 24 h postinjection. The mRNA levels of the alpha subunit and GtH-IIbeta increased after 6 h (4- and 6-fold, respectively), while the GtH-Ibeta mRNA levels increased only 2-fold after 24 h. Interestingly, GnRHa stimulation caused a significant increase in beta-actin mRNA levels. GnRHa treatment also resulted in a 2-fold decrease in pituitary GtH-II content, associated with a dramatic increase of plasma GtH-II levels from undetectable levels (< 0.2 ng/ml) to 13+/-2 ng/ml after 6 h. These results demonstrate that both GtH-Ibeta and -Ilbeta are expressed during striped bass spermatogenesis and that the two genes are subjected to differential regulation by GnRHa.

  12. Human chorionic gonadotropin (HCG) treatment of obesity.

    PubMed

    Shetty, K R; Kalkhoff, R K

    1977-02-01

    After a nine-day control period, six hospitalized obese women were placed on 500 calorie diets and were given 125 IU of human chorionic gonadotropin (HCG) intramuscularly daily for 30 days. Another five obese women received injections of diluent only and consumed identical diets for the same period. Mean weight loss in the HCG-treated group was nearly identical to that achieved by women given the placebo. Reduction of triceps skinfold thickness or circumferential body measurements of the chest, waist, hips, and thighs were not different. Patters of change of a variety of plasma and urine substrates, electrolytes, and hormones were similar in the two groups and consistent with semistarvation and weight loss. These results indicate that HCG has no effects on chemical and hormonal parameters measured and offers no advantage over calorie restriction in promoting weight loss. PMID:836112

  13. Effects of low subchronic doses of methoxychlor on the rat hypothalamic-pituitary reproductive axis.

    PubMed

    Goldman, J M; Cooper, R L; Rehnberg, G L; Hein, J F; McElroy, W K; Gray, L E

    1986-12-01

    The pesticide methoxychlor (MXC) is known to possess a weak estrogenic action and has been found to have a number of toxic effects on the rodent reproductive system, primarily at the gonadal level. The purpose of this study was to explore the influence of MXC on the pituitary and hypothalamic components of the male reproductive system at dose levels that were without detectable testicular effects. At 21 days, male Long-Evans rats were gavaged daily with 25 or 50 mg/kg MXC in corn oil. Controls received vehicle only. After 8 weeks of dosing, no significant changes were seen in serum LH, FSH, or prolactin, nor in the pituitary concentrations of LH or FSH. Pituitary prolactin was elevated for both doses, and pituitary fragments perifused in vitro released more prolactin than did controls. The concentration of gonadotropin-releasing hormone (GnRH) was higher in the mediobasal hypothalamus, but only for the 50-mg/kg group. At this dose, there was a corresponding increase in the KCl-stimulated release of GnRH. The data suggest that previously reported reproductive effects of MXC may be mediated, at least in part, through an elevation in prolactin concentration and release, which in turn is able to influence hypothalamic levels of GnRH. This prolactinemic effect may well represent an early component of the adverse action of MXC on the reproductive system.

  14. Endopeptidase-24.15 in rat hypothalamic/pituitary/gonadal axis.

    PubMed

    Pierotti, A R; Lasdun, A; Ayala, J M; Roberts, J L; Molineaux, C J

    1991-04-01

    Endopeptidase-24.15 (E.C. 3.4.24.15; EP-24.15) cleaves several substrates found in the hypothalamic/pituitary/gonadal axis, including gonadotropin-releasing hormone (GnRH) and the opioid peptides of the dynorphin family. We have examined the activity of EP-24.15 in these tissues as a function of maturation, of the estrous cycle, and in response to ovariectomy and estrogen replacement. A developmental regulation of EP-24.15-specific activity is apparent in anterior pituitary, in hypothalamus, and in the gonads. EP-24.15 is increased in the preoptic area and is decreased in the anterior pituitary in both male and female rats prior to puberty. The specific activity of EP-24.15 was increased following ovariectomy in the anterior pituitary and within medial and lateral preoptic nuclei. Testicular specific activity of EP-24.15 increased with age in a linear fashion, while ovarian EP-24.15 activity increased immediately prior to puberty, but returned to prepubertal levels by 65 days of age. The relevance of EP-24.15 to the metabolism of specific peptides is discussed.

  15. The recreational drug ecstasy disrupts the hypothalamic-pituitary-gonadal reproductive axis in adult male rats.

    PubMed

    Dickerson, Sarah M; Walker, Deena M; Reveron, Maria E; Duvauchelle, Christine L; Gore, Andrea C

    2008-01-01

    Reproductive function involves an interaction of three regulatory levels: hypothalamus, pituitary, and gonad. The primary drive upon this system comes from hypothalamic gonadotropin-releasing hormone (GnRH) neurosecretory cells, which receive afferent inputs from other neurotransmitter systems in the central nervous system to result in the proper coordination of reproduction and the environment. Here, we hypothesized that the recreational drug (+/-)-3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy'), which acts through several of the neurotransmitter systems that affect GnRH neurons, suppresses the hypothalamic-pituitary-gonadal reproductive axis of male rats. Adult male Sprague-Dawley rats self-administered saline or MDMA either once (acute) or for 20 days (chronic) and were euthanized 7 days following the last administration. We quantified hypothalamic GnRH mRNA, serum luteinizing hormone concentrations, and serum testosterone levels as indices of hypothalamic, pituitary, and gonadal functions, respectively. The results indicate that the hypothalamic and gonadal levels of the hypothalamic-pituitary-gonadal axis are significantly altered by MDMA, with GnRH mRNA and serum testosterone levels suppressed in rats administered MDMA compared to saline. Furthermore, our finding that hypothalamic GnRH mRNA levels are suppressed in the context of low testosterone concentrations suggests that the central GnRH neurosecretory system may be a primary target of inhibitory regulation by MDMA usage.

  16. Animal models of pituitary neoplasia

    PubMed Central

    Lines, K.E.; Stevenson, M.; Thakker, R.V.

    2016-01-01

    Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies. PMID:26320859

  17. Dural invasion by pituitary tumours.

    PubMed

    Shaffi, O M; Wrightson, P

    1975-04-23

    In 12 cases of pituitary tumour the dura mater of the sella turcica or diaphragma sellae in contact with the tumour was examined histologically. In nine cases tumour cells were found lying deep in the substance of the dura. Dura from the sella of seven subjects without pituitary disease, obtianed at autopsy, showed no inclusions of pituitary tissue. Four of the cases studied were known before death to suffer from an invasive pituitary adenoma. Of eight surviving cases operated upon in the last two years, five showed dural invasion by tumour. The present report suggests that the condition may be more frequent than expected and that with more study it may provide an index of prognosis. It also defines a requirement for the surgeon aiming to prevent recurrence of tumour after operation or to achieve a complete endocrine ablation.

  18. Pituitary: Non-Secretory Tumors

    MedlinePlus

    ... categories—tumor mass effects and hyposecretion effects. Tumor mass effects Visual field disturbances, most commonly loss of ... surgery. The goal is to completely remove the mass or cyst and preserve normal pituitary, brain, and ...

  19. GnRH decreases adiponectin expression in pituitary gonadotropes via the calcium and PKA pathways.

    PubMed

    Kim, Jonathan; Zheng, Weiming; Grafer, Constance; Mann, Merry Lynn; Halvorson, Lisa M

    2013-08-01

    As endocrinologically active cells, adipocytes are capable of secreting various adipocytokines such as leptin, resistin, and adiponectin to impact metabolic function. Although adipocytes remain to be the primary site of synthesis and secretion, there is now growing evidence that supports the presence of adiponectin and its receptors within the hypothalamic-pituitary-gonadal axis, providing a possible link between obesity and abnormal reproductive physiology. It has been demonstrated that adiponectin may reduce gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus as well as modulate gonadal steroid hormone production. Furthermore, prior data indicate that adiponectin may play a role in decreasing luteinizing hormone secretion from pituitary gonadotropes. We aimed to identify the hormonal regulators of adiponectin and its receptors, AdipoR1 and AdipoR2, in pituitary gonadotropes using immortalized gonadotropic LβT2 cells and primary rat pituitary cells. Our study shows significant alterations in adiponectin expression across the estrous cycle. In addition, we present a novel finding that GnRH suppresses pituitary adiponectin expression via the calcium and protein kinase A intracellular pathways in both cultured rat primary pituitary cells and the LβT2 gonadotrope cell line. The GnRH did not alter expression of the adiponectin receptors, AdipoR1 and AdipoR2, in cultured gonadotropes. Expression of the adiponectin receptors, AdipoR1 and AdipoR2, was not altered by GnRH in cell culture but in vivo or in vitro. Our data suggest that gonadotrope function may be modulated by GnRH-mediated changes in adiponectin expression.

  20. A history of pituitary pathology.

    PubMed

    Asa, Sylvia L; Mete, Ozgur

    2014-03-01

    The history of pituitary pathology is a long one that dates back to biblical times, but the last 25 years have represented an era of "coming of age." The role of the pituitary in health and disease was the subject of many studies over the last century. With the development of electron microscopy, immunoassays, and immunohistochemistry, the functional alterations associated with pituitary disease have been clarified. The additional information provided by molecular genetic studies has allowed progress in understanding the pathogenesis of pituitary disorders. Nevertheless, many questions remain to be answered. For example, pathologists cannot morphologically distinguish locally aggressive adenomas from carcinomas when tumor is confined to the sella. Sadly, basal cell carcinoma, the most common carcinoma of skin, usually causes less morbidity than pituitary adenomas, which occur in almost 20 % of the general population, can cause significant illness and even death, and yet are still classified as benign. The opportunity to increase awareness of the impact of these common lesions on quality of life is the current challenge for physicians and patients. We anticipate that ongoing multidisciplinary approaches to pituitary disease research will offer new insights into diseases arising from this fascinating organ.

  1. Hypothalamic-pituitary axis remains intact after interferon-alpha treatment in hematologic diseases.

    PubMed

    Kauppila, M; Koskinen, P; Remes, K; Viikari, J; Irjala, K

    1997-09-01

    Many endocrinologic disturbances have been reported during and after interferon-alpha (IFN-alpha) treatment. These disturbances have often been caused by autoantibodies. The aim of this prospective study was to evaluate whether IFN-alpha causes hormonal changes and if it is necessary to search for such disturbances routinely. Ten patients with hematologic malignancies were examined before and after 4 months of IFN-alpha treatment. Pituitary function was tested by hypothalamic releasing hormones (thyrotropin-releasing hormone, TRH, growth hormone-releasing hormone, GHRH, gonadotropin-releasing hormone, GnRH). The adrenal glands were tested with the adrenocorticotropin (ACTH) test. The human chorionic gonadotropin (hCG) test was performed on the men (n = 4). The IFN treatment was well tolerated, and no long-term hormonal side effects were found. The testosterone/sex hormone binding globulin (SHBG) index tended to improve. There were no significant differences between the hormone responses before and after IFN-alpha treatment. We conclude that the hypothalamic-pituitary axis remains intact after IFN-alpha treatment. There is no need to follow patients endocrinologically if the patients are not predisposed by autoantibodies.

  2. Quadruple Injection of Hypothalamic Peptides to Evaluate Pituitary Function in Normal Subjects

    PubMed Central

    Kaltenborn, K. C.; Jubiz, William

    1985-01-01

    A single intravenous injection of four hypothalamic releasing hormones—corticotropin-, growth hormone-, gonadotropin- and thyrotropin-releasing hormones—was administered to normal subjects. Except for the plasma adrenocorticotropic hormone (ACTH) level, a statistically significant increase in all anterior pituitary hormone levels occurred. Transient flushing was the only consistent side effect. In the same persons, results were compared with those obtained with insulin-induced hypoglycemia and a single-dose overnight metyrapone test. Growth hormone and cortisol responses to insulin-induced hypoglycemia were similar but prolactin increment was less than that obtained by the peptide injection. ACTH increments from both tests were substantially less than those obtained by the overnight metyrapone test. We conclude that pituitary function can be effectively studied in normal subjects by the combination of a metyrapone test with a triple bolus of growth hormone-, thytropin- and gonadotropin-releasing hormones, but not by a quadruple bolus of the hypothalamic peptides. Compared with insulin-induced hypoglycemia, this approach yields more information with fewer side effects. PMID:3919507

  3. The role of kisspeptin and gonadotropin inhibitory hormone in the seasonal regulation of reproduction in sheep.

    PubMed

    Smith, J T

    2012-08-01

    Sheep are seasonal breeders, experiencing an annual period of reproductive quiescence in response to increased photoperiod during the late-winter into spring and renaissance during the late summer. The nonbreeding (anestrous) season is characterized by a reduction in the pulsatile secretion of GnRH from the brain, in part because of an increase in negative feedback activity of estrogen. Neuronal populations in the hypothalamus that produce kisspeptin and gonadotropin-inhibitory hormone (GnIH) appear to be important for the seasonal shift in reproductive activity, and the former are also mandatory for puberty onset. Kisspeptin cells in the arcuate nucleus (ARC) and preoptic area appear to regulate GnRH neurons and transmit sex-steroid feedback signals to these neurons. Moreover, kisspeptin expression in the ARC is markedly up-regulated at the onset of the breeding season, as too are the number of kisspeptin fibers in close apposition to GnRH neurons. The lower levels of kisspeptin seen during the nonbreeding season can be "corrected" by infusion of kisspeptin, which causes ovulation in seasonally acyclic females. The role of GnIH is less clear, but mounting evidence supports a role for this neuropeptide in the inhibitory regulation of both GnRH secretion and gonadotropin release from the pituitary gland. Contrary to kisspeptin, GnIH expression is markedly reduced at the onset of the breeding season. In addition, the number of GnIH fibers in close apposition to GnRH neurons also decreases during this time. Importantly, exogenous GnIH treatment can block both the pulsatile release of LH and the preovulatory LH surge during the breeding season. In summary, it is most likely the integrated function of both these neuropeptide systems that modulate the annual shift in photoperiod to a physiological change in fertility.

  4. Both hyper- and hypogonadotropic hypogonadism occur transiently in acute illness: bio- and immunoactive gonadotropins.

    PubMed

    Spratt, D I; Bigos, S T; Beitins, I; Cox, P; Longcope, C; Orav, J

    1992-12-01

    Previous reports of hypogonadotropic hypogonadism in critically ill men may not reflect the complexity of changes in the hypothalamic-pituitary-gonadal (HPG) axis during acute illness. We sampled blood throughout hospitalization in 55 men admitted to acute care units to delineate the spectrum of changes in circulating gonadotropin and sex steroid levels at the onset and during recovery from acute illness. Bioactive LH and FSH were measured in a subset of patients. Percent free testosterone was measured to assess changes in binding to sex hormone binding globulin. Medications and serum estrogen and prolactin levels were monitored as potential causes of hypogonadotropism. Sustained suppression of serum testosterone levels below the normal range occurred in 62% of men with varying diagnoses and disease severity. Percent free testosterone remained constant. Hypogonadotropism was observed in most men (60%) and occurred independently from head injury, surgery, medications, or hyperprolactinemia. In a subset of men (n = 16), LH and/or FSH rose transiently above the normal range. Bioactivity of both LH and FSH remained constant while serum testosterone levels decreased. In contrast to serum testosterone levels, mean serum levels of E1, E2 and androstenedione were not less than control values. We conclude that both primary and secondary hypogonadism occur transiently in acutely ill men and cannot be explained solely by medications, hyperprolactinemia, or hyperestrogenemia. Neither biopotency of gonadotropins nor binding of testosterone to SHBG change across the course of acute illness. The hypogonadism, often severe and prolonged, may contribute to the persistent catabolic state observed in many critically ill patients.

  5. Heme oxygenase-derived carbon monoxide modulates gonadotropin-releasing hormone release in immortalized hypothalamic neurons.

    PubMed

    Errico, Stefania; Shohreh, Rugia; Barone, Eugenio; Pusateri, Angela; Mores, Nadia; Mancuso, Cesare

    2010-03-01

    Heme oxygenase (HO), the main enzyme deputed to heme metabolism, has been identified as two main isoforms called HO-1 and HO-2 both present in the central nervous system. Heme oxygenase has been shown to regulate the hypothalamic release of neuropeptides such as corticotrophin-releasing hormone and arginin-vasopressin. The aim of this study was to investigate and further characterize the presence of HO in gonadotropin-releasing hormone (GnRH) secreting hypothalamic neurons, GT1-7 and the role of HO by-products on GnRH secretion. The pulsatile release of GnRH from scattered hypothalamic neurons is the key regulator of mammalian fertility in the central nervous system. GT1-7 cells are immortalized hypothalamic neurons, characterized by spontaneous electrical activity and pulsatile GnRH release, resembling the central control pathway of the hypothalamic pituitary gonadal axis (HPG) in mammals. Hemin, the substrate of HO, significantly stimulated HO activity in static cultures, causing a rapid increase in GnRH release. Neither biliverdin nor bilirubin were able to mimic this rapid stimulatory effect, which was instead caused by carbon monoxide. Evidence of a possible involvement of prostaglandin E(2) in the HO by-product modulated GnRH secretion was reported. The hemin-evoked effect on GT1-7 neurons suggests a direct activity of HO by-products on the hypothalamic neuropeptide secretion, and claims for a possible role of CO in both the modulation of gonadotropin secretion and crosstalk among HPG and stress axis within the mammalian hypothalamus.

  6. The effects of opiate antagonism on gonadotropin secretion in children and in women with hypothalamic amenorrhea.

    PubMed

    Sauder, S E; Case, G D; Hopwood, N J; Kelch, R P; Marshall, J C

    1984-04-01

    The effects of opiate antagonism [naloxone infusion, 1 mg/(m2 X h)] on gonadotropin secretion were examined in four children (one female and three males: two late prepubertal and two pubertal; chronologic age, range 11.8-15.9 yr; bone age, range 8.5-13.5 yr) and in four women with hypothalamic amenorrhea (two at normal body weight and two at low body weight). Naloxone had no effect on daytime gonadotropin secretion in three children who were biologically the youngest in the group, two late prepubertal and one early pubertal [plasma luteinizing hormone (LH) means +/- SE: control day, 1.2 +/- 0.1; control night, 4.5 +/- 0.4; and naloxone day, 1.3 +/- 0.1 mIU/ml]. In contrast, opiate blockade produced a slight but discernible increase in plasma LH in the child whose hypothalamic-pituitary-gonadal axis was the most mature, a boy at mid-puberty. Naloxone produced a striking increase in plasma LH in the amenorrheic women at normal body weight (LH, means +/- SE: control day, 3.4 +/- 0.3; control night, 7.0 +/- 1.0; and naloxone day, 7.4 +/- 0.7 mIU/ml) as well as in those at low body weight (LH, means +/- SE: control day, 3.5 +/- 0.3; control night, 2.8 +/- 0.2; naloxone day, 4.9 +/- 0.4; and naloxone night, 6.7 +/- 0.5 mIU/ml). Antagonism of endogenous opiate activity increased LH pulse frequency in all four women.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Pituitary tumours: acromegaly.

    PubMed

    Chanson, Philippe; Salenave, Sylvie; Kamenicky, Peter; Cazabat, Laure; Young, Jacques

    2009-10-01

    Excessive production of the growth hormone (GH) is responsible for acromegaly. It is related to a pituitary GH-secreting adenoma in most cases. Prevalence is estimated 40-130 per million inhabitants. It is characterised by slowly progressive acquired somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The rheumatologic, cardiovascular, respiratory and metabolic consequences determine its prognosis. The diagnosis is confirmed by an increased serum GH concentration, unsuppressible by an oral glucose load and by detection of increased levels of insulin-like growth factor-I (IGF-I). Treatment is aimed at correcting (or preventing) tumour compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. When surgery, the usual first-line treatment, fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogues and/or radiotherapy can be used. The GH-receptor antagonist (pegvisomant) is helpful in patients who are resistant to somatostatin analogues. Thanks to this multistep therapeutic strategy, adequate hormonal disease control is achieved in most cases, allowing a normal life expectancy. PMID:19945023

  8. Hypothalamus-pituitary-gonad axis of rainbow trout (Oncorhynchus mykiss) during early ovarian development and under dense rearing condition.

    PubMed

    Hou, Zhi-Shuai; Wen, Hai-Shen; Li, Ji-Fang; He, Feng; Li, Yun; Tao, Ya-Xiong

    2016-09-15

    The objective of this study was to determine the hypothalamus-pituitary-gonad (HPG) axis of female rainbow trout (Oncorhynchus mykiss) during early ovarian development and under high rearing density. Trouts were sampled from 240 (ovarian stage II) to 540 (ovarian stage IV) days following hatching (DFH) as control group (Ctrl, 4.6-31.1kg/m(3)) to determine HPG axis during early ovarian development. Trouts from the same batch of fertilized eggs were reared in two higher densities during 240-540 DFH as stocking density 1 and 2 (SD1, 6.6-40.6kg/m(3); SD2, 8.6-49.3kg/m(3)) to elucidate effects of high density on reproductive parameters. Dopamine, E2 (estradiol), 17α,20β-P (17α,20β-dihydroxy4-pregnen-3-one) and P4 (progesterone) were evaluated by radioimmunoassay or ELISA. mRNA expression of hypothalamic gnrh-1, -2 (gonadotropin-releasing hormone-1, -2), pituitary gonadotropins (fsh/lh, follicle-stimulating hormone/luteinizing hormone) and their cognate receptors (fshr/lhr) in ovaries were examined by qRT-PCR. Our findings demonstrated mRNA expression of hypothalamic sgnrh-1, pituitary fsh and ovarian fshr increased in early ovarian development (360 DFH). Serum 17α,20β-P and pituitary lh mRNA expression first increased when trouts were in ovarian stage III (420 DFH). Ovaries were at different stages when reared in different densities. Long-term high density treatment (over 31.7kg/m(3)) resulted in decreased hypothalamic sgnrh-1, pituitary fsh, ovarian fshr, serum E2, and increased hypothalamus gnrh-2 and serum dopamine during vitellogenin synthesis, suggesting HPG of rainbow trout might be retarded under dense rearing condition.

  9. Hypothalamus-pituitary-gonad axis of rainbow trout (Oncorhynchus mykiss) during early ovarian development and under dense rearing condition.

    PubMed

    Hou, Zhi-Shuai; Wen, Hai-Shen; Li, Ji-Fang; He, Feng; Li, Yun; Tao, Ya-Xiong

    2016-09-15

    The objective of this study was to determine the hypothalamus-pituitary-gonad (HPG) axis of female rainbow trout (Oncorhynchus mykiss) during early ovarian development and under high rearing density. Trouts were sampled from 240 (ovarian stage II) to 540 (ovarian stage IV) days following hatching (DFH) as control group (Ctrl, 4.6-31.1kg/m(3)) to determine HPG axis during early ovarian development. Trouts from the same batch of fertilized eggs were reared in two higher densities during 240-540 DFH as stocking density 1 and 2 (SD1, 6.6-40.6kg/m(3); SD2, 8.6-49.3kg/m(3)) to elucidate effects of high density on reproductive parameters. Dopamine, E2 (estradiol), 17α,20β-P (17α,20β-dihydroxy4-pregnen-3-one) and P4 (progesterone) were evaluated by radioimmunoassay or ELISA. mRNA expression of hypothalamic gnrh-1, -2 (gonadotropin-releasing hormone-1, -2), pituitary gonadotropins (fsh/lh, follicle-stimulating hormone/luteinizing hormone) and their cognate receptors (fshr/lhr) in ovaries were examined by qRT-PCR. Our findings demonstrated mRNA expression of hypothalamic sgnrh-1, pituitary fsh and ovarian fshr increased in early ovarian development (360 DFH). Serum 17α,20β-P and pituitary lh mRNA expression first increased when trouts were in ovarian stage III (420 DFH). Ovaries were at different stages when reared in different densities. Long-term high density treatment (over 31.7kg/m(3)) resulted in decreased hypothalamic sgnrh-1, pituitary fsh, ovarian fshr, serum E2, and increased hypothalamus gnrh-2 and serum dopamine during vitellogenin synthesis, suggesting HPG of rainbow trout might be retarded under dense rearing condition. PMID:27401261

  10. Postpartum reproduction in protein restricted beef cows: effect on the hypothalamic-pituitary-ovarian axis.

    PubMed

    Nolan, C J; Bull, R C; Sasser, R G; Ruder, C A; Panlasigui, P M; Schoeneman, H M; Reeves, J J

    1988-12-01

    The influence of dietary CP on circulating LH and anterior pituitary and hypothalamic function was examined. In Exp. 1, 28 cows were randomly assigned to four treatment groups: adequate CP (ADQ; .96 kg/d) or deficient CP (DEF; .32 kg/d) beginning at 90, 60 and 30 d before parturition and continued at a 33% increase in feed consumption after parturition. Cows were bled at 15-min intervals for 8 h on d 20, 40 and 60 after parturition. Pituitaries were collected on d 62 to analyze GnRH receptor numbers and gonadotropin content. Frequency of pulsatile LH release increased (P less than .05) from 20 to 60 d in ADQ cows. Basal and mean LH were not affected (P greater than .10) by CP restriction or by days after parturition. Crude protein did not affect pituitary GnRH receptors (P greater than .10), but it did affect pituitary LH content, FSH content and FSH concentration (P less than .05). In Exp. 2, 28 cows were assigned to treatment groups as in Exp. 1. All cows were challenged with GnRH (.22 micrograms/kg BW) at 20, 40 and 60 d after parturition and were bled every 30 min for 6 h. Responsiveness to GnRH increased with increased time after parturition (P less than .07). Deficient CP decreased GnRH-induced LH release (P less than .05). In Exp. 3, 12 cows were randomly assigned to ADQ or DEF CP beginning 120 d before parturition. All cows received 1 mg estradiol-17 beta (E2) on d 19, 39 and 59 after parturition and were bled every 30 min for 14 h beginning 14 h following E2. Response to E2 was unaffected by CP restriction (P greater than .10), whereas time to E2-induced LH peak decreased as time after parturition increased in ADQ cows (P less than .05). Results suggest that delayed return to estrus in CP-deficient postpartum beef cows might be due to reduced gonadotropin release from the anterior pituitary and decreased anterior pituitary responsiveness to GnRH.

  11. Pituitary function following treatment with reproductive toxins

    SciTech Connect

    Cooper, R.L.; Goldman, J.M.; Rehnberg, G.L.

    1986-12-01

    Appropriate regulation of reproductive processes are dependent upon the integrity of pituitary function. In this selected review, the authors evaluate the evidence that certain environmental compounds exert their effect on reproductive function via a direct action on the pituitary gland. They also discuss examples of changes in pituitary hormone secretion that occur in response to changes in neuronal or gonadal control of the pituitary. A limited number of studies suggest that measures of pituitary hormone secretion provide an early and sensitive measure of a compound's potential effects on the reproductive system. However, the most striking aspect of this area is the sparse and inconsistent information describing pituitary function following exposure to environmental pollutants.

  12. Imaging of the pituitary and parasellar region.

    PubMed

    Zee, Chi S; Go, John L; Kim, Paul E; Mitchell, David; Ahmadi, Jamshid

    2003-01-01

    The pituitary is part of a chain of enormous biologic amplification, which is regulated by a small amount of releasing factors in the portal blood from the hypothalamus. The pituitary is a master gland that regulates a number of hormones. A subtle abnormality in the pituitary can cause significant changes in body metabolism. Because the pituitary glands are small structures, high-resolution imaging techniques are required to satisfactorily evaluate the gland. It is imperative for the radiologist to be familiar with the anatomy, physiology, and pathology of the pituitary gland, which provides a solid foundation for accurate interpretation of the imaging studies of the pituitary gland. PMID:12690979

  13. Kisspeptin-1 directly stimulates LH and GH secretion from goldfish pituitary cells in a Ca(2+)-dependent manner.

    PubMed

    Chang, John P; Mar, Alan; Wlasichuk, Michael; Wong, Anderson O L

    2012-10-01

    It has been established that kisspeptin regulates reproduction via stimulation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion, which then induces pituitary luteinizing hormone (LH) release. Kisspeptin also directly stimulates pituitary hormone release in some mammals. However, in goldfish, whether kisspeptin directly affects pituitary hormone release is controversial. In this study, synthetic goldfish kisspeptin-1((1-10)) (gKiss1) enhances LH and growth hormone (GH) release from primary cultures of goldfish pituitary cells in column perifusion. gKiss1 stimulation of LH and GH secretion were still manifested in the presence of the two native goldfish GnRHs, salmon (s)GnRH (goldfish GnRH-3) and chicken (c)GnRH-II (goldfish GnRH-2), but were attenuated by two voltage-sensitive calcium channel blockers, verapamil and nifedipine. gKiss-induced increases in intracellular Ca(2+) in Fura-2AM pre-loaded goldfish pars distalis cells were also inhibited by nifedipine. These results indicate that, in goldfish, (1) direct gKiss1 actions on pituitary LH and GH secretion exist, (2) these actions are independent of GnRH and (3) they involve Ca(2+) signalling.

  14. Dissecting the Roles of Gonadotropin-Inhibitory Hormone in Mammals: Studies Using Pharmacological Tools and Genetically Modified Mouse Models

    PubMed Central

    Leon, Silvia; Tena-Sempere, Manuel

    2016-01-01

    Reproduction is essential for perpetuation of the species and, hence, is controlled by a sophisticated network of regulatory factors of central and peripheral origin that integrate at the hypothalamic–pituitary–gonadal (HPG) axis. Among the central regulators of reproduction, kisspeptins, as major stimulatory drivers of gonadotropin-releasing hormone (GnRH) neurosecretion, have drawn considerable interest in the last decade. However, the dynamic, if not cyclic (in the female), nature of reproductive function and the potency of kisspeptins and other stimulatory signals of the HPG axis make tenable the existence of counterbalance inhibitory mechanisms, which may keep stimulation at check and would allow adaptation of reproductive maturation and function to different endogenous and environmental conditions. In this context, discovery of the gonadotropin-inhibitory hormone (GnIH) in birds, and its mammalian homolog, RFRP, opened up the exciting possibility that this inhibitory signal might operate centrally to suppress, directly or indirectly, GnRH/gonadotropin secretion, thus reciprocally cooperating with other stimulatory inputs in the dynamic regulation of the reproductive hypothalamic–pituitary unit. After more than 15 years of active research, the role of GnIH/RFRP in the control of the HPG axis has been documented in different species. Yet, important aspects of the physiology of this system, especially regarding its relative importance and actual roles in the control of key facets of reproductive function, remain controversial. In the present work, we aim to provide a critical review of recent developments in this area, with special attention to studies in rodent models, using pharmacological tools and functional genomics. In doing so, we intend to endow the reader with an updated view of what is known (and what is not known) about the physiological role of GnIH/RFRP signaling in the control of mammalian reproduction. PMID:26779117

  15. Effects of diverse mammalian and nonmammalian gonadotropins in a rat granulosa cell bioassay for follicle-stimulating hormone.

    PubMed

    Dahl, K D; Papkoff, H; Hsueh, A J

    1989-03-01

    The biopotencies of pituitary gonadotropins purified from a marsupial (kangaroo), two avian (ostrich and turkey), a reptile (turtle), an amphibian (bullfrog), and two fish (sturgeon and teleost) species were examined using an in vitro rat granulosa cell bioassay for follicle-stimulating hormone (FSH). Treatment of cultured granulosa cells with increasing concentrations of gonadotropin preparations from these species resulted in dose-dependent increases in estrogen production from negligible amounts to maximal levels of approximately 2-29 ng/culture. The relative biopotencies of these FSH preparations from most potent to least potent were in the order of human greater than ostrich greater than turkey greater than kangaroo greater than turtle greater than sturgeon greater than bullfrog greater than teleost with ED50 values of human 8.7 ng/well; ostrich 10.5 ng/well; turkey 22.5 ng/well; kangaroo 58.2 ng/well; turtle 62.5 ng/well; sturgeon 260 ng/well; bullfrog 750 ng/well; teleost greater than 1000 ng/well. In contrast, luteinizing hormone (LH) preparations were considerably less effective for ostrich, turkey, kangaroo, turtle, and bullfrog, being six-, five-, three-, and twofold less potent than FSH preparations for the same species, demonstrating the specificity of this assay for FSH. An LH preparation from bullfrog was unable to significantly stimulate estrogen production below 500 ng/ml. Thus, the present in vitro bioassay (GAB) using rat granulosa cells provides a sensitive and specific assay for measuring FSH activities of gonadotropins from diverse mammalian and nonmammalian species.

  16. Delayed sequelae of pituitary irradiation.

    PubMed

    Woodruff, K H; Lyman, J T; Lawrence, J H; Tobias, C A; Born, J L; Fabrikant, J I

    1984-01-01

    Since 1958, 781 patients at Lawrence Berkeley Laboratory have received helium-particle stereotactic radiosurgery to the adenohypophysis. Autopsy findings in 15 of these patients are reported. Ten patients received pituitary radiation (average dose, 116 Gy in six fractions) for progressive neovascularization retinopathy due to diabetes mellitus. Evidence of a time-dependent course of progressive fibrosis in their pituitary glands was found. Five patients were treated for eosinophilic adenomas. Although they had lower average doses of radiation (56 Gy in six fractions), their pituitary glands showed cystic cavitation of the adenomas. The adenomas thus appeared more radiosensitive than the normal pars anterior, which, in turn, was more radiosensitive than the adjacent neurohypophysis. No significant radiation changes were found in the surrounding brain or cranial nerves. The endocrine organs under pituitary control showed varying degrees of atrophy, and clinical tests revealed progressive hypofunction. It was concluded that charged-particle therapy produced a sharply delineated focal radiation lesion confined to the pituitary gland but did not cause injury to the critical structures of the surrounding central nervous system.

  17. [Familial isolated pituitary adenoma syndrome].

    PubMed

    Dénes, Judit; Korbonits, Márta; Hubina, Erika; Kovács, Gábor László; Kovács, László; Görömbey, Zoltán; Czirják, Sándor; Góth, Miklós

    2011-05-01

    Familial pituitary adenomas occur in multiple endocrine neoplasia type 1, Carney complex, as well as in familial isolated pituitary adenoma syndrome. Familial isolated pituitary adenoma syndrome is an autosomal dominant disease with incomplete penetrance. Pituitary adenomas occur in familial setting but without any other specific tumors. In 20-40% of families with this syndrome, mutations have been identified in the aryl hydrocarbon receptor interacting protein gene while in the rest of the families the causative gene or genes have not been identified. Families carrying aryl hydrocarbon receptor interacting protein gene mutations have a distinct phenotype with younger age at diagnosis and a predominance of somatotroph and lactotroph adenomas. Germline mutations of the aryl hydrocarbon receptor interacting protein gene can be occasionally identified in usually young-onset seemingly sporadic cases. Genetic and clinical testing of relatives of patients with aryl hydrocarbon receptor interacting protein gene mutations can lead to earlier diagnosis and treatment at an earlier stage of the pituitary tumor. PMID:21498161

  18. Delayed sequelae of pituitary irradiation

    SciTech Connect

    Woodruff, K.H.; Lyman, J.T.; Lawrence, J.H.; Tobias, C.A.; Born, J.L.; Fabrikant, J.I.

    1984-01-01

    Since 1958, 781 patients at Lawrence Berkeley Laboratory have received helium-particle stereotactic radiosurgery to the adenohypophysis. Autopsy findings in 15 of these patients are reported. Ten patients received pituitary radiation (average dose, 116 Gy in six fractions) for progressive neovascularization retinopathy due to diabetes mellitus. Evidence of a time-dependent course of progressive fibrosis in their pituitary glands was found. Five patients were treated for eosinophilic adenomas. Although they had lower average doses of radiation (56 Gy in six fractions), their pituitary glands showed cystic cavitation of the adenomas. The adenomas thus appeared more radiosensitive than the normal pars anterior, which, in turn, was more radiosensitive than the adjacent neurohypophysis. No significant radiation changes were found in the surrounding brain or cranial nerves. The endocrine organs under pituitary control showed varying degrees of atrophy, and clinical tests revealed progressive hypofunction. It was concluded that charged-particle therapy produced a sharply delineated focal ral tests revealed progressive hypofunction. It was concluded that charged-particle therapy produced a sharply delineated focal radiation lesion confined to the pituitary gland but did not cause injury to the critical structures of the surrounding central nervous system.

  19. The Regulation and Function of Fibroblast Growth Factor 8 and Its Function during Gonadotropin-Releasing Hormone Neuron Development

    PubMed Central

    Chung, Wilson C. J.; Linscott, Megan L.; Rodriguez, Karla M.; Stewart, Courtney E.

    2016-01-01

    Over the last few years, numerous studies solidified the hypothesis that fibroblast growth factor (FGF) signaling regulates neuroendocrine progenitor cell proliferation, fate specification, and cell survival and, therefore, is critical for the regulation and maintenance of homeostasis of the body. One important example that underscores the involvement of FGF signaling during neuroendocrine cell development is gonadotropin-releasing hormone (GnRH) neuron ontogenesis. Indeed, transgenic mice with reduced olfactory placode (OP) Fgf8 expression do not have GnRH neurons. This observation indicates the requirement of FGF8 signaling for the emergence of the GnRH neuronal system in the embryonic OP, the putative birth place of GnRH neurons. Mammalian reproductive success depends on the presence of GnRH neurons to stimulate gonadotropin secretion from the anterior pituitary, which activates gonadal steroidogenesis and gametogenesis. Together, these observations are critical for understanding the function of GnRH neurons and their control of the hypothalamus–pituitary–gonadal (HPG) axis to maintain fertility. Taken together, these studies illustrate that GnRH neuron emergence and hence HPG function is vulnerable to genomic and molecular signals that abnormally modify Fgf8 expression in the developing mouse OP. In this short review, we focus on research that is aimed at unraveling how androgen, all-trans retinoic acid, and how epigenetic factors modify control mouse OP Fgf8 transcription in the context of GnRH neuronal development and mammalian reproductive success. PMID:27656162

  20. The Regulation and Function of Fibroblast Growth Factor 8 and Its Function during Gonadotropin-Releasing Hormone Neuron Development

    PubMed Central

    Chung, Wilson C. J.; Linscott, Megan L.; Rodriguez, Karla M.; Stewart, Courtney E.

    2016-01-01

    Over the last few years, numerous studies solidified the hypothesis that fibroblast growth factor (FGF) signaling regulates neuroendocrine progenitor cell proliferation, fate specification, and cell survival and, therefore, is critical for the regulation and maintenance of homeostasis of the body. One important example that underscores the involvement of FGF signaling during neuroendocrine cell development is gonadotropin-releasing hormone (GnRH) neuron ontogenesis. Indeed, transgenic mice with reduced olfactory placode (OP) Fgf8 expression do not have GnRH neurons. This observation indicates the requirement of FGF8 signaling for the emergence of the GnRH neuronal system in the embryonic OP, the putative birth place of GnRH neurons. Mammalian reproductive success depends on the presence of GnRH neurons to stimulate gonadotropin secretion from the anterior pituitary, which activates gonadal steroidogenesis and gametogenesis. Together, these observations are critical for understanding the function of GnRH neurons and their control of the hypothalamus–pituitary–gonadal (HPG) axis to maintain fertility. Taken together, these studies illustrate that GnRH neuron emergence and hence HPG function is vulnerable to genomic and molecular signals that abnormally modify Fgf8 expression in the developing mouse OP. In this short review, we focus on research that is aimed at unraveling how androgen, all-trans retinoic acid, and how epigenetic factors modify control mouse OP Fgf8 transcription in the context of GnRH neuronal development and mammalian reproductive success.

  1. Hypothalamic-pituitary-gonadal axis in the mutant weaver mouse.

    PubMed

    Schwartz, N B; Szabo, M; Verina, T; Wei, J; Dlouhy, S R; Won, L; Heller, A; Hodes, M E; Ghetti, B

    1998-12-01

    The weaver (wv) mutant mouse manifests severe locomotor defects, a deficiency in granule cells of the cerebellum, and cellular deficits in the midbrain dopaminergic system. The wv phenotype is associated with a missense mutation in the pore region of the G-protein-gated inwardly rectifying potassium channel, GIRK2. The homozygous male wv mouse is essentially infertile due to an inadequate level of sperm production. Females are fertile although they also manifest the neurological phenotype. Homozygotes of both sexes have reduced body weight. We have evaluated the hypothalamic-pituitary-gonadal axis in heterozygote and homozygote male and female wv mutants in comparison with wild-type controls. Testicular weight was significantly reduced in the homozygous males, due to degenerative changes of seminiferous epithelium. Serum and pituitary content of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were normal in all groups, and the normal sex differences were noted (FSH and LH higher in males, prolactin higher in females). Pituitary growth hormone (GH) concentration was normal, with control and mutant males showing higher GH than females. Serum testosterone levels were normal in the mutants, as was testicular testosterone. Testicular alpha-inhibin content was mildly reduced, but high in proportion to testicular weight. The defect in spermatogenesis appeared predominantly in the postmeiotic stages. In situ hybridization was consistent with expression of some GIRK2 mRNA isoforms in seminiferous epithelium. There were no significant differences between genotypes in the levels of dopamine, dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid in the mediobasal and preoptic hypothalamic regions. Homovanillic acid levels in these two areas were, however, reduced in wv homozygotes compared to wild-type animals. In the light of normal pituitary hormone levels, normal hypothalamic monoamine concentrations and normal sex differences in

  2. Identification and localization of gonadotropin-inhibitory hormone (GnIH) orthologs in the hypothalamus of the red-eared slider turtle, Trachemys scripta elegans.

    PubMed

    Ukena, Kazuyoshi; Iwakoshi-Ukena, Eiko; Osugi, Tomohiro; Tsutsui, Kazuyoshi

    2016-02-01

    Gonadotropin-inhibitory hormone (GnIH) was discovered in 2000 as a novel hypothalamic neuropeptide that inhibited gonadotropin release in the Japanese quail. GnIH and its orthologs have a common C-terminal LPXRFamide (X=L or Q) motif, and have been identified in vertebrates from agnathans to humans, apart from reptiles. In the present study, we characterized a cDNA encoding GnIH orthologs in the brain of the red-eared slider turtle. The deduced precursor protein consisted of 205 amino-acid residues, encoding three putative peptide sequences that included the LPXRFamide motif at their C-termini. In addition, the precursor sequence was most similar to those of avian species. Immunoaffinity purification combined with mass spectrometry confirmed that three mature peptides were produced in the brain. In situ hybridization and immunohistochemistry showed that turtle GnIH-containing cells were restricted to the periventricular hypothalamic nucleus. Immunoreactive fibers were densely distributed in the median eminence. Thus, GnIH and related peptides may act on the pituitary to regulate pituitary hormone release in turtles as well as other vertebrates.

  3. Early development of the gonadotropin-releasing hormone neuronal network in transgenic zebrafish.

    PubMed

    Zhao, Yali; Lin, Meng-Chin A; Farajzadeh, Matthew; Wayne, Nancy L

    2013-01-01

    Understanding development of gonadotropin-releasing hormone (GnRH) neuronal circuits is fundamental to our understanding of reproduction, but not yet well understood. Most studies have been focused on GnRH neurons located in the hypothalamus and preoptic area (POA), which directly regulate the pituitary-gonadal axis. In zebrafish (Danio rerio), two forms of GnRH have been identified: GnRH2 and GnRH3. GnRH3 neurons in this species plays two roles: hypophysiotropic and neuromodulatory, depending on their location. GnRH3 neurons in the ventral telencephalon, POA, and hypothalamus control pituitary-gonadal function; in other areas (e.g., terminal nerve), they are neuromodulatory and without direct action on reproduction. To investigate the biology of GnRH neurons, a stable line of transgenic zebrafish was generated in which the GnRH3 promoter drives expression of a bright variant of green fluorescent protein (Emerald GFP, or EMD). This provides unprecedented sensitivity in detecting and imaging GnRH3 neurons during early embryogenesis in the transparent embryo. Using timelapse confocal imaging to monitor the time course of GnRH3:EMD expression in the live embryo, we describe the emergence and development of GnRH3 neurons in the olfactory region, hypothalamus, POA, and trigeminal ganglion. By 50 h post fertilization, these diverse groups of GnRH3 neurons project broadly in the central and peripheral nervous systems and make anatomical connections with each other. Immunohistochemistry of synaptic vesicle protein 2 (a marker of synaptic transmission) in this transgenic model suggests synaptic formation is occurring during early development of the GnRH3 neural network. Electrophysiology reveals early emergence of responsiveness to the stimulatory effects of kisspeptin in terminal nerve GnRH3 neurons. Overall, our findings reveal that the GnRH3 neuronal system is comprised of multiple populations of neurons as a complicated network. PMID:24009601

  4. Negative feedback regulation of gonadotropin secretion by androgens in fetal rhesus macaques.

    PubMed

    Resko, J A; Ellinwood, W E

    1985-09-01

    Previously we described sex differences in circulating gonadotropin concentrations (greater in females) in fetal rhesus macaques, and demonstrated that these sex differences relate, at least in part, to the negative feedback actions of testicular secretions. A fully functional gonadal-hypothalamic-pituitary feedback relationship is present as early as Day 100 of gestation in fetal males because castration at this time results in a dramatic increase (greater than 10-fold) in fetal luteinizing hormone (LH) concentrations. Although short-term (6-h) treatment of fetuses with testosterone (T) 3 wk after gonadectomy (GX) does not lower LH levels in males, it is completely effective in females. These data suggest that either T is not the primary testicular factor responsible for feedback suppression of LH in fetal males, or the hypothalamic-pituitary axis becomes insensitive to T after GX. To determine if immediate treatment with T after GX is effective in maintaining LH levels, we gonadectomized five fetal rhesus males on Days 98-104 of gestation and immediately implanted crystalline-T-containing intraabdominal Silastic capsules. An additional five fetuses were treated with the nonaromatizable androgen dihydrotestosterone (DHT). Umbilical arterial samples for hormone analysis were obtained prior to GX and again approximately 3 wk later. Serum from control males (n = 11) castrated in utero on Day 100 of gestation contained significantly greater concentrations of LH and follicle-stimulating hormone (FSH) 3 wk after the operation than before GX. Five sham-operated male fetuses did not have elevated levels of either LH or FSH in their serum on Day 120 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54.

    PubMed

    Messager, Sophie; Chatzidaki, Emmanouella E; Ma, Dan; Hendrick, Alan G; Zahn, Dirk; Dixon, John; Thresher, Rosemary R; Malinge, Isabelle; Lomet, Didier; Carlton, Mark B L; Colledge, William H; Caraty, Alain; Aparicio, Samuel A J R

    2005-02-01

    We have recently described a molecular gatekeeper of the hypothalamic-pituitary-gonadal axis with the observation that G protein-coupled receptor 54 (GPR54) is required in mice and men for the pubertal onset of pulsatile luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion to occur. In the present study, we investigate the possible central mode of action of GPR54 and kisspeptin ligand. First, we show that GPR54 transcripts are colocalized with gonadotropin-releasing hormone (GnRH) neurons in the mouse hypothalamus, suggesting that kisspeptin, the GPR54 ligand, may act directly on these neurons. Next, we show that GnRH neurons seem anatomically normal in gpr54-/- mice, and that they show projections to the median eminence, which demonstrates that the hypogonadism in gpr54-/- mice is not due to an abnormal migration of GnRH neurons (as occurs with KAL1 mutations), but that it is more likely due to a lack of GnRH release or absence of GnRH neuron stimulation. We also show that levels of kisspeptin injected i.p., which stimulate robust LH and FSH release in wild-type mice, have no effect in gpr54-/- mice, and therefore that kisspeptin acts directly and uniquely by means of GPR54 signaling for this function. Finally, we demonstrate by direct measurement, that the central administration of kisspeptin intracerebroventricularly in sheep produces a dramatic release of GnRH into the cerebrospinal fluid, with a parallel rise in serum LH, demonstrating that a key action of kisspeptin on the hypothalamo-pituitary-gonadal axis occurs directly at the level of GnRH release. The localization and GnRH release effects of kisspeptin thus define GPR54 as a major control point in the reproductive axis and suggest kisspeptin to be a neurohormonal effector.

  6. Evolutionary origin of the structure and function of gonadotropin-inhibitory hormone: insights from lampreys.

    PubMed

    Osugi, Tomohiro; Daukss, Dana; Gazda, Kristen; Ubuka, Takayoshi; Kosugi, Takayoshi; Nozaki, Masumi; Sower, Stacia A; Tsutsui, Kazuyoshi

    2012-05-01

    Gonadotropin (GTH)-inhibitory hormone (GnIH) is a novel hypothalamic neuropeptide that inhibits GTH secretion in mammals and birds by acting on gonadotropes and GnRH neurons within the hypothalamic-pituitary-gonadal axis. GnIH and its orthologs that have an LPXRFamide (X = L or Q) motif at the C terminus (LPXRFamide peptides) have been identified in representative species of gnathostomes. However, the identity of an LPXRFamide peptide had yet to be identified in agnathans, the most ancient lineage of vertebrates, leaving open the question of the evolutionary origin of GnIH and its ancestral function(s). In this study, we identified an LPXRFamide peptide gene encoding three peptides (LPXRFa-1a, LPXRFa-1b, and LPXRFa-2) from the brain of sea lamprey by synteny analysis and cDNA cloning, and the mature peptides by immunoaffinity purification and mass spectrometry. The expression of lamprey LPXRFamide peptide precursor mRNA was localized in the brain and gonad by RT-PCR and in the hypothalamus by in situ hybridization. Immunohistochemistry showed appositions of lamprey LPXRFamide peptide immunoreactive fibers in close proximity to GnRH-III neurons, suggesting that lamprey LPXRFamide peptides act on GnRH-III neurons. In addition, lamprey LPXRFa-2 stimulated the expression of lamprey GnRH-III protein in the hypothalamus and GTHβ mRNA expression in the pituitary. Synteny and phylogenetic analyses suggest that the LPXRFamide peptide gene diverged from a common ancestral gene likely through gene duplication in the basal vertebrates. These results suggest that one ancestral function of LPXRFamide peptides may be stimulatory compared with the inhibitory function seen in later-evolved vertebrates (birds and mammals).

  7. Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats.

    PubMed

    Kirby, Elizabeth D; Geraghty, Anna C; Ubuka, Takayoshi; Bentley, George E; Kaufer, Daniela

    2009-07-01

    The subjective experience of stress leads to reproductive dysfunction in many species, including rodents and humans. Stress effects on reproduction result from multilevel interactions between the hormonal stress response system, i.e., the hypothalamic-pituitary-adrenal (HPA) axis, and the hormonal reproductive system, i.e., the hypothalamic-pituitary-gonadal (HPG) axis. A novel negative regulator of the HPG axis known as gonadotropin-inhibitory hormone (GnIH) was recently discovered in quail, and orthologous neuropeptides known as RFamide-related peptides (RFRPs) have also been identified in rodents and primates. It is currently unknown, however, whether GnIH/RFRPs influence HPG axis activity in response to stress. We show here that both acute and chronic immobilization stress lead to an up-regulation of RFRP expression in the dorsomedial hypothalamus (DMH) of adult male rats and that this increase in RFRP is associated with inhibition of downstream HPG activity. We also show that adrenalectomy blocks the stress-induced increase in RFRP expression. Immunohistochemistry revealed that 53% of RFRP cells express receptors for glucocorticoids (GCs), indicating that adrenal GCs can mediate the stress effect through direct action on RFRP cells. It is thought that stress effects on central control of reproduction are largely mediated by direct or indirect effects on GnRH-secreting neurons. Our data show that stress-induced increases in adrenal GCs cause an increase in RFRP that contributes to hypothalamic suppression of reproductive function. This novel insight into HPA-HPG interaction provides a paradigm shift for work on stress-related reproductive dysfunction and infertility, and indicates that future work on stress and reproductive system interactions must include investigation of the role of GnIH/RFRP.

  8. Early Development of the Gonadotropin-Releasing Hormone Neuronal Network in Transgenic Zebrafish

    PubMed Central

    Zhao, Yali; Lin, Meng-Chin A.; Farajzadeh, Matthew; Wayne, Nancy L.

    2013-01-01

    Understanding development of gonadotropin-releasing hormone (GnRH) neuronal circuits is fundamental to our understanding of reproduction, but not yet well understood. Most studies have been focused on GnRH neurons located in the hypothalamus and preoptic area (POA), which directly regulate the pituitary-gonadal axis. In zebrafish (Danio rerio), two forms of GnRH have been identified: GnRH2 and GnRH3. GnRH3 neurons in this species plays two roles: hypophysiotropic and neuromodulatory, depending on their location. GnRH3 neurons in the ventral telencephalon, POA, and hypothalamus control pituitary-gonadal function; in other areas (e.g., terminal nerve), they are neuromodulatory and without direct action on reproduction. To investigate the biology of GnRH neurons, a stable line of transgenic zebrafish was generated in which the GnRH3 promoter drives expression of a bright variant of green fluorescent protein (Emerald GFP, or EMD). This provides unprecedented sensitivity in detecting and imaging GnRH3 neurons during early embryogenesis in the transparent embryo. Using timelapse confocal imaging to monitor the time course of GnRH3:EMD expression in the live embryo, we describe the emergence and development of GnRH3 neurons in the olfactory region, hypothalamus, POA, and trigeminal ganglion. By 50 h post fertilization, these diverse groups of GnRH3 neurons project broadly in the central and peripheral nervous systems and make anatomical connections with each other. Immunohistochemistry of synaptic vesicle protein 2 (a marker of synaptic transmission) in this transgenic model suggests synaptic formation is occurring during early development of the GnRH3 neural network. Electrophysiology reveals early emergence of responsiveness to the stimulatory effects of kisspeptin in terminal nerve GnRH3 neurons. Overall, our findings reveal that the GnRH3 neuronal system is comprised of multiple populations of neurons as a complicated network. PMID:24009601

  9. The progestin levonorgestrel disrupts gonadotropin expression and sex steroid levels in pubertal roach (Rutilus rutilus).

    PubMed

    Kroupova, H K; Trubiroha, A; Lorenz, C; Contardo-Jara, V; Lutz, I; Grabic, R; Kocour, M; Kloas, W

    2014-09-01

    The aim of the present study was to investigate the effects of the synthetic progestin levonorgestrel (LNG) on the reproductive endocrine system of a teleost fish, the roach (Rutilus rutilus). Pubertal roach were exposed for 28 days in a flow-through system to four concentrations of LNG (3, 31, 312, and 3124 ng/l). Both males and females treated with 3124 ng/l LNG exhibited the upregulated levels of vitellogenin and oestrogen receptor 1 mRNA in the liver. At the same concentration, LNG caused a significant upregulation of the mRNA expression of the gene encoding luteinising hormone β-subunit (lhβ) and the suppression of the mRNA expression of the gene encoding follicle-stimulating hormone β-subunit (fshβ) in the pituitary of both male and female roach. A lower LNG concentration (312 ng/l) suppressed mRNA expression of fshβ in males only. Females treated with 3124 ng/l LNG exhibited significantly lower plasma 11-ketotestosterone (11-KT) and oestradiol (E2) concentrations, whereas their testosterone (T) level was higher compared with the control. Females exposed to 312 ng/l LNG presented significantly lower plasma E2 concentrations. Males exposed to ≥31 ng/l LNG exhibited significantly reduced 11-KT levels. As determined through a histological analysis, the ovaries of females were not affected by LNG exposure, whereas the testes of males exposed to 31 and 312 ng/l LNG exhibited a significantly higher percentage of spermatogonia B compared with the control. The results of the present study demonstrate that LNG disrupts the reproductive system of pubertal roach by affecting the pituitary gonadotropin expression and the sex steroid levels. This disruption was determined to occur in males after exposure to an environmentally relevant concentration (31 ng/l). Moreover, the highest tested concentration of LNG (3124 ng/l) exerted an oestrogenic effect on fish of both sexes. PMID:24893273

  10. The effect of selective estrogen receptor modulator administration on the hypothalamic-pituitary-testicular axis in men with idiopathic oligozoospermia.

    PubMed

    Tsourdi, Elena; Kourtis, Anargyros; Farmakiotis, Dimitrios; Katsikis, Ilias; Salmas, Marios; Panidis, Dimitrios

    2009-04-01

    This study evaluates, compares, and contrasts the effects of three selective estrogen receptor modulators (SERMs), namely, tamoxifen, toremifene, and raloxifene, on the hypothalamic-pituitary-testicular axis in 284 consecutive subfertile men with idiopathic oligozoospermia using three therapeutic protocols: [1] tamoxifen, 20 mg, once daily (n = 94); [2] toremifene, 60 mg, once daily (n = 99); and [3] raloxifene, 60 mg, once daily (n = 91). The antiestrogenic effects of SERMs at the hypothalamic level result in a statistically significant increase of gonadotropin levels, which is more marked for tamoxifen and toremifene compared with raloxifene.

  11. The genetics of pituitary adenomas.

    PubMed

    Vandeva, Silvia; Jaffrain-Rea, Marie-Lise; Daly, Adrian F; Tichomirowa, Maria; Zacharieva, Sabina; Beckers, Albert

    2010-06-01

    Pituitary adenomas are one of the most frequent intracranial tumors with a prevalence of clinically-apparent tumors close to 1:1000 of the general population. They are clinically significant because of hormone overproduction and/or tumor mass effects in addition to the need for neurosurgery, medical therapies and radiotherapy. The majority of pituitary adenomas have a sporadic origin with recognized genetic mutations seldom being found; somatotropinomas are an exception, presenting frequent somatic GNAS mutations. In this and other phenotypes, tumorigenesis could possibly be explained by altered function of genes implicated in cell cycle regulation, growth factors or their receptors, cell-signaling pathways, specific hormonal factors or other molecules with still unclear mechanisms of action. Genetic changes, such as allelic loss or gene amplification, and epigenetic changes, usually by promoter methylation, have been implicated in abnormal gene expression, but alternative mechanisms may be present. Familial cases of pituitary adenomas represent 5% of all pituitary tumors. MEN1 mutations cause multiple endocrine neoplasia type 1 (MEN1), while the Carney complex (CNC) is characterized by mutations in the protein kinase A regulatory subunit-1alpha (PRKAR1A) gene or changes in a locus at 2p16. Recently, a MEN1-like condition, MEN4, was found to be related to mutations in the CDKN1B gene. The clinical entity of familial isolated pituitary adenomas (FIPA) is characterized by genetic defects in the aryl hydrocarbon receptor interacting protein (AIP) gene in about 15% of all kindreds and 50% of homogenous somatotropinoma families. Identification of familial cases of pituitary adenomas is important as these tumors may be more aggressive than their sporadic counterparts. PMID:20833337

  12. Identification of a regulatory loop for the synthesis of neurosteroids: a steroidogenic acute regulatory protein-dependent mechanism involving hypothalamic-pituitary-gonadal axis receptors.

    PubMed

    Meethal, Sivan Vadakkadath; Liu, Tianbing; Chan, Hsien W; Ginsburg, Erika; Wilson, Andrea C; Gray, Danielle N; Bowen, Richard L; Vonderhaar, Barbara K; Atwood, Craig S

    2009-08-01

    Brain sex steroids are derived from both peripheral (primarily gonadal) and local (neurosteroids) sources and are crucial for neurogenesis, neural differentiation and neural function. The mechanism(s) regulating the production of neurosteroids is not understood. To determine whether hypothalamic-pituitary-gonadal axis components previously detected in the extra-hypothalamic brain comprise a feedback loop to regulate neuro-sex steroid (NSS) production, we assessed dynamic changes in expression patterns of steroidogenic acute regulatory (StAR) protein, a key regulator of steroidogenesis, and key hypothalamic-pituitary-gonadal endocrine receptors, by modulating peripheral sex hormone levels in female mice. Ovariectomy (OVX; high serum gonadotropins, low serum sex steroids) had a differential effect on StAR protein levels in the extrahypothalamic brain; increasing the 30- and 32-kDa variants but decreasing the 37-kDa variant and is indicative of cholesterol transport into mitochondria for steroidogenesis. Treatment of OVX animals with E(2), P(4), or E(2) + P(4) for 3 days, which decreases OVX-induced increases in GnRH/gonadotropin production, reversed this pattern. Suppression of gonadotropin levels in OVX mice using the GnRH agonist leuprolide acetate inhibited the processing of the 37-kDa StAR protein into the 30-kDa StAR protein, confirming that the differential processing of brain StAR protein is regulated by gonadotropins. OVX dramatically suppressed extra-hypothalamic brain gonadotropin-releasing hormone 1 receptor expression, and was further suppressed in E(2)- or P(4)-treated OVX mice. Together, these data indicate the existence of endocrine and autocrine/paracrine feedback loops that regulate NSS synthesis. Further delineation of these feedback loops that regulate NSS production will aid in developing therapies to maintain brain sex steroid levels and cognition.

  13. Pituitary function and morphology in Fabry disease.

    PubMed

    Maione, Luigi; Tortora, Fabio; Modica, Roberta; Ramundo, Valeria; Riccio, Eleonora; Daniele, Aurora; Belfiore, Maria Paola; Colao, Annamaria; Pisani, Antonio; Faggiano, Antongiulio

    2015-11-01

    Endocrine abnormalities are known to affect patients with Fabry disease (FD). Pituitary gland theoretically represents an ideal target for FD because of high vascularization and low proliferation rate. We explored pituitary morphology and function in a cohort of FD patients through a prospectic, monocentric study at an Academic Tertiary Center. The study population included 28 FD patients and 42 sex and age-matched normal subjects. The protocol included a contrast enhancement pituitary MRI, the assessment of pituitary hormones, anti-pituitary, and anti-hypothalamus antibodies. At pituitary MRI, an empty sella was found in 11 (39%) FD patients, and in 2 (5%) controls (p < 0.001). Pituitary volume was significantly smaller in FD than in controls (p < 0.001). Determinants of pituitary volume were age and alpha-galactosidase enzyme activity. Both parameters resulted independently correlated at multivariate analysis. Pituitary function was substantially preserved in FD patients. Empty sella is a common finding in patients with FD. The major prevalence in the elderly supports the hypothesis of a progressive pituitary shrinkage overtime. Pituitary function seems not to be impaired in FD. An endocrine workup with pituitary hormone assessment should be periodically performed in FD patients, who are already at risk of cardiovascular complications.

  14. Relaxin-3 stimulates the hypothalamic-pituitary-gonadal axis.

    PubMed

    McGowan, B M; Stanley, S A; Donovan, J; Thompson, E L; Patterson, M; Semjonous, N M; Gardiner, J V; Murphy, K G; Ghatei, M A; Bloom, S R

    2008-08-01

    The hypothalamus plays a key role in the regulation of both energy homeostasis and reproduction. Evidence suggests that relaxin-3, a recently discovered member of the insulin superfamily, is an orexigenic hypothalamic neuropeptide. Relaxin-3 is thought to act in the brain via the RXFP3 receptor, although the RXFP1 receptor may also play a role. Relaxin-3, RXFP3, and RXFP1 are present in the hypothalamic paraventricular nucleus, an area with a well-characterized role in the regulation of energy balance that also modulates reproductive function by providing inputs to hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Other members of the relaxin family are known to play a role in the regulation of reproduction. However, the effects of relaxin-3 on reproductive function are unknown. We studied the role of relaxin-3 in the regulation of the hypothalamo-pituitary-gonadal (HPG) axis. Intracerebroventricular (5 nmol) and intraparaventricular (540-1,620 pmol) administration of human relaxin-3 (H3) in adult male Wistar rats significantly increased plasma luteinizing hormone (LH) 30 min postinjection. This effect was blocked by pretreatment with a peripheral GnRH antagonist. Central administration of human relaxin-2 showed no significant effect on plasma LH. H3 dose-dependently stimulated the release of GnRH from hypothalamic explants and GT(1)-7 cells, which express RXFP1 and RXFP3, but did not influence LH or follicle-stimulating hormone release from pituitary fragments in vitro. We have demonstrated a novel role for relaxin-3 in the stimulation of the HPG axis, putatively via hypothalamic GnRH neurons. Relaxin-3 may act as a central signal linking nutritional status and reproductive function.

  15. Human chorionic gonadotropin measurements in parathyroid carcinoma

    PubMed Central

    Rubin, Mishaela R; Bilezikian, John P; Birken, Steven; Silverberg, Shonni J

    2010-01-01

    Objective Preoperatively, it is difficult to differentiate between parathyroid cancer (PtCa) and severe primary hyperparathyroidism (PHPT) due to a benign tumor. Human chorionic gonadotropin (hCG) is a tumor marker in trophoblastic and nontrophoblastic cancers and hyperglycosylated hCG is increased in hCG-secreting malignancies. We investigated whether hCG can distinguish PtCa cancer from benign disease and add prognostic information. Design Observational study. Methods Measurement of urinary hCG (total and malignant isoforms) and serum malignant hCG in 8 subjects with PtCa and in 18 subjects with PHPT (measurement of urine in ten and serum in eight). Results Total urinary hCG was normal in the benign PHPT control subjects (range: 0–17 fmol/mg Cr; nl < 50). In the PtCa subjects, three had normal total urinary hCG levels and survived complication free for at least 2 years; three had persistently elevated total urinary hCG levels (range: 217–1986 fmol/mg Cr) and sustained hip fracture (n = 3) and died (n = 2) within 3 and 6 months respectively; two had a rise in total urinary hCG and had hip fracture (n = 1) and died (n = 2) within 4 and 10 months respectively. Elevated urinary hCG was of the malignant hyperglycosylated isoform. Serum malignant hyperglycosylated hCG values in all of the cancer patients exceeded the maximal serum malignant hCG level of the PHPT subjects with benign disease (3.77 pmol/l). Conclusion hCG, especially itshyperglycosylated isoform, might add diagnostic and prognostic information in PtCa. Further studies would help to elucidate the role of hCG as a potential tumor marker in this disease. PMID:18625691

  16. The effects of estradiol on gonadotropin-releasing hormone neurons in the developing mouse brain.

    PubMed

    Grober, M S; Winterstein, G M; Ghazanfar, A A; Eroschenko, V P

    1998-12-01

    The hypothalamic-pituitary-gonadal (HPG) axis plays a critical role in the control of reproduction. Two key hormonal components of the HPG axis are gonadal steroids and gonadotropin-releasing hormone (GnRH). Gonadal steroids are known to organize the development of neural substrates which control adult reproductive behavior; GnRH is required for normal reproductive structure and function. The possibility that gonadal steroids may produce organizational changes in the pattern of GnRH staining observed in the brain is investigated through the use of injections of estradiol to neonatal mice and subsequent GnRH immunocytochemistry at 2 months of age. Our results indicate that the number of GnRH-immunoreactive (GnRH-ir) cells is normally lower in females than males. Estradiol did not affect the number of GnRH-ir cells in females, but significantly increased the number of GnRH-ir cells in males, suggesting that early exposure to estradiol results in masculinization of the GnRH axis of males.

  17. [Gonadotropin-releasing hormone (GnRH) in selecting patients for varicocelectomy].

    PubMed

    Segenreich, E; Israilov, S; Shmueli, J; Niv, E; Servadio, C

    1997-03-01

    The gonadotropin-releasing hormone (GnRH) test was performed on 182 patients with various degrees of varicocele before and after low, inguinal, spermatic vein ligation, and on 18 controls. The levels of follicle-stimulating hormone (FSH) and luteinizing hormone, a synthetic GnRH (LH), were evaluated before and 45 minutes after intravenous injection of 100 mcg relisorm L. FSH levels increased more than 2-fold in 118 patients [64.8%] and LH levels increased more than 5-fold in 135 patients [74.1%]). In the control group the increase was less in all cases. Therefore, whenever FSH increased more than 2-fold and LH more than 5-fold, we considered the test positive (pathologic); On this basis the GnRH test was positive in 126 (69.2%) and negative (normal) in 56 (30.7%). Of the 126 with positive tests, only 32 (27.3%) still had a positive result 5-6 months after operation. There was correlation between a positive GnRH test and significant improvement in sperm parameters after varicocelectomy: of the 126 with positive tests before operation, sperm parameters improved in 87 patients (69%), while in the 56 patients with negative tests before operation, in only 7 (12.5%) was there improvement after correction. We conclude that a positive GnRH test indicates impairment of the hypothalamic-pituitary-gonadal axis caused by varicocele and could serve as a marker for surgical intervention with good prediction of outcome.

  18. Androgen receptor repression of gonadotropin-releasing hormone gene transcription via enhancer 1.

    PubMed

    Brayman, Melissa J; Pepa, Patricia A; Mellon, Pamela L

    2012-11-01

    Gonadotropin-releasing hormone (GnRH) plays a major role in the hypothalamic-pituitary-gonadal (HPG) axis, and synthesis and secretion of GnRH are regulated by gonadal steroid hormones. Disruptions in androgen levels are involved in a number of reproductive defects, including hypogonadotropic hypogonadism and polycystic ovarian syndrome. Androgens down-regulate GnRH mRNA synthesis in vivo and in vitro via an androgen receptor (AR)-dependent mechanism. Methyltrienolone (R1881), a synthetic AR agonist, represses GnRH expression through multiple sites in the proximal promoter. In this study, we show AR also represses GnRH transcription via the major enhancer (GnRH-E1). A multimer of the -1800/-1766 region was repressed by R1881 treatment. Mutation of two bases, -1792 and -1791, resulted in decreased basal activity and a loss of AR-mediated repression. AR bound to the -1796/-1791 sequence in electrophoretic mobility shift assays, indicating a direct interaction with DNA or other transcription factors in this region. We conclude that AR repression of GnRH-E1 acts via multiple AR-responsive regions, including the site at -1792/-1791.

  19. Androgen receptor repression of gonadotropin-releasing hormone gene transcription via enhancer 1.

    PubMed

    Brayman, Melissa J; Pepa, Patricia A; Mellon, Pamela L

    2012-11-01

    Gonadotropin-releasing hormone (GnRH) plays a major role in the hypothalamic-pituitary-gonadal (HPG) axis, and synthesis and secretion of GnRH are regulated by gonadal steroid hormones. Disruptions in androgen levels are involved in a number of reproductive defects, including hypogonadotropic hypogonadism and polycystic ovarian syndrome. Androgens down-regulate GnRH mRNA synthesis in vivo and in vitro via an androgen receptor (AR)-dependent mechanism. Methyltrienolone (R1881), a synthetic AR agonist, represses GnRH expression through multiple sites in the proximal promoter. In this study, we show AR also represses GnRH transcription via the major enhancer (GnRH-E1). A multimer of the -1800/-1766 region was repressed by R1881 treatment. Mutation of two bases, -1792 and -1791, resulted in decreased basal activity and a loss of AR-mediated repression. AR bound to the -1796/-1791 sequence in electrophoretic mobility shift assays, indicating a direct interaction with DNA or other transcription factors in this region. We conclude that AR repression of GnRH-E1 acts via multiple AR-responsive regions, including the site at -1792/-1791. PMID:22877652

  20. Response of micropenis to topical testosterone and gonadotropin.

    PubMed

    Klugo, R C; Cerny, J C

    1978-05-01

    Five patients were treated with gonadotropin and topical testosterone for micropenis associated with hypothalamic hypogonadotropic hypogonadism. All patients received 1,000 units of gonadotropin weekly for 3 weeks, with a 6-week interval followed by 10% topical testosterone cream twice daily for 3 weeks. Serum testosterone levels were measured and remained equivalent for both modes of therapy. Average penile growth response with gonadotropin was 14.3% increase in length and 5.0% increase of girth. Topical testosterone produced an average increase of 60% in penile length and 52.9% in girth. The greatest growth response occurred in prepubertal male subjects with a minimal response in postpubertal male subjects. This study suggests that 10% topical testosterone cream twice daily will produce effective penile growth. The response appears to be greater in younger children, which is consistent with previously published studies of age-related 5 reductase activity.

  1. Genetically Engineered Mouse Models of Pituitary Tumors

    PubMed Central

    Cano, David A.; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso

    2014-01-01

    Animal models constitute valuable tools for investigating the pathogenesis of cancer as well as for preclinical testing of novel therapeutics approaches. However, the pathogenic mechanisms of pituitary-tumor formation remain poorly understood, particularly in sporadic adenomas, thus, making it a challenge to model pituitary tumors in mice. Nevertheless, genetically engineered mouse models (GEMMs) of pituitary tumors have provided important insight into pituitary tumor biology. In this paper, we review various GEMMs of pituitary tumors, highlighting their contributions and limitations, and discuss opportunities for research in the field. PMID:25136513

  2. Pituitary gigantism: Causes and clinical characteristics.

    PubMed

    Rostomyan, Liliya; Daly, Adrian F; Beckers, Albert

    2015-12-01

    Acromegaly and pituitary gigantism are very rare conditions resulting from excessive secretion of growth hormone (GH), usually by a pituitary adenoma. Pituitary gigantism occurs when GH excess overlaps with the period of rapid linear growth during childhood and adolescence. Until recently, its etiology and clinical characteristics have been poorly understood. Genetic and genomic causes have been identified in recent years that explain about half of cases of pituitary gigantism. We describe these recent discoveries and focus on some important settings in which gigantism can occur, including familial isolated pituitary adenomas (FIPA) and the newly described X-linked acrogigantism (X-LAG) syndrome. PMID:26585365

  3. Pituitary gigantism: Causes and clinical characteristics.

    PubMed

    Rostomyan, Liliya; Daly, Adrian F; Beckers, Albert

    2015-12-01

    Acromegaly and pituitary gigantism are very rare conditions resulting from excessive secretion of growth hormone (GH), usually by a pituitary adenoma. Pituitary gigantism occurs when GH excess overlaps with the period of rapid linear growth during childhood and adolescence. Until recently, its etiology and clinical characteristics have been poorly understood. Genetic and genomic causes have been identified in recent years that explain about half of cases of pituitary gigantism. We describe these recent discoveries and focus on some important settings in which gigantism can occur, including familial isolated pituitary adenomas (FIPA) and the newly described X-linked acrogigantism (X-LAG) syndrome.

  4. Patterns of hypothalamic-pituitary-gonadal dysfunction in men with liver disease due to differing etiologies.

    PubMed

    van Thiel, D H; Gavaler, J S; Spero, J A; Egler, K M; Wright, C; Sanghvi, A T; Hasiba, U; Lewis, J H

    1981-01-01

    The hypothalamic-pituitary-gonadal axis was evaluated in two groups of age-matched men with documented biochemical and histologic liver disease and compared to that of age-matched normal controls. Basal testosterone levels (p less than 0.05), spermatozoa concentrations (p less than 0.01), and seminal plasma volume (p less than 0.01) were reduced in the alcoholics studied with liver disease, but not the hemophiliacs with liver disease when compared to the normal controls. No difference in estradiol levels was noted between groups. Basal follicle-stimulating hormone and luteinizing hormone (LH) concentrations were increased (both p less than 0.01) in the alcoholics while only LH concentrations were increased (p less than 0.01) in the hemophiliacs compared to the normal controls. Gonadotropins (follicle-stimulating hormone and LH) and testosterone responses to clomiphene and to luteinizing hormone-releasing factor (LH only) in the alcoholic population studied, further distinguished the alcoholics from the hemophiliacs and the normal controls. The basal levels of the other anterior pituitary hormones (growth hormone and thyroid-stimulating hormone) as well as their provocative responses to thyrotropin-releasing hormone also distinguished the alcoholics from the hemophiliac population. Based upon these results, we propose that factors other than the liver disease per se are responsible for the disturbances of hypothalamic-pituitary-gonadal function observed in men with biochemically as well as histologically advanced stable liver disease.

  5. Exogenous action of 5-lipoxygenase by its metabolites on luteinizing hormone release in rat pituitary cells.

    PubMed

    Przylipiak, A; Kiesel, L; Habenicht, A J; Przylipiak, M; Runnebaum, B

    1990-02-12

    The stimulatory effect of exogenously administered potato 5-lipoxygenase (0.1-0.3 U/2 ml) on luteinizing hormone (LH) release was demonstrated in rat anterior pituitary cells in a superfusion system. Nordihydroguaiaretic acid (NDGA), an inhibitor of 5-lipoxygenase, abolished the effect of the enzyme on LH secretion. The secretory effect on LH after 5-lipoxygenase administration was biphasic and dependent on Ca2+ indicating that 5-lipoxygenase affects LH release through its oxygenation reaction. Another series of experiments demonstrated that activation of 5-lipoxygenase, expressed as production of leukotriene (LT) B4 and C4 (728 +/- 127 pg/10(6) cells and 178 +/- 23 pg/10(6) cells, respectively) occurs in rat pituitary cells after addition of Ca2+ ionophore A23187. However, LTB4 and LTC4 were not formed by pituitary cells that had previously been desensitized by gonadotropin-releasing hormone (GnRH), the physiological ligand of LH release. These results are consistent with a role of 5-lipoxygenase metabolites in the mechanism of GnRH-induced LH secretion. PMID:2157615

  6. Direct effects of triiodothyronine on production of anterior pituitary hormones and gonadal steroids in goldfish.

    PubMed

    Allan, Euan R O; Habibi, Hamid R

    2012-09-01

    The present study investigated the effects of triiodothyronine (T3) on pituitary gonadotropin (GTH) subunits, thyroid stimulating hormone (TSH) β subunit, and growth hormone (GH) mRNA levels, as well as gonadal steroid secretion during different stages of reproduction in goldfish. Goldfish pituitary cells cultured with T3 exhibited lower tshβ mRNA levels in all reproductive stages and lower luteinising hormone β (lhβ) mRNA levels in early recrudescence, whereas gh and fshβ mRNA levels were not altered. T3 injections significantly reduced circulating oestrogen (OE2) concentrations in early and mid recrudescent male goldfish, but were without effect on the circulating level of OE2 in female fish. T3 injections also reduced circulating levels of testosterone in both male and female goldfish during the mid stage of gonadal recrudescence. In vitro culture of goldfish ovarian follicles at the late stage of gonadal recrudescence, in the presence of T3, resulted in reduced OE2 secretion; no consistent effect of T3 on testosterone secretion was observed in cultured goldfish ovarian follicles and testis. These findings support the hypothesis that T3 impairs reproduction by inhibiting production of gonadal steroids and pituitary luteinising hormone production in goldfish.

  7. Pharmacological characterization of a novel nonpeptide antagonist of the human gonadotropin-releasing hormone receptor, NBI-42902.

    PubMed

    Struthers, R Scott; Xie, Qui; Sullivan, Susan K; Reinhart, Greg J; Kohout, Trudy A; Zhu, Yun-Fei; Chen, Chen; Liu, Xin-Jun; Ling, Nicholas; Yang, Weidong; Maki, Richard A; Bonneville, Anne K; Chen, Ta-Kung; Bozigian, Haig P

    2007-02-01

    Suppression of the hypothalamic-pituitary-gonadal axis by peptides that act at the GnRH receptor has found widespread use in clinical practice for the management of sex-steroid-dependent diseases (such as prostate cancer and endometriosis) and reproductive disorders. Efforts to develop orally available GnRH receptor antagonists have led to the discovery of a novel, potent nonpeptide antagonist, NBI-42902, that suppresses serum LH concentrations in postmenopausal women after oral administration. Here we report the in vitro and in vivo pharmacological characterization of this compound. NBI-42902 is a potent inhibitor of peptide radioligand binding to the human GnRH receptor (K(i) = 0.56 nm). Tritiated NBI-42902 binds with high affinity (K(d) = 0.19 nm) to a single class of binding sites and can be displaced by a range of peptide and nonpeptide GnRH receptor ligands. In vitro experiments demonstrate that NBI-42902 is a potent functional, competitive antagonist of GnRH stimulated IP accumulation, Ca(2+) flux, and ERK1/2 activation. It did not stimulate histamine release from rat peritoneal mast cells. Finally, it is effective in lowering serum LH in castrated male macaques after oral administration. Overall, these data provide a benchmark of pharmacological characteristics required for a nonpeptide GnRH antagonist to effectively suppress gonadotropins in humans and suggest that NBI-42902 may have clinical utility as an oral agent for suppression of the hypothalamic-pituitary-gonadal axis.

  8. Management of nonfunctioning pituitary incidentaloma.

    PubMed

    Galland, Françoise; Vantyghem, Marie-Christine; Cazabat, Laure; Boulin, Anne; Cotton, François; Bonneville, Jean-François; Jouanneau, Emmanuel; Vidal-Trécan, Gwénaelle; Chanson, Philippe

    2015-07-01

    Prevalence of pituitary incidentaloma is variable: between 1.4% and 27% at autopsy, and between 3.7% and 37% on imaging. Pituitary microincidentalomas (serendipitously discovered adenoma <1cm in diameter) may increase in size, but only 5% exceed 10mm. Pituitary macroincidentalomas (serendipitously discovered adenoma>1cm in diameter) show increased size in 20-24% and 34-40% of cases at respectively 4 and 8years' follow-up. Radiologic differential diagnosis requires MRI centered on the pituitary gland. Initial assessment of nonfunctioning (NF) microincidentaloma is firstly clinical, the endocrinologist looking for signs of hypersecretion (signs of hyperprolactinemia, acromegaly or Cushing's syndrome), followed up by systematic prolactin and IGF-1 assay. Initial assessment of NF macroincidentaloma is clinical, the endocrinologist looking for signs of hormonal hypersecretion or hypopituitarism, followed up by hormonal assay to screen for hypersecretion or hormonal deficiency and by ophthalmologic assessment (visual acuity and visual field) if and only if the lesion is near the optic chiasm (OC). NF microincidentaloma of less than 5mm requires no surveillance; those of≥5mm are not operated on but rather monitored on MRI at 6months and then 2years. Macroincidentaloma remote from the OC is monitored on MRI at 1year, with hormonal exploration (for anterior pituitary deficiency), then every 2years. When macroincidentaloma located near the OC is managed by surveillance rather than surgery, MRI is recommended at 6months, with hormonal and visual exploration, then annual MRI and hormonal and visual assessment every 6months. Surgery is indicated in the following cases: evolutive NF microincidentaloma, NF macroincidentaloma associated with hypopituitarism or showing progression, incidentaloma compressing the OC, possible malignancy, non-compliant patient, pregnancy desired in the short-term, or context at risk of apoplexy.

  9. [Two autopsy cases of primary pituitary carcinoma].

    PubMed

    Negishi, K; Suzuki, T; Masuda, Y; Masugi, Y; Teramoto, A; Ohama, E

    1988-05-01

    We studied two autopsy cases of primary pituitary carcinoma. Case-1. A 45 year old female was admitted on Oct. 4 1978, with a complaint of right homonymous hemianopsia. And diagnosis was pituitary adenoma. Partial removal of pituitary tumor was performed on Oct. 23 1978. She died on Dec. 5 1978 due to bleeding of gastrointestinal tract. Autopsy disclosed a pituitary carcinoma invading the left hypothalamus, mamillary body, optic and V cranial nerves, and mid brain as well as sphenoid bone. No extracranial metastasis was noted. Case-2. A 44 year old female with a history of acromegaly for 6 years was admitted with a complaint of headache on May 8 1976. She was diagnosed as having pituitary adenoma. The subtotal removal of pituitary tumor was performed on May 21 1976 and followed by 4500 rad irradiation. At this time, pathological diagnosis was eosinophilic adenoma. Seven years later, she complained of progressive right hearing disturbance, dysarthria and ataxic gait 1983. The second subtotal removal of pituitary tumor was performed with a diagnosis of recurrence of pituitary adenoma on Oct. 7 1983. After the operation, she complicated sepsis and died on Jan. 14 1984. An autopsy disclosed a pituitary carcinoma from residual pituitary gland, continuously extending to the subarachnoid space of the pons, and invading right cerebello-pontine angle and cerebellum. The histological examination revealed pituitary carcinoma with high pleomorphism and glioblastoma multiform-like feature were within the tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Pituitary adenomas in childhood and adolescence.

    PubMed

    Jackman, Suzanne; Diamond, Frank

    2013-07-01

    Scientific advances are revealing the complexity of pituitary development, which is controlled by multiple transcription factors and signaling molecules. Unregulated pituitary cell growth, resulting in pituitary adenoma, is usually sporadic and results from monoclonal expansion of a single mutated cell. However, some adenomas develop as part of a genetic syndrome. Prolactinoma is the most common hormonally active pituitary adenoma in children. The non-functioning (non-secreting) pituitary adenoma is the second most common and often stains positive for GH, PRL, and/or TSH. While Cushing disease, resulting from an ACTH-secreting adenoma, commonly manifests as weight gain with growth deceleration in children, GH excess causes gigantism with rapid, accelerated growth inappropriate for the height of the family. TSH secreting pituitary adenomas are rare, and biochemical analysis will show an elevated thyroxine level with a non-suppressed or high TSH. Though the natural history of pituitary incidentalomas in children is unknown, adult practice guidelines are established. PMID:23957196

  11. Pituitary apoplexy presenting with anorexia and hyponatraemia.

    PubMed

    Sasaki, Yosuke; Nakata, Kenji; Suzuki, Kenichi; Ando, Yasuyo

    2015-04-09

    Pituitary apoplexy, a syndrome caused by haemorrhage into the pituitary gland, typically manifests as sudden severe headache, visual symptoms and hypopituitarism, including adrenal insufficiency. We report a case of a 65-year-old man with adrenal insufficiency due to pituitary apoplexy presenting with anorexia following temporal headache and diagnosed through evaluation for hyponatraemia. MRI focusing on the pituitary gland helped to confirm the diagnosis. Our experience serves as a useful reminder of this atypical presentation of pituitary apoplexy, also known as 'subclinical pituitary apoplexy,' and underscores the importance of careful evaluation for hyponatraemia using serial urine osmolality, which is useful to distinguish hypovolaemic hyponatraemia from euvolaemic hyponatraemia. Clinicians should consider pituitary apoplexy as a differential diagnosis in cases of anorexia, loss of energy or hyponatraemia, following headache even when the patient is lacking classical symptoms such as severe headache or visual symptoms.

  12. Biologically Active Chorionic Gonadotropin: Synthesis by the Human Fetus

    NASA Astrophysics Data System (ADS)

    McGregor, W. G.; Kuhn, R. W.; Jaffe, R. B.

    1983-04-01

    The kidney, and to a slight extent the liver, of human fetuses were found to synthesize and secrete the α subunit common to glycoprotein hormones. Fetal lung and muscle did not synthesize this protein. Since fetal kidney and liver were previously found to synthesize β chorionic gonadotropin, their ability to synthesize bioactive chorionic gonadotropin was also determined. The newly synthesized hormone bound to mouse Leydig cells and elicited a biological response: namely, the synthesis of testosterone. These results suggest that the human fetus may participate in metabolic homeostasis during its development.

  13. Gonadotropin-releasing hormone/human chorionic gonadotropin beta based recombinant antibodies and vaccines.

    PubMed

    Talwar, G P; Vyas, Hemant K; Purswani, Shilpi; Gupta, Jagdish C

    2009-12-01

    Gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) are unique targets for the control of fertility. Immunological approaches to neutralizing these hormones have additional utility in cancer treatment. Vaccines have been developed against both GnRH and hCG and these have undergone Phase I/II clinical trials documenting their safety, reversibility and efficacy. The heterospecies dimer hCG vaccine prevented pregnancy in women of proven fertility without impairment of ovulation or derangement of menstrual regularity and bleeding profiles. The protective threshold of antibody titers to achieve efficacy was determined in these first-ever trials. Recently, a recombinant vaccine against the beta subunit of hCG linked to the B subunit of heat labile enterotoxin has been made and expressed as a glycosylated conjugate in Pichia pastoris. Experiments indicate its ability to generate antibodies above the protective threshold in all immunized Balb/c mice. Ectopic expression of hCG/hCGbeta is observed in many advanced stage cancers of various origins. A chimeric high affinity and specific recombinant antibody against hCGbeta linked to curcumin kills hCGbeta expressing T lymphoblastic leukemia cells without any deleterious effect. Several synthetic and recombinant vaccines have been developed against GnRH. These reduce serum testosterone to castration levels causing atrophy of the prostate. Three Phase I/II clinical trials conducted in India and Austria have shown that these vaccines elicit non-surgical reduction of testosterone, a fall in prostate specific antigen and clinical improvement of prostate carcinoma patients. A multimer recombinant vaccine against GnRH has high efficacy for sterilization of pigs and other animals. PMID:19854518

  14. [Diagnostic significance of LH-RH two step test in women with normoestrogenic amenorrhea: analysis of the self-priming effect of the anterior pituitary glands].

    PubMed

    Takahashi, M; Makino, T; Yokokura, T; Nakayama, A; Takahashi, S; Lin, B L; Suekane, H; Iizuka, R

    1984-05-01

    To investigate the self-priming effect of gonadotropin on the anterior pituitary glands, the response of serum gonadotropins to the "LH-RH two step test" (two step administration of 100 micrograms of synthetic LH-RH at a 60 minute interval) was studied in 20 women with normoestrogenic amenorrhea who were responsive to the progesterone test. The patients were divided into two groups according to the results of the clomiphene test. Blood samples were collected before LH-RH stimulation and 30, 60, 90, 120, 180 minutes after the first stimulation, respectively. The P1P2 ratio (2nd peak level/1st peak level) and delta 1 delta 2 ratio (delta 2/delta 1 = 2nd peak level-60 min. level/1st peak level-0 min. level) of LH and FSH in the clomiphene-positive group were significantly higher than those in the clomiphene-negative group. These ratios are regarded as the degree of the self-priming effect, and at least partially reflect the capacity for the synthesis of pituitary gonadotropins. The results demonstrate that the self-priming effect is more restored in the clomiphene-positive group than in the clomiphene-negative group, and the data also indicate that the analysis of the self-priming effect with the "LH-RH two step test" is useful in developing new diagnostic criteria on ovarian dysfunction.

  15. Molecular regulation of hypothalamus-pituitary-gonads axis in males.

    PubMed

    Jin, Jia-Min; Yang, Wan-Xi

    2014-11-01

    The hypothalamic-pituitary-gonadal axis (HPG) plays vital roles in reproduction and steroid hormone production in both sexes. The focus of this review is upon gene structures, receptor structures and the signaling pathways of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The hormones' functions in reproduction as well as consequences resulting from mutations are also summarized. Specific characteristics of hormones such as the pulsatile secretions of GnRH are also covered. The different regulators of the HPG axis are introduced including kisspeptin, activin, inhibin, follistatin, androgens and estrogen. This review includes not only their basic information, but also their unique function in the HPG axis. Here we view the HPG axis as a whole, so relations between ligands and receptors are well described crossing different levels of the HPG axis. Hormone interactions and transformations are also considered. The major information of this article is depicted in three figures summarizing the current discoveries on the HPG axis. This article systematically introduces the basic knowledge of the HPG axis and provides information of the current advances relating to reproductive hormones.

  16. Behavioral regulation of gonadotropin-releasing hormone.

    PubMed

    Rissman, E F

    1996-02-01

    GnRH controls the hypothalamic-pituitary-gonadal axis in all vertebrate species. Yet despite intense efforts, limited progress has been made toward determining how production of this neuropeptide is regulated. An alternative approach to this problem is to study species whose reproductive status is sensitive to behavioral influences and then to use behavioral interactions to probe the GnRH neuronal system. In this review, data on behaviorally induced alterations in the GnRH system will be presented. In several species of fishes, reproductive status and sex can be altered in adults by changes in the social environment. In these fishes, the numbers and size of GnRH-immunoreactive (GnRH-ir) neurons are modified by an individual's social and sexual status. In the ring dove, courtship activates ovarian follicular development and stimulates androgen production in males. During courtship, mast cells containing GnRH-like immunoreactivity enter the brain. This finding presents a new avenue for examining behavioral endocrine and immune interactions. In the musk shrew, most aspects of female reproduction are activated by contact with a male. Interactions with males trigger changes in the numbers of GnRH-ir cells and rapid production of GnRH peptide. The use of comparative animal models provides us with new insights into neuronal plasticity, neuroendoimmunology, and reproductive biology.

  17. Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary

    PubMed Central

    Mathioudakis, Nestoras; Sundaresh, Ram; Larsen, Alexandra; Ruff, William; Schiller, Jennifer; Cázares, Hugo Guerrero; Burger, Peter; Salvatori, Roberto; Quiñones-Hinojosa, Alfredo

    2014-01-01

    Purpose Recent studies suggest that adult pituitary stem cells may play a role in pituitary tumorigenesis. We sought to explore whether the Glial cell-line derived neurotrophic factor receptor alpha 2 (GFRα2), a recently described pituitary stem/progenitor marker, might be differentially expressed in pituitary adenomas versus normal pituitary. Methods The expression of GFRα2 and other members of the GFR receptor family (GFRα1, α3, α4) were analyzed using RT-PCR, western blot, and immunohistochemistry in 39 pituitary adenomas, 14 normal pituitary glands obtained at autopsy, and cDNA from 3 normal pituitaries obtained commercially. Results GFRα2 mRNA was ~2.6 fold under-expressed in functioning adenomas (P <0.01) and ~3.5 fold over-expressed in non-functioning adenomas (NFAs) (P <0.05) compared to normal pituitary. Among NFAs, GFRα2 was significantly over-expressed (~5-fold) in the gonadotropinoma subtype only (P<0.05). GFRα2 protein expression appeared to be higher in most NFAs, although there was heterogeneity in protein expression in this group. GFRα2 protein expression appeared consistently lower in functioning adenomas by IHC and western blot. In normal pituitary, GFRα2 was localized in Rathke’s remnant, the putative pituitary stem cell niche, and in corticotropes. Conclusion Our results suggest that the pituitary stem cell marker GFRα2 is under-expressed in functioning adenomas and over-expressed in NFAs, specifically gonadotropinomas. Further studies are required to elucidate whether over-expression of GFRα2 in gonadotropinomas might play a role in pituitary tumorigenesis. PMID:24402129

  18. Testicular Steroidogenesis and Locomotor Activity Are Regulated by Gonadotropin-Inhibitory Hormone in Male European Sea Bass

    PubMed Central

    Paullada-Salmerón, José A.; Cowan, Mairi; Aliaga-Guerrero, María; López-Olmeda, José F.; Mañanós, Evaristo L.; Zanuy, Silvia

    2016-01-01

    Gonadotropin-inhibitory hormone (GnIH) is a neurohormone that suppresses reproduction by acting at both the brain and pituitary levels. In addition to the brain, GnIH may also be produced in gonads and can regulate steroidogenesis and gametogenesis. However, the function of GnIH in gonadal physiology has received little attention in fish. The main objective of this study was to evaluate the effects of peripheral sbGnih-1 and sbGnih-2 implants on gonadal development and steroidogenesis during the reproductive cycle of male sea bass (Dicentrarchus labrax). Both Gnihs decreased testosterone (T) and 11-ketotestosterone (11-KT) plasma levels in November and December (early- and mid-spermatogenesis) but did not affect plasma levels of the progestin 17,20β-dihydroxy-4-pregnen-3-one (DHP). In February (spermiation), fish treated with sbGnih-1 and sbGnih-2 exhibited testicles with abundant type A spermatogonia and partial spermatogenesis. In addition, we determined the effects of peripheral Gnih implants on plasma follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) levels, as well as on brain and pituitary expression of the main reproductive hormone genes and their receptors during the spermiation period (February). Treatment with sbGnih-2 increased brain gnrh2, gnih, kiss1r and gnihr transcript levels. Whereas, both Gnihs decreased lhbeta expression and plasma Lh levels, and sbGnih-1 reduced plasmatic Fsh. Finally, through behavioral recording we showed that Gnih implanted animals exhibited a significant increase in diurnal activity from late spermatogenic to early spermiogenic stages. Our results indicate that Gnih may regulate the reproductive axis of sea bass acting not only on brain and pituitary hormones but also on gonadal physiology and behavior. PMID:27788270

  19. Development of a flatfish-specific enzyme-linked immunosorbent assay for Fsh using a recombinant chimeric gonadotropin.

    PubMed

    Chauvigné, François; Verdura, Sara; Mazón, María José; Boj, Mónica; Zanuy, Silvia; Gómez, Ana; Cerdà, Joan

    2015-09-15

    In flatfishes with asynchronous and semicystic spermatogenesis, such as the Senegalese sole (Solea senegalensis), the specific roles of the pituitary gonadotropins during germ cell development, particularly of the follicle-stimulating hormone (Fsh), are still largely unknown in part due to the lack of homologous immunoassays for this hormone. In this study, an enzyme-linked immunosorbent assay (ELISA) for Senegalese sole Fsh was developed by generating a rabbit antiserum against a recombinant chimeric single-chain Fsh molecule (rFsh-C) produced by the yeast Pichia pastoris. The rFsh-C N- and C-termini were formed by the mature sole Fsh β subunit (Fshβ) and the chicken glycoprotein hormone common α subunit (CGA), respectively. Depletion of the antiserum to remove anti-CGA antibodies further enriched the sole Fshβ-specific antibodies, which were used to develop the ELISA using the rFsh-C for the standard curve. The sensitivity of the assay was 10 and 50 pg/ml for Fsh measurement in plasma and pituitary, respectively, and the cross-reactivity with a homologous recombinant single-chain luteinizing hormone was 1%. The standard curve for rFsh-C paralleled those of serially diluted plasma and pituitary extracts of other flatfishes, such as the Atlantic halibut, common sole and turbot. In Senegalese sole males, the highest plasma Fsh levels were found during early spermatogenesis but declined during enhanced spermiation, as found in teleosts with cystic spermatogenesis. In pubertal males, however, the circulating Fsh levels were as high as in adult spermiating fish, but interestingly the Fsh receptor in the developing testis containing only spermatogonia was expressed in Leydig cells but not in the primordial Sertoli cells. These results indicate that a recombinant chimeric Fsh can be used to generate specific antibodies against the Fshβ subunit and to develop a highly sensitive ELISA for Fsh measurements in diverse flatfishes.

  20. Expression patterns of gonadotropin hormones and their receptors during early sexual differentiation in Nile tilapia Oreochromis niloticus.

    PubMed

    Yan, Hongwei; Ijiri, Shigeho; Wu, Quan; Kobayashi, Tohru; Li, Shuang; Nakaseko, Taro; Adachi, Shinji; Nagahama, Yoshitaka

    2012-11-01

    In Nile tilapia, sex-specific expression of foxl2 and cyp19a1a in XX gonads and dmrt1 in XY gonads at 5-6 days after hatching (dah) is critical for differentiation of the gonads into either ovaries or testes. The factors triggering sexually dimorphic expression of these genes are unknown, and whether the gonadotropin hormones are involved in early gonadal sex differentiation of the Nile tilapia has been unclear. In the present study, we determined the precise timing of expression of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the pituitary and that of their receptors (fshra and lhcgrbb) in the undifferentiated gonad in both XX and XY tilapia fry by quantitative RT-PCR and immunohistochemical analysis. Expression of fshb mRNA and Fsh protein in the pituitary was detected from the first sampling day (3 dah) to 25 dah in both XX and XY tilapia larvae without sexual dimorphism and increased gradually after 25 dah in the pituitary. fshra mRNA was expressed beginning 5 dah and was present at significantly higher levels in XX gonads than in the XY gonads at 6-25 dah. These results indicate that the level of Fsh protein in the pituitary was not critical for differentiation of gonads into ovaries or testes, but the expression level of its receptor, fshra, in undifferentiated gonads appeared to be involved in determining gonadal sexual differentiation. Based on these observations, it is likely that in XX gonads, up-regulation of fshra may be necessary to induce cyp19a1a expression, which stimulates estradiol-17beta (E(2)) production and subsequent ovarian differentiation. On the other hand, lhb mRNA was not detected until 25 dah in the pituitaries of both sexes, and sexual dimorphism in lhcgrbb mRNA levels appeared later (10-25 dah) than that of fshra in the gonads, indicating the limited role of LH and lhcgrbb in gonadal differentiation of the Nile tilapia.

  1. Effects of the benomyl metabolite, carbendazim, on the hypothalamic-pituitary reproductive axis in the male rat.

    PubMed

    Goldman, J M; Rehnberg, G L; Cooper, R L; Gray, L E; Hein, J F; McElroy, W K

    1989-07-17

    Carbendazim (MBC), the bioactive metabolite of the fungicide benomyl, has been reported to induce a number of testicular alterations in male rats. Since it is possible that extragonadal changes contribute to the appearance of such effects, the present study focused on the presence of concurrent endocrine changes in the hypothalamic and pituitary components of the brain-pituitary-testicular axis. Subchronic administration of MBC (50, 100, 200 or 400 mg/kg) was found to cause a dose-related elevation in serum follicle stimulating hormone (FSH) and pituitary luteinizing hormone (LH). Values for prolactin and thyroid-stimulating hormone remained unchanged. No statistical differences in gonadotropin-releasing hormone concentrations were present in mediobasal hypothalamus, although an elevation in anterior hypothalamic values was found at the low dose, followed by a dose-related decline. These findings demonstrate that previously reported gonadal differences following subchronic exposure to carbendazim are accompanied by alterations elsewhere in the reproductive system which appear to involve both changes in Sertoli cell-pituitary feedback signals and direct effects of the compound on the central nervous system.

  2. Pituitary hormone mRNA expression in European sea bass Dicentrarchus labrax in seawater and following acclimation to fresh water.

    PubMed

    Varsamos, Stamatis; Xuereb, Benoît; Commes, Thérèse; Flik, Gert; Spanings-Pierrot, Céline

    2006-11-01

    The mRNA expression of pituitary prolactin (prl), growth hormone (gh), somatolactin (sl), proopiomelanocortin (pomc), and gonadotropins (gthI and gthII) was quantified by real-time PCR, in sea bass, Dicentrarchus labrax, adapted for 1 month to seawater (SW) or freshwater (FW). In addition, IGF-I (igfI) mRNA expression in liver and branchial Na+/K+ -ATPase activity were determined. L17 ribosomal protein (rpL17) and elongation factor 1alpha (ef1alpha) were validated as reference genes in real-time PCR in the experimental context. The real-time PCR assays were validated for the different hormone genes considered. Expression of pituitary pomc, gthI, gthII, gh, and liver igfI was not significantly different between FW and SW fish. Pituitary prlwas 4.5-foldhigher in FWthan in SW, whereas pituitary sl was 1.8-fold higher in SW- compared with FW-adapted fish. Gill Na+/K+ -ATPase specific activity was 2.3-fold higher in FW sea bass compared with SW fish. Plasma cortisol levels were 6.5-fold lower in SW- than in FW-adapted specimens. The results are discussed in relation to the osmoregulatory strategy of this euryhaline SW species, which displays features that do not fit present models based on salmonids and FWeuryhaline teleosts.

  3. Effect of LPS on reproductive system at the level of the pituitary of anestrous ewes.

    PubMed

    Herman, A P; Romanowicz, K; Tomaszewska-Zaremba, D

    2010-12-01

    In our research we focused our attention on the effect of the immune stress induced by bacterial endotoxin-lipopolysaccharide (LPS) on the hypothalamic-pituitary-gonadal axis (HPG) at the pituitary level. We examined the effect of intravenous (i.v.) LPS injection on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release from the anterior pituitary gland (AP) in anestrous ewes. The effect of endotoxin on prolactin and cortisol circulating levels was also determined. We also researched the effect of immune challenge on the previously mentioned pituitary hormones and their receptors genes expression in the AP. Our results demonstrate that i.v. LPS injection decreased the plasma concentration of LH (23%; p < 0.05) and stimulates cortisol (245%; p < 0.05) and prolactin (60%; p < 0.05) release but has no significant effect on the FSH release assayed during 6 h after LPS treatment in comparison with the control levels. The LPS administration affected the genes expression of gonadotropins' β-subunits, prolactin and their receptors in the AP. Endotoxin injection significantly decreased the LHβ and LH receptor (LHR) gene expression (60%, 64%; p < 0.01 respectively), increased the amount of mRNA encoding FSHβ, FSH receptor (FSHR) (124%, 0.05; 166%, p < 0.01; respectively), prolactin and prolactin receptor (PRLR) (50%, 47%, p < 0.01; respectively). The presented, results suggest that immune stress is a powerful modulator of the HPG axis at the pituitary level. The changes in LH secretion could be an effect of the processes occurring in the hypothalamus. However, the direct effect of immune mediators, prolactin, cortisol and other components of the hypothalamic pituitary-adrenal (HPA) axis on the activity of gonadotropes has to be considered as well. Those molecules could affect LH synthesis directly through a modulation at all stages of LHβ secretion as well as indirectly influencing the GnRHR expression and leading to reduced

  4. Ontogenic expression profiles of gonadotropins (fshb and lhb) and growth hormone (gh) during sexual differentiation and puberty onset in female zebrafish.

    PubMed

    Chen, Weiting; Ge, Wei

    2012-03-01

    In the zebrafish model, the ontogenic expression profiles of all pituitary hormones have been reported except gonadotropins, partly because they are not supposed to be expressed in the embryonic stage. The spatiotemporal expression patterns of gonadotropins, namely follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh), in this species therefore remain largely unknown. As the master hormones controlling reproduction, the information on this issue would be valuable for understanding the roles of gonadotropins in early sexual development. Using double-colored fluorescent in situ hybridization (FISH) and real-time quantitative PCR (qPCR), this study was undertaken to analyze the ontogenic expression patterns of FSHbeta (fshb) and LHbeta (lhb) subunits in the zebrafish pituitary, with particular emphasis on the stage of sexual differentiation (∼25-30 dpf [days postfertilization]) and puberty onset (∼45 dpf). As a control, growth hormone (gh) was also examined throughout the study. The zebrafish were collected at different time points of early development, including 4, 5, 6, 8, 10, 13, 16, 19, 22, 25, 28, 38, 48, and 53 dpf. The head of each fish, including the brain and pituitary, was sampled for double-colored FISH analysis, whereas the body was fixed for histological examination of sex and gonadal developmental stage. Our results showed that the expression of fshb started much earlier than that of lhb, with its mRNA signal detectable (∼2-3 cells per pituitary) shortly after hatching (4 dpf). In contrast, lhb expression became detectable much later, at the time of sex differentiation (∼25 dpf). In female zebrafish, the first morphological sign for puberty is the first wave of follicle transition from the primary growth to previtellogenic stage, which occurs around 45 dpf and is marked by the appearance of cortical alveoli in the oocytes. Interestingly, the number of lhb-expressing cells was very low (∼5-6 cells per pituitary) before this transition

  5. Postoperative radiosurgery of pituitary adenomas.

    PubMed

    Valentino, V

    1991-01-01

    From 1984-1990, 52 patients with pituitary adenomas had postoperative radiosurgery for incomplete surgical removal or regrowth of the tumor. The atraumatic Greitz-Bergström fixation head device was adopted for the stereotactic procedure and irradiation was performed with a linear accelerator. Because of the variability of the tumor response, a 10-20 Gy single dose was directed at 1-2 targets and radiosurgery repeated if the result was unsatisfactory. The median radiation dose was 30 Gy. No adverse effects occurred. Regression of pretreatment symptoms caused by tumor mass was observed in 67% of patients. GH and PRL activity decreased in 20 patients, was stable in 11 and increased in 2 prolactinomas. CT studies showed disappearance of the tumor in 4 patients and shrinkage in 36. Postoperative radiosurgery is a valuable method of treatment whenever pituitary surgery has been incomplete.

  6. Inhibition of cyclic gonadotropin secretion by endogenous human prolactin.

    PubMed

    Tyson, J E; Khojandi, M; Huth, J; Smith, B; Thomas, P

    1975-02-01

    The resumption of cyclic uterine bleeding reportedly accompanies the use of human prolactin (HPRL)-suppressing agents in postpill galactorrhea-amenorrhea. In this laboratory, HPRL suppression with L-dopa was variable and short lived. Basal plasma HPRL levels were elevated before and after as much as five months of therapy. Galactorrhea persisted and mean gonadotropin concentrations were subnormal. An immediate and sustained attenuation of HPRL secretion ( less than 200 per cent) followed the use of 2-Br-alpha-ergocryptine (CB-154). Cyclic gonadotropin secretion resumed and was accompanied by ovulation and, in one instance, pregnancy. The cessation of galactorrhea was positively correlated with the rise in the daily concentration of 17 beta-estradiol. Cyclic postovulatory menstruation continued after the cessation of CB-154 treatment. HPRL levels remained normal. The daily patterns of human follicle-stimulating hormone (HFSH) and human tuteinizing hormone (HLH) secretion created by the suppression of HPRL displayed an inherent rhythmicity identical to that observed at the time of menarche. The inhibitory effects of HPRL appeared directed at cyclic rather than tonic gonadotropin secretion. At the same time, diminished ovarian estrogen production seemed to increase mammary gland sensitivity to HPRL, leading to lactation. One may postulate, therefore, that the ingestion of sex steroids is associated with an over-all suppression of endogenous cyclic and, to a lesser extent, tonic gonadotropin secretion secondary to which ovarian function is attenuated. Without physiologic concentration of circulating estrogen, HPRL induces mammary alveolar function with the production of a milklike secretion.

  7. Diagnostic Accuracy of Perioperative Measurement of Basal Anterior Pituitary and Target Gland Hormones in Predicting Adrenal Insufficiency After Pituitary Surgery.

    PubMed

    Cerina, Vatroslav; Kruljac, Ivan; Radosevic, Jelena Marinkovic; Kirigin, Lora Stanka; Stipic, Darko; Pecina, Hrvoje Ivan; Vrkljan, Milan

    2016-03-01

    The insulin tolerance test (ITT) is the gold standard for diagnosing adrenal insufficiency (AI) after pituitary surgery. The ITT is unpleasant for patients, requires close medical supervision and is contraindicated in several comorbidities. The aim of this study was to analyze whether tumor size, remission rate, preoperative, and early postoperative baseline hormone concentrations could serve as predictors of AI in order to increase the diagnostic accuracy of morning serum cortisol. This prospective study enrolled 70 consecutive patients with newly diagnosed pituitary adenomas. Thirty-seven patients had nonfunctioning pituitary adenomas (NPA), 28 had prolactinomas and 5 had somatotropinomas. Thyroxin (T4), thyrotropin (TSH), prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and insulin-like growth factor 1 (IGF-I) were measured preoperatively and on the sixth postoperative day. Serum morning cortisol was measured on the third postoperative day (CORT3) as well as the sixth postoperative day (CORT6). Tumor mass was measured preoperatively and remission was assessed 3 months after surgery. An ITT was performed 3 to 6 months postoperatively. Remission was achieved in 48% of patients and AI occurred in 51%. Remission rates and tumor type were not associated with AI. CORT3 had the best predictive value for AI (area under the curve (AUC) 0.868, sensitivity 82.4%, specificity 83.3%). Tumor size, preoperative T4, postoperative T4, and TSH were also associated with AI in a multivariate regression model. A combination of all preoperative and postoperative variables (excluding serum cortisol) had a sensitivity of 75.0% and specificity of 77.8%. The predictive power of CORT3 substantially improved by adding those variables into the model (AUC 0.921, sensitivity 94.1%, specificity 78.3%, PPV 81.9%, NPV of 92.7%). In a subgroup analysis that included only female patients with NPA, LH had exactly the same predictive value as CORT3. The addition

  8. Diagnostic Accuracy of Perioperative Measurement of Basal Anterior Pituitary and Target Gland Hormones in Predicting Adrenal Insufficiency After Pituitary Surgery

    PubMed Central

    Cerina, Vatroslav; Kruljac, Ivan; Radosevic, Jelena Marinkovic; Kirigin, Lora Stanka; Stipic, Darko; Pecina, Hrvoje Ivan; Vrkljan, Milan

    2016-01-01

    Abstract The insulin tolerance test (ITT) is the gold standard for diagnosing adrenal insufficiency (AI) after pituitary surgery. The ITT is unpleasant for patients, requires close medical supervision and is contraindicated in several comorbidities. The aim of this study was to analyze whether tumor size, remission rate, preoperative, and early postoperative baseline hormone concentrations could serve as predictors of AI in order to increase the diagnostic accuracy of morning serum cortisol. This prospective study enrolled 70 consecutive patients with newly diagnosed pituitary adenomas. Thirty-seven patients had nonfunctioning pituitary adenomas (NPA), 28 had prolactinomas and 5 had somatotropinomas. Thyroxin (T4), thyrotropin (TSH), prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and insulin-like growth factor 1 (IGF-I) were measured preoperatively and on the sixth postoperative day. Serum morning cortisol was measured on the third postoperative day (CORT3) as well as the sixth postoperative day (CORT6). Tumor mass was measured preoperatively and remission was assessed 3 months after surgery. An ITT was performed 3 to 6 months postoperatively. Remission was achieved in 48% of patients and AI occurred in 51%. Remission rates and tumor type were not associated with AI. CORT3 had the best predictive value for AI (area under the curve (AUC) 0.868, sensitivity 82.4%, specificity 83.3%). Tumor size, preoperative T4, postoperative T4, and TSH were also associated with AI in a multivariate regression model. A combination of all preoperative and postoperative variables (excluding serum cortisol) had a sensitivity of 75.0% and specificity of 77.8%. The predictive power of CORT3 substantially improved by adding those variables into the model (AUC 0.921, sensitivity 94.1%, specificity 78.3%, PPV 81.9%, NPV of 92.7%). In a subgroup analysis that included only female patients with NPA, LH had exactly the same predictive value as CORT3. The

  9. Fibrosarcoma complicating irradiated pituitary adenoma

    SciTech Connect

    Shi, T.; Farrell, M.A.; Kaufmann, J.C.

    1984-09-01

    Eight years after radiation therapy (5000 rads of 60Co) for a pituitary adenoma, a patient developed a sellar fibrosarcoma. The tumor had an aggressive growth pattern: it infiltrated the optic nerve, sphenoidal air sinus, hypothalamus, and both cavernous sinuses, where compression of the left internal carotid artery resulted in a massive hemispheric infarction. Surgery was ineffective in arresting rapid growth of the lesion; death occurring 5 months after onset of symptoms.

  10. Transsphenoidal surgery for pituitary tumours

    PubMed Central

    Massoud, A; Powell, M; Williams, R; Hindmarsh, P; Brook, C

    1997-01-01

    Accepted 29 January 1997
 OBJECTIVES—Transsphenoidal surgery (TSS) is the preferred method for the excision of pituitary microadenomas in adults. This study was carried out to establish the long term efficacy and safety of TSS in children.
STUDY DESIGN—A 14 year retrospective analysis was carried out on 23 children (16 boys and seven girls), all less than 18 years of age, who had undergone TSS at our centre.
RESULTS—Twenty nine transsphenoidal surgical procedures were carried out. The most common diagnosis was an adrenocorticotrophic hormone (ACTH) secreting adenoma (14 (61%) patients). The median length of follow up was 8.0 years (range 0.3-14.0 years). Eighteen (78%) patients were cured after the first procedure. No death was related to the operation. The most common postoperative complication was diabetes insipidus, which was transient in most patients. Other complications were headaches in two patients and cerebrospinal fluid leaks in two patients. De novo endocrine deficiencies after TSS in children were as follows: three (14%) patients developed panhypopituitarism, eight (73%) developed growth hormone insufficiency, three (14%) developed secondary hypothyroidism, and four (21%) developed gonadotrophin deficiency. Permanent ACTH deficiency occurred in five (24%) patients, though all patients received postoperative glucocorticoid treatment until dynamic pituitary tests were performed three months after TSS.
CONCLUSIONS—TSS in children is a safe and effective treatment for pituitary tumours, provided it is performed by surgeons with considerable experience and expertise. Surgical complications are minimal. Postoperative endocrine deficit is considerable, but is only permanent in a small proportion of patients.

 • Transsphenoidal surgery is a safe and effective treatment for pituitary tumours in children • Transsphenoidal surgery should be performed by surgeons with considerable experience and expertise • Surgical complications of

  11. Immunocytochemical and ultrastructural identification of pituitary cell types in the protogynous Thalassoma duperrey during adult sexual ontogeny

    USGS Publications Warehouse

    Parhar, I.S.; Nagahama, Y.; Grau, E.G.; Ross, R.M.

    1998-01-01

    Protogynous wrasses (Thalassoma duperrey): females (F), primary males (PM) along with a few terminal-phase males (TM) and sex-changed males (SM), were used to characterize the topographical organization of the pituitary. In general, immunocytochemical and ultrastructural features of the adenohypophyseal cell types of the saddleback wrasse pituitary resemble those of other teleosts. In the rostral pars distalis (RPD), corticotropic cells were found bordering the neurohypophysis (NH) and surrounding the centroventrally located prolactin cells. Thyrotropic cells formed a small group in the anteriodorsal part of the rostral and proximal pars distalis (PPD). The somatotropic cells were distributed in large clusters, mostly organized in cell cords around the interdigitations of the NH of the dorsal PPD. Cells containing gonadotropin I?? subunit were localized in the dorsal parts of the PPD, in close association with somatotropic cells and gonadotropin II?? subunit containing cells were seen in the centroventral parts of the PPD and along the periphery of the pars intermedia (PI). The pars intermedia was composed of melanotropic cells and somatolactin cells that lined the neurohypohysis. Distinct ultrastructural differences in corticotropic and somatotropic cells were not observed between the four groups. In all groups, prolactin cells in the ventral-most RPD could be immature cells or actively secreting prolactin. Gonadotropic II cells of PM and F had relatively higher incidence of "nuclear budding" and cell organelles compared to TM and SM. Besides gonadotropic, the active melanotropic and somatolactin cells might be associated with some aspect(s) of reproduction.

  12. Differential effects of short-term fasting on pulsatile thyrotropin, gonadotropin, and alpha-subunit secretion in healthy men--a clinical research center study.

    PubMed

    Samuels, M H; Kramer, P

    1996-01-01

    In healthy subjects, short term fasting suppresses the hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal (HPG) axes, with decreased serum levels of TSH and LH. However, effects of fasting on pulsatile release of TSH, LH, FSH, and alpha-subunit are less clear. Eleven healthy young men each underwent two 2-day studies: a baseline study during normal caloric intake and a fasting study during 56 h of caloric deprivation. During the final 24 h of each study, blood samples were drawn every 15 min for measurement of serum TSH, LH, FSH, and alpha-subunit pulses. Fifty-six hours of fasting caused a 50% suppression of mean TSH levels and TSH pulse amplitude, without altering TSH pulse frequency. Nocturnal TSH pulse amplitude decreased by 60%, with abolition of the usual nocturnal TSH surge. Fasting suppressed mean LH levels and LH pulse amplitude by 30%, without affecting LH pulse frequency. In contrast, mean FSH levels only decreased by 13%, without changes in FSH pulse parameters, whereas mean alpha-subunit levels and pulse amplitude decreased by 20%. These data show that short term fasting has a greater suppressive effect on the hypothalamic-pituitary-thyroid axis than on the HPG axis. Within the HPG axis, FSH is more resistant to fasting-induced suppression than LH, implying discordant regulation of the two gonadotropins during nutritional deprivation. alpha-Subunit suppression during fasting appears to parallel that seen for LH.

  13. Coexisting rathke cleft cyst and pituitary adenoma presenting with pituitary apoplexy: report of two cases.

    PubMed

    Gessler, Florian; Coon, Valerie C; Chin, Steven S; Couldwell, William T

    2011-11-01

    The authors report two cases of coexisting Rathke cleft cyst (RCC) and pituitary macroadenoma. Both patients presented at the university hospital with pituitary apoplexy symptoms of sudden-onset headache while undergoing treatment with Coumadin (warfarin). Magnetic resonance imaging was consistent with a pituitary adenoma in one case and RCC in the other. Intraoperative findings and pathological work-up identified RCC along with adenomatous tissue displaying hemorrhagic pituitary adenoma in one and hemorrhagic RCC in the other. Clinical symptoms of pituitary apoplexy were present in both cases, making pituitary and RCC apoplexy clinically indistinguishable. RCC and concomitant pituitary adenoma are a rare intraoperative finding that must be considered as a differential diagnosis in patients with symptoms of pituitary adenoma apoplexy.

  14. Pituitary function following treatment with reproductive toxins.

    PubMed Central

    Cooper, R L; Goldman, J M; Rehnberg, G L

    1986-01-01

    Appropriate regulation of reproductive processes are dependent upon the integrity of pituitary function. In this selected review, we evaluate the evidence that certain environmental compounds exert their effect on reproductive function via a direct action on the pituitary gland. We also discuss examples of changes in pituitary hormone secretion that occur in response to changes in neuronal or gonadal control of the pituitary. A limited number of studies suggest that measures of pituitary hormone secretion provide an early and sensitive measure of a compound's potential effects on the reproductive system. However, the most striking aspect of this area is the sparse and inconsistent information describing pituitary function following exposure to environmental pollutants. PMID:3830104

  15. Exercise training-induced changes in anterior pituitary gonadotrope of the female rat.

    PubMed

    Caston, A L; Farrell, P A; Deaver, D R

    1995-07-01

    Chronic exercise training may alter the hypothalamic-pituitary-ovarian axis by affecting gonadotropin secretion and structural indexes of the anterior pituitary gonadotropes. Young female Harlan Sprague-Dawley rats were randomly assigned to either a 12-wk intensive treadmill-running program (n = 16) or to a sedentary untrained group [untrained-proestrus (UTP), n = 16]. After training for 3 mo, animals were killed on proestrous morning, and individual pituitary glands were enzymatically dispersed into single-cell suspensions. Trained rats maintained either predominantly regular estrous cycles [trained-proestrus (TP), n = 11] or exhibited anestrous vaginal cytology [trained-anestrus (TA), n = 5]. At death, plasma estradiol concentrations for TP (57.4 +/- 6 pg/ml, mean +/- SE) and UTP (54.6 +/- 5 pg/ml) were similar. However, TA had plasma estradiol levels (2.7 +/- 0.2 pg/ml; P < 0.05) reflecting their anestrous status. Basal luteinizing hormone (LH) secretion (20-h static incubation) was significantly reduced in gonadotropes from TA (7.8 +/- 1.1 ng/pooled wells) compared with TP (13.6 +/- 1.6 ng/pooled wells) and UTP (12.6 +/- 1.0 ng/pooled wells). Immunofluorescence LH staining and cytoplasmic granularity were significantly lower within the TA gonadotrope population compared with those of TP and UTP rats. Evidence of impaired basal LH secretion, reduced gonadotrope LH-specific fluorescein content, and reduced gonadotrope cytoplasmic granularity in TA rats suggests that, concomitant with proposed changes in the central neural drive, there are important exercise training-induced alterations of the anterior pituitary gonadotrope that influence rats' estrous cycles and affect their reproductive status.

  16. Female-Specific Induction of Rat Pituitary Dentin Matrix Protein-1 by GnRH

    PubMed Central

    Kucka, Marek; Bjelobaba, Ivana; Clokie, Samuel J. H.; Klein, David C.

    2013-01-01

    Hypothalamic GnRH is the primary regulator of reproduction in vertebrates, acting via the G protein-coupled GnRH receptor (GnRHR) in pituitary gonadotrophs to control synthesis and release of gonadotropins. To identify elements of the GnRHR-coupled gene network, GnRH was applied in a pulsatile manner for 6 hours to a mixed population of perifused pituitary cells from cycling females, mRNA was extracted, and RNA sequencing analysis was performed. This revealed 83 candidate-regulated genes, including a large number coding for secreted proteins. Most notably, GnRH induces a greater than 600-fold increase in expression of dentin matrix protein-1 (Dmp1), one of five members of the small integrin-binding ligand N-linked glycoprotein gene family. The Dmp1 response is mediated by the GnRHR, not elicited by other hypothalamic releasing factors, and is approximately 20-fold smaller in adult male pituitary cells. The sex-dependent Dmp1 response is established during the peripubertal period and independent of the developmental pattern of Gnrhr expression. In vitro, GnRH-induced expression of this gene is coupled with release of DMP1 in extracellular medium through the regulated secretory pathway. In vivo, pituitary Dmp1 expression in identified gonadotrophs is elevated after ovulation. Cell signaling studies revealed that the GnRH induction of Dmp1 is mediated by the protein kinase C signaling pathway and reflects opposing roles of ERK1/2 and p38 MAPK; in addition, the response is facilitated by progesterone. These results establish that DMP1 is a novel secretory protein of female rat gonadotrophs, the synthesis and release of which are controlled by the hypothalamus through the GnRHR signaling pathway. This advance raises intriguing questions about the intrapituitary and downstream effects of this new player in GnRH signaling. PMID:24085820

  17. Polymorphisms in gonadotropin and gonadotropin receptor genes as markers of ovarian reserve and response in in vitro fertilization.

    PubMed

    La Marca, Antonio; Sighinolfi, Giovanna; Argento, Cindy; Grisendi, Valentina; Casarini, Livio; Volpe, Annibale; Simoni, Manuela

    2013-03-15

    Since gonadotropins are the fundamental hormones that control ovarian activity, genetic polymorphisms may alter gonadal responsiveness to glycoproteins; hence they are important regulators of hormone activity at the target level. The establishment of the pool of primordial follicles takes place during fetal life and is mainly under genetic control. Consequently, single nucleotide polymorphisms (SNPs) in gonadotropins and their receptors do not seem to be associated with any significant modification in the endowment of nongrowing follicles in the ovary. Indeed, the age at menopause, a biological characteristic strongly related to ovarian reserve, as well as markers of functional ovarian reserve such as anti-Müllerian hormone and antral follicle count, are not different in women with different genetic variants. Conversely, some polymorphisms in FSH receptor (FSHR) seem to be associated with modifications in ovarian activity. In particular, studies suggest that the Ser680 genotype for FSHR is a factor of relative resistance to FSH stimulation resulting in slightly higher FSH serum levels, thus leading to a prolonged duration of the menstrual cycle. Moreover, some FSHR gene polymorphisms show a positive association with ovarian response to exogenous gonadotropin administration, hence exhibiting some potential for a pharmacogenetic estimation of the FSH dosage in controlled ovarian stimulation. The study of SNPs of the FSHR gene is an interesting field of research that could provide us with new information about the way each woman responds to exogenous gonadotropin administration during ovulation induction.

  18. Impact of food restriction on ovarian development, RFamide-related peptide-3 and the hypothalamic-pituitary-ovarian axis in pre-pubertal ewes.

    PubMed

    Li, H; Song, H; Huang, M; Nie, H; Wang, Z; Wang, F

    2014-10-01

    RFamide-related peptide-3 (RFRP-3), the mammalian ortholog of gonadotropin-inhibiting hormone, has been implicated as a mediator between reproduction and energy balance. This study aimed to investigate the physiological effects of RFRP-3 on the process of ovarian development in food-restricted pre-pubertal ewes. The results showed that food restriction significantly inhibited the ovarian development and follicular growth. The data of qPCR in the hypothalamic-pituitary-ovarian (HPO) axis showed that food restriction not only upregulated RFRP-3 mRNA expression but also downregulated the mRNA expression of gonadotropin-releasing-hormone receptor, follicle-stimulating hormone receptor and luteinizing hormone receptor (LHR). Immunohistochemistry of RFRP-3 in the ovaries suggested that RFRP-3 may regulate the follicular development. These results suggested that the changes of RFRP-3 in response to food restriction might influence the HPO axis and inhibit ovarian development.

  19. [Old phenotype and new genotypes. Pituitary adenomas].

    PubMed

    Gérard, C; Jedidi, H; Petrossians, P; Krzesinski, F; Daly, A; Beckers, A

    2015-11-01

    Gigantism and acromegaly, usually caused by a pituitary adenoma linked inappropriate secretion of growth hormone (GH), are generally considered as very rare diseases, even if, according to some authors, their cumulative prevalence is about 1/5000. Starting from the historical case of a giant from Liège we shall describe the different types of GH pituitary adenomas and their pathophysiology. We shall particularly discuss rare forms of inherited GH secreting pituitary adenomas like the FIPA (familial inherited isolated pituitary adenomas) and the X-LAG (X linked acrogigantism), both described for the first time in Liège, in 2000 and 2014, respectively. PMID:26738269

  20. [Old phenotype and new genotypes. Pituitary adenomas].

    PubMed

    Gérard, C; Jedidi, H; Petrossians, P; Krzesinski, F; Daly, A; Beckers, A

    2015-11-01

    Gigantism and acromegaly, usually caused by a pituitary adenoma linked inappropriate secretion of growth hormone (GH), are generally considered as very rare diseases, even if, according to some authors, their cumulative prevalence is about 1/5000. Starting from the historical case of a giant from Liège we shall describe the different types of GH pituitary adenomas and their pathophysiology. We shall particularly discuss rare forms of inherited GH secreting pituitary adenomas like the FIPA (familial inherited isolated pituitary adenomas) and the X-LAG (X linked acrogigantism), both described for the first time in Liège, in 2000 and 2014, respectively.

  1. Impact of gonadotropin-releasing hormone antagonist addition on pregnancy rates in gonadotropin-stimulated intrauterine insemination cycles

    PubMed Central

    Jain, Shikha; Majumdar, Abha

    2016-01-01

    OBJECTIVES: The objective of the study is to evaluate the efficacy of gonadotropin-releasing hormone (GnRH) antagonist in improving clinical pregnancy rate in gonadotropin-stimulated intrauterine insemination (IUI) cycles in patients of unexplained infertility. STUDY DESIGN: This was a prospective, randomized case-controlled study. SETTINGS: The study was conducted in the infertility clinic of a tertiary care center. MATERIALS AND METHODS: Four hundred twenty-seven women undergoing IUI following controlled ovarian stimulation with gonadotropins (recombinant follicle-stimulating hormone [r-FSH] 75 IU/day) were randomly divided into two groups. Women in Group I received GnRH antagonist (Cetrorelix 0.25 mg/day) in a multiple dose flexible protocol. Women in Group II received r-FSH alone. Ovulatory trigger was given with human chorionic gonadotropin 5000 IU when dominant follicle was ≥18 mm. IUI was performed within 44–48 h. Both groups received similar luteal phase support. Primary outcome measure was clinical pregnancy rate. The trial was powered to detect an absolute increase in clinical pregnancy rate by 13% from an assumed 20% clinical pregnancy rate in the control group, with an alpha error level of 0.05 and a beta error level of 0.20. RESULTS: Clinical pregnancy rate in Groups I and II was 27.6% (n = 56) and 26.5% (n = 54), respectively (P=0.800). Ongoing pregnancy and multiple pregnancy rates were likewise similar between the groups. CONCLUSIONS: Addition of GnRH antagonist to gonadotropin-stimulated IUI cycles results in no significant difference in clinical pregnancy rate. PMID:27803582

  2. Pituitary adenoma-neuronal choristoma is a pituitary adenoma with ganglionic differentiation.

    PubMed

    Nguyen, Michaela T; Lavi, Ehud

    2015-12-01

    The presence of ganglion cells within an endocrine pituitary tumor has been named hamartoma, choristoma, gangliocytoma, or most recently pituitary adenoma-neuronal choristoma (PANCH). The presence of neuronal differentiation in regular pituitary adenomas has been previously suggested, however, its origin, the extent of its presence, and the relationship between the neuronal elements and the pituitary adenoma remain uncertain. Thus, to further explore the neuronal potential of pituitary tumors, we used immunohistochemistry on pituitary tumors of different grades, with a neuronal antigen protein (NeuN) antibody as a specific marker for mature neuronal differentiation. We found NeuN expression in 26.47% (9/34) cases of pituitary tumors without ganglionic differentiation (7 adenomas, 1 atypical adenoma and 1 pituitary carcinoma), in addition to NeuN expression in pituitary adenomas with ganglionic cells (2/2). Thus, neuronal expression is an innate property of pituitary adenomas. We propose that the rare presence of ganglionic cells in pituitary adenomas is not the result of a separate lesion or "collision sellar tumors", as previously suggested, but a ganglionic neuronal differentiation in an endocrine neoplasm. The ganglionic cells may be arising from uncommitted stem/progenitor cells that contain both neuronal and endocrine properties. A label of "pituitary adenoma with ganglionic differentiation" would better reflect the dual differentiation in a neuroendocrine tumor than the current label "PANCH".

  3. A Computational Model of the Rainbow Trout Hypothalamus-Pituitary-Ovary-Liver Axis

    PubMed Central

    Gillies, Kendall; Krone, Stephen M.; Nagler, James J.; Schultz, Irvin R.

    2016-01-01

    Reproduction in fishes and other vertebrates represents the timely coordination of many endocrine factors that culminate in the production of mature, viable gametes. In recent years there has been rapid growth in understanding fish reproductive biology, which has been motivated in part by recognition of the potential effects that climate change, habitat destruction and contaminant exposure can have on natural and cultured fish populations. New approaches to understanding the impacts of these stressors are being developed that require a systems biology approach with more biologically accurate and detailed mathematical models. We have developed a multi-scale mathematical model of the female rainbow trout hypothalamus-pituitary-ovary-liver axis to use as a tool to help understand the functioning of the system and for extrapolation of laboratory findings of stressor impacts on specific components of the axis. The model describes the essential endocrine components of the female rainbow trout reproductive axis. The model also describes the stage specific growth of maturing oocytes within the ovary and permits the presence of sub-populations of oocytes at different stages of development. Model formulation and parametrization was largely based on previously published in vivo and in vitro data in rainbow trout and new data on the synthesis of gonadotropins in the pituitary. Model predictions were validated against several previously published data sets for annual changes in gonadotropins and estradiol in rainbow trout. Estimates of select model parameters can be obtained from in vitro assays using either quantitative (direct estimation of rate constants) or qualitative (relative change from control values) approaches. This is an important aspect of mathematical models as in vitro, cell-based assays are expected to provide the bulk of experimental data for future risk assessments and will require quantitative physiological models to extrapolate across biological scales. PMID

  4. A Computational Model of the Rainbow Trout Hypothalamus-Pituitary-Ovary-Liver Axis.

    PubMed

    Gillies, Kendall; Krone, Stephen M; Nagler, James J; Schultz, Irvin R

    2016-04-01

    Reproduction in fishes and other vertebrates represents the timely coordination of many endocrine factors that culminate in the production of mature, viable gametes. In recent years there has been rapid growth in understanding fish reproductive biology, which has been motivated in part by recognition of the potential effects that climate change, habitat destruction and contaminant exposure can have on natural and cultured fish populations. New approaches to understanding the impacts of these stressors are being developed that require a systems biology approach with more biologically accurate and detailed mathematical models. We have developed a multi-scale mathematical model of the female rainbow trout hypothalamus-pituitary-ovary-liver axis to use as a tool to help understand the functioning of the system and for extrapolation of laboratory findings of stressor impacts on specific components of the axis. The model describes the essential endocrine components of the female rainbow trout reproductive axis. The model also describes the stage specific growth of maturing oocytes within the ovary and permits the presence of sub-populations of oocytes at different stages of development. Model formulation and parametrization was largely based on previously published in vivo and in vitro data in rainbow trout and new data on the synthesis of gonadotropins in the pituitary. Model predictions were validated against several previously published data sets for annual changes in gonadotropins and estradiol in rainbow trout. Estimates of select model parameters can be obtained from in vitro assays using either quantitative (direct estimation of rate constants) or qualitative (relative change from control values) approaches. This is an important aspect of mathematical models as in vitro, cell-based assays are expected to provide the bulk of experimental data for future risk assessments and will require quantitative physiological models to extrapolate across biological scales. PMID

  5. A Computational Model of the Rainbow Trout Hypothalamus-Pituitary-Ovary-Liver Axis.

    PubMed

    Gillies, Kendall; Krone, Stephen M; Nagler, James J; Schultz, Irvin R

    2016-04-01

    Reproduction in fishes and other vertebrates represents the timely coordination of many endocrine factors that culminate in the production of mature, viable gametes. In recent years there has been rapid growth in understanding fish reproductive biology, which has been motivated in part by recognition of the potential effects that climate change, habitat destruction and contaminant exposure can have on natural and cultured fish populations. New approaches to understanding the impacts of these stressors are being developed that require a systems biology approach with more biologically accurate and detailed mathematical models. We have developed a multi-scale mathematical model of the female rainbow trout hypothalamus-pituitary-ovary-liver axis to use as a tool to help understand the functioning of the system and for extrapolation of laboratory findings of stressor impacts on specific components of the axis. The model describes the essential endocrine components of the female rainbow trout reproductive axis. The model also describes the stage specific growth of maturing oocytes within the ovary and permits the presence of sub-populations of oocytes at different stages of development. Model formulation and parametrization was largely based on previously published in vivo and in vitro data in rainbow trout and new data on the synthesis of gonadotropins in the pituitary. Model predictions were validated against several previously published data sets for annual changes in gonadotropins and estradiol in rainbow trout. Estimates of select model parameters can be obtained from in vitro assays using either quantitative (direct estimation of rate constants) or qualitative (relative change from control values) approaches. This is an important aspect of mathematical models as in vitro, cell-based assays are expected to provide the bulk of experimental data for future risk assessments and will require quantitative physiological models to extrapolate across biological scales.

  6. Paradoxical effects of D-Trp6-luteinizing hormone-releasing hormone on the hypothalamic-pituitary-gonadal axis in immature female rats.

    PubMed

    Vilchez-Martinez, J A; Pedroza, E; Arimura, A; Schally, A V

    1979-06-01

    The effect of administration of a superactive and long-acting analog of luteinizing hormone-releasing hormone (LH-RH), D-Trp6-LH-RH, in doses of 0.05 or 1 microgram/day for 10 days on the hypothalamic-pituitary-gonadal axis was studied in immature female rats. Treatment with a 0.05-microgram dose of analog produced few changes as compared with the control group. Treatment with 1 microgram of D-Trp6-LH-RH did not affect the body weight or the pituitary weight, but increased ovarian weight and decreased uterine weight; elevated serum gonadotropin levels; and lowered the pituitary LH content. This depletion of pituitary LH content was associated with a low pituitary responsiveness to LH-RH. Serum estradiol levels were not modified, suggesting that decreased uterine weight reflects a direct and extrapituitary effect of this analog. The hypothalamic LH-RH content was higher, indicating a possible inhibition of the release of endogenous LH-RH. A delay in vaginal opening was also observed. This indicates that large doses of D-Trp6-LH-RH may interfere with the process of puberty in rats. These findings extend other reports about the paradoxical antifertility effects of large doses of stimulatory analogs of LH-RH.

  7. The pituitary-gonadal axis in experimental nephrotic syndrome in male rats.

    PubMed

    Elias, A N; Carreon, G; Vaziri, N D; Pandian, M R; Oveisi, F

    1992-12-01

    Basal and luteinizing releasing hormone-stimulated gonadotropin secretion were studied in male rats made nephrotic with puromycin, and in pair-fed and normal control animals. In addition, plasma concentrations of testosterone, androstenedione, estradiol, and estrone were measured in the three groups of animals. Urinary testosterone concentrations were also measured in the three experimental groups. The data showed that basal luteinizing hormone concentration was significantly elevated in the nephrotic group compared with the pair-fed and normal control groups. Gonadotropin response to luteinizing releasing hormone stimulation was not significantly different in the three groups, suggesting an intact hypothalamic-pituitary axis in nephrotic syndrome. Urinary testosterone concentration in the nephrotic animals was significantly higher than in the pair-fed and normal control groups. Plasma testosterone, androstenedione, estradiol, and estrone concentrations were significantly lower in the nephrotic and pair-fed animals than in the normal control animals, indicating possibly impaired gonadal steroidogenesis in these two groups that may be related to the catabolic state of the animals. It thus appears that urinary loss of protein-bound (sex hormone binding globulin-bound) testosterone in the nephrotic syndrome leads to increased basal secretion of luteinizing hormone, presumably as a result of increased luteinizing releasing hormone secretion. This occurs to compensate for the abnormal urinary testosterone loss and is an attempt to restore plasma testosterone concentrations to normal. The higher basal plasma luteinizing hormone concentration in the nephrotic group supports this conclusion.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Free β-human chorionic gonadotropin, total human chorionic gonadotropin and maternal risk of breast cancer

    PubMed Central

    Toriola, Adetunji T; Tolockiene, Egle; Schock, Helena; Surcel, Helja-Marja; Zeleniuch-Jacquotte, Anne; Wadell, Goran; Toniolo, Paolo; Lundin, Eva; Grankvist, Kjell; Lukanova, Annekatrin

    2014-01-01

    Background We investigated whether the free β-human chorionic gonadotropin (free β-hCG) would provide additional information to that provided by total hCG alone and thus be useful in future epidemiological studies relating hCG to maternal breast cancer risk. Materials & methods Cases (n = 159) and controls (n = 286) were a subset of our previous study within the Northern Sweden Maternity Cohort on total hCG during primiparous pregnancy and breast cancer risk. Results The associations between total hCG (hazard ratio: 0.79; 95% CI: 0.49–1.27), free β-hCG (hazard ratio: 0.85; 95% CI: 0.33–2.18) and maternal risk of breast cancer were very similar in all analyses and mutual adjustment for either one had minor effects on the risk estimates. Conclusion In the absence of a reliable assay on intact hCG, total hCG alone can be used in epidemiological studies investigating hCG and breast cancer risk, as free β-hCG does not appear to provide any additional information. PMID:24559445

  9. How to contribute to the progress of neuroendocrinology: New insights from discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions.

    PubMed

    Tsutsui, Kazuyoshi

    2016-02-01

    Obtaining new insights by discovering novel neuropeptides and neurosteroids regulating pituitary and brain functions is essential for the progress of neuroendocrinology. At the beginning of 1970s, gonadotropin-releasing hormone (GnRH) was discovered in mammals. Since then, it was generally accepted that GnRH is the only hypothalamic neuropeptide regulating gonadotropin release in vertebrates. In 2000, however, gonadotropin-inhibitory hormone (GnIH), a novel hypothalamic neuropeptide that actively inhibits gonadotropin release, was discovered in quail. The follow-up studies demonstrated that GnIH acts as a new key player for regulation of reproduction across vertebrates. It now appears that GnIH acts on the pituitary and the brain to serve a number of behavioral and physiological functions. On the other hand, a new concept has been established that the brain synthesizes steroids, called neurosteroids. The formation of neurosteroids in the brain was originally demonstrated in mammals and subsequently in other vertebrates. Recently, 7α-hydroxypregnenolone was discovered as a novel bioactive neurosteroid inducing locomotor behavior of vertebrates, indicating that neurosteroidogenesis in the brain is still incompletely elucidated in vertebrates. At the beginning of 2010s, it was further found that the pineal gland actively produces neurosteroids. Pineal neurosteroids act on the brain to regulate locomotor rhythms and neuronal survival. Furthermore, the interaction of neuropeptides and neurosteroids is becoming clear. GnIH decreases aggressive behavior by regulating neuroestrogen synthesis in the brain. This review summarizes these new insights by discovering novel neuropeptides and neurosteroids in the field of neuroendocrinology.

  10. The origins of the vertebrate hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-thyroid (HPT) endocrine systems: new insights from lampreys.

    PubMed

    Sower, Stacia A; Freamat, Mihael; Kavanaugh, Scott I

    2009-03-01

    The acquisition of a hypothalamic-pituitary axis was a seminal event in vertebrate evolution leading to the neuroendocrine control of many complex functions including growth, reproduction, osmoregulation, stress and metabolism. Lampreys as basal vertebrates are the earliest evolved vertebrates for which there are demonstrated functional roles for two gonadotropin-releasing hormones (GnRHs) that act via the hypothalamic-pituitary-gonadal axis controlling reproductive processes. With the availability of the lamprey genome, we have identified a novel GnRH form (lamprey GnRH-II) and a novel glycoprotein hormone receptor, lGpH-R II (thyroid-stimulating hormone-like receptor). Based on functional studies, in situ hybridization and phylogenetic analysis, we hypothesize that the newly identified lamprey GnRH-II is an ancestral GnRH to the vertebrate GnRHs. This finding opens a new understanding of the GnRH family and can help to delineate the evolution of the complex neuro/endocrine axis of reproduction. A second glycoprotein hormone receptor (lGpH-R II) was also identified in the sea lamprey. The existing data suggest the existence of a primitive, overlapping yet functional HPG and HPT endocrine systems in this organism, involving one possibly two pituitary glycoprotein hormones and two glycoprotein hormone receptors as opposed to three or four glycoprotein hormones interacting specifically with three receptors in gnathostomes. We hypothesize that the glycoprotein hormone/glycoprotein hormone receptor systems emerged as a link between the neuro-hormonal and peripheral control levels during the early stages of gnathostome divergence. The significance of the results obtained by analysis of the HPG/T axes in sea lamprey may transcend the limited scope of the corresponding physiological compartments by providing important clues in respect to the interplay between genome-wide events (duplications), coding sequence (mutation) and expression control level evolutionary mechanisms

  11. Purves symposium: 2. Pituitary morphology in relationship to function. General principles.

    PubMed

    Purves, H D

    1974-12-25

    ," which prod uced thyrotrophin, and "gonadotrophs," which produced gonadotropin. The granules were considered to be the stored hormone product of the cells. It seemed that follicle stimulating hormone was secreted by 1 cell type and luteinizing hormone by another. Each specific hormonal function was thought to be performed by a specific cell type. In the fish pituitary gland, 5 distinctive cell types are recognizable by selective staining. In human problems, the inactivity of the thyrotrophs in pituitary glands from Graves' disease patients confirms that the source of thyroid stimulation comes from outside the pituitary gland. In Cushing's disease, that the adrenal stimulation was caused by basophilic adenomata in the adenohypophysis was confirmed.

  12. Early-Life Social Isolation Impairs the Gonadotropin-Inhibitory Hormone Neuronal Activity and Serotonergic System in Male Rats.

    PubMed

    Soga, Tomoko; Teo, Chuin Hau; Cham, Kai Lin; Idris, Marshita Mohd; Parhar, Ishwar S

    2015-01-01

    Social isolation in early life deregulates the serotonergic system of the brain, compromising reproductive function. Gonadotropin-inhibitory hormone (GnIH) neurons in the dorsomedial hypothalamic nucleus are critical to the inhibitory regulation of gonadotropin-releasing hormone neuronal activity in the brain and release of luteinizing hormone by the pituitary gland. Although GnIH responds to stress, the role of GnIH in social isolation-induced deregulation of the serotonin system and reproductive function remains unclear. We investigated the effect of social isolation in early life on the serotonergic-GnIH neuronal system using enhanced green fluorescent protein (EGFP)-tagged GnIH transgenic rats. Socially isolated rats were observed for anxious and depressive behaviors. Using immunohistochemistry, we examined c-Fos protein expression in EGFP-GnIH neurons in 9-week-old adult male rats after 6 weeks post-weaning isolation or group housing. We also inspected serotonergic fiber juxtapositions in EGFP-GnIH neurons in control and socially isolated male rats. Socially isolated rats exhibited anxious and depressive behaviors. The total number of EGFP-GnIH neurons was the same in control and socially isolated rats, but c-Fos expression in GnIH neurons was significantly reduced in socially isolated rats. Serotonin fiber juxtapositions on EGFP-GnIH neurons were also lower in socially isolated rats. In addition, levels of tryptophan hydroxylase mRNA expression in the dorsal raphe nucleus were significantly attenuated in these rats. These results suggest that social isolation in early-life results in lower serotonin levels, which reduce GnIH neuronal activity and may lead to reproductive failure. PMID:26617573

  13. Early-Life Social Isolation Impairs the Gonadotropin-Inhibitory Hormone Neuronal Activity and Serotonergic System in Male Rats

    PubMed Central

    Soga, Tomoko; Teo, Chuin Hau; Cham, Kai Lin; Idris, Marshita Mohd; Parhar, Ishwar S.

    2015-01-01

    Social isolation in early life deregulates the serotonergic system of the brain, compromising reproductive function. Gonadotropin-inhibitory hormone (GnIH) neurons in the dorsomedial hypothalamic nucleus are critical to the inhibitory regulation of gonadotropin-releasing hormone neuronal activity in the brain and release of luteinizing hormone by the pituitary gland. Although GnIH responds to stress, the role of GnIH in social isolation-induced deregulation of the serotonin system and reproductive function remains unclear. We investigated the effect of social isolation in early life on the serotonergic–GnIH neuronal system using enhanced green fluorescent protein (EGFP)-tagged GnIH transgenic rats. Socially isolated rats were observed for anxious and depressive behaviors. Using immunohistochemistry, we examined c-Fos protein expression in EGFP–GnIH neurons in 9-week-old adult male rats after 6 weeks post-weaning isolation or group housing. We also inspected serotonergic fiber juxtapositions in EGFP–GnIH neurons in control and socially isolated male rats. Socially isolated rats exhibited anxious and depressive behaviors. The total number of EGFP–GnIH neurons was the same in control and socially isolated rats, but c-Fos expression in GnIH neurons was significantly reduced in socially isolated rats. Serotonin fiber juxtapositions on EGFP–GnIH neurons were also lower in socially isolated rats. In addition, levels of tryptophan hydroxylase mRNA expression in the dorsal raphe nucleus were significantly attenuated in these rats. These results suggest that social isolation in early-life results in lower serotonin levels, which reduce GnIH neuronal activity and may lead to reproductive failure. PMID:26617573

  14. Pituitary Gigantism: A Case Report

    PubMed Central

    Bhattacharjee, Rana; Roy, Ajitesh; Goswami, Soumik; Selvan, Chitra; Chakraborty, Partha P.; Ghosh, Sujoy; Biswas, Dibakar; Dasgupta, Ranen; Mukhopadhyay, Satinath; Chowdhury, Subhankar

    2012-01-01

    Objective: To present a rare case of gigantism. Case Report: A 25-year-old lady presented with increased statural growth and enlarged body parts noticed since the age of 14 years, primary amenorrhea, and frontal headache for the last 2 years. She has also been suffering from non-inflammatory low back pain with progressive kyphosis and pain in the knees, ankles, and elbows for the last 5 years. There was no history of visual disturbance, vomiting, galactorrhoea, cold intolerance. She had no siblings. Family history was non-contributory. Blood pressure was normal. Height 221 cm, weight 138 kg, body mass index (BMI)28. There was coarsening of facial features along with frontal bossing and prognathism, large hands and feet, and small goitre. Patient had severe kyphosis and osteoarthritis of knees. Confrontation perimetry suggested bitemporal hemianopia. Breast and pubic hair were of Tanner stage 1. Serum insulin like growth factor-1 (IGF1) was 703 ng/ml with all glucose suppressedgrowth hormone (GH)values of >40 ng/ml. Prolactin was 174 ng/ml. Basal serum Lutenising Hormone (LH), follicle stimulating Hormone (FSH) was low. Oral glucose tolerance test (OGTT), liver and renal function tests, basal cortisol and thyroid profile, Calcium, phosphorus and Intact Parathyroid hormone (iPTH) were normal. Computed tomographyscan of brain showed large pituitary macroadenoma. Automated perimetry confirmed bitemporal hemianopia. A diagnosis of gigantism due to GH secreting pituitary macroadenoma with hypogonadotrophichypogonadism was made. Debulking pituitary surgery followed by somatostatin analogue therapy with gonadal steroid replacement had been planned, but the patient refused further treatment. PMID:23565401

  15. Pituitary gigantism causing diabetic ketoacidosis.

    PubMed

    Alvi, N S; Kirk, J M

    1999-01-01

    Although growth hormone excess (acromegaly) in association with glucose intolerance and diabetes mellitus is well documented in adult medicine, it is much less common in the paediatric age group. We report the case of a 13 year-old boy who presented with tall stature secondary to a large growth hormone secreting adenoma of the pituitary gland. Random growth hormone was 630 mIU/l and did not suppress during an oral glucose tolerance test. Following debulking of the tumour, he developed diabetic ketoacidosis requiring insulin treatment, but after further surgery glucose handling returned to normal. He has been started on testosterone to arrest further increase in height. PMID:10614552

  16. Anatomy, Physiology, and Laboratory Evaluation of the Pituitary Gland.

    PubMed

    Hong, Gregory K; Payne, Spencer C; Jane, John A

    2016-02-01

    The pituitary gland functions prominently in the control of most endocrine systems in the body. Diverse processes such as metabolism, growth, reproduction, and water balance are tightly regulated by the pituitary in conjunction with the hypothalamus and various downstream endocrine organs. Benign tumors of the pituitary gland are the primary cause of pituitary pathology and can result in inappropriate secretion of pituitary hormones or loss of pituitary function. First-line management of clinically significant tumors often involves surgical resection. Understanding of normal pituitary physiology and basic testing strategies to assess for pituitary dysfunction should be familiar to any skull base surgeon. PMID:26614827

  17. Effect of human chorionic gonadotropin on mammary gland differentiation and carcinogenesis.

    PubMed

    Russo, I H; Koszalka, M; Russo, J

    1990-10-01

    The observation that mammary carcinogenesis is inhibited in rats which completed a pregnancy prior to exposure to the chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) led us to determine whether the protective effect of pregnancy could be mimicked by treatment with the placental hormone chorionic gonadotropin (hCG). We also studied the effect of this treatment on mammary gland structure and differentiation, and determined whether hCG exerts toxic or collateral effects on body weight and endocrine organs. The systemic effect of hCG on body wt and endocrine organs and mammary gland was studied in outbred virgin Sprague-Dawley rats which at the age of 50 days started receiving 100 IU hCG i.p. daily for 21 days. The animals were subdivided into nine groups of five animals each; one group was killed on the first day of and the others at 5, 10, 15 and 21 days of injection and 5, 10, 15 and 21 days post injection. The effect of the hormonal treatment on the estrous cycle was determined by studying the vaginal smears taken during and after the injection period. The following parameters were determined: body wt, weight and morphology of pituitary gland, adrenals, ovaries and uterine horns. Mammary glands were processed for histology, autoradiography for determination of DNA labeling index (DNA-LI) and whole mount preparation for morphometric studies. The effect of hCG on mammary carcinogenesis was studied in two groups of virgin rats; group I, which at the age of 50 days started receiving a daily i.p. injection of 100 IU hCG for 21 days; 21 days after the last injection they were given 8 mg DMBA/100 g body wt. Group II animals received DMBA only. hCG treated animals gained weight as a function of age at the same rate as controls. Treatment did not modify the weight of adrenal glands. The weight of ovaries, uterus and pituitary gland were transitorily increased by the 15th day of treatment, but had returned to the same values of controls by the time of DMBA

  18. Luteinizing hormone and human chorionic gonadotropin: origins of difference.

    PubMed

    Choi, Janet; Smitz, Johan

    2014-03-01

    Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are widely recognized for their roles in ovulation and the support of early pregnancy. Aside from the timing of expression, however, the differences between LH and hCG have largely been overlooked in the clinical realm because of their similar molecular structures and shared receptor. With technologic advancements, including the development of highly purified and recombinant gonadotropins, researchers now appreciate that these hormones are not as interchangeable as once believed. Although they bind to a common receptor, emerging evidence suggests that LH and hCG have disparate effects on downstream signaling cascades. Increased understanding of the inherent differences between LH and hCG will foster more effective diagnostic and prognostic assays for use in a variety of clinical contexts and support the individualization of treatment strategies for conditions such as infertility.

  19. The Enigma behind Pituitary and Sella Turcica

    PubMed Central

    Gopalakrishnan, Umarevathi; Mahendra, Lodd; Rangarajan, Sumanth; Madasamy, Ramasamy; Ibrahim, Mohammad

    2015-01-01

    The pituitary gland's role as a functional matrix for sella turcica has not been suggested in orthodontic literature. This paper is an attempt to correlate the role of pituitary gland in the development of sella turcica. A case report of dwarfism associated with hypopituitarism is presented to highlight the above hypothesis. PMID:26199763

  20. Reversible suprasellar pituitary mass secondary to hypothyroidism

    SciTech Connect

    Atchison, J.A.; Lee, P.A.; Albright, A.L. Children's Hospital of Pittsburgh, PA )

    1989-12-08

    Sellar enlargement and suprasellar extension of a pituitary mass, demonstrated by magnetic resonance imaging or computed tomographic scanning in three children with primary hypothyroidism, resolved after treatment with levothyroxine sodium. This condition, a logical consequence of the pathogenesis of primary hypothyroidism, must be considered in patients with pituitary and suprasellar masses.

  1. Effect of exogenous FSH on ovulation rate in homozygous carriers or noncarriers of the Booroola FecB gene after hypothalamic-pituitary disconnection or after treatment with a GnRH agonist.

    PubMed

    Hudson, N L; O'Connell, A R; Shaw, L; Clarke, I J; McNatty, K P

    1999-01-01

    We have tested the hypothesis "that the ovulation rate in homozygous carriers (BB) and noncarriers (+2) of the Booroola FecB gene would not be different if the plasma concentrations of follicle-stimulating hormone (FSH) in the two genotypes were similar." For this purpose we used two experimental animal models: 1) the hypothalamic-pituitary disconnected (HPD) ovary-intact ewe; and 2) and GnRH agonist (i.e., Deslorelin)-treated ewe. Following HPD or Deslorelin treatment, the animals had low plasma concentrations of gonadotropins and were anovulatory. In both animal models, BB and +2 ewes were treated with exogenous pregnant mares serum gonadotropin (PMSG) and varying doses of FSH to induce preovulatory follicular growth, and human chorionic gonadotropin (hCG) to induce ovulation. HPD or Deslorelin-treated animals administered with pregnant mares serum gonadotropin without FSH followed by human chorionic gonadotropin failed to ovulate. However for both animal models, the proportion of BB and +2 ewes ovulating to various doses of FSH differed such that significantly greater proportions of +2 animals ovulated relative to the BB genotype (P < 0.05). When HPD or Deslorelin-treated BB and +2 ewes were administered identical doses of FSH, the mean ovulation rate and plasma concentrations of FSH in those animals which ovulated was the same in both genotypes. These findings confirm, at least in part, the aforementioned hypothesis. The results also demonstrated that higher ovulation rates were obtained in both genotypes as the FSH dose was increased. Collectively, these findings infer that the higher mean ovulation rate in normal intact BB ewes compared to the +2 genotype is attributable to effects of the FecB gene at the level of ovarian follicular development as well as at the level of pituitary FSH release.

  2. The HMG-box transcription factor Sox4b is required for pituitary expression of gata2a and specification of thyrotrope and gonadotrope cells in zebrafish.

    PubMed

    Quiroz, Yobhana; Lopez, Mauricio; Mavropoulos, Anastasia; Motte, Patrick; Martial, Joseph A; Hammerschmidt, Matthias; Muller, Marc

    2012-06-01

    The pituitary is a complex gland comprising different cell types each secreting specific hormones. The extensive network of signaling molecules and transcription factors required for determination and terminal differentiation of specific cell types is still not fully understood. The SRY-like HMG-box (SOX) transcription factor Sox4 plays important roles in many developmental processes and has two homologs in zebrafish, Sox4a and Sox4b. We show that the sox4b gene is expressed in the pituitary anlagen starting at 24 h after fertilization (hpf) and later in the entire head region including the pituitary. At 48 hpf, sox4b mRNA colocalizes with that for TSH (tshβ), glycoprotein subunit α (gsuα), and the Zn finger transcription factor Gata2a. Loss of Sox4b function, using morpholino knockdown or expression of a dominant-negative Sox4 mutant, leads to a drastic decrease in tshβ and gsuα expression and reduced levels of gh, whereas other anterior pituitary gland markers including prl, slβ, pomc, and lim3 are not affected. Sox4b is also required for expression of gata2a in the pituitary. Knockdown of gata2a leads to decreased tshβ and gsuα expression at 48 hpf, similar to sox4b morphants. Injection of gata2a mRNA into sox4b morphants rescued tshβ and gsuα expression in thyrotrope cells. Finally, sox4b or gata2a knockdown causes a significant decrease of gonadotropin expression (lhβ and fshβ) at 4 d after fertilization. In summary, our results indicate that Sox4b is expressed in zebrafish during pituitary development and plays a crucial role in the differentiation of thyrotrope and gonadotrope cells through induction of gata2a expression in the developing pituitary.

  3. Deficits in reproduction and pro-gonadotropin-releasing hormone processing in male Cpefat mice.

    PubMed

    Srinivasan, Sudha; Bunch, Donna O; Feng, Yun; Rodriguiz, Ramona M; Li, Min; Ravenell, Roneka L; Luo, Guo X; Arimura, Akira; Fricker, Lloyd D; Eddy, Edward M; Wetsel, William C

    2004-04-01

    Cpe(fat/fat) mice are obese, diabetic, and infertile. These animals have a point mutation in carboxypeptidase E (CPE), an exopeptidase that removes C-terminal basic amino acids from peptide intermediates. The mutation renders the enzyme unstable, and it is rapidly degraded. Although the infertility of Cpe(fat/fat) mice has not been systematically investigated, it is thought to be due to a deficit in GnRH processing. We have evaluated this hypothesis and found hypothalamic GnRH levels to be reduced by 65-78% and concentrations of pro-GnRH and C-terminal-extended intermediates to be high. Basal serum gonadotropin contents are similar among wild-type, heterozygous, and homozygous mice. Testis morphology and function are abnormal in older obese Cpe(fat/fat) mice. Matings between homozygous mutants yield a 5% pregnancy rate. By comparison, when 50-d-old Cpe(fat/fat) males are paired with heterozygous females, rates increase to 43%, and they rapidly decrease to negligible levels by 120 d. As fertility declines without accompanying changes in the hypothalamic-pituitary-gonadal axis and before obesity is evident, reproduction is more complex than originally thought. This suspicion is confirmed in 90-d-old Cpe(fat/fat) males, who readily interact with females, but rarely mount and fail to show intromission or ejaculation behaviors. Together, these findings show that CPE is a key enzyme for pro-GnRH processing in vivo; however, the reproductive deficits in Cpe(fat/fat) males appear to be due primarily to abnormal sexual behavior.

  4. Müllerian inhibiting substance production and cleavage is modulated by gonadotropins and steroids.

    PubMed

    Kuroda, T; Lee, M M; Ragin, R C; Hirobe, S; Donahoe, P K

    1991-12-01

    Analysis of the ontogeny and localization of the amino (N)-terminal and carboxy (C)-terminal cleavage products of Müllerian Inhibiting Substance (MIS) and their modulation by hormones of the hypothalamic-pituitary gonadal axis by immunohistochemistry and Northern analysis led to the discovery of a novel mode of posttranslational regulation of this differentiating agent. Antibody to both holo- and C-terminal MIS identically stained the cytosol of testicular Sertoli cells from 21-day fetal rats, whereas staining of antibody to N-terminal MIS localized to the basement membrane of seminiferous tubules. In addition, when studied longitudinally, basement membrane staining for N-terminal MIS persisted; cytosolic staining for C-terminal MIS was no longer detectable in post-natal testes, but marked basement membrane staining for the N-terminal fragment could still be observed in the testes of untreated 7-day postnatal animals. When 19-day fetuses were injected with FSH, testes collected 2 days later showed less immunohistochemical staining for holo-, N-, and C-terminal MIS, and less MIS messenger RNA. This suggested that FSH downregulates MIS transcription, as had been shown previously in neonatal testes treated with FSH. Testes collected at 21 days from fetuses treated at day 19 in utero with human CG or testosterone, also showed less staining for holo-MIS, but, surprisingly, increased staining for the N- and C-terminal fragments. These changes in MIS protein were accompanied by no or minimal changes in MIS messenger RNA levels, indicating that human CG and testosterone do not affect transcription, but may regulate the cleavage and/or dissociation of MIS. This study describes a form of post-translational regulation of MIS and shows that both transcription and processing of MIS may be differentially modulated by gonadotropins and sex steroids.

  5. Regulation of serum testosterone in men with steroid sulfatase deficiency: response to human chorionic gonadotropin.

    PubMed

    Ruokonen, A; Oikarinen, A; Vihko, R

    1986-07-01

    Human chorionic gonadotropin (hCG; 5000 IU) was administered to 6 control men and 6 patients with recessive x-linked ichthyosis (RXLI) with verified 3 beta-hydroxysteroid sulfate sulfatase (3 beta-HSS) deficiency in their skin biopsy samples. Concentrations of steroids and their sulfate conjugates were determined in peripheral serum specimens collected a day before and 4 days after hCG administration. Testosterone concentrations were identical in patients and controls. Baseline serum LH concentrations were also identical in the 2 groups showing that there were no major differences in the regulation of the hypothalamic-pituitary-gonadal axis. The significantly increased (31-82%) serum concentrations of sulfated pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone and 5-androstene-3 beta,17 beta-diol in patients compared with controls indicated that their circulating concentrations were regulated by 3 beta-HSS. This is in line with the fact that the baseline concentrations of the same unconjugated steroids were significantly lower (32-90%) in patients with RXLI, suggesting that a proportion of these circulating steroids were derived from the corresponding sulfated precursors. The response patterns and actual concentrations of testosterone, 17-hydroxyprogesterone and estradiol were similar in the patients and the controls after hCG. The decreased concentrations of testosterone sulfated at carbon 17 under baseline conditions and after hCG in patients with RXLI remains enigmatic. In conclusion, testosterone production and the response to hCG seem to be identical in patients with RXLI and controls despite the fact that significant differences were observed in the circulating concentrations of several unconjugated and sulfated testosterone precursors.

  6. Immunological properties of prolactin and studies on a gonadotropin binding inhibitor

    SciTech Connect

    Chang, Y.S.

    1985-01-01

    The physiological role of prolactin in horses has not yet been well defined. With the availability of highly purified ePRL for inducing antibody formation in rabbits and for radiolabeling with Na/sup 125/I, a very sensitive (0.4-0.6 ng/ml) and highly specific homologous RIA for ePRL was developed. A heterologous RIA using /sup 125/I-labeled ovine PRL and anti-ePRL antiserum was also developed and compared to the homologous RIA for ePRL. Of the two systems, it is concluded that this homologous RIA system is more suitable and more reliable for measuring prolactin concentration in horse serum samples. Until now, biochemical information on PRL has not been available for reptilian species. Sea turtle (Chelonia mydas) prolactin was purified from pituitary extracts by selective precipitation, DEAE-cellulose chromatography and gel filtration. Similar to other species of PRL, sea turtle PRL is a 22,000-24,000 daltons protein and contains a high content of glutamic acid, aspartic acid, serine and leucine, the N-terminal amino acid residue. Gonadotropin (FSH) binding inhibitor was partially purified from sheep testes by ammonium sulfate fractionation and ion exchange chromatography. The FSH-BI (molecular weight: 50,000 daltons, estimated by gel filtration) contains a protein moiety necessary for binding inhibitory activity. The inhibition of the binding of /sup 125/I-labeled ovine FSH to its receptor by the FSH-BI is not competitive. Both in vivo and in vitro biological studies of FSH-BI preparations in rats indicated various effects on FSH and LH activities at the gonadal level. These findings suggest a physiological role for FSH-BI in the regulation of reproduction.

  7. Mollusc gonadotropin-releasing hormone directly regulates gonadal functions: a primitive endocrine system controlling reproduction.

    PubMed

    Treen, Nicholas; Itoh, Naoki; Miura, Hanae; Kikuchi, Ippei; Ueda, Takenori; Takahashi, Keisuke G; Ubuka, Takayoshi; Yamamoto, Kazutoshi; Sharp, Peter J; Tsutsui, Kazuyoshi; Osada, Makoto

    2012-04-01

    Gonadotropin-releasing hormone (GnRH) is central to the control of vertebrate reproductive cycles and since GnRH orthologs are also present in invertebrates, it is likely that the common ancestor of bilateral animals possessed a GnRH-like peptide. In order to understand the evolutionary and comparative biology of GnRH peptides we cloned the cDNA transcripts of prepro GnRH-like peptides from two species of bivalve molluscs, the Yesso scallop Patinopecten yessoensis and the Pacific oyster Crassostrea gigas. We compared their deduced uncleaved and mature amino acid sequences with those from other invertebrates and vertebrates, and determined their sites of expression and biological activity. The two molluscan GnRH sequences increased the number of known protostome GnRHs to six different forms, indicating the current classification of protostome GnRHs requires further revision. In both molluscs, RT-PCR analysis showed that the genes were highly expressed in nervous tissue with lower levels present in peripheral tissues including the gonads, while immunocytochemistry, using anti-octopus GnRH-like peptide, demonstrated the presence of GnRH-like peptide in neural tissue. Putative scallop GnRH-like peptide stimulated spermatogonial cell division in cultured scallop testis, but the scallop GnRH-like peptide did not stimulate LH release from cultured quail pituitary cells. This is the first report of the cloning of bivalve GnRH-like peptide genes and of molluscan GnRH-like peptides that are biologically active in molluscs, but not in a vertebrate.

  8. Evaluating the ovarian cancer gonadotropin hypothesis: A candidate gene study

    PubMed Central

    Lee, Alice W.; Tyrer, Jonathan P.; Doherty, Jennifer A.; Stram, Douglas A.; Kupryjanczyk, Jolanta; Dansonka-Mieszkowska, Agnieszka; Plisiecka-Halasa, Joanna; Spiewankiewicz, Beata; Myers, Emily J.; Chenevix-Trench, Georgia; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Hein, Alexander; Vergote, Ignace; Van Nieuwenhuysen, Els; Lambrechts, Diether; Wicklund, Kristine G.; Eilber, Ursula; Wang-Gohrke, Shan; Chang-Claude, Jenny; Rudolph, Anja; Sucheston-Campbell, Lara; Odunsi, Kunle; Moysich, Kirsten B.; Shvetsov, Yurii B.; Thompson, Pamela J.; Goodman, Marc T.; Wilkens, Lynne R.; Dörk, Thilo; Hillemanns, Peter; Dürst, Matthias; Runnebaum, Ingo B.; Bogdanova, Natalia; Pelttari, Liisa M.; Nevanlinna, Heli; Leminen, Arto; Edwards, Robert P.; Kelley, Joseph L.; Harter, Philipp; Schwaab, Ira; Heitz, Florian; du Bois, Andreas; Orsulic, Sandra; Lester, Jenny; Walsh, Christine; Karlan, Beth Y.; Hogdall, Estrid; Kjaer, Susanne K.; Jensen, Allan; Vierkant, Robert A.; Cunningham, Julie M.; Goode, Ellen L.; Fridley, Brooke L.; Southey, Melissa C.; Giles, Graham G.; Bruinsma, Fiona; Wu, Xifeng; Hildebrandt, Michelle A.T.; Lu, Karen; Liang, Dong; Bisogna, Maria; Levine, Douglas A.; Weber, Rachel Palmieri; Schildkraut, Joellen M.; Iversen, Edwin S.; Berchuck, Andrew; Terry, Kathryn L.; Cramer, Daniel W.; Tworoger, Shelley S.; Poole, Elizabeth M.; Olson, Sara H.; Orlow, Irene; Bandera, Elisa V.; Bjorge, Line; Tangen, Ingvild L.; Salvesen, Helga B.; Krakstad, Camilla; Massuger, Leon F.A.G.; Kiemeney, Lambertus A.; Aben, Katja K.H.; van Altena, Anne M.; Bean, Yukie; Pejovic, Tanja; Kellar, Melissa; Le, Nhu D.; Cook, Linda S.; Kelemen, Linda E.; Brooks-Wilson, Angela; Lubinski, Jan; Gronwald, Jacek; Cybulski, Cezary; Jakubowska, Anna; Wentzensen, Nicolas; Brinton, Louise A.; Lissowska, Jolanta; Yang, Hannah; Nedergaard, Lotte; Lundvall, Lene; Hogdall, Claus; Song, Honglin; Campbell, Ian G.; Eccles, Diana; Glasspool, Rosalind; Siddiqui, Nadeem; Carty, Karen; Paul, James; McNeish, Iain A.; Sieh, Weiva; McGuire, Valerie; Rothstein, Joseph H.; Whittemore, Alice S.; McLaughlin, John R.; Risch, Harvey A.; Phelan, Catherine M.; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Harrington, Patricia; Pike, Malcolm C.; Modugno, Francesmary; Rossing, Mary Anne; Ness, Roberta B.; Pharoah, Paul D.P.; Stram, Daniel O.; Wu, Anna H.; Pearce, Celeste Leigh

    2016-01-01

    Objective Ovarian cancer is a hormone-related disease with a strong genetic basis. However, none of its high-penetrance susceptibility genes and GWAS-identified variants to date are known to be involved in hormonal pathways. Given the hypothesized etiologic role of gonadotropins, an assessment of how variability in genes involved in the gonadotropin signaling pathway impacts disease risk is warranted. Methods Genetic data from 41 ovarian cancer study sites were pooled and unconditional logistic regression was used to evaluate whether any of the 2185 SNPs from 11 gonadotropin signaling pathway genes was associated with ovarian cancer risk. A burden test using the admixture likelihood (AML) method was also used to evaluate gene-level associations. Results We did not find any genome-wide significant associations between individual SNPs and ovarian cancer risk. However, there was some suggestion of gene-level associations for four gonadotropin signaling pathway genes: INHBB (p = 0.045, mucinous), LHCGR (p = 0.046, high-grade serous), GNRH (p = 0.041, high-grade serous), and FSHB (p = 0.036, overall invasive). There was also suggestive evidence for INHA (p = 0.060, overall invasive). Conclusions Ovarian cancer studies have limited sample numbers, thus fewer genome-wide susceptibility alleles, with only modest associations, have been identified relative to breast and prostate cancers. We have evaluated the majority of ovarian cancer studies with biological samples, to our knowledge, leaving no opportunity for replication. Using both our understanding of biology and powerful gene-level tests, we have identified four putative ovarian cancer loci near INHBB, LHCGR, GNRH, and FSHB that warrant a second look if larger sample sizes and denser genotype chips become available. PMID:25528498

  9. Pituitary Involvement in Granulomatosis With Polyangiitis

    PubMed Central

    De Parisot, Audrey; Puéchal, Xavier; Langrand, Corinne; Raverot, Gerald; Gil, Helder; Perard, Laurent; Le Guenno, Guillaume; Berthier, Sabine; Tschirret, Olivier; Eschard, Jean Paul; Vinzio, Stephane; Guillevin, Loïc; Sève, Pascal

    2015-01-01

    Abstract Pituitary dysfunction is a rare manifestation of granulomatosis with polyangiitis (GPA) (Wegener). The main aim of this multicenter retrospective study was to describe the characteristics and outcomes of pituitary manifestations in patients with GPA included in the French Vasculitis Study Group database. Among the 819 GPA patients included in the database, 9 (1.1%) had pituitary involvement. The median age at diagnosis of GPA and pituitary involvement was 46 and 50.8 years, respectively. Pituitary involvement was present at onset of GPA in 1 case and occurred later in 8 patients after a median follow up of 58.5 months. When pituitary dysfunction occurred, 8 patients had active disease at other sites including ENT (n = 6), eye (n = 4), or central nervous system (n = 3) involvement. The most common hormonal dysfunctions were diabetes insipidus (n = 7) and hypogonadism (n = 7). Magnetic resonance imaging was abnormal in 7 patients. The most common lesions were an enlargement of the pituitary gland, thickening of the pituitary stalk, and loss of posterior hypersignal on T1-weighed images. All patients were treated with corticosteroid therapy and 8 patients received immunosuppressive agents for the pituitary involvement, including cyclophosphamide (n = 3), rituximab (n = 2), and methotrexate (n = 3). After a median follow-up of 9.2 years, GPA was in complete remission in 7 patients, but 8 patients were still under hormone replacement therapy. Among the 5 patients who had a subsequent MRI, 2 had complete resolution of pituitary lesions.By combining our study and the literature review, the frequency of hypogonadism and diabetes insipidus, among the patients with pituitary dysfunction, can be estimated at 78% and 71% respectively. Despite a high rate of systemic disease remission on maintenance therapy, 86% of the patients had persistent pituitary dysfunction. The patients who recovered from pituitary dysfunction had all been

  10. A case of pituitary abscess presenting without a source of infection or prior pituitary pathology

    PubMed Central

    Kern, Philip A

    2016-01-01

    Summary Pituitary abscess is a relatively uncommon cause of pituitary hormone deficiencies and/or a suprasellar mass. Risk factors for pituitary abscess include prior surgery, irradiation and/or pathology of the suprasellar region as well as underlying infections. We present the case of a 22-year-old female presenting with a spontaneous pituitary abscess in the absence of risk factors described previously. Her initial presentation included headache, bitemporal hemianopia, polyuria, polydipsia and amenorrhoea. Magnetic resonance imaging (MRI) of her pituitary showed a suprasellar mass. As the patient did not have any risk factors for pituitary abscess or symptoms of infection, the diagnosis was not suspected preoperatively. She underwent transsphenoidal resection and purulent material was seen intraoperatively. Culture of the surgical specimen showed two species of alpha hemolytic Streptococcus, Staphylococcus capitis and Prevotella melaninogenica. Urine and blood cultures, dental radiographs and transthoracic echocardiogram failed to show any source of infection that could have caused the pituitary abscess. The patient was treated with 6weeks of oral metronidazole and intravenous vancomycin. After 6weeks of transsphenoidal resection and just after completion of antibiotic therapy, her headache and bitemporal hemianopsia resolved. However, nocturia and polydipsia from central diabetes insipidus and amenorrhoea from hypogonadotrophic hypogonadism persisted. Learning points Pituitary abscesses typically develop in patients who have other sources of infection or disruption of the normal suprasellar anatomy by either surgery, irradiation or pre-existing pathology; however, they can develop in the absence of known risk factors. Patients with pituitary abscesses typically complain of headache, visual changes and symptoms of pituitary hormone deficiencies. As other pituitary neoplasms present with similar clinical findings, the diagnosis of pituitary abscess is often not

  11. Somatotroph pituitary tumors in budgerigars (Melopsittacus undulatus).

    PubMed

    Langohr, I M; Garner, M M; Kiupel, M

    2012-05-01

    A series of 11 pituitary tumors in budgerigars were classified on the basis of their clinical, gross, microscopic, and immunohistochemical characteristics. Affected birds were young to middle-aged. Clinically, neurologic signs--including difficulties flying, ataxia, and blindness--were most commonly reported. Additional clinical signs included weight loss, abnormal feathers or molting, increased respiratory efforts, and exophthalmos. Nine birds were diagnosed with chromophobic pituitary adenomas, and 2 birds had chromophobic pituitary carcinomas. Only 1 tumor was delimited to the pituitary gland; the other 10 variably invaded the brain, skull, and retrobulbar space. Distant metastases were identified in 2 birds. All tumors were immunohistochemically strongly positive for growth hormone, consistent with the diagnosis of somatotroph tumors. The common occurrence and early onset may suggest a genetic predisposition of budgerigars to develop somatotroph pituitary tumors with a high incidence of local invasion and with metastatic potential. PMID:21900544

  12. Estradiol and its membrane-impermeable conjugate estradiol-BSA inhibit tamoxifen-stimulated prolactin secretion in incubated rat pituitaries.

    PubMed

    Aguilar, R; Bellido, C; Garrido-Gracia, J C; Alonso, R; Sánchez-Criado, J E

    2006-04-01

    In the absence of estrogen (E), the selective E receptor modulator tamoxifen (TX) has two agonist effects in the rat pituitary: induction of progesterone receptor (PR)-dependent GnRH self-priming in the gonadotrope, and stimulation of prolactin (PRL) secretion in the lactotrope. TX-induced gonadotropin (GnRH) self-priming is absent when 10(-8) M estradiol-17beta (E2) is added to the incubation medium of pituitaries from TX-treated rats. The present experiments investigated whether PR-independent PRL release into the incubation medium of pituitaries from TX-treated ovariectomized (OVX) rats was affected by E2, and the effect of different ER ligands (ICI182780, TX, estradiol-17alpha, E2 -BSA) on TX-stimulated PRL secretion. Moreover, the effect of E2 on TRH-stimulated PRL secretion in pituitaries collected from estradiol benzoate- and TX-treated OVX rats was studied. It was found that: i) incubation with E2 supressed the PRL releasing effect of injected TX; ii) whereas coincubation with the pure anti-E type II ICI182780 antagonized the inhibitory effect of E2, coincubation with the anti-E type I TX did not; iii) estradiol-17alpha lacked inhibitory action, whereas a dose-dependent inhibitory effect of both E2 and E2 -BSA was noticed; and iv) TRH stimulatory effect on PRL release in pituitaries from TX-treated rats was blocked by addition of E2 to the medium. Taken together, these data argue in favor of the presence of specific membrane recognition sites for E in the lactotrope involved in steroid-specific E2 inhibition of TX-stimulated PRL secretion.

  13. Estradiol and its membrane-impermeable conjugate estradiol-BSA inhibit tamoxifen-stimulated prolactin secretion in incubated rat pituitaries.

    PubMed

    Aguilar, R; Bellido, C; Garrido-Gracia, J C; Alonso, R; Sánchez-Criado, J E

    2006-04-01

    In the absence of estrogen (E), the selective E receptor modulator tamoxifen (TX) has two agonist effects in the rat pituitary: induction of progesterone receptor (PR)-dependent GnRH self-priming in the gonadotrope, and stimulation of prolactin (PRL) secretion in the lactotrope. TX-induced gonadotropin (GnRH) self-priming is absent when 10(-8) M estradiol-17beta (E2) is added to the incubation medium of pituitaries from TX-treated rats. The present experiments investigated whether PR-independent PRL release into the incubation medium of pituitaries from TX-treated ovariectomized (OVX) rats was affected by E2, and the effect of different ER ligands (ICI182780, TX, estradiol-17alpha, E2 -BSA) on TX-stimulated PRL secretion. Moreover, the effect of E2 on TRH-stimulated PRL secretion in pituitaries collected from estradiol benzoate- and TX-treated OVX rats was studied. It was found that: i) incubation with E2 supressed the PRL releasing effect of injected TX; ii) whereas coincubation with the pure anti-E type II ICI182780 antagonized the inhibitory effect of E2, coincubation with the anti-E type I TX did not; iii) estradiol-17alpha lacked inhibitory action, whereas a dose-dependent inhibitory effect of both E2 and E2 -BSA was noticed; and iv) TRH stimulatory effect on PRL release in pituitaries from TX-treated rats was blocked by addition of E2 to the medium. Taken together, these data argue in favor of the presence of specific membrane recognition sites for E in the lactotrope involved in steroid-specific E2 inhibition of TX-stimulated PRL secretion. PMID:16595727

  14. Plasma kisspeptin levels are elevated in cord blood and present sexual dimorphism in the adult population: relation with leptin, gonadotropins and anthropometrical data.

    PubMed

    Pita, Jimena; Rado-Peralta, Sandra; Gavela-Pérez, Teresa; Aragón, Isabel; Barrios, Vicente; Rovira, Adela; Argente, Jesús; Soriano-Guillén, Leandro

    2011-05-01

    Kisspeptin, the product of the hypothalamic KISS1 gene, is a main regulator of the hypothalamic-pituitary-gonadal axis and could be a link between metabolism and reproduction through its interaction with leptin. Kisspeptin could be involved in gonadotropin regulation and responsive to leptin levels from the first stages of life, exhibiting, as does leptin, sexual dimorphism. To test our hypothesis, we have analyzed plasma kisspeptin levels and their possible relationship with gonadotropins and leptin in a cohort composed of newborns (n = 86) and adults (n = 55). Plasma kisspeptin, gonadotropin and leptin levels were measured by RIA and multiplexed bead immunoassays, respectively. We have built a multivariate linear regression model (analyzing kisspeptin and LH separately as dependent variables) by stepwise analysis, incorporating the variables that had shown significant correlation in the univariate analysis. Cord blood samples exhibited high kisspeptin levels 127.01(113-141.02 pmol/l), but these were not sexually dimorphic. The adult population exhibited sexual dimorphism (3.72(2.95-4.49) vs. 1.77(1.23-2.31)pmol/l women vs. men, p<0.05). Leptin levels showed sexual dimorphism in cord blood samples and also in the adult population. Furthermore, there was a significant interaction between LH and kisspeptin levels and kisspeptin was negatively correlated with age. The high kisspeptin levels observed in cord blood, with no sexual dimorphism, suggest a placental source. The sexual dimorphism exhibited in adulthood supports the notion that there are different sources and/or differential kisspeptin regulation between men and women.

  15. Expression profiles of gonadotropins and their receptors during 17α-methyltestosterone implantation-induced sex change in the orange-spotted grouper (Epinephelus coioides).

    PubMed

    Hu, Xuesong; Liu, Xiaochun; Zhang, Haifa; Zhang, Yong; Li, Shuisheng; Sang, Qing; Wang, Qian; Luo, Wenna; Liu, Qizhi; Lu, Danqi; Meng, Zining; Lin, Haoran

    2011-06-01

    It is known that the hypothalamic-pituitary-gonadal axis participates in the sex change of hermaphrodite teleosts, and gonadal steroid hormones mediate this physiological process. The secretion of gonadal steroids is directly regulated by signaling pathways involving gonadotropins (GtHs) and gonadotropin receptors (GtHRs) in teleosts. To gain insight into the involvement of GtH/GtHR systems in the sex change process, cDNAs encoding follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) were firstly isolated from gonads of orange-spotted grouper (Epinephelus coioides), a protogynous hermaphrodite fish. Reverse transcription-PCR (RT-PCR) analysis demonstrated that the expression of the FSHR was confined to the brain, pituitary gland, ovary, and testis, while the LHR was expressed only in the brain, ovary, and testis. Furthermore, the expression profiles of GtH subunits (FSHβ and LHβ) and their receptors were analyzed in parallel with the serum levels of estradiol-17β (E(2) ), testosterone (T), and 11-ketotestosterone (11-KT) during 17α-methyltestosterone (MT)-induced sex change. Quantitative real-time PCR determined that the abundances of FSHβ and FSHR were significantly inhibited after MT treatment for 2 and 4 weeks, but subsequently returned to the control level after 6 weeks. In contrast, the mRNA levels of LHβ and LHR were significantly elevated throughout the sex change process. During MT-induced sex change, serum concentrations of E(2) remained constant while T and 11-KT levels were significantly increased. Taken together, our results suggest that GtH/GtHR systems are involved in MT-induced sex change, and two signaling pathways may have distinct roles in modulating the variations of the corresponding steroid hormones in the orange-spotted grouper.

  16. Toxic effects of methoxychlor administered subcutaneously on the hypothalamic-pituitary-testicular axis in adult rats.

    PubMed

    Lafuente, A; Cabaleiro, T; Caride, A; Esquifino, A I

    2008-05-01

    This study was undertaken to evaluate the effects of methoxychlor MTX at the hypothalamic-pituitary-testicular axis in adult male rats. This global objective comprises three major aims: (1) to analyze the possible differential MTX effects in norepinephrine and serotonin concentration an in serotoninergic metabolism in anterior, mediobasal and posterior hypothalamus and median eminence; (2) to evaluate effects induced by MTX exposure on gonadotropins and testosterone; 93 to elucidate whether the regulatory interactions in the hypothalamic-pituitary-testicular axis are modified by this pesticide. Animals were administered subcutaneously 25mg/kg/day of MTX for 1 month. MTX increased norepinephrine and serotonin content in anterior hypothalamus (P < or = 0.05), but decreased serotonin concentration in posterior hypothalamus (P < or = 0.05). MTX diminished serotonin turnover in anterior hypothalamus (P < or = 0.01) and decreased plasma LH (P < or = 0.001) and testosterone (P < or = 0.05) levels but those of FSH remained unmodified. We can conclude that MTX exposure: (1) could exert differential effects in norepinephrine and serotonin concentration an in serotoninergic metabolism in anterior, mediobasal and posterior hypothalamus and median eminence, being the anterior hypothalamus the most sensitive region to the pesticide; (2) could inhibit LH and testosterone secretion without changing FSH; (3) four potential pathways might be involved in MTX effects on testosterone secretion (changing LH secretion; modifying serotonin and norepinephrine at the hypothalamic level; alterating the direct neural pathway between brain and testes; and/or by a direct effect in testes).

  17. SOX2 regulates the hypothalamic-pituitary axis at multiple levels

    PubMed Central

    Jayakody, Sujatha A.; Andoniadou, Cynthia L.; Gaston-Massuet, Carles; Signore, Massimo; Cariboni, Anna; Bouloux, Pierre M.; Le Tissier, Paul; Pevny, Larysa H.; Dattani, Mehul T.; Martinez-Barbera, Juan P.

    2012-01-01

    Sex-determining region Y (SRY) box 2 (SOX2) haploinsufficiency causes a form of hypopituitarism in humans that is characterized by gonadotrophin deficiency known as hypogonadotrophic hypogonadism. Here, we conditionally deleted Sox2 in mice to investigate the pathogenesis of hypogonadotrophic hypogonadism. First, we found that absence of SOX2 in the developing Rathke pouch of conditional embryos led to severe anterior lobe hypoplasia with drastically reduced expression of the pituitary-specific transcription factor POU class 1 homeobox 1 (POU1F1) as well as severe disruption of somatotroph and thyrotroph differentiation. In contrast, corticotrophs, rostral-tip POU1F1-independent thyrotrophs, and, interestingly, lactotrophs and gonadotrophs were less affected. Second, we identified a requirement for SOX2 in normal proliferation of periluminal progenitors; in its absence, insufficient precursors were available to produce all cell lineages of the anterior pituitary. Differentiated cells derived from precursors exiting cell cycle at early stages, including corticotrophs, rostral-tip thyrotrophs, and gonadotrophs, were generated, while hormone-producing cells originating from late-born precursors, such as somatotrophs and POU1F1-dependent thyrotrophs, were severely reduced. Finally, we found that 2 previously characterized patients with SOX2 haploinsufficiency and associated hypogonadotrophic hypogonadism had a measurable response to gonadotropin-releasing hormone (GnRH) stimulation, suggesting that it is not the absence of gonadotroph differentiation, but rather the deficient hypothalamic stimulation of gonadotrophs, that underlies typical hypogonadotrophic hypogonadism. PMID:22945632

  18. Caffeine stimulates in vitro pituitary LH secretion in lipopolysaccharide-treated ewes.

    PubMed

    Herman, Andrzej Przemysław; Herman, Anna; Skipor, Janina; Krawczyńska, Agata; Bochenek, Joanna; Tomaszewska-Zaremba, Dorota

    2015-03-01

    The study was designed to determine the effects of caffeine on luteinizing hormone (LH) secretion and gene expression of caffeine-associated receptors in anterior pituitary (AP) explants obtained from saline- and lipopolysaccharide (LPS)-treated ewes. Animals had been treated with LPS or saline daily for seven days. Three hours after the last injection of LPS/saline, the AP were collected and divided into four explants. The explants were incubated with: 1/medium-199 (control explants), 2/gonadotropin-releasing hormone (GnRH; 100 pmol/mL; a positive control), 3/caffeine (10 mmol/L), or 4/GnRH+caffeine. Caffeine stimulated (p<0.05) LH release by explants from both saline (19.7 vs. control 12.6 ng/mg) and LPS (28.3 vs. control 13.9 ng/mg) treated animals. The effect of caffeine on LH secretion was stronger in the LPS-treated group than in saline-treated group, and the observed LH release was similar to that induced by GnRH alone (27.2 ng/mg). Caffeine increased (p<0.05) LHβ gene expression only in explants from LPS-treated animals. In conclusion, the results of the present study demonstrated a stimulatory in vitro effect of caffeine on LH secretion by ovine pituitary explants. The potency of the caffeine-induced LH secretion was affected by in vivo treatment of the animals with endotoxin.

  19. Stem cells in the canine pituitary gland and in pituitary adenomas.

    PubMed

    van Rijn, Sarah J; Tryfonidou, Marianna A; Hanson, Jeanette M; Penning, Louis C; Meij, Björn P

    2013-12-01

    Cushing's disease (CD) or pituitary-dependent hypercortisolism is a common endocrinopathy in dogs, with an estimated prevalence of 1 or 2 in 1000 dogs per year. It is caused by an adrenocorticotropic hormone secreting adenoma in the pars distalis or pars intermedia of the pituitary gland. The pituitary gland is a small endocrine gland located in the pituitary fossa. In the postnatal individual, the hypothalamus-pituitary axis plays a central role in maintaining homeostatic functions, like control of metabolism, reproduction, and growth. Stem cells are suggested to play a role in the homeostatic adaptations of the adult pituitary gland, such as the rapid specific cell-type expansion in response to pregnancy or lactation. Several cell populations have been suggested as pituitary stem cells, such as Side Population cells and cells expressing Sox2 or Nestin. These cell populations are discussed in this review. Also, stem and progenitor cells are thought to play a role in pituitary tumorigenesis, such as the development of pituitary adenomas in dogs. There are limited reports on the role of stem cells in pituitary adenomas, especially in dogs. Further studies are needed to identify and characterize this cell population and to develop specific cell targeting therapeutic strategies as a new way of treating canine CD.

  20. Gonadal and pituitary responsiveness of stallions is not down-regulated by prolonged pulsatile administration of GnRH.

    PubMed

    Brinsko, S P; Squires, E L; Pickett, B W; Nett, T M

    1998-01-01

    The objective of this study was to determine if prolonged pulsatile administration of homologous gonadotropin-releasing hormone (GnRH) at therapeutic or 5x therapeutic doses would cause down-regulation of the stallion's hypothalamic-pituitary-testicular axis. Fifteen stallions were randomly assigned to three treatment groups (n=5/group) and received a 0.5 ml subcutaneous dose of saline (group 1), 50 microg GnRH (group 2), or 250 microg GnRH (group 3) every 2 hours for 75 days. Weekly evaluations of follicle stimulating hormone, luteinizing hormone, and testosterone and monthly evaluations of daily sperm output and spermatozoal motility failed to demonstrate any decreased pituitary or gonadal responsiveness within or among treatment groups (P > 0.1) as a result of treatment with GnRH. Results of this study demonstrate that the hypothalamic-pituitary-testicularaxis of the stallion, unlike that of other domestic species, is remarkably refractory to GnRH-induced down-regulation.

  1. Narcotics and the hypothalamic-pituitary-gonadal axix: acute effects on luteinizing hormone, testosterone and androgen-dependent systems.

    PubMed

    Cicero, T J; Bell, R D; Meyer, E R; Schweitzer, J

    1977-04-01

    The effects of narcotics on several aspects of the hypothalamic-pituitary-gonadal axis were examined in the male rat. Our results indicate that a large number of narcotics acutely depress serum luteinizing hormone levels and that these reduced gonadotropin levels lead to a subsequent fall (1-2 hours later) in serum testosterone levels. The luteinizing hormone-depleting effect of the narcotics appears to represent a specific narcotic action since the (-)-isomers of the narcotics were much more effective than the ()-isomers, naloxone antagonized their effects and tolerance rapidly developed. Further, our studies indicate that the impairment of the functional and structural integrity of the secondary sex organs produced by chronic narcotic administration is not due to a direct effect of these drugs since they have no effect on the uptake of subcellular distribution of testosterone in the secondary sex organs or on the androgen-dependent accumulation of myo-inositol. Consequently, it appears that the testosterone depletion produced by the narcotics is solely responsible for their adverse effect on the secondary sex organs. The results of these studies suggest that the effects of the narcotics on the hypothalamic-pituitary-gonadal axis are confined to either the hypthalamus or the pituitary gland.

  2. Castration-induced changes in the response of the hypothalamic-pituitary axis to alcohol in the male rat.

    PubMed

    Cicero, T J; Greenwald, J; Nock, B; O'Connor, L

    1990-02-01

    In an attempt to determine the direct effects of alcohol on the hypothalamic-pituitary aspect of the hypothalamic-pituitary-gonadal axis, we examined the effects of alcohol on serum luteinizing hormone (LH) levels in the normal and testosterone-depleted castrated male rat. We found that within several days after castration (2-4 days) alcohol, at low to moderate doses, was only modestly effective in suppressing serum LH levels, whereas in sham-operated controls it was maximally effective at all doses tested. Surprisingly, at very high doses (4-6 g/kg), alcohol not only did not depress serum LH levels in long-term castrated rats, but elevated them by 2- to 4-fold when compared to saline-injected controls. The loss of sensitivity of the hypothalamic-pituitary axis to alcohol observed in castrated rats appeared to be selective, inasmuch as the mortality rate at high doses of alcohol was significantly (P less than .01) greater in castrated rats, when compared to sham-operated controls, and other measures of central nervous system impairment were equivalent in both groups. At the present time, it is difficult to explain this biphasic effect of alcohol on serum LH in the castrated animal, but our results are consistent with the hypothesis that the effects of alcohol on gonadotropin release may be dependent to a significant degree on the steroid milieu at the time of the experiments.

  3. Otx2 induction of the gonadotropin-releasing hormone promoter is modulated by direct interactions with Grg co-repressors.

    PubMed

    Larder, Rachel; Mellon, Pamela L

    2009-06-19

    Hormonal communication between the hypothalamus, pituitary, and gonads orchestrates the development and regulation of mammalian reproductive function. In mice, gonadotropin-releasing hormone (GnRH) expression is limited to approximately 1000 neurons that originate in the olfactory placode then migrate to specific positions scattered throughout the hypothalamus. Coordination of the hypothalamic-pituitary-gonadal axis is dependent upon correct migration of GnRH neurons into the hypothalamus followed by the appropriate synthesis and pulsatile secretion of GnRH. Defects in any one of these processes can cause infertility. Recently, substantial progress has been made in identifying transcription factors, and their cofactors, that regulate not only adult expression of GnRH, but also the maturation of GnRH neurons. Here, we show that expression of Otx2, a homeodomain protein required for the formation of the forebrain, is dramatically up-regulated during GnRH neuronal maturation and that overexpression of Otx2 increases GnRH promoter activity in GnRH neuronal cell lines. Furthermore, Otx2 transcriptional activity is modulated by Grg4, a member of the Groucho-related-gene (Grg) family. Using mutational analysis, we show that a WRPW peptide motif within the Otx2 protein is required for physical interaction between Otx2 and Grg4. Without this physical interaction, Grg4 cannot repress Otx2-dependent activation of GnRH gene transcription. Taken together, these data show that Otx2 is important for GnRH expression and that direct interaction between Otx2 and Grg co-repressors regulates GnRH gene expression in hypothalamic neurons.

  4. Hypothalamic gonadotropin-releasing hormone (GnRH) receptor neurons fire in synchrony with the female reproductive cycle.

    PubMed

    Schauer, Christian; Tong, Tong; Petitjean, Hugues; Blum, Thomas; Peron, Sophie; Mai, Oliver; Schmitz, Frank; Boehm, Ulrich; Leinders-Zufall, Trese

    2015-08-01

    Gonadotropin-releasing hormone (GnRH) controls mammalian reproduction via the hypothalamic-pituitary-gonadal (hpg) axis, acting on gonadotrope cells in the pituitary gland that express the GnRH receptor (GnRHR). Cells expressing the GnRHR have also been identified in the brain. However, the mechanism by which GnRH acts on these potential target cells remains poorly understood due to the difficulty of visualizing and identifying living GnRHR neurons in the central nervous system. We have developed a mouse strain in which GnRHR neurons express a fluorescent marker, enabling the reliable identification of these cells independent of the hormonal status of the animal. In this study, we analyze the GnRHR neurons of the periventricular hypothalamic nucleus in acute brain slices prepared from adult female mice. Strikingly, we find that the action potential firing pattern of these neurons alternates in synchrony with the estrous cycle, with pronounced burst firing during the preovulatory period. We demonstrate that GnRH stimulation is sufficient to trigger the conversion from tonic to burst firing in GnRHR neurons. Furthermore, we show that this switch in the firing pattern is reversed by a potent GnRHR antagonist. These data suggest that endogenous GnRH acts on GnRHR neurons and triggers burst firing in these cells during late proestrus and estrus. Our data have important clinical implications in that they indicate a novel mode of action for GnRHR agonists and antagonists in neurons of the central nervous system that are not part of the classical hpg axis.

  5. LPXRFa, the piscine ortholog of GnIH, and LPXRF receptor positively regulate gonadotropin secretion in Tilapia (Oreochromis niloticus).

    PubMed

    Biran, Jakob; Golan, Matan; Mizrahi, Naama; Ogawa, Satoshi; Parhar, Ishwar S; Levavi-Sivan, Berta

    2014-11-01

    LPXRFamide (LPXRFa) peptides have been characterized for their ability to inhibit gonadotropin (GTH) release in birds and stimulate growth hormone (GH) release in frogs. However, their involvement in regulating the reproductive hypothalamo-pituitary-gonadal axis in mammals and fish is inconclusive. To study the role of LPXRFa peptides in the regulation of GTH secretion, we cloned tilapia LPXRFa and LPXRF receptor (LPXRF-R). Processing of the tilapia preproLPXRFa liberated three mature LPXRFa peptides that varied in size and post-translational modifications. Phylogenetic analysis of LPXRFa and the closely related RFamide peptide PQRFa showed clear clustering of each peptide sequence with its orthologs from various vertebrates. Signal-transduction analysis of the tilapia LPXRF-R in COS-7 cells showed clear stimulation of CRE-dependent luciferase activity, whereas the human NPFFR1 showed suppression of forskolin-induced CRE-dependent activity in this system. Administration of the tilapia pyroglutaminated LPXRFa-2 peptide to primary cell culture of tilapia pituitaries, or to reproductive female tilapia by ip injection, positively regulated both LH and FSH release in vivo and in vitro. Using double-labeled fluorescent in-situ hybridization and immunofluorescence, βLH cells were found to co-express both tilapia lpxrf and tilapia lpxrf-r mRNA, whereas some of the βFSH cells coexpressed only lpxrf-r mRNA. No coexpression of tilapia lpxrf-r was identified in GH-positive cells. These findings suggest that the LPXRFa system is a potent positive regulator of the reproductive neuroendocrine axis of tilapia. PMID:25144920

  6. Hypothalamic gonadotropin-releasing hormone (GnRH) receptor neurons fire in synchrony with the female reproductive cycle

    PubMed Central

    Schauer, Christian; Tong, Tong; Petitjean, Hugues; Blum, Thomas; Peron, Sophie; Mai, Oliver; Schmitz, Frank; Boehm, Ulrich

    2015-01-01

    Gonadotropin-releasing hormone (GnRH) controls mammalian reproduction via the hypothalamic-pituitary-gonadal (hpg) axis, acting on gonadotrope cells in the pituitary gland that express the GnRH receptor (GnRHR). Cells expressing the GnRHR have also been identified in the brain. However, the mechanism by which GnRH acts on these potential target cells remains poorly understood due to the difficulty of visualizing and identifying living GnRHR neurons in the central nervous system. We have developed a mouse strain in which GnRHR neurons express a fluorescent marker, enabling the reliable identification of these cells independent of the hormonal status of the animal. In this study, we analyze the GnRHR neurons of the periventricular hypothalamic nucleus in acute brain slices prepared from adult female mice. Strikingly, we find that the action potential firing pattern of these neurons alternates in synchrony with the estrous cycle, with pronounced burst firing during the preovulatory period. We demonstrate that GnRH stimulation is sufficient to trigger the conversion from tonic to burst firing in GnRHR neurons. Furthermore, we show that this switch in the firing pattern is reversed by a potent GnRHR antagonist. These data suggest that endogenous GnRH acts on GnRHR neurons and triggers burst firing in these cells during late proestrus and estrus. Our data have important clinical implications in that they indicate a novel mode of action for GnRHR agonists and antagonists in neurons of the central nervous system that are not part of the classical hpg axis. PMID:26063780

  7. Interactions between protein kinase C and arachidonic acid in the gonadotropin response to salmon and chicken gonadotropin-releasing hormone-II in goldfish.

    PubMed

    Chang, J P; Van Goor, F; Neumann, C M

    1994-03-01

    Previous studies have shown that, in goldfish, the gonadotropin (GTH) response to salmon GTH-releasing hormone (sGnRH) is partly mediated by arachidonic acid (AA) metabolism via the lipoxygenase enzyme system, whereas protein kinase C (PKC) participates in both sGnRH- and chicken (c)GnRH-II-induced GTH secretion. In this study, the interactions between AA- and PKC-dependent pathways in mediating the long-term GnRH stimulation of GTH release were further investigated using dispersed goldfish pituitary cell cultures in static incubation. Treatments with AA or the PKC activator tetradecanoylphorbol acetate (TPA) increased GTH release. The GTH responses to AA and TPA were additive. The lipoxygenase inhibitor nordihydroguairetic acid (NDGA) and the PKC inhibitor H7 selectively reduced AA- and TPA-stimulated GTH release, respectively. These findings suggest that the GTH responses to stimulation by AA- and PKC-dependent signaling pathways are independent of one another. In other experiments, the GTH response to cGnRH-II was unaffected by NDGA but was abolished by H7. In contrast, sGnRH-induced GTH release was attenuated by NDGA and H7. Furthermore, in the presence of both NDGA and H7, the GTH response to sGnRH was abolished. These data suggest that sGnRH stimulation of GTH secretion involves both AA- and PKC-dependent mechanisms; in contrast, cGnRH-II action is not dependent on AA metabolism. The pathway by which AA might be mobilized in response to a GnRH challenge was also investigated by pharmacological manipulations. The diacylglcerol (DG) lipase inhibitor, U-57908, did not decrease sGnRH- and cGnRH-II-induced GTH secretion. On the other hand, the phospholipase A2 (PLA2) inhibitors, bromophenacyl bromide (BPB), chloroquine, and quinacrine, reduced sGnRH-elicited, but not cGnRH-II-stimulated GTH release. The addition of AA reversed the inhibitory action of BPB on sGnRH-elicited GTH release. In addition, the GTH response to AA was additive to the cGnRH-II-induced, but

  8. Hereditary Pituitary Hyperplasia with Infantile Gigantism

    PubMed Central

    Gläsker, Sven; Vortmeyer, Alexander O.; Lafferty, Antony R. A.; Hofman, Paul L.; Li, Jie; Weil, Robert J.; Zhuang, Zhengping

    2011-01-01

    Context: We report hereditary pituitary hyperplasia. Objective: The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. Design: The study is a retrospective analysis of three cases from one family. Setting: The study was conducted at the National Institutes of Health, a tertiary referral center. Patients: A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. Interventions: The condition was treated by total hypophysectomy. Main Outcome Measure(s): We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. Results: All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. Conclusions: This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development. PMID:21976722

  9. Prolactin-Secreting Pituitary Adenomas

    PubMed Central

    Martin, Mary C.; Schriock, Eldon D.; Jaffe, Robert B.

    1983-01-01

    Prolactin-secreting pituitary adenoma is a common cause of gynecologic problems that include oligomenorrhea, infertility, amenorrhea and galactorrhea. Diagnosis requires a combination of endocrine testing and radiologic evaluation. The diagnosis of macroadenomas is usually straightforward and these large tumors may be associated with mass effects such as severe headache, nerve palsies or visual changes. Microadenomas may be more subtle in presentation, and the diagnosis of hyperprolactinemia without radiologic evidence of a tumor frequently is problematic. The management of prolactin-secreting adenoma remains controversial, with no clear consensus or indication for surgical versus medical treatment. Surgical intervention is a realistic option for those patients who have access to an experienced neurosurgeon and who have tumor characteristics that offer a reasonable hope for cure. Many questions remain to be answered, including the cause, natural history of development and the optimum treatment for individual cases. Images PMID:6659490

  10. Subcellular localization of pituitary enzymes

    NASA Technical Reports Server (NTRS)

    Smith, R. E.

    1970-01-01

    A cytochemical procedure is reported for identifying subcellular sites of enzymes hydrolyzing beta-naphthylamine substrates, and to study the sites of reaction product localization in cells of various tissues. Investigations using the substrate Leu 4-methoxy-8-naphthylamine, a capture with hexonium pararosaniline, and the final chelation of osmium have identified the hydrolyzing enzyme of rat liver cells; this enzyme localized on cell membranes with intense deposition in the areas of the parcanaliculi. The study of cells in the anterior pituitary of the rat showed the deposition of reaction product on cell membrane; and on the membranes of secretion granules contained within the cell. The deposition of reaction product on the cell membrane however showed no increase or decrease with changes in the physiological state of the gland and release of secretion granules from specific cells.

  11. Hypothalamus-Pituitary-Thyroid Axis.

    PubMed

    Ortiga-Carvalho, Tania M; Chiamolera, Maria I; Pazos-Moura, Carmen C; Wondisford, Fredic E

    2016-01-01

    The hypothalamus-pituitary-thyroid (HPT) axis determines the set point of thyroid hormone (TH) production. Hypothalamic thyrotropin-releasing hormone (TRH) stimulates the synthesis and secretion of pituitary thyrotropin (thyroid-stimulating hormone, TSH), which acts at the thyroid to stimulate all steps of TH biosynthesis and secretion. The THs thyroxine (T4) and triiodothyronine (T3) control the secretion of TRH and TSH by negative feedback to maintain physiological levels of the main hormones of the HPT axis. Reduction of circulating TH levels due to primary thyroid failure results in increased TRH and TSH production, whereas the opposite occurs when circulating THs are in excess. Other neural, humoral, and local factors modulate the HPT axis and, in specific situations, determine alterations in the physiological function of the axis. The roles of THs are vital to nervous system development, linear growth, energetic metabolism, and thermogenesis. THs also regulate the hepatic metabolism of nutrients, fluid balance and the cardiovascular system. In cells, TH actions are mediated mainly by nuclear TH receptors (210), which modify gene expression. T3 is the preferred ligand of THR, whereas T4, the serum concentration of which is 100-fold higher than that of T3, undergoes extra-thyroidal conversion to T3. This conversion is catalyzed by 5'-deiodinases (D1 and D2), which are TH-activating enzymes. T4 can also be inactivated by conversion to reverse T3, which has very low affinity for THR, by 5-deiodinase (D3). The regulation of deiodinases, particularly D2, and TH transporters at the cell membrane control T3 availability, which is fundamental for TH action. © 2016 American Physiological Society. Compr Physiol 6:1387-1428, 2016. PMID:27347897

  12. Neonatal haemochromatosis with reversible pituitary involvement.

    PubMed

    Indolfi, Giuseppe; Bèrczes, Rita; Pelliccioli, Isabella; Bosisio, Michela; Agostinis, Cristina; Resti, Massimo; Zambelli, Marco; Lucianetti, Alessandro; Colledan, Michele; D'Antiga, Lorenzo

    2014-08-01

    Neonatal haemochromatosis is a rare alloimmune gestational disease with a high mortality. The hallmark of neonatal haemochromatosis is severe neonatal liver failure associated with extrahepatic siderosis. Thus far, no pituitary dysfunction has been reported to result from the tissue damage associated with extrahepatic siderosis. The present report describes a neonate with neonatal haemochromatosis and secondary hypothyroidism associated with pituitary iron deposition. Both the conditions were successfully treated by ABO-incompatible liver transplantation. Pituitary gland dysfunction is another possible extrahepatic manifestation of neonatal haemochromatosis, and it is reversible after liver transplantation.

  13. The Molecular Pathogenesis of Pituitary Adenomas: An Update

    PubMed Central

    Jiang, Xiaobing

    2013-01-01

    Pituitary tumors represent the most common intracranial neoplasms accompanying serious morbidity through mass effects and inappropriate secretion of pituitary hormones. Understanding the etiology of pituitary tumorigenesis will facilitate the development of satisfactory treatment for pituitary adenomas. Although the pathogenesis of pituitary adenomas is largely unknown, considerable evidence indicates that the pituitary tumorigenesis is a complex process involving multiple factors, including genetic and epigenetic changes. This review summarized the recent progress in the study of pituitary tumorigenesis, focusing on the role of tumor suppressor genes, oncogenes and microRNAs. PMID:24396688

  14. Hypothalamic-pituitary gonadal axis and immune response imbalance during chronic filarial infections.

    PubMed

    Mavoungou, Donatien; Poaty-Mavoungou, Virginie; Ongali, Brice; Akoume, Marie Yvonne; Maka, Gontran; Mavoungou, Elie

    2005-11-01

    Bi-directional relationships operate between the hypothalamic-pituitary-gonadal axis and the immune system. Cytokines, peptide hormones and their shared receptors/ligands are used as a common biological language for communication within and between the immune and neuroendocrine systems. Such communication suggests an immunoregulatory role for the brain and a sensory function for the immune system. We used a radioimmunoassay to measure the concentrations of steroid hormones (cortisol, testosterone, estradiol and progesterone) and pituitary hormones [follicle stimulating hormone (FSH), luteinizing hormone (LH) human chorionic gonadotropin (HCG) and prolactin] in peripheral blood plasma from 78 young Gabonese women with chronic filarial infections. We used an enzyme-linked immunosorbent assay to determine the concentrations of four proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), gamma interferon (IFN-gamma), interleukin-1 (IL-1) and IL-6] in the same plasma samples. Progesterone was unchanged and all other steroid hormone plasma concentrations were lower in microfilaremic women than in amicrofilaremic women. The concentration of LH was higher in amicrofilaremic women, whereas the prolactin concentration was higher in microfilaremics. The plasma concentrations of TNF-alpha, IFN-gamma, IL-1 and IL-6 were higher in microfilaremic women. A strong negative correlation was found between the steroid and pituitary hormones and the pro-inflammatory cytokines. Conversely, a strong positive correlation was found between prolactin and the same cytokines. These data provide first evidence of immune system and hormonal system disturbance during chronic filarial infections and suggest that the observed imbalance should be taken into account in the diagnosis and treatment of filarial infections.

  15. Naltrexone effects on pituitary and gonadal hormones in male and female rhesus monkeys.

    PubMed

    Mello, N K; Mendelson, J H; Bree, M P; Skupny, A

    1988-11-01

    The long-acting opioid antagonist, naltrexone, stimulates LH and FSH in women during the early follicular phase of the menstrual cycle and is a new provocative test of hypothalamic-pituitary function (42,63). The acute effects of naltrexone (0.25, 0.50 and 1.0 mg/kg IV) on anterior pituitary (LH, FSH, PRL) and gonadal steroid (T or E2) hormones were studied in 7 female and 4 male rhesus monkeys (Macaca mulatta). Integrated plasma samples were collected at 20 min intervals for 60 min before and for 300 min after intravenous infusion of naltrexone over 10 min. In females studied during the early follicular phase (cycle days 1-3), naltrexone did not stimulate LH and significantly suppressed E2 (p less than 0.0003-0.0001) and FSH (p less than 0.006-0.0001). Naltrexone (0.50 and 1.0 mg/kg) also did not stimulate LH release in late follicular phase females (cycle days 10-12) when estradiol levels were in the peri-ovulatory range. FSH and E2 were significantly suppressed (p less than 0.01-0.05) after 1.0 mg/kg naltrexone, but not after 0.5 mg/kg naltrexone. However, in males all doses of naltrexone significantly stimulated LH (p less than 0.003-0.0001) and T (p less than 0.001-0.0001) but not FSH. LH increased significantly above baseline within 20 to 40 min and T increased significantly within 60 min. These gender differences in naltrexone's effects on pituitary gonadotropins and gonadal steroid hormones were unanticipated. These data are not concordant with clinical studies which report significant naltrexone stimulation of LH in men and in women during the early follicular phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3150786

  16. Cell Type-Specific Sexual Dimorphism in Rat Pituitary Gene Expression During Maturation1

    PubMed Central

    Bjelobaba, Ivana; Janjic, Marija M.; Kucka, Marek; Stojilkovic, Stanko S.

    2015-01-01

    The most obvious functional differences between mammalian males and females are related to the control of reproductive physiology and include patterns of GnRH and gonadotropin release, the timing of puberty, sexual and social behavior, and the regulation of food intake and body weight. Using the rat as the best-studied mammalian model for maturation, we examined the expression of major anterior pituitary genes in five secretory cell types of developing males and females. Corticotrophs show comparable Pomc profiles in both sexes, with the highest expression occurring during the infantile period. Somatotrophs and lactotrophs also exhibit no difference in Gh1 and Prl profiles during embryonic to juvenile age but show the amplification of Prl expression in females and Gh1 expression in males during peripubertal and postpubertal ages. Gonadotrophs exhibit highly synchronized Lhb, Fshb, Cga, and Gnrhr expression in both sexes, but the peak of expression occurs during the infantile period in females and at the end of the juvenile period in males. Thyrotrophs also show different developmental Tshb profiles, which are synchronized with the expression of gonadotroph genes in males but not in females. These results indicate the lack of influence of sex on Pomc expression and the presence of two patterns of sexual dimorphism in the expression of other pituitary genes: a time shift in the peak expression during postnatal development, most likely reflecting the perinatal sex-specific brain differentiation, and modulation of the amplitude of expression during late development, which is secondary to the establishment of the hypothalamic-pituitary-gonadal and -thyroid axes. PMID:26063874

  17. Congenital adrenal hyperplasia complicated by central precocious puberty: linear growth during infancy and treatment with gonadotropin-releasing hormone analog.

    PubMed

    Soliman, A T; AlLamki, M; AlSalmi, I; Asfour, M

    1997-05-01

    Some children with congenital adrenal hyperplasia (CAH) develop true precocious puberty with early maturation of the hypothalamic-pituitary-gonadal axis. We have seen six such children who had the diagnosis of CAH with late initiation of corticosteroid treatment and/or poor compliance who developed central precocious puberty (CPP). These patients were treated with standard-dose hydrocortisone and fludrocortisone. Administration of depot leuprorelin (3.75 mg subcutaneously every 28 days) for 2 years or longer was effective in arresting the manifestations of puberty, decelerating the pretreatment growth velocity ([GV] 10.8 +/- 1.5 v3.65 +/- 0.95 cm/yr), increasing the predicted adult height ([PAHT] 147.5 +/- 7.8 v 153.4 +/- 8.3 cm), and decreasing the bone age to statural age ratio (1.26 +/- 0.13 v 1.16 +/- 0.09). Analysis of auxanological data during the first 2 years of life showed that linear growth was significantly accelerated and bone age was advanced in patients who developed CPP compared with 11 age-matched patients. It appears that proper glucocorticoid replacement to achieve adequate control of hyperandrogenemia during early life might prevent development of CPP in these patients. Gonadotropin-releasing hormone agonist (GnRHa) therapy can improve the final adult height, bringing it closer to that expected from the genetic potential.

  18. Chapter 2: hypothalamic neural systems controlling the female reproductive life cycle gonadotropin-releasing hormone, glutamate, and GABA.

    PubMed

    Maffucci, Jacqueline A; Gore, Andrea C

    2009-01-01

    The hypothalamic-pituitary-gonadal (HPG) axis undergoes a number of changes throughout the reproductive life cycle that are responsible for the development, puberty, adulthood, and senescence of reproductive systems. This natural progression is dictated by the neural network controlling the hypothalamus including the cells that synthesize and release gonadotropin-releasing hormone (GnRH) and their regulatory neurotransmitters. Glutamate and GABA are the primary excitatory and inhibitory neurotransmitters in the central nervous system, and as such contribute a great deal to modulating this axis throughout the lifetime via their actions on receptors in the hypothalamus, both directly on GnRH neurons as well as indirectly through other hypothalamic neural networks. Interactions among GnRH neurons, glutamate, and GABA, including the regulation of GnRH gene and protein expression, hormone release, and modulation by estrogen, are critical to age-appropriate changes in reproductive function. Here, we present evidence for the modulation of GnRH neurosecretory cells by the balance of glutamate and GABA in the hypothalamus, and the functional consequences of these interactions on reproductive physiology across the life cycle.

  19. Developmental regulation of gonadotropin-releasing hormone gene expression by the MSX and DLX homeodomain protein families.

    PubMed

    Givens, Marjory L; Rave-Harel, Naama; Goonewardena, Vinodha D; Kurotani, Reiko; Berdy, Sara E; Swan, Christo H; Rubenstein, John L R; Robert, Benoit; Mellon, Pamela L

    2005-05-13

    Gonadotropin-releasing hormone (GnRH) is the central regulator of the hypothalamic-pituitary-gonadal axis, controlling sexual maturation and fertility in diverse species from fish to humans. GnRH gene expression is limited to a discrete population of neurons that migrate through the nasal region into the hypothalamus during embryonic development. The GnRH regulatory region contains four conserved homeodomain binding sites (ATTA) that are essential for basal promoter activity and cell-specific expression of the GnRH gene. MSX and DLX are members of the Antennapedia class of non-Hox homeodomain transcription factors that regulate gene expression and influence development of the craniofacial structures and anterior forebrain. Here, we report that expression patterns of the Msx and Dlx families of homeodomain transcription factors largely coincide with the migratory route of GnRH neurons and co-express with GnRH in neurons during embryonic development. In addition, MSX and DLX family members bind directly to the ATTA consensus sequences and regulate transcriptional activity of the GnRH promoter. Finally, mice lacking MSX1 or DLX1 and 2 show altered numbers of GnRH-expressing cells in regions where these factors likely function. These findings strongly support a role for MSX and DLX in contributing to spatiotemporal regulation of GnRH transcription during development.

  20. Review of outcomes after cessation of gonadotropin-releasing hormone agonist treatment of girls with precocious puberty.

    PubMed

    Thornton, Paul; Silverman, Lawrence A; Geffner, Mitchell E; Neely, E Kirk; Gould, Errol; Danoff, Theodore M

    2014-03-01

    Although gonadotropin-releasing hormone agonists (GnRHa) have been the standard of care of central precocious puberty (CPP) management for many years, there are still questions about the long-term consequences of treatment. With increased utilization of GnRHa treatment, it is now possible to assess posttreatment outcomes in the immediate posttreatment period and into adulthood. This literature review reports on the long-term effects of GnRHa therapy in girls with CPP after therapy has been discontinued. Published reports confirm the reversibility of hypothalamic-pituitary-ovarian axis suppression in females after cessation of GnRHa therapy, with the majority of patients achieving ovulatory menstrual cycles of normal timing and duration. GnRHa therapy does not appear to induce polycystic ovary syndrome or have long-term negative repercussions on either bone mineral density or body composition. Evidence is currently insufficient to identify agent-specific differences in outcomes, reproductive function, and health of offspring.

  1. Semaphorin 4D regulates gonadotropin hormone-releasing hormone-1 neuronal migration through PlexinB1-Met complex.

    PubMed

    Giacobini, Paolo; Messina, Andrea; Morello, Francesca; Ferraris, Nicoletta; Corso, Simona; Penachioni, Junia; Giordano, Silvia; Tamagnone, Luca; Fasolo, Aldo

    2008-11-01

    In mammals, reproduction is dependent on specific neurons secreting the neuropeptide gonadotropin hormone-releasing hormone-1 (GnRH-1). These cells originate during embryonic development in the olfactory placode and migrate into the forebrain, where they become integral members of the hypothalamic-pituitary-gonadal axis. This migratory process is regulated by a wide range of guidance cues, which allow GnRH-1 cells to travel over long distances to reach their appropriate destinations. The Semaphorin4D (Sema4D) receptor, PlexinB1, is highly expressed in the developing olfactory placode, but its function in this context is still unknown. Here, we demonstrate that PlexinB1-deficient mice exhibit a migratory defect of GnRH-1 neurons, resulting in reduction of this cell population in the adult brain. Moreover, Sema4D promotes directional migration in GnRH-1 cells by coupling PlexinB1 with activation of the Met tyrosine kinase (hepatocyte growth factor receptor). This work identifies a function for PlexinB1 during brain development and provides evidence that Sema4D controls migration of GnRH-1 neurons.

  2. Effects of norethindrone on gonadotropin and ovarian steroid secretion when used for cycle programming during in vitro fertilization.

    PubMed

    Anderson, R E; Stein, A L; Paulson, R J; Stanczyk, F Z; Vijod, A G; Lobo, R A

    1990-07-01

    Norethindrone (NET) has been used for cycle programming and may result in attenuated responses to controlled ovarian hyperstimulation. The effects of NET on gonadotropin secretion, its bioavailability to the ovary, and its effect on ovarian steroidogenesis in vivo and in vitro were assessed. Endogenous secretion of luteinizing hormone and follicle-stimulating hormone was attenuated by 59% and 50%, respectively, after 2 weeks of orally administered NET. Twelve hours after a single 10-mg oral dose, significant levels of NET were measured in samples of peripheral (8.8 +/- 1.9 ng/mL) and ovarian venous blood (10.5 +/- 3.1 ng/mL), follicular fluid (7.1 +/- 2.1 ng/mL), and homogenates of ovarian tissue (8.0 +/- 0.6 ng/g). Furthermore, NET was detectable in follicular fluid 2 weeks after its withdrawal (863 +/- 149 pg/mL). However, there were no effects of NET on follicular fluid levels of estradiol and progesterone in vivo or on luteinized granulosa cell steroidogenesis in vitro. We conclude that when used for cycle programming in in vitro fertilization, NET does not inhibit ovarian steroidogenesis but does affect the hypothalamic-pituitary axis.

  3. Gonadotropins in doping: pharmacological basis and detection of illicit use

    PubMed Central

    Stenman, U-H; Hotakainen, K; Alfthan, H

    2008-01-01

    Parenteral administration of human chorionic gonadotropin (hCG) or luteinizing hormone (LH) stimulates the production of testosterone in males and these gonadotropins can therefore be used by athletes to enhance muscle strength. However, they are more expensive and less efficient than testosterone and anabolic steroids. Therefore their main use is probably to stimulate gonadal testosterone production during and after self-administration of testosterone or anabolic steroids. A positive effect of hCG on muscle strength has not been demonstrated in women and elevated concentrations of hCG in females are often caused by pregnancy. The use of gonadotropins is therefore prohibited only in males but not in females. HCG occurs at low but measurable concentrations in plasma and urine of healthy males and can be measured by sensitive methods. However, the characteristics of the method to be used for doping control have not been defined. Virtually all commercially available hCG assays have been designed for determination of hCG in serum rather than urine, which is used for doping control. Methods based on mass spectrometric detection of fragments derived from hCG extracted from urine by immunoadsorption have been developed but their suitability for doping control remains to be determined. The concentrations of LH in serum and urine are variable and more then 10-fold higher than those hCG. It is therefore difficult to detect illicit use of LH. The characteristics and reference values for hCG and LH assays used in doping control and the cutoff values need to be defined. PMID:18414398

  4. Genetics Home Reference: combined pituitary hormone deficiency

    MedlinePlus

    ... People with combined pituitary hormone deficiency may have hypothyroidism, which is underactivity of the butterfly-shaped thyroid gland in the lower neck. Hypothyroidism can cause many symptoms, including weight gain and ...

  5. MicroRNAs in Human Pituitary Adenomas

    PubMed Central

    Wang, Elaine Lu; Qian, Zhi Rong

    2014-01-01

    MicroRNAs (miRNAs) are a class of recently identified noncoding RNAs that regulate gene expression at posttranscriptional level. Due to the large number of genes regulated by miRNAs, miRNAs play important roles in many cellular processes. Emerging evidence indicates that miRNAs are dysregulated in pituitary adenomas, a class of intracranial neoplasms which account for 10–15% of diagnosed brain tumors. Deregulated miRNAs and their targets contribute to pituitary adenomas progression and are associated with cell cycle control, apoptosis, invasion, and pharmacological treatment of pituitary adenomas. To provide an overview of miRNAs dysregulation and functions of these miRNAs in pituitary adenoma progression, we summarize the deregulated miRNAs and their targets to shed more light on their potential as therapeutic targets and novel biomarkers. PMID:25548562

  6. Genetics Home Reference: familial isolated pituitary adenoma

    MedlinePlus

    ... 1,000 people. FIPA, though, is quite rare, accounting for approximately 2 percent of pituitary adenomas. More ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management These resources address the diagnosis or management of ...

  7. Primary immune thrombocytopenia accompanied by pituitary apoplexy.

    PubMed

    Tsuji, Takahiro; Mochinaga, Hiromi; Yamasaki, Hiroshi; Tsuda, Hiroyuki

    2016-07-01

    An 83-year-old woman was admitted to our hospital with a severe headache and purpura. She had previously been diagnosed with idiopathic thrombocytopenia purpura (ITP) and achieved complete remission with steroid therapy. Steroid therapy had been completed one week prior to the current admission. The recurrence of severe thrombocytopenia (<1.0×10(4) platelets/μl) was detected and a CT scan revealed pituitary hemorrhage without pituitary adenoma. She received steroid therapy combined with intravenous immunoglobulin, which resulted in the amelioration of ITP and improvements in the pituitary hemorrhage. Intracranial hemorrhage, which is the most serious bleeding manifestation in ITP, is relatively uncommon. Pituitary apoplexy in ITP is extremely rare. PMID:27498733

  8. Multitasking in Gonadotropin-Releasing Hormone Neuron Dendrites.

    PubMed

    Iremonger, Karl J; Herbison, Allan E

    2015-01-01

    Gonadotropin-releasing hormone (GnRH) neurons integrate synaptic information in their dendrites in order to precisely control GnRH secretion and hence fertility. Recent discoveries concerning the structure and function of GnRH neuron dendrites have shed new light on the control of GnRH neuron excitability and GnRH secretion. This work suggests that GnRH neurons have a unique projection to the median eminence that possesses both dendritic and axonal properties. We propose that this 'dendron' projection allows GnRH neurons to multitask and integrate information in ways that would not be possible in a classically envisioned axon projection. PMID:25300776

  9. Double pituitary adenomas: six surgical cases.

    PubMed

    Sano, T; Horiguchi, H; Xu, B; Li, C; Hino, A; Sakaki, M; Kannuki, S; Yamada, S

    1999-05-01

    While double pituitary adenomas have been found in approximately 1% of autopsy pituitaries, those in surgically resected material have been only rarely reported. We report herein 6 cases of double pituitary adenomas, which consisted of two histologically and/or immunohistochemically different areas among approximately 450 surgical specimens. Five out of 6 patients were men and the age was ranged between 18 and 61 years old. All these 6 patients presented acromegaly or acrogigantism and hyperprolactinemia was noted in 3 patients. In 2 patients (cases 1 and 2) the two adenomas belonged to different adenoma groups (GH-PRL-TSH group and FSH/LH group), while in the remaining 4 patients (cases 3-6) the two adenomas belonged to the same group (GH-PRL-TSH group). Thus, in all patients at least one of the two adenomas was GH-producing adenoma. Reasons for a high incidence of GH-producing adenomas in surgically resected double pituitary adenomas may include the presence of a variety of histologic subtypes among GH-producing adenomas and the advantage of cytokeratin immunostaining to distinguish these subtypes. In regard to pathogenesis of double pituitary adenomas, adenomas in cases 1 and 2 may be of multicentric occurrence, while those in cases 3-6 may occur through different clonal proliferation within originally one adenoma, resulting in diverse phenotypic expressions. Since there were patients with familial MEN 1 (case 2) and familial pituitary adenoma unrelated MEN 1 (case 3), genetic background should be also considered. Double pituitary adenomas in surgically resected material may not be so infrequent. Further molecular analysis will provide new insights into understanding the pathogenesis of pituitary adenomas and their mechanisms of multidirectional phenotypic diffrentiation.

  10. Double pituitary adenomas: six surgical cases.

    PubMed

    Sano, T; Horiguchi, H; Xu, B; Li, C; Hino, A; Sakaki, M; Kannuki, S; Yamada, S

    1999-05-01

    While double pituitary adenomas have been found in approximately 1% of autopsy pituitaries, those in surgically resected material have been only rarely reported. We report herein 6 cases of double pituitary adenomas, which consisted of two histologically and/or immunohistochemically different areas among approximately 450 surgical specimens. Five out of 6 patients were men and the age was ranged between 18 and 61 years old. All these 6 patients presented acromegaly or acrogigantism and hyperprolactinemia was noted in 3 patients. In 2 patients (cases 1 and 2) the two adenomas belonged to different adenoma groups (GH-PRL-TSH group and FSH/LH group), while in the remaining 4 patients (cases 3-6) the two adenomas belonged to the same group (GH-PRL-TSH group). Thus, in all patients at least one of the two adenomas was GH-producing adenoma. Reasons for a high incidence of GH-producing adenomas in surgically resected double pituitary adenomas may include the presence of a variety of histologic subtypes among GH-producing adenomas and the advantage of cytokeratin immunostaining to distinguish these subtypes. In regard to pathogenesis of double pituitary adenomas, adenomas in cases 1 and 2 may be of multicentric occurrence, while those in cases 3-6 may occur through different clonal proliferation within originally one adenoma, resulting in diverse phenotypic expressions. Since there were patients with familial MEN 1 (case 2) and familial pituitary adenoma unrelated MEN 1 (case 3), genetic background should be also considered. Double pituitary adenomas in surgically resected material may not be so infrequent. Further molecular analysis will provide new insights into understanding the pathogenesis of pituitary adenomas and their mechanisms of multidirectional phenotypic diffrentiation. PMID:11081204

  11. Ovarian hyperstimulation syndrome prevention strategies: oral contraceptive pills-dual gonadotropin-releasing hormone agonist suppression with step-down gonadotropin protocols.

    PubMed

    Damario, Mark A

    2010-11-01

    The identification of patients at high risk for excessive responses to ovarian stimulation for in vitro fertilization and embryo transfer is essential in the tailoring of safe and effective treatment strategies. Known factors associated with increased sensitivity to gonadotropins include polycystic ovary syndrome, young age, prior ovarian hyperstimulation syndrome (OHSS), high baseline antral follicle count, and high baseline ovarian volume. Although several treatment strategies have been proposed for these patients, this report describes the experience using the dual suppression with gonadotropin step-down protocol. This protocol uses oral contraceptive pretreatment in combination with a long gonadotropin-releasing hormone agonist followed by a programmed step-down in gonadotropin dosing. Hormonal characteristics of dual suppression include an improved luteinizing hormone-to-follicle-stimulating hormone ratio and lower serum androgens, particularly dehydroepiandrosterone sulfate. Clinical characteristics of the protocol include a lower cancellation rate and favorable clinical and ongoing pregnancy rates per initiated cycle while mitigating the risk of OHSS.

  12. Pituitary Carcinoma: Difficult Diagnosis and Treatment

    PubMed Central

    2011-01-01

    Context: Although pituitary tumors are common, pituitary carcinoma is very rare and is only diagnosed when pituitary tumor noncontiguous with the sellar region is demonstrated. Diagnosis is difficult, resulting in delays that may adversely effect outcome that is traditionally poor. Barriers to earlier diagnosis and management strategies for pituitary carcinoma are discussed. Evidence Acquisition: PubMed was employed to identify relevant studies, a review of the literature was conducted, and data were summarized and integrated from the author's perspective. Evidence Synthesis: The available data highlight the difficulties in diagnosis and management and practical challenges in conducting clinical trials in this rare condition. They suggest that earlier diagnosis with aggressive multimodal therapy may be advantageous in some cases. Conclusions: Although pituitary carcinoma remains difficult to diagnose and treat, recent developments have led to improved outcomes in selected cases. With broader use of molecular markers, efforts to modify current histopathological criteria for pituitary carcinoma diagnosis may now be possible. This would assist earlier diagnosis and, in combination with targeted therapies, potentially improve long-term survival. PMID:21956419

  13. Efficacy of exogenous gonadotropins on the maintenance of spermatogenesis in pethidine treated albino rats.

    PubMed

    Patil, S R; Sonar, A; Londonkar, R; Patil, S R; Patil, S B

    1998-10-01

    An attempt is made to induce the pethidine suppressed gonadal activities by the administration of exogenous gonadotropins (hCG, PMSG, hCG + PMSG). Administration of 5 IU gonadotropins either separately or in combination to the rats treated with pethidine for 30 days resulted in the significant increase in the weight of testis, diameter of testis and seminiferous tubules. Gonadotropin(s) treatment stimulated the spermatogenic activity which was inhibited by pethidine. Therefore the number of spermatogonia, spermatocytes, spermatids in the seminiferous tubules and spermatozoa in cauda epididymis is increased significantly. Decreased testicular cholesterol, increased protein content and weight of accessory sex organs indicate the rejuvenation of steroidogenesis. Combination of both the gonadotropins is more effective in bringing all these activities.

  14. Abnormal pituitary development and function in three siblings of a Jamaican family: A new syndrome involving the Pit-1 gene

    SciTech Connect

    Sanchez, J.C.; Schiavi, A.; Parks, J.

    1994-09-01

    In 1967 Mckusick et al. reported three siblings in Canada who had combine pituitary hormone deficiencies (CPHD). Since that report there have been several families with multiple affected members who share the common characteristics of autosomal recessive inheritance and clinical expression of pituitary deficiencies at an early age. We report here a CPHD family of Jamaican origin with three affected and two unaffected siblings. The affected siblings have evidence of severe growth failure, growth hormone deficiency, hypothyroidism and variable prolactin deficiency. Recently, in some families with CPHD a defect has been detected in the Pit-1 gene, which encodes a transcription factor involved in the differentiation of the pituitary and the production of growth hormone, TSH and prolactin. We are studying the Pit-1 gene in this family as a candidate gene that may explain the family phenotype. The Pit-1 gene has been analyzed in DNA extracted from blood. No gross deletion were detected in exons 2, 3, 4, 5 and 6 using exon-specific PCR assay developed in our laboratory. Exon 1 is also currently being analyzed. Single stand conformational polymorphism (SSCP) analysis, a screening technique for point mutations within genes, is being used to identify putative base pair changes in the Pit-1 gene. The exon findings will be confirmed using standard DNA sequencing procedures. If a Pit-1 gene is detected, this family would provide a novel presentation, since gonadotropin deficiency appears to be present. Alternatively, this family may represent a mutation on another yet unknown factor involved in normal pituitary development.

  15. High Prevalence of Chronic Pituitary and Target-Organ Hormone Abnormalities after Blast-Related Mild Traumatic Brain Injury

    PubMed Central

    Wilkinson, Charles W.; Pagulayan, Kathleen F.; Petrie, Eric C.; Mayer, Cynthia L.; Colasurdo, Elizabeth A.; Shofer, Jane B.; Hart, Kim L.; Hoff, David; Tarabochia, Matthew A.; Peskind, Elaine R.

    2011-01-01

    Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least 1 year after injury, in 25–50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP) to be unrelated to injury severity. Growth hormone deficiency (GHD) and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI), an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least 1 year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I) levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and rehabilitation. PMID

  16. Radiation and hypothalamic-pituitary function.

    PubMed

    Littley, M D; Shalet, S M; Beardwell, C G

    1990-03-01

    In adults, hypopituitarism is a common consequence of external radiotherapy. The clinical manifestations may be subtle and develop insidiously many years after radiotherapy. Anterior pituitary deficiencies can therefore only be detected by regular testing, including dynamic tests of GH and ACTH reserve. Although the deficiencies most commonly develop in the order GH, gonadotrophins, ACTH then TSH, this sequence may not be predictable in an individual patient and comprehensive testing is therefore required. The tests should ideally be performed annually for at least 10 years after treatment or until deficiency has been detected and treated. It is not only the patients with pituitary disease who are at risk of developing hypopituitarism after radiotherapy. Any patient who receives a total dose of irradiation of 20 Gy or more to the hypothalamic-pituitary axis is at risk of hypopituitarism, although the threshold dose may be lower than this. This is particularly important in the long-term survivors of malignant disease in whom endocrine morbidity may be relatively common and in whom this can be easily treated, with consequent improvement in quality of life. Whilst patients who receive a high total dose of irradiation are at increased risk of developing multiple deficiencies, a higher fraction size also increases the risk of anterior pituitary failure. There is good evidence that the earliest damage to the hypothalamic-pituitary axis after external radiotherapy is at the level of the hypothalamus. However, patients who undergo pituitary ablation with interstitial radiotherapy or heavy particle beams are likely to sustain direct damage to the pituitary. In these patients, the sequence in which individual pituitary hormone deficiencies develop is generally the same as that observed with the hypothalamic damage after conventional external radiotherapy. The increasing use of radiotherapy as a means of treatment for malignant disease means that new groups of patients with

  17. Investigation of hypothalamic-pituitary disease.

    PubMed

    Lamberton, R P; Jackson, I M

    1983-11-01

    It can be readily appreciated from the preceding discussion that many endocrine and non-endocrine tests are available for the evaluation of patients with suspected hypothalamic-pituitary disease. The endocrine evaluation of these subjects should be tailored according to the type and extent of pathology suspected (see Tables 2 and 3). For patients with pituitary adenomas and clinical features of hyperpituitarism, such as hyperprolactinaemia, Cushing's disease or acromegaly, the initial tests should be directed at the hormone whose excess is suspected. For example, a glucose suppression test for acromegaly or dexamethasone suppression test for Cushing's disease should be performed early in the evaluation. The possibility of deficiencies of the other pituitary hormones should then be addressed in patients with secretory tumours, but initially in those with apparent non-functioning adenomas. In patients with large macroadenomas pituitary hormone deficiencies are almost invariable with GH and FSH/LH being the most commonly affected, followed by TSH and ACTH in that order (Snyder et al, 1979a; Valenta et al, 1982). Basal thyroid function tests, serum oestradiol or testosterone, and basal gonodotrophins should be routinely obtained in patients with macroadenomas. Additionally, the integrity of the pituitary-adrenal axis should be determined and an overnight water deprivation test for assessment of neurohypophyseal function is also recommended. GH stimulation testing is valuable as a test of pituitary function in patients with suspected pituitary tumours since GH reserve is lost very early in the development of hypopituitarism. Evaluation of the pituitary-thyroid axis with TRH or the pituitary gonadal axis with LHRH generally provides limited additional information of diagnostic value in individual patients with macroadenomas. However, the 'paradoxical' responses to TRH and LHRH may be useful as a biological marker following therapy in patients with GH- or ACTH

  18. Superovulation in cattle: practical aspects of gonadotropin treatment and insemination.

    PubMed

    Kanitz, Wilhelm; Becker, Frank; Schneider, Falk; Kanitz, Ellen; Leiding, Claus; Nohner, Hans-Peter; Pöhland, Ralf

    2002-01-01

    Embryo transfer (ET) in cattle has been used for the realisation of breeding programmes world-wide for more than 20 years. The efficiency of breeding technology, i.e. the breeding progress and costs, depends to a large extent on the results of superovulatory treatment and artificial insemination (A.I.). The results of this step are characterised by a high degree of variation. Numerous attempts have been undertaken to explain the reason(s) for this. Numerous attempts have also been made to clarify the importance of different factors affecting the results. Undoubtedly, the applied hormones and the scheme of insemination itself are main factors, which influence the number and the portion of transferable embryos. Therefore this paper is focused on the following aspects of superovulatory treatment with FSH: dose-response relations, bioactivity of the glycoprotein, FSH/LH ratio, ovulation time and time-oriented insemination, frequency of gonadotropin administration and follicular population at the time of gonadotropin application. PMID:12625423

  19. Advances in the molecular understanding of gonadotropins-receptors interactions.

    PubMed

    el Tayar, N

    1996-12-20

    The extracellular domain (ECD) of gonadotropin receptors belong to the leucine-rich repeat (LRR) protein superfamily and their transmembrane domain (TMD) is characteristic of the seven alpha-helices G-protein-coupled receptors (GPCR). The availability of the X-ray structures of porcine ribonuclease inhibitor (RI), a LRR protein, and bacteriorhodopsin (bR) allows the construction of 3D models of the ECD and the TMD of gonadotropin receptors, respectively. The predicted models are to a large extent consistent with currently available biochemical and mutational data. The models provide a reliable basis for understanding how the hormone binds and activates its receptor. The ECD, in particular the LRR region, serves as a baseball glove which efficiently catches the large hormone and optimally orient the appropriate parts of it for interaction with the seven-transmembrane-helix domain of the receptor. This in turn is expected to lead to a conformational change to be sensed by the appropriate G-protein complex leading to the stimulation of cAMP synthesis and steroids production.

  20. Effect of stress on the activity of the hypothalamic-pituitary-gonadal axis: peripheral and central mechanisms.

    PubMed

    Rivier, C; Rivest, S

    1991-10-01

    This article reviews the mechanisms believed to mediate stress-induced inhibition of reproductive functions and the anatomical sites at which these effects take place. Particular emphasis is placed on the potential modulating role of hormones or neurotransmitters released during stress. At the level of the gonads, adrenal corticoids, pro-opiomelanocortin (POMC)-like peptides, and corticotropin-releasing factor (CRF) are reported to interfere with the stimulatory action of gonadotropins on sex steroid-producing cells. Increased circulating corticosteroid levels may also decrease pituitary responsiveness to GnRH. There is, however, increasing evidence that these mechanisms are primarily involved in mediating the effects of prolonged stress, but not those of an acute stimulus. In contrast, a variety of hormones or neurotransmitters, including CRF, POMC peptides, and biogenic amines act within the brain to mediate the inhibitory influence of both acute and prolonged stresses on reproductive function.

  1. Early spring sex differences in luteinizing hormone response to gonadotropin releasing hormone in co-occurring resident and migrant dark-eyed juncos (Junco hyemalis).

    PubMed

    Greives, Timothy J; Fudickar, Adam M; Atwell, Jonathan W; Meddle, Simone L; Ketterson, Ellen D

    2016-09-15

    To optimally time reproduction, animals must coordinate changes in the hypothalamo-pituitary-gonadal (HPG) axis. The extent of intra-species variation in seasonal timing of reproductive function is considerable, both within and among populations. Dark-eyed junco (Junco hyemalis) populations are known to differ in their reproductive timing response to cues experienced in the same habitat in late winter/early spring. Specifically in juncos cohabitating on shared wintering grounds, residents initiate breeding and reproductive activity but migrants delay reproductive development and prepare to migrate before breeding. Here, we test the hypothesis that the pituitary gland acts as a 'control point' to modulate differential HPG axis activity across populations. We sampled free-living resident and migrant juncos on their shared over-wintering grounds in March, thus all individuals were experiencing the same environmental cues, including photoperiod. We predicted that during this critical time of transition, residents would more readily respond to repeated gonadotropin releasing hormone (GnRH) stimulation with increases in luteinizing hormone (LH), in contrast to migrants, which should delay full reproductive activity. Our data indicate that migrant females, while still on the overwintering grounds, have a reduced LH response to repeated GnRH injections compared to resident females. Male migrant and resident birds did not differ in their responsiveness to repeated GnRH. Our results suggest a sex difference in the costs of mistimed activation of the HPG axis, with female migrants being less responsive than residents females and males to repeated stimulation. Further, our data implicate a key role for the pituitary in regulating appropriate reproductive timing responses. PMID:27374492

  2. Therapeutic Neuroendocrine Agonist and Antagonist Analogs of Hypothalamic Neuropeptides as Modulators of the Hypothalamic-Pituitary-Gonadal Axis.

    PubMed

    Newton, Claire L; Anderson, Ross C; Millar, Robert P

    2016-01-01

    Reproductive hormones play a role at all stages of life and affect most tissues of the body. Gonadotropin-releasing hormone (GnRH) synthesized in the hypothalamus stimulates the secretion of gonadotropins which in turn stimulate gonadal sex hormone production and gamete formation. This hypothalamic-pituitary-gonadal (HPG) axis has, therefore, been the target for the development of numerous drugs which regulate it at various points. These include sex steroid agonists and antagonists, inhibitors of sex steroid biosynthesis, and GnRH agonists and antagonists, which have found extensive applications in treating numerous conditions such as precocious puberty, delayed puberty, prostate cancer, benign prostatic hyperplasia, endometriosis, uterine fibroids and also in in vitro fertilization protocols. The novel neuroendocrine peptides, kisspeptin (KP) and neurokinin B (NKB), were recently discovered as upstream regulators of GnRH, and inactivating mutations of KP and NKB ligands or receptors result in a failure to progress through puberty. Agonists and antagonists of KP and NKB are being developed as more subtle modulators of the HPG axis. These new drugs offer additional and alternative therapeutic options in pediatric and adult hormone-dependent diseases.

  3. The hypothalamic-pituitary-luteal axis in women: effects of long-term orally active opioid antagonist (naltrexone) administration.

    PubMed

    Fulghesu, A M; Lanzone, A; Apa, R; Guido, M; Ciampelli, M; Cucinelli, F; Caruso, A; Mancuso, S

    1997-01-01

    Aim of our study is to assess the effect of a long-term oral opiate antagonist treatment during the luteal phase on the hypothalamic-pituitary-ovarian axis. Fourteen normovulatory women participated to the study. Immediately after the ovulation, the patients were randomly divided in two groups: in the first one women received naltrexone 50 mg/die orally (Antaxone Zambon Italy) from day 1 of the luteal phase for 7 days. In the second patients were treated with placebo for the same period and served as control group. On day 7, patients were hospitalized for a pulse pattern study followed by a GnRH test. LH, FSH, Estradiol, Progesterone were assayed. The naltrexone administration strongly increased the number as well as the amplitude of the gonadotropin pulses. The circulating P levels were also significantly higher in treated patients. The GnRH injection significantly increases the gonadotropin secretion in all patients. The stimulated LH and FSH secretion was significantly greater in treated patients when compared to controls. Such discharge of LH determined a significant increase of progesterone production in controls, but failed to stimulate the corpus luteum in treated patients. In conclusion the present paper strengthen an important role of the opioidergic system in the regulation of GnRH pulsatility in luteal phase. Moreover, our findings confirms the sensibility of the corpus luteum to LH and the possibility to stimulate the P secretion during the luteal phase.

  4. Long-term treatment with cimetidine does not essentially affect the hypothalamic-pituitary-gonadal axis in man.

    PubMed

    Bianchi Porro, G; Ragni, G; Ruspa, M; Petrillo, M; Barattini, G

    1985-04-01

    The effect of cimetidine maintenance treatment on gonadal function has been assessed by seminal analysis plus prolactin and gonadotropin blood level concentrations. Nine patients, all with duodenal ulcer, 5 of whom had received 400 mg cimetidine at night for 18, 3 for 24 and 1 for 36 months, were studied. All patients were presumably fertile, having fathered a child born not more than 3 years before the start of cimetidine treatment. In all patients two seminal analyses were performed and blood specimens were obtained for radioimmunoassay estimation of FSH, LH and prolactin concentrations both in basal conditions and 20', 30' and 60' after the i.v. injection of Gn-RH (100 micrograms) and TRH (200 micrograms). All but one patient, in whom mild oligoasthenozoospermia was detected, had normal sperm counts and motility; moreover hormonal levels both in basal conditions and after releasing factor stimulation were found to be similar to those observed in a control group. Cimetidine maintenance treatment has no effect on sexual activity, the quality of seminal fluid or the pituitary secretion of gonadotropins or prolactin.

  5. Heshouwu decoction, a Chinese herb for tonifying kidney, ameliorates hypothalamic-pituitary- testicular axis secretion in aging rats.

    PubMed

    Niu, Siyun; Kou, Suru; Zhou, Xiaochun; Ding, Liang

    2012-07-25

    An increasing amount of evidence demonstrates the anti-aging effect of Heshouwu in pill form. In this study, a subacute aging rat model was established by continuous intraperitoneal injection of D-galactose and treated with Heshouwu decoction (a Chinese herb for tonifying the kidney, comprising Heshouwu pill, Herba Epimedii, Radix Salviae Miltiorrhiae, and Poria). Heshouwu pill treated rats were the positive control group. Radioimmunoassay, immunohistochemical staining, and western blot assay showed hypothalamic gonadotropin-releasing hormone, hypothalamic substance P, and serum gonadotropin levels to be significantly increased in the model rats; the concentrations of hypothalamic β-endorphin, and serum levels of insulin-like growth factor 1 and testosterone were significantly decreased. 17β- and 3β-hydroxysteroid dehydrogenase expression in testicular tissue was also decreased. Intragastric administration of Heshouwu decoction at high (9.6 g/mL/100 g), medium (4.8 g/mL/100 g), and low (2.4 g/mL/100 g) doses, Heshouwu decoction pretreatment at a medium dose (4.8 g/mL/100 g), and Heshouwu pill (2.06 g/mL/100 g) significantly reversed these changes. Heshouwu decoction pretreatment and high-dose Heshouwu decoction had the greatest anti-aging effects. These experimental findings indicate that Heshouwu decoction can improve hypothalamic-pituitary-testicular axis secretion in a subacute aging rat model, and prevent and delay gonadal axis aging, with an effect superior to that of Heshouwu pill.

  6. Acute toxic effects of 3,3'-iminodipropionitrile on hypothalamic-pituitary-gonadal axis in male rats.

    PubMed

    Takahashi, Noriyuki; Hamada, Naomi; Ishizuka, Bunpei

    2014-01-01

    Exposure to 3,3'-iminodipropionitrile (IDPN) causes persistent neurotoxicity, while its reproductive toxicity in female rats is transient, indicating that gonadotropin-releasing hormone (GnRH) neurons and gonadotrophs receive little or no damage from IDPN and that the transient gonadal toxicity may be also observed in males. To clarify these points, the acute toxic effects of IDPN on hypothalamic-pituitary-gonadal axis of male rats were examined histologically, biochemically and serologically. A single intraperitoneal injection of IDPN (1000 mg/kg body weight) induced signs of neurotoxicity within a day; nevertheless, GnRH neurons were not affected throughout the experimental period. Four days after IDPN treatment, the plasma level of testosterone but not gonadotropins decreased and active caspase 3-immunopositive spermatids increased; both parameters returned to normal levels afterwards. Data from our studies revealed that while IDPN had little or no toxic effect on GnRH neurons or gonadotrophs it was transiently toxic to gonads in both sexes.

  7. Familial idiopathic gonadotropin deficiency not linked to gene for gonadotropin-releasing hormone (GnRH) in Brazilian kindred

    SciTech Connect

    Faraco, J.; Francke, U.; Toledo, S.

    1994-09-01

    Familial idiopathic gonadotropin deficiency (FIGD) is an autosomal recessive disorder which results in failure to develop secondary sexual characteristics. The origin is a hypothalamic defect resulting in insufficient secretion of gonadotropin-releasing hormone GnRH (also called LHRH, luteinizing hormone releasing hormone) and follicle-stimuating hormone (FSH). FIGD has been determined to be a separate entity from Kallmann syndrome which presents with hypogonadism as well as anosmia. The FIGD phenotype appears to be analogous to the phenotype of the hpg (hypogonadal) mouse. Because the hpg phenotype is the result of a structurally abnormal GnRH gene, we have studied the GnRH gene in individuals from a previously reported Brazilian FIGD family. An informative dimorphic marker in the signal peptide sequence of the GnRH gene allowed assessment of linkage between the disease gene and the GnRH locus in this pedigree. We have concluded that the GnRH locus is not linked to the disease-causing mutation in these hypogonadal individuals. Recent evidence suggests that neuropeptide Y (NPY) may play a role in the initiation of puberty. We hypothesize that mutations in NPY may result in failure to secrete GnRH. We have characterized three diallelic frequent-cutter restriction fragment length polymorphisms within the human NPY locus, and are currently using these markers to determine if the NPY gene is linked to, and possibly the site of the disease mutation in this kindred.

  8. Fertility Rates of Ewes Treated with Medroxyprogesterone and Injected with Equine Chorionic Gonadotropin plus Human Chorionic Gonadotropin in Anoestrous Season

    PubMed Central

    Santos, I. W.; Binsfeld, L. C.; Weiss, R. R.; Kozicki, L. E.

    2010-01-01

    The aim of the present paper was to investigate the efficiency of the equine chorionic gonadotropin (eCG) plus human chorionic gonadotropin (hCG) associated with medroxyprogesterone acetate (MAP) to estrous ewes synchronization. Ninety Texel ewes were investigated during seasonal anoestrous. The ewes received intravaginal sponges containing MAP (60 mg) for nine days. At the time of sponges' withdrawal, the ewes were divided into three groups (G): (1) receiving 2 mL of saline i.m. (n = 30), (2) receiving eCG 400 IU i.m. (n = 30), and (3) receiving eCG 400 IU plus hCG 200 IU i.m. (n = 30). Twelve h after sponges' removal, teaser rams were used to estrus check and remained with the ewes for 96 h. The artificial insemination was made with fresh semen 10 h after estrus detection. The effect of the treatment was not significant for the estrous rates among the groups: 73%, 90%, and 86%, respectively. The main effect was observed in the pregnancy and lambing rates among the groups: 70%, 86%, 56%, and 80%, 120%, 56%, respectively. Based on these results from our study, the use of the MAP—eCG is the best choice to improve the fertility rate on ewes. PMID:20953333

  9. Dysregulation of the hypothalamic-pituitary-gonadal axis with menopause and andropause promotes neurodegenerative senescence.

    PubMed

    Atwood, Craig S; Meethal, Sivan Vadakkadath; Liu, Tianbing; Wilson, Andrea C; Gallego, Miguel; Smith, Mark A; Bowen, Richard L

    2005-02-01

    Senescence is characterized neurologically by a decline in cognitive function, which we propose is the result of degenerative processes initiated by the dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis with menopause and andropause. Compelling epidemiologic evidence to support this assertion includes the increased prevalence of Alzheimer disease (AD) in women, the correlation of serum HPG hormones with disease and the decreased incidence, and delay in the onset of AD following hormone replacement therapy. Dysregulation of the axis at this time leads to alterations in the concentrations of all serum HPG hormones (decreased neuronal sex steroid signaling, but increased neuronal gonadotropin releasing hormone, luteinizing hormone, and activin signaling). Hormones of the HPG axis, receptors for which are present in the adult brain, are important regulators of cell proliferation and differentiation during growth and development. Based on this, we propose that dysregulated HPG hormone signaling with menopause/andropause leads to the abortive reentry of differentiated neurons into the cell cycle via a process we term "dyosis." Interestingly, the major biochemical and neuropathologic changes reported for the AD brain also are intimately associated with neuron division: altered AbetaPP metabolism, Abeta deposition, tau phosphorylation, mitochondrial alterations, chromosomal replication, synapse loss, and death of differentiated neurons. Recent evidence supports the premise that AD-related biochemical changes are likely the combined result of increased mitotic signaling by gonadotropins and GnRH, decreased differentiative and neuroprotective signaling via sex steroids, and increased differentiative signaling via activins. This results in a hormonal milieu that is permissive of cell cycle reentry but does not allow completion of metaphase. Partial resetting of the axis following administration of normal endogenous sex steroids delays the onset and decreases the

  10. Interface between metabolic balance and reproduction in ruminants: focus on the hypothalamus and pituitary.

    PubMed

    Clarke, Iain J

    2014-06-01

    This article is part of a Special Issue "Energy Balance". The interface between metabolic regulators and the reproductive system is reviewed with special reference to the sheep. Even though sheep are ruminants with particular metabolic characteristics, there is a broad consensus across species in the way that the reproductive system is influenced by metabolic state. An update on the neuroendocrinology of reproduction indicates the need to account for the way that kisspeptin provides major drive to gonadotropin releasing hormone (GnRH) neurons and also mediates the feedback effects of gonadal steroids. The way that kisspeptin function is influenced by appetite regulating peptides (ARP) is considered. Another newly recognised factor is gonadotropin inhibitory hormone (GnIH), which has a dual function in that it suppresses reproductive function whilst also acting as an orexigen. Our understanding of the regulation of food intake and energy expenditure has expanded exponentially in the last 3 decades and historical perspective is provided. The function of the regulatory factors and the hypothalamic cellular systems involved is reviewed with special reference to the sheep. Less is known of these systems in the cow, especially the dairy cow, in which a major fertility issue has emerged in parallel with selection for increased milk production. Other endocrine systems--the hypothalamo-pituitary-adrenal axis, the growth hormone (GH) axis and the thyroid hormones--are influenced by metabolic state and are relevant to the interface between metabolic function and reproduction. Special consideration is given to issues such as season and lactation, where the relationship between metabolic hormones and reproductive function is altered.

  11. Interface between metabolic balance and reproduction in ruminants: focus on the hypothalamus and pituitary.

    PubMed

    Clarke, Iain J

    2014-06-01

    This article is part of a Special Issue "Energy Balance". The interface between metabolic regulators and the reproductive system is reviewed with special reference to the sheep. Even though sheep are ruminants with particular metabolic characteristics, there is a broad consensus across species in the way that the reproductive system is influenced by metabolic state. An update on the neuroendocrinology of reproduction indicates the need to account for the way that kisspeptin provides major drive to gonadotropin releasing hormone (GnRH) neurons and also mediates the feedback effects of gonadal steroids. The way that kisspeptin function is influenced by appetite regulating peptides (ARP) is considered. Another newly recognised factor is gonadotropin inhibitory hormone (GnIH), which has a dual function in that it suppresses reproductive function whilst also acting as an orexigen. Our understanding of the regulation of food intake and energy expenditure has expanded exponentially in the last 3 decades and historical perspective is provided. The function of the regulatory factors and the hypothalamic cellular systems involved is reviewed with special reference to the sheep. Less is known of these systems in the cow, especially the dairy cow, in which a major fertility issue has emerged in parallel with selection for increased milk production. Other endocrine systems--the hypothalamo-pituitary-adrenal axis, the growth hormone (GH) axis and the thyroid hormones--are influenced by metabolic state and are relevant to the interface between metabolic function and reproduction. Special consideration is given to issues such as season and lactation, where the relationship between metabolic hormones and reproductive function is altered. PMID:24568750

  12. Neuroanatomy and physiology of the avian hypothalamic/pituitary axis: clinical aspects.

    PubMed

    Ritchie, Midge

    2014-01-01

    This article describes the anatomy of the avian hypothalamic/pituitary axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, the somatotrophic axis, and neurohypophysis.

  13. Paediatric pituitary adenomas: a decade of change.

    PubMed

    Guaraldi, Federica; Storr, Helen L; Ghizzoni, Lucia; Ghigo, Ezio; Savage, Martin O

    2014-01-01

    Pituitary adenomas, although rare in the paediatric age range and mostly benign, represent very challenging disorders for diagnosis and management. The recent identification of genetic alterations in young individuals with pituitary adenomas has broadened the scope of molecular investigations and contributed to the understanding of mechanisms of tumorigenesis. Recent identification of causative mutations of genes such as GNAS, PRKAR1A, MEN1 and AIP has introduced the concept of molecular screening of young apparently healthy family members. Population-based studies have reported a significantly higher number of affected subjects and genetic variations than expected. Radiological techniques have advanced, yet many microadenomas remain undetectable on scanning. However, experience with transsphenoidal and endoscopic pituitary surgery has led to higher rates of cure. Prolactinomas, corticotroph and somatotroph adenomas remain the most prevalent, with each diagnosis presenting its own challenges. As paediatric pituitary adenomas occur very infrequently within the paediatric age range, paediatric endocrine units cannot provide expert management in isolation. Consequently, close co-operation with adult endocrinology colleagues with experience of pituitary disease is strongly recommended. PMID:24525527

  14. Cytokines and hypothalamic-pituitary function.

    PubMed

    Jones, T H; Kennedy, R L

    1993-11-01

    Several cytokines are now known to affect the release of anterior pituitary hormones by an action on the hypothalamus and/or the pituitary gland. The major cytokines involved are IL-1, IL-2, IL-6, TNF-alpha and interferon-tau. Their predominant effects are to stimulate the hypothalamic-pituitary-adrenal axis and to suppress the hypothalamic-pituitary-thyroid and gonadal axes, and growth hormone release. The relative importance of systemically and locally produced cytokines in achieving these responses and their precise sites of action have not been fully established. There are indeed conflicting reports on the individual effects of each cytokine which need to be clarified. There is now cumulating evidence that there are important interactions between the immune and neuroendocrine systems which may explain in part, some of the effects on growth, thyroid, adrenal and reproductive functions which occur in acute and chronic disease. This article reviews the current knowledge of the effects of some cytokines on hypothalamic-pituitary function.

  15. Stellate Cell Networks in the Teleost Pituitary

    PubMed Central

    Golan, Matan; Hollander-Cohen, Lian; Levavi-Sivan, Berta

    2016-01-01

    The folliculostellate cells of the mammalian pituitary are non-endocrine cells that are implicated in long-distance communication and paracrine signaling, but to date, these cells have yet to be characterized in teleosts. We found that the stellate cells of the teleost pituitary share many common attributes with mammalian folliculostellate cells. By labeling of stellate cells in live preparations of tilapia pituitaries we investigated their distribution, association with other endocrine cells and their anatomical and functional coupling. In the pars intermedia, stellate cells were arranged around neuronal bundles and their processes extended into the pars distalis. Within the pars distalis, stellate cells formed close associations with FSH cells and, to a lesser degree, with GH and LH cells, suggesting differential paracrine regulation of the two gonadotrope populations. The production of follistatin by stellate cells further corroborates the notion of a paracrine role on FSH release. We also found stellate cells to form gap junctions that enabled dye transfer to neighboring stellate cells, implicating that these cells form a large-scale network that connects distant parts of the pituitary. Our findings represent the first wide-scale study of stellate cells in teleosts and provide valuable information regarding their functional roles in pituitary function. PMID:27086978

  16. Idiopathic Granulomatous Hypophysitis Mimicking Pituitary Abscess

    PubMed Central

    Kong, Xiangyi; Wang, Renzhi; Yang, Yi; Wu, Huanwen; Su, Changbao; Ma, Wenbin; Li, Yongning; Xing, Bing; Lian, Wei; Xu, Zhiqin; Yao, Yong; Ren, Zuyuan

    2015-01-01

    Abstract Idiopathic granulomatous hypophysitis (IGH) is a rare inflammatory disease of the pituitary that commonly presents with enlargement of the pituitary gland. Clinically and radiologically, IGH is a rare sellar entity easily to be misdiagnosed as a pituitary adenoma. Through such a case, we aim to present this rarity and emphasize the importance to correctly diagnose confusing pituitary lesions comprehensively by clinical presentations, radiological signs, and biopsy. We present an uncommon case of IGH in a 19-year-old man. The patient was admitted to the hospital with severe headache, vomiting, and vision's sharp decline. Magnetic resonance imaging showed a sellar lesion with obvious cystic change and ring enhancement. The disease course including diagnosis and treatment was presented and analyzed in detail. The pertinent literature is reviewed regarding this uncommon entity. The patient underwent surgical exploration and partial resection via the transsphenoidal approach. The pathologic findings suggested IGH giving no significant evidences of systemic granulomatous disease and venereal disease. Large dose methylprednisolone was then used. The pituitary function recovered, but there was no apparent improvement of his vision. IGH is a rarely occurred inflammatory disease of unknown etiology. It is difficult to diagnose preoperatively and is often misdiagnosed. Although rare, IGH should be kept in mind in terms of differential diagnosis of sellar region lesions. PMID:26181544

  17. Pituitary function in patients with hereditary haemochromatosis.

    PubMed

    Uitz, P M; Hartleb, S; Schaefer, S; Al-Fakhri, N; Kann, P H

    2013-01-01

    Haemochromatosis may impair the function of endocrine organs, amongst others the pituitary gland. It was the aim of this study to determine pituitary function in adult patients with genetically defined hereditary haemochromatosis in a prospective diagnostic study using a standardised stimulation test. Therefore, 22 patients (7 females, 15 males; age at diagnosis of haemochromatosis 48.1 ± 7.9 years; age at study inclusion 50.7 ± 7.7 years) with genetically defined hereditary haemochromatosis were investigated by a combined pituitary stimulation test (CRH, GHRH/arginine, GnRH, TRH). In 11 patients (50% of the study population; 2 females, 9 males), pituitary insufficiencies were detected [isolated corticotrophic insufficiency (peak cortisol < 181.25 μg/l/500 nmol/l) n=10 (2 females, 8 males); combined corticotrophic and borderline gonadotrophic insufficiency (basal testosterone 2.4-3.0 μg/l without basal LH-elevation) in 1 male]. Somatotrophic pituitary insufficiencies were not found. IFG-1 concentrations below -2 standard deviations in 7 patients (32%) may be attributed to impaired hepatic IGF-1 synthesis. Hypopituitarism, particularly corticotrophic insufficiency, seems to be prevalent in a considerable number of middle-aged patients with hereditary haemochromatosis. Despite normal somatotrophic function, low IGF-1 serum concentrations may be found in a subgroup of haemochromatosis patients.

  18. Stellate Cell Networks in the Teleost Pituitary.

    PubMed

    Golan, Matan; Hollander-Cohen, Lian; Levavi-Sivan, Berta

    2016-01-01

    The folliculostellate cells of the mammalian pituitary are non-endocrine cells that are implicated in long-distance communication and paracrine signaling, but to date, these cells have yet to be characterized in teleosts. We found that the stellate cells of the teleost pituitary share many common attributes with mammalian folliculostellate cells. By labeling of stellate cells in live preparations of tilapia pituitaries we investigated their distribution, association with other endocrine cells and their anatomical and functional coupling. In the pars intermedia, stellate cells were arranged around neuronal bundles and their processes extended into the pars distalis. Within the pars distalis, stellate cells formed close associations with FSH cells and, to a lesser degree, with GH and LH cells, suggesting differential paracrine regulation of the two gonadotrope populations. The production of follistatin by stellate cells further corroborates the notion of a paracrine role on FSH release. We also found stellate cells to form gap junctions that enabled dye transfer to neighboring stellate cells, implicating that these cells form a large-scale network that connects distant parts of the pituitary. Our findings represent the first wide-scale study of stellate cells in teleosts and provide valuable information regarding their functional roles in pituitary function. PMID:27086978

  19. Human chorionic gonadotropin (hCG) in the male reproductive tract.

    PubMed

    Berger, P; Gruschwitz, M; Spoettl, G; Dirnhofer, S; Madersbacher, S; Gerth, R; Merz, W E; Plas, E; Sampson, N

    2007-01-01

    Normal hypothalamic-pituitary testicular and prostatic functions are essential for maintenance of male fertility, whereby glycoprotein hormones (GPH) as well as androgens are major endocrine and local regulators. We have investigated whether the GPH human chorionic gonadotropin (hCG) and the free alpha and beta subunits thereof are produced in the target organs themselves and potentially act as auto/paracrine modulators of fertility. Immunofluorometric assays (IFMAs) based on our panel of highly selective monoclonal antibodies, immunohistochemistry (IHC), confocal laser scanning microscopy (CLSM) and 1- and 2D gel electrophoreses with subsequent western blotting have been utilized for the detection of hCGalpha, hCGbeta and its metabolite hCGbeta core fragment (cf) in human testis, prostate and seminal plasma. Both organs synthesize hCGalpha and hCGbeta, which are subsequently detectable at high concentrations in seminal plasma of healthy probands (n=17): hCGalpha 2630+/-520 ng/mL (mean+/-S.E.M.), hCGbeta 2+/-0.28 ng/mL, hCGbetacf and hCG 0.19+/-0.039 ng/mL. These parameters significantly exceed physiological values, e.g. ten thousand-fold in the case of hCGalpha, in serum of young men (n=20): hCGalpha 0.142+/-0.054 ng/mL (mean+/-S.E.M.), hCGbeta 0.05 ng/mL and hCG 0.004+/-0.003 ng/mL. Levels of these markers were not correlated with sperm counts. Of all body fluids including those of pregnant women seminal plasma is the richest physiological source for genuine free i.e. non-dissociated GPHalpha (M(r,app) 23k) which may even appear as di- or tetramers. Its concentration is similar to that observed in maternal serum (weeks 10-12 of gestation) and in extra-embryonic coelomic fluid. In contrast to those fluids where ratios of free subunits to hCG are in the range of 1:100 highly inverse ratios in the range of 10.000:1.000:1 were observed for hCGalpha:hCGbeta:hCG in seminal plasma. hCGalpha is not derived from heterodimeric GPH suggesting hCG-independent functions of h

  20. New discoveries on the biology and detection of human chorionic gonadotropin.

    PubMed

    Cole, Laurence A

    2009-01-26

    Human chorionic gonadotropin (hCG) is a glycoprotein hormone comprising 2 subunits, alpha and beta joined non covalently. While similar in structure to luteinizing hormone (LH), hCG exists in multiple hormonal and non-endocrine agents, rather than as a single molecule like LH and the other glycoprotein hormones. These are regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG. For 88 years regular hCG has been known as a promoter of corpus luteal progesterone production, even though this function only explains 3 weeks of a full gestations production of regular hCG. Research in recent years has explained the full gestational production by demonstration of critical functions in trophoblast differentiation and in fetal nutrition through myometrial spiral artery angiogenesis. While regular hCG is made by fused villous syncytiotrophoblast cells, extravillous invasive cytotrophoblast cells make the variant hyperglycosylated hCG. This variant is an autocrine factor, acting on extravillous invasive cytotrophoblast cells to initiate and control invasion as occurs at implantation of pregnancy and the establishment of hemochorial placentation, and malignancy as occurs in invasive hydatidiform mole and choriocarcinoma. Hyperglycosylated hCG inhibits apoptosis in extravillous invasive cytotrophoblast cells promoting cell invasion, growth and malignancy. Other non-trophoblastic malignancies retro-differentiate and produce a hyperglycosylated free beta-subunit of hCG (hCG free beta). This has been shown to be an autocrine factor antagonizing apoptosis furthering cancer cell growth and malignancy. New applications have been demonstrated for total hCG measurements and detection of the 3 hCG variants in pregnancy detection, monitoring pregnancy outcome, determining risk for Down syndrome fetus, predicting preeclampsia, detecting pituitary hCG, detecting and managing gestational trophoblastic diseases, diagnosing quiescent gestational trophoblastic

  1. High divergence in primate-specific duplicated regions: Human and chimpanzee Chorionic Gonadotropin Beta genes

    PubMed Central

    2008-01-01

    Background Low nucleotide divergence between human and chimpanzee does not sufficiently explain the species-specific morphological, physiological and behavioral traits. As gene duplication is a major prerequisite for the emergence of new genes and novel biological processes, comparative studies of human and chimpanzee duplicated genes may assist in understanding the mechanisms behind primate evolution. We addressed the divergence between human and chimpanzee duplicated genomic regions by using Luteinizing Hormone Beta (LHB)/Chorionic Gonadotropin Beta (CGB) gene cluster as a model. The placental CGB genes that are essential for implantation have evolved from an ancestral pituitary LHB gene by duplications in the primate lineage. Results We shotgun sequenced and compared the human (45,165 bp) and chimpanzee (39,876 bp) LHB/CGB regions and hereby present evidence for structural variation resulting in discordant number of CGB genes (6 in human, 5 in chimpanzee). The scenario of species-specific parallel duplications was supported (i) as the most parsimonious solution requiring the least rearrangement events to explain the interspecies structural differences; (ii) by the phylogenetic trees constructed with fragments of intergenic regions; (iii) by the sequence similarity calculations. Across the orthologous regions of LHB/CGB cluster, substitutions and indels contributed approximately equally to the interspecies divergence and the distribution of nucleotide identity was correlated with the regional repeat content. Intraspecies gene conversion may have shaped the LHB/CGB gene cluster. The substitution divergence (1.8–2.59%) exceeded two-three fold the estimates for single-copy loci and the fraction of transversional mutations was increased compared to the unique sequences (43% versus ~30%). Despite the high sequence identity among LHB/CGB genes, there are signs of functional differentiation among the gene copies. Estimates for dn/ds rate ratio suggested a purifying

  2. New discoveries on the biology and detection of human chorionic gonadotropin

    PubMed Central

    Cole, Laurence A

    2009-01-01

    Human chorionic gonadotropin (hCG) is a glycoprotein hormone comprising 2 subunits, alpha and beta joined non covalently. While similar in structure to luteinizing hormone (LH), hCG exists in multiple hormonal and non-endocrine agents, rather than as a single molecule like LH and the other glycoprotein hormones. These are regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG. For 88 years regular hCG has been known as a promoter of corpus luteal progesterone production, even though this function only explains 3 weeks of a full gestations production of regular hCG. Research in recent years has explained the full gestational production by demonstration of critical functions in trophoblast differentiation and in fetal nutrition through myometrial spiral artery angiogenesis. While regular hCG is made by fused villous syncytiotrophoblast cells, extravillous invasive cytotrophoblast cells make the variant hyperglycosylated hCG. This variant is an autocrine factor, acting on extravillous invasive cytotrophoblast cells to initiate and control invasion as occurs at implantation of pregnancy and the establishment of hemochorial placentation, and malignancy as occurs in invasive hydatidiform mole and choriocarcinoma. Hyperglycosylated hCG inhibits apoptosis in extravillous invasive cytotrophoblast cells promoting cell invasion, growth and malignancy. Other non-trophoblastic malignancies retro-differentiate and produce a hyperglycosylated free beta-subunit of hCG (hCG free beta). This has been shown to be an autocrine factor antagonizing apoptosis furthering cancer cell growth and malignancy. New applications have been demonstrated for total hCG measurements and detection of the 3 hCG variants in pregnancy detection, monitoring pregnancy outcome, determining risk for Down syndrome fetus, predicting preeclampsia, detecting pituitary hCG, detecting and managing gestational trophoblastic diseases, diagnosing quiescent gestational trophoblastic

  3. Testosterone selectively increases serum follicle-stimulating hormonal (FSH) but not luteinizing hormone (LH) in gonadotropin-releasing hormone antagonist-treated male rats: evidence for differential regulation of LH and FSH secretion.

    PubMed

    Bhasin, S; Fielder, T J; Swerdloff, R S

    1987-08-01

    Both testosterone (T) and gonadotropin-releasing hormone (GnRH)-antagonist (GnRH-A) when given alone lower serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in intact and castrated rats. However, when graded doses of testosterone enanthate (T.E.) were given to GnRH-A-treated intact male rats, a paradoxical dose-dependent increase in serum FSH occurred; whereas serum LH remained suppressed. This surprising finding led us to ask whether the paradoxical increase in serum FSH in GnRH-A-suppressed animals was a direct stimulatory effect of T on the hypothalamic-pituitary axis or the result of a T effect on a testicular regulator of FSH. To test these hypotheses, we treated adult male castrated rats with GnRH-A and graded doses of T.E. In both intact and castrated rats, serum LH remained undetectable in GnRH-A-treated rats with or without T.E. However, addition of T.E. to GnRH-A led to a dose-dependent increase in serum FSH in castrated animals as well, thus pointing against mediation by a selective testicular regulator of FSH. These data provide evidence that pituitary LH and FSH responses may be differentially regulated under certain conditions. When the action of GnRH is blocked (such as in GnRH-A-treated animals), T directly and selectively increases pituitary FSH secretion.

  4. Polymicrobial Pituitary Abscess Predominately Involving Escherichia coli in the Setting of an Apoplectic Pituitary Prolactinoma

    PubMed Central

    Beatty, Norman; Medina-Garcia, Luis; Al Mohajer, Mayar; Zangeneh, Tirdad T.

    2016-01-01

    Pituitary abscess is a rare intracranial infection that can be life-threatening if not appropriately diagnosed and treated upon presentation. The most common presenting symptoms include headache, anterior pituitary hypofunction, and visual field disturbances. Brain imaging with either computed tomography or magnetic resonance imaging usually reveals intra- or suprasellar lesion(s). Diagnosis is typically confirmed intra- or postoperatively when pathological analysis is done. Clinicians should immediately start empiric antibiotics and request a neurosurgical consult when pituitary abscess is suspected. Escherichia coli (E. coli) causing intracranial infections are not well understood and are uncommon in adults. We present an interesting case of an immunocompetent male with a history of hypogonadism presenting with worsening headache and acute right eye vision loss. He was found to have a polymicrobial pituitary abscess predominantly involving E.   coli in addition to Actinomyces odontolyticus and Prevotella melaninogenica in the setting of an apoplectic pituitary prolactinoma. The definitive etiology of this infection was not determined but an odontogenic process was suspected. A chronic third molar eruption and impaction in close proximity to the pituitary gland likely led to contiguous spread of opportunistic oral microorganisms allowing for a polymicrobial pituitary abscess formation. PMID:27006841

  5. A pediatric case of pituitary macroadenoma presenting with pituitary apoplexy and cranial nerve involvement: case report

    PubMed Central

    Özçetin, Mustafa; Karacı, Mehmet; Toroslu, Ertuğ; Edebali, Nurullah

    2016-01-01

    Pituitary adenomas usually arise from the anterior lobe of the pituitary gland and are manifested with hormonal disorders or mass effect. Mass effect usually occurs in nonfunctional tumors. Pituitary adenomas may be manifested with visual field defects or rarely in the form of total oculomotor palsy. Visual field defect is most frequently in the form of bitemporal hemianopsia and superior temporal defect. Sudden loss of vision, papilledema and ophthalmoplegia may be observed. Pituitary apoplexy is defined as an acute clinical syndrome characterized with headache, vomiting, loss of vision, ophthalmoplegia and clouding of consciousness. The problem leading to pituitary apoplexy may be decreased blood supply in the adenoma and hemorrhage following this decrease or hemorrhage alone. In this article, we present a patient who presented with fever, vomiting and sudden loss of vision and limited outward gaze in the left eye following trauma and who was found to have pituitary macroadenoma causing compression of the optic chiasma and optic nerve on the left side on cranial and pituitary magnetic resonance imaging. PMID:27738402

  6. Hypothalamic-pituitary-testicular function in prepubertal children with chronic liver disease.

    PubMed

    Vaiani, Elisa; Ciocca, Mirta; Cuarterolo, Miriam; Imventarza, Oscar; Rivarola, Marco A; Belgorosky, Alicia

    2002-03-01

    Adult patients with chronic liver disease (CLD) show clinical and biochemical signs of hypogonadism and estrogenization. However, no information is available on hypothalamo-pituitary-testicular function in prepubertal or early pubertal children with CLD. Eighteen prepubertal children with CLD, aged 5.8+/-5.5 years (mean +/- SD; range 0.32-12.8), were studied. Most of them had moderate liver function abnormality. Height was slightly decreased (SDS: -1.44-/+1.88) but weight for height was adequate. Serum gonadotropins were evaluated as a function of age. In the age group younger than 1 year (n = 7), serum LH was elevated (4.88+/-6.22 IU/l) when compared with a group of 39 control children (1.2+/-1.65), while serum FSH was normal. In this young group, serum testosterone was normal, but serum estradiol was significantly increased (24.1+/-19.7 pg/ml) when compared with the control group (6.5+/-3.54). In contrast, in the age group older than 2 years, no difference between patients with CLD and controls was observed, either in serum gonadotropins or in serum sex hormones. Taking the 18 patients with CLD together, serum SHBG (113.7+/-51 nmol/l; mean +/- SD) was significantly higher than in normal controls (76+/-38 nmol/l, n = 91, p <0.001). Moreover, and different from normal controls, no change with age was observed in serum SHBG, total testosterone or bioavailable testosterone (non-SHBG-bound). Normal testosterone response to hCG stimulation (>1 ng/ml) was found in a subgroup of 11 children with CLD. By contrast, eight of 11 patients with CLD had an inadequate decrease in SHBG after androgen stimulation. In conclusion, we observed that during the first year of life, a period which includes the postnatal activation of the hypothalamo-pituitary-testicular axis, there is an elevation of serum LH and serum estradiol that suggests the existence of a moderate deficiency of Leydig cell function. This disorder is no longer observed in older prepubertal children. Similar to

  7. Evaluation of the hypothalamic-pituitary-gonadal axis in eugonadal men with type 2 diabetes mellitus.

    PubMed

    Costanzo, P R; Suárez, S M; Scaglia, H E; Zylbersztein, C; Litwak, L E; Knoblovits, P

    2014-01-01

    Men with type 2 diabetes mellitus (DM2) have lower testosterone levels and a higher prevalence of hypogonadism. It still remains unclear the mechanism by which there is a relationship between hypogonadism and DM2. The objective was to evaluate the hypothalamic-pituitary-gonadal axis at different levels in eugonadal patients with DM2. Fourteen patients with DM2 (DM2 group) and 15 subjects without DM2 (normal glucose tolerance test) as control group (CG) were included. We assessed: (i) fasting glucose, insulin, Homeostasis Model Assessment (HOMA); (ii) luteinizing hormone (LH) pulsatility through blood collections every 10 min for 4 h; (iii) gonadotropin-releasing hormone (GnRH) test: basal LH and 30, 60 and 90 min after 100 μg of i.v. GnRH; (iv) human chorionic gonadotropin (hCG) test: basal total testosterone (TT), bioavailable testosterone (BT), free testosterone (FT), estradiol (E2), bioavailable E2 (BE2) and sex hormone-binding globulin (SHBG) and 72 h post 5000 IU of i.m. hCG. There were no differences in age, body mass index and waist circumference between groups. Glucose was higher in the DM2 group vs. CG: 131.1 ± 25.5 vs. 99.1 ± 13.6 mg/dL, p = 0.0005. There were no difference in basal insulin, HOMA, TT, BT, FT, E2, BE2, SHBG and LH levels between groups. The DM2 group had lower LH pulse frequency vs. CG: 0.8 ± 0.8 vs. 1.5 ± 0.5 pulses, p = 0.009. Differences in LH pulse amplitude were not found. A negative correlation was found between the number of LH pulses and glucose, r: -0.39, p = 0.03. There were no differences in the response of LH to GnRH between groups nor in the response of sexual steroids and SHBG to hCG. Patients with DM2 showed lower hypothalamic pulse frequency without changes in the pituitary response to GnRH nor testicular response to hCG. Glucose levels negatively correlated with the number of LH pulses which suggests a negative effect of hyperglycaemia in the hypothalamic secretion of GnRH.

  8. The pituitary growth hormone cell in space

    NASA Technical Reports Server (NTRS)

    Hymer, Wesley C.; Grindeland, R.

    1989-01-01

    Growth hormone (GH), produced and secreted from specialized cells in the pituitary gland, controls the metabolism of protein, fat, and carbohydrate. It is also probably involved in the regulation of proper function of bone, muscle and immune systems. The behavior of the GH cell system was studied by flying either isolated pituitary cells or live rats. In the latter case, pituitary GH cells are prepared on return to earth and then either transplanted into hypophysectomized rats or placed into cell culture so that function of GH cells in-vivo vs. in-vitro can be compared. The results from three flights to date (STS-8, 1983; SL-3, 1985; Cosmos 1887, 1987) established that the ability of GH cells to release hormone, on return to earth, is compromised. The mechanism(s) responsible for this attenuation response is unknown. However, the data are sufficiently positive to indicate that the nature of the secretory defect resides directly within the GH cells.

  9. Subclinical hyperfunctioning pituitary adenomas: The silent tumors

    PubMed Central

    Cooper, Odelia; Melmed, Shlomo

    2012-01-01

    Pituitary adenomas are classified by function as defined by clinical symptoms and signs of hormone hypersecretion with subsequent confirmation on immunohistochemical staining. However, positive immunostaining for pituitary cell types has been shown for clinically nonfunctioning adenomas, and this entity is classified as silent functioning adenoma. Most common in these subtypes include silent gonadotroph adenomas, silent corticotroph adenomas and silent somatotroph adenomas. Less commonly, silent prolactinomas and thyrotrophinomas are encountered. Appropriate classification of these adenomas may affect follow-up care after surgical resection. Some silent adenomas such as silent corticotroph adenomas follow a more aggressive course, necessitating closer surveillance. Furthermore, knowledge of the immunostaining characteristics of silent adenomas may determine postoperative medical therapy. This article reviews the incidence, clinical behavior, and pathologic features of clinically silent pituitary adenomas. PMID:22863387

  10. [Clinical and genetic characterization of FIPA (familial isolated pituitary adenomas)].

    PubMed

    Beckers, A; Apetrii, P; Daly, A; Tichomirova, M; Vanbellingen, J F; Georges, M; Bours, V

    2009-01-01

    Pituitary adenomas are common brain tumours at autopsy and radiological series of unselected population. Historically, few epidemiologic data regarding the prevalence of clinically apparent pituitary adenomas have been available. Recently, a cross-sectional study conducted in Liège, Belgium, noted that clinically-apparent pituitary adenomas occurred with a prevalence of 1:1064 inhabitants, which is 3.5-5 times the previously reported prevalence. Pituitary adenomas occur predominantly as sporadic tumors, but also in a familial setting or associated to some familial/isolated tumoral syndromes. The recent characterization of the novel clinical entity FIPA (Familial Isolated Pituitary Adenomas) increased the prevalence of familial pituitary adenomas which account now for about 5% of pituitary tumors. Distinct genetic mechanisms are continuously identified and increase our understanding of the complex clinical presentation and sometimes unpredictable evolution of pituitary adenomas.

  11. Leptin regulates gonadotropins and steroid receptors in the rats ovary.

    PubMed

    Silveira Cavalcante, Fernanda; Aiceles, Verónica; da Fonte Ramos, Cristiane

    2013-01-01

    The leptin hormone is important to satiety and an important link between the nutritional status and reproductive processes. Owing to the contradictory effects of leptin on the ovary and the failure to clarify the precise mechanism by which leptin affects the ovary, our aim was to contribute to evaluation if leptin can directly regulate the gene expression of leptin itself and its receptors, and the expression of several genes related to the ovary function by a model of tissue culture. Ovaries from Wistar dams were used at 90 days of age and were submitted to medium with presence and absence of leptin. The results can demonstrate that leptin regulates gonadotropins and steroid receptors, which could suggest that the ovarian leptin role could be secondary to the changes in these receptors expression in rats.

  12. Incidental Superior Hypophygeal Artery Aneurysm Embedded within Pituitary Adenoma

    PubMed Central

    Choi, Hong-Seok; Kim, Min-Su; Jung, Young-Jin

    2013-01-01

    Intra-cranial aneurysm can be incidental findings in patients with pituitary adenomas, and are usually located outside the pituitary region. However, the coexistence of intrasellar (not intracranial) aneurysms with pituitary adenomas is extremely rare. We report a patient with an incidental superior hypophygeal aneurysm embedded within a non-functional pituitary adenoma which was treated by transsphenoidal surgery after endovascular coil embolization. PMID:24278658

  13. The pituitary - Aging and spaceflown rats

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Grindeland, R. E.

    1991-01-01

    Decrements in growth hormone (GH) release we observed in two spaceflight experiments and four tail-suspended rat studies mimic age-associated changes in the mammalian pituitary GH system seen by Meites and others. The spaceflight data suggest that formation of high molecular weight bioactive disulfide-linked aggregates of the 20 and 22K monomeric GH forms may be reduced in microgravity, thereby, reducing target tissue activity. Correlative studies to confirm spaceflight as a model for pituitary GH system aging should include: (1) investigation of mechanisms of intracellular hormone packaging, (2) consequences to biological activity of the hormone molecule, and (3) study of intracellular microtubule dynamics.

  14. Serotonin involvement in pituitary-adrenal function

    NASA Technical Reports Server (NTRS)

    Vernikos-Danellis, J.; Kellar, K. J.; Kent, D.; Gonzales, C.; Berger, P. A.; Barchas, J. D.

    1977-01-01

    Experiments clarifying the effects of serotonin (5-HT) in the regulation of the hypothalamic-pituitary-adrenocortical system are surveyed. Lesion experiments which seek to determine functional maps of serotonergic input to areas involved in regulation are reported. Investigations of the effects of 5-HT levels on the plasma ACTH response to stress and the diurnal variation in basal plasma corticosterone are summarized, and the question of whether serotonergic transmission is involved in the regulation of all aspects of pituitary-adrenal function is considered with attention to the stimulatory and inhibitory action of 5-HT.

  15. Hypothalamic-pituitary function in myotonic dystrophy.

    PubMed

    Mahler, C; Parizel, G

    1982-01-01

    Function of the hypothalamic-pituitary axis was investigated in seven patients with myotonic dystrophy (MD). HGH and ACTH secretion were normal. TSH response to TRH was impaired in about half the cases, without concomitant thyroid dysfunction. LH and FSH levels were often elevated, with inconsistent response to LH-RH stimulation, Gonadotrophin disturbances in MD have previously been attributed to a primary gonadal lesion, characteristically seen in this disease. High prolactin levels in six of our seven patients however suggest that gonadal failure may be also be due to hyperprolactinemia through the direct anti-gonadal effect of prolactin and its interference with hypothalamic-pituitary regulation of gonadotrophin secretion.

  16. Brain serotonin and pituitary-adrenal functions

    NASA Technical Reports Server (NTRS)

    Vernikos-Danellis, J.; Berger, P.; Barchas, J. D.

    1973-01-01

    It had been concluded by Scapagnini et al. (1971) that brain serotonin (5-HT) was involved in the regulation of the diurnal rhythm of the pituitary-adrenal system but not in the stress response. A study was conducted to investigate these findings further by evaluating the effects of altering brain 5-HT levels on the daily fluctuation of plasma corticosterone and on the response of the pituitary-adrenal system to a stressful or noxious stimulus in the rat. In a number of experiments brain 5-HT synthesis was inhibited with parachlorophenylalanine. In other tests it was tried to raise the level of brain 5-HT with precursors.

  17. Pituitary abscess: a case report and review of the literature

    PubMed Central

    Karagiannis, Apostolos K A; Dimitropoulou, Fotini; Papatheodorou, Athanasios; Lyra, Stavroula; Seretis, Andreas

    2016-01-01

    Summary Pituitary abscess is a rare life-threating entity that is usually misdiagnosed as a pituitary tumor with a definite diagnosis only made postoperatively. Over the last several decades, advances in healthcare have led to a significant decrease in morbidity and mortality due to pituitary abscess. We report a case of a 34-year-old woman who was admitted to our department for investigation of a pituitary mass and with symptoms of pituitary dysfunction, headaches and impaired vision. During her admission, she developed meningitis-like symptoms and was treated with antibiotics. She eventually underwent transsphenoidal surgery for excision of the pituitary mass. A significant amount of pus was evident intraoperatively; however, no pathogen was isolated. Six months later, the patient was well and had full recovery of the anterior pituitary function. Her menses returned, and she was only on treatment with desmopressin for diabetes insipidus that developed postoperatively. Learning points Pituitary abscess is a rare disease and the reported clinical features vary mimicking other pituitary lesions. The diagnosis of pituitary abscess is often very difficult to make and rarely included in the differential. The histological findings of acute inflammatory infiltration confirm the diagnosis of pituitary abscess. Medical and surgical treatment is usually recommended upon diagnosis of a pituitary abscess. PMID:27274845

  18. 21 CFR 522.1820 - Pituitary luteinizing hormone for injection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Pituitary luteinizing hormone for injection. 522... ANIMAL DRUGS § 522.1820 Pituitary luteinizing hormone for injection. (a) Specifications. The drug is a... standard pituitary luteinizing hormone and is reconstituted for use by addition of 5 milliliters of...

  19. 21 CFR 522.1820 - Pituitary luteinizing hormone for injection.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Pituitary luteinizing hormone for injection. 522... ANIMAL DRUGS § 522.1820 Pituitary luteinizing hormone for injection. (a) Specifications. The drug is a... standard pituitary luteinizing hormone and is reconstituted for use by addition of 5 milliliters of...

  20. 21 CFR 522.1820 - Pituitary luteinizing hormone for injection.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Pituitary luteinizing hormone for injection. 522... ANIMAL DRUGS § 522.1820 Pituitary luteinizing hormone for injection. (a) Specifications. The drug is a... standard pituitary luteinizing hormone and is reconstituted for use by addition of 5 milliliters of...