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Sample records for fsh

  1. Pharmacogenetics of FSH action

    PubMed Central

    Laan, Maris; Grigorova, Marina; Huhtaniemi, Ilpo T.

    2012-01-01

    Purpose of the review To review the current knowledge of genetic variants in the two genes affecting the individual responsiveness to follicle-stimulating hormone (FSH) action—the FSH beta-subunit (FSHB) and the FSH receptor (FSHR), as well as the pharmacogenetic ramifications of the findings. Recent findings Four common variants in FSHB/FSHR were shown to exhibit significant effect on FSH action: linked FSHR variants Thr307Ala and Asn680Ser determining common receptorisoforms, andgene expression affecting polymorphisms FSHR –29G/A and FSHB–211G/T. In women, the FSHR Thr307Ala/Asn680Ser polymorphisms show consistent predictive value for estimating the most optimal rFSH dosage in controlled ovarian hyperstimulation(COH).The same variants exhibit a potential for the pharmacogenetic assessment of the treatment ofPCOS. The FSHR–29G/A variant was also shown to contribute to ovarian response to COH. Pilot studies have suggestedthe FSHB–211TT-homozygous oligozoospermicmen with genetically determined low concentration of FSH, as potentially the best responders to FSH treatment; furthermore, modulation of this response by FSHR polymorphisms is possible. Summary Genetic variants in FSHB/FSHRexhibit a potential for pharmacogenetic applications in selecting appropriate treatment options (timing and dosage) in male and female conditions requiring or benefitting from FSH therapy. PMID:22499219

  2. A synthetic peptide corresponding to human FSH. beta. -subunit 33-53 binds to FSH receptor, stimulates basal estradiol biosynthesis, and is a partial antagonist of FSH

    SciTech Connect

    Santa Coloma, T.A.; Dattatreyamurty, B.; Reichert, L.E. Jr. )

    1990-02-06

    The authors have previously shown that hFSH-{beta} 34-37 (KTCT) and 49-52 (TRDL) inhibit binding of {sup 125}I-hFSH to FSH receptor in calf testis membranes and that hFSH-{beta} 33-53, which encompasses these tetrapeptides, inhibits binding with increased potency. hFSH-{beta} 33-53 rapidly dimerizes under conditions utilized in the receptor binding assay (pH 7.5) so that the binding inhibition reported earlier was due to the hFSH-{beta} 33-53 dimer rather than the monomer. At pH 6.5, conversion to dimer does not occur, and binding inhibition could be unequivocally attributed to the monomer. Radioiodinated and alkylated hFSH-{beta} 33-53 binds to the FSH receptor. The biological activity of hFSH-{beta} 33-53 was assessed by its ability to affect the conversion of androstenedione to estradiol in rat Sertoli cells cultures. This result demonstrates that the free R-SH group at Cys51 is not responsible for the inhibition. FSH-{beta} 33-53 also significantly stimulated basal levels of estradiol synthesis, but not to maximal levels observed with FSH (partial agonist). Neither the carbohydrate content of hFSH-{beta} nor the {alpha} subunit of FSH appears to be essential for signal transduction and expression of the hormone effect of FSH-{beta} 33-53.

  3. Follicle-stimulating hormone (FSH) blood test

    MedlinePlus

    ... the test done on certain days of your menstrual cycle. ... In women, FSH helps manage the menstrual cycle and stimulates the ovaries to produce eggs. The test is used to help diagnose or evaluate: Menopause Women who have polycystic ovary ...

  4. Glycosylation Effects on FSH-FSHR Interaction Dynamics: A Case Study of Different FSH Glycoforms by Molecular Dynamics Simulations

    PubMed Central

    Meher, Biswa Ranjan; Dixit, Anshuman; Bousfield, George R.; Lushington, Gerald H.

    2015-01-01

    The gonadotropin known as follicle-stimulating hormone (FSH) plays a key role in regulating reproductive processes. Physiologically active FSH is a glycoprotein that can accommodate glycans on up to four asparagine residues, including two sites in the FSHα subunit that are critical for biochemical function, plus two sites in the β subunit, whose differential glycosylation states appear to correspond to physiologically distinct functions. Some degree of FSHβ hypo-glycosylation seems to confer advantages toward reproductive fertility of child-bearing females. In order to identify possible mechanistic underpinnings for this physiological difference we have pursued computationally intensive molecular dynamics simulations on complexes between the high affinity site of the gonadal FSH receptor (FSHR) and several FSH glycoforms including fully-glycosylated (FSH24), hypo-glycosylated (e.g., FSH15), and completely deglycosylated FSH (dgFSH). These simulations suggest that deviations in FSH/FSHR binding profile as a function of glycosylation state are modest when FSH is adorned with only small glycans, such as single N-acetylglucosamine residues. However, substantial qualitative differences emerge between FSH15 and FSH24 when FSH is decorated with a much larger, tetra-antennary glycan. Specifically, the FSHR complex with hypo-glycosylated FSH15 is observed to undergo a significant conformational shift after 5–10 ns of simulation, indicating that FSH15 has greater conformational flexibility than FSH24 which may explain the more favorable FSH15 kinetic profile. FSH15 also exhibits a stronger binding free energy, due in large part to formation of closer and more persistent salt-bridges with FSHR. PMID:26402790

  5. FSH (Follicle-Stimulating Hormone) Test

    MedlinePlus

    ... FSH and LH may be ordered when a boy or girl does not appear to be entering puberty at ... hair Growth of the testicles and penis in boys Beginning of menstruation in girls ^ Back to top What does the test result ...

  6. Hypo-glycosylated Human Follicle-Stimulating Hormone (hFSH21/18) is much more active in vitro than Fully-glycosylated hFSH (hFSH24)

    PubMed Central

    Bousfield, George R.; Butnev, Vladimir Y.; Butnev, Viktor Y.; Hiromasa, Yasuaki; Harvey, David J.; May, Jeffrey V.

    2014-01-01

    Hypo-glycosylated hFSH21/18 (possesses FSHβ21 and FSH18 bands) was isolated from hLH preparations by immunoaffinity chromatography followed by gel filtration. Fully-glycosylated hFSH24 was prepared by combining the fully-glycosylated FSHβ24 variant with hCGα and isolating the heterodimer. The hFSH21/18 glycoform preparation was significantly smaller than the hFSH24 preparation and possessed 60% oligomannose glycans, which is unusual for hFSH. Hypo-glycosylated hFSH21/18 was 9- to 26-fold more active than fully-glycosylated hFSH24 in FSH radioligand assays. Significantly greater binding of 125I-hFSH21/18 tracer than hFSH24 tracer was observed in all competitive binding assays. In addition, higher binding of hFSH21/18 was noted in association and saturation binding assays, in which twice as much hFSH21/18 was bound as hFSH24. This suggests that more ligand binding sites are available to hFSH21/18 in FSHR than to hFSH24. Hypo-glycosylated hFSH21/18 also bound rat FSHRs more rapidly, exhibiting almost no lag in binding, whereas hFSH24 specific binding proceeded very slowly for almost the first hour of incubation. PMID:24291635

  7. Breed differences in clearance of porcine FSH in hypophysectomized rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Extracts of anterior pituitary (AP) glands were infused iv into hypophysectomized male rats followed by sequential sampling of blood for 120 min. Determination of follicle-stimulating hormone (FSH) concentrations established that FSH from Chinese Meishan males decreased in the circulation of rats mo...

  8. Avian LH and FSH: comparison of several radioimmunoassays

    SciTech Connect

    Goldsmith, A.R.; Follett, B.K.

    1983-04-01

    Comparisons were made between various LH and FSH radioimmunoassays currently being used to measure avian hormones. The two LH assays were the homologous chicken system of Follett et al. (1972) and the turkey assay of Burke et al. (1979). These assays were also used in heterologous arrangement by interchanging the iodinated LH fractions and antisera. Five FSH assays were analyzed: two homologous chicken systems (Scanes et al., 1977; Sakai and Ishii, 1980) an assay based on mammalian materials (rat FSH and anti-ovine FSH antiserum, and one using labelled turkey FSH (Burke et al., 1979) with an anti-chicken FSH antiserum. The potencies of purified chicken and turkey gonadotrophin preparations and of a range of plasma samples from Japanese quail were measured in each assay. The two LH systems showed some degree of species specificity, such that chicken LH was more active than turkey LH in the chicken assay, whereas the reverse was true in the turkey LH assay. The potency estimates of the purified hormones in the various FSH assays were very consistent. The qualitative changes in plasma hormone levels were similar in all assays, although there were some differences in the magnitude of the responses.

  9. Impact of urinary FSH price: a cost-effectiveness analysis of recombinant and urinary FSH in assisted reproduction techniques in the USA.

    PubMed

    Silverberg, K; Schertz, J; Falk, B; Beresniak, A

    2002-01-01

    This study compares the cost-effectiveness of recombinant human FSH (r(h)FSH, Gonal-F) and urinary FSH (uFSH) in assisted reproduction techniques in the USA, using several hypothetical prices for uFSH. A specifically designed Markov model and Monte-Carlo simulation techniques were used to model the possible outcomes during three treatment cycles. Data included in the model were derived from randomized clinical trials and databases. An expert panel determined probability distributions for each decision point throughout each virtual treatment cycle. The assumed unit cost of r(h)FSH was $58.52 (based on the average retail cost) and three unit prices ($49, $45, $40) were used for uFSH. A total of 5000 simulations was performed on a virtual cohort of 100,000 patients. The mean number of assisted reproduction treatment cycles/success (ongoing pregnancy at 12 weeks) was 4.34 with r(h)FSH and 4.75 with uFSH. The total number of pregnancies achieved was 40,665 and 37,890, respectively. The mean cost per successful pregnancy with r(h)FSH was $40 688. For uFSH at unit costs of $40, $45 and $49, the mean costs per successful pregnancy were $43,500, $44,400 and $45,000, respectively (each P < 0.0001 versus r(h)FSH). Thus, despite its greater cost per unit dose, r(h)FSH is more cost-effective than uFSH over a wide range of uFSH prices, reflecting the greater clinical efficacy of r(h)FSH. PMID:12470524

  10. Induction of ovulation in seasonally anestrous mares under ambient lights using recombinant equine FSH (reFSH).

    PubMed

    Meyers-Brown, Geraldine A; McCue, Patrick M; Troedsson, Mats H T; Klein, Claudia; Zent, Walter; Ferris, Ryan A; Lindholm, Alicia R G; Scofield, David B; Claes, Anthony N; Morganti, Monica; Colgin, Mark A; Wetzel, Robert L; Peters, Andrew R; Roser, Janet F

    2013-09-15

    Traditionally, mares are put under artificial lights to advance the first ovulation of the year. The aim of the present study was to determine the efficacy of recombinant equine FSH (reFSH) in stimulating follicular development and advancing the first ovulation of the year in seasonally anestrous mares compared with anestrous mares given a placebo. Both groups of mares were housed under ambient light conditions. Sixty deep anestrous mares of light horse breeds (follicular diameters ≤ 20 mm in diameter and progesterone <1 ng/mL) were maintained under a natural photoperiod at three different sites: University of California, Davis, Colorado State University, and University of Kentucky Gluck Centre. Twenty mares at each site were randomly allocated to receive either 0.65 mg of reFSH (group A: treatment; n = 10) or a placebo (group B: control; n = 10) twice daily by im beginning on January 31. Treatment continued until one or more preovulatory follicles developed or up to a maximum of 15 days. Randomized treatments were blinded. Follicular development was closely monitored by transrectal ultrasonography. When the largest follicle reached ≥ 35 mm in diameter, reFSH treatment was discontinued and an injection of 2500 international units of hCG was administered iv 36 hours later to induce ovulation. Jugular blood samples were collected daily from all mares at University of California, Davis, and processed for LH, FSH, progesterone, estradiol-17β, and immunoreactive-inhibin by RIA. All 30 mares receiving reFSH (group A) developed follicles ≥ 35 mm within 7.4 ± 1.6 days of treatment. Twenty-three of the 30 reFSH-treated mares (group A) ovulated within 72 hours after hCG administration. In contrast, mares in group B (placebo, control) did not exhibit significant follicular development and none ovulated within the 15-day observation period. Mares in group A had significantly higher plasma levels of FSH, estradiol-17β, and immunoreactive-inhibin during treatment but

  11. Production, purification, and characterization of recombinant hFSH glycoforms for functional studies

    PubMed Central

    Butnev, Viktor Y.; Butnev, Vladimir Y.; May, Jeffrey V.; Shuai, Bin; Tran, Patrick; White, William K.; Brown, Alan; Hall, Aaron Smalter; Harvey, David J.; Bousfield, George R.

    2015-01-01

    Summary Previously, our laboratory demonstrated the existence of a β-subunit glycosylation-deficient human FSH glycoform, hFSH21. A third variant, hFSH18, has recently been detected in FSH glycoforms isolated from purified pituitary hLH preparations. Human FSH21 abundance in individual female pituitaries progressively decreased with increasing age. Hypo-glycosylated glycoform preparations are significantly more active than fully-glycosylated hFSH preparations. The purpose of this study was to produce, purify and chemically characterize both glycoform variants expressed by a mammalian cell line. Recombinant hFSH was expressed in a stable GH3 cell line and isolated from serum-free cell culture medium by sequential, hydrophobic and immunoaffinity chromatography. FSH glycoform fractions were separated by Superdex 75 gel-filtration. Western blot analysis revealed the presence of both hFSH18 and hFSH21 glycoforms in the low molecular weight fraction, however, their electrophoretic mobilities differed from those associated with the corresponding pituitary hFSH variants. Edman degradation of FSH21/18 -derived β-subunit before and after peptide-N-glycanase F digestion confirmed that it possessed a mixture of both mono-glycosylated FSHβ subunits, as both Asn7 and Asn24 were partially glycosylated. FSH receptor-binding assays confirmed our previous observations that hFSH21/18 exhibits greater receptor-binding affinity and occupies more FSH binding sites when compared to fully-glycosylated hFSH24. Thus, the age-related reduction in hypo-glycosylated hFSH significantly reduces circulating levels of FSH biological activity that may further compromise reproductive function. Taken together, the ability to express and isolate recombinant hFSH glycoforms opens the way to study functional differences between them both in vivo and in vitro. PMID:25661536

  12. Costs and outcomes associated with IVF using recombinant FSH.

    PubMed

    Ledger, W; Wiebinga, C; Anderson, P; Irwin, D; Holman, A; Lloyd, A

    2009-09-01

    Cost and outcome estimates based on clinical trial data may not reflect usual clinical practice, yet they are often used to inform service provision and budget decisions. To expand understanding of assisted reproduction treatment in clinical practice, an economic evaluation of IVF/intracytoplasmic sperm injection (ICSI) data from a single assisted conception unit (ACU) in England was performed. A total of 1418 IVF/ICSI cycles undertaken there between October 2001 and January 2006 in 1001 women were analysed. The overall live birth rate was 22% (95% CI: 19.7-24.2), with the 30- to 34-year age group achieving the highest rate (28%). The average recombinant FSH (rFSH) dose/cycle prescribed was 1855 IU. Average cost of rFSH/cycle was 646 pound(SD: 219 pound), and average total cost/cycle was 2932 pound (SD: 422 pound). Economic data based on clinical trials informing current UK guidance assumes higher doses of rFSH dose/cycle (1750-2625 IU), higher average cost of drugs/cycle (1179 pound), and higher average total cost/cycle (3266 pound). While the outcomes in this study matched UK averages, total cost/cycle was lower than those cited in UK guidelines. Utilizing the protocols and (lower) rFSH dosages reported in this study may enable other ACU to provide a greater number of IVF/ICSI cycles to patients within given budgets. PMID:19778478

  13. Comparative assessment of the consistency and quality of a highly purified FSH extracted from human urine (urofollitropin) and a recombinant human FSH (follitropin alpha).

    PubMed

    Lispi, M; Bassett, R; Crisci, C; Mancinelli, M; Martelli, F; Ceccarelli, D; De Bellis, C; Mendola, D

    2006-08-01

    The revolutionary development of biotechnology-derived therapeutic proteins has provided the expected improvements in quality, purity and consistency, as demonstrated in recombinant human FSH (rhFSH). However, the development of urine-derived gonadotrophins has not always shown comparable improvements. More recently, highly purified urine-derived FSH (uFSH-HP) products have become widely available. The relative purity, level of urine-derived contaminants, and consistency of one such highly purified human uFSH (uhFSH) (urofollitropin) has been assessed and directly compared with rhFSH (follitropin alpha). It has been demonstrated that the highly purified urofollitropin contains variable levels of urine-derived contaminant proteins and demonstrates a variable level of FSH purity, FSH isoforms, and delivered dose. These variable factors may contribute to the control of ovarian stimulation. The relative purity, variable consistency and the presence of contaminants indicates that the urofollitropin is, at best, a partially purified uFSH that is not able to meet the quality attributes of follitropin alpha (rhFSH). PMID:16895630

  14. Biosimilar FSH preparations- are they identical twins or just siblings?

    PubMed

    Orvieto, Raoul; Seifer, David B

    2016-01-01

    As patents expire on innovator products, there is increasing interest in developing biosimilar products globally. Biosimilars are not exact copies and are not considered generic versions of the reference product. They may differ in strength, purity and contain different composition of isoforms and/or various glycosylation profiles, with the consequent alterations in clinical efficacy or safety. Recently 2 new recombinant FSH preparations were introduced to clinical practice following randomized controlled, phase 3 clinical trials. Both, Bemfola and Ovaleap® were referred to the FSH innovator product Gonal-f™ (Follitropin alpha), and were found to yield an equivalent number of oocytes (primary end-point), following a long GnRH agonist suppressive protocol in "ideal" patients, i.e., young, normal responders. However, a closer look at these RCTs reveals a non-significant 4 % difference in clinical and ongoing pregnancy rates, in favor of Gonal f over the biosimilar products, accompanied by half the incidence of OHSS (2.9 vs 5.2 %, respectively). These studies were underpowered with reference to pregnancy rates, Thus, we believe that further comparative studies are needed in additional patient populations, e.g.,older,, poor responders, patients with repeated IVF failures and/or polycystic ovary syndrome, before the universal implementation of biosimilar products for clinical use. Biosimilars are actually a regulatory synonym, facilitating a fast track introduction of a FSH preparation to the COH armamentarium. We therefore recommend against interchanging or substituting innovator and biosimilar agents in clinical practice, and believe that the decision whether to use an innovator or a biosimilar product, should be reserved to the discretion of the treating physician. Furthermore, we believe the time has come that the measurement of the biological activity of FSH in humans should require other methods rather than the Steelman-Pohley assay, such as the determination

  15. Increased Prevalance of the −211 T Allele of Follicle Stimulating Hormone (FSH) β Subunit Promoter Polymorphism and Lower Serum FSH in Infertile Men

    PubMed Central

    Grigorova, Marina; Punab, Margus; Poolamets, Olev; Kelgo, Piret; Ausmees, Kristo; Korrovits, Paul; Vihljajev, Vladimir; Laan, Maris

    2010-01-01

    Context: The human FSHB promoter polymorphism (rs10835638; −211 G/T) has been associated with serum FSH in a cohort of young Estonian men. The minor allele carriers had reduced serum FSH (15.7% in GT heterozygotes; 40% in TT homozygotes) compared with GG homozygotes. Objective: Because FSH is essential for normal spermatogenesis and fertility, we speculated that abnormalities in FSH action could contribute to male infertility. We sought to study whether genetically inherited constitutively reduced FSH levels may affect male reproduction and replicate the association between rs10835638 and serum FSH among infertile male patients. Design: Genotyping of rs10835638 in a cohort of infertile men (n = 1029; Andrology Center of the Tartu University Clinics, Estonia), including idiopathic infertility cases (IIFC; n = 750). Patients: Patients included male partners (sperm concentration <20 × 106/ml) of infertile couples failing to conceive a child for 12 months or longer. Results: A significant excess of TT homozygotes (1.1 vs. 2.4%) as well as GT heterozygotes (22.4 vs. 25.1%) was detected among infertile men compared with the young male cohort (χ2 test, P < 0.05). The T allele of rs10835638 was associated with reduced serum FSH (analysis of covariance; full cohort: P = 1.20 × 10−6, F = 13.8; IIFC: P = 7.70 × 10−7, F = 14.3) as well as with low FSH to LH ratio (full cohort: P = 1.52 × 10−11, F = 25.6; IIFC: P = 3.25 × 10−9, F = 20.4). The median serum FSH levels differed between the GG and TT carriers by 48.5%. All IIFC with TT genotype exhibited low (<1.8) FSH to LH ratio. Conclusions: In perspective, this genetic marker may have clinical significance in molecular diagnostics of male reproductive success and a potential to identify positive responders to FSH treatment. PMID:19897680

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

    PubMed Central

    2010-01-01

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

  17. How the FSH/LH ratio and dose numbers in the p-FSH administration treatment regimen, and insemination schedule affect superovulatory response in ewes.

    PubMed

    D'Alessandro, A G; Martemucci, G; Taibi, L

    2005-04-01

    We wished to evaluate the effects of FSH/LH ratio and number of doses of p-FSH during a superovulatory treatment on ovulation rate and embryo production (Experiment I). In Experiment II, we studied the efficacy of fertilization after various insemination schedules in superovulated donors. In Experiment I estrus was synchronized in 40 ewes (FGA, for 9 days plus PGF2alpha on Day 7) and the ewes were randomly assigned to four treatment groups as follows (n = 10 ewes each): Group A: four p-FSH doses with the FSH/LH ratio held constant (1.6); Group B: four p-FSH doses with the FSH/LH ratio decreasing (FSH/LH 1.6-1.0-0.6-0.3); Group C: eight p-FSH doses with the FSH/LH ratio held constant (1.6); Group D: eight p-FSH doses and FSH/LH ratio decreasing (1.6-1.6, 1.0-1.0, 0.6-0.6, 0.3-0.3). p-FSH administrations were performed twice daily 12 h apart. The ewes were mated at the onset of estrus and again after 12 and 24 h; then, one ram per four ewes was maintained with the ewes for two additional days. Ovarian response and embryo production were assessed on Day 7 after estrus. Experiment II. Three groups (n = 10 each) of superovulated ewes were inseminated as follows: Group M: mated at onset of estrus; Group AI: artificial insemination 30 h after onset of estrus; M + AI) mating at onset of estrus and intrauterine AI performed 30 h from estrus with fresh semen. Results of Experiment I showed that treatment (D) improved (P < 0.05) ovulatory response in comparison to Groups (C) and (A). The fertilization rate was lower (P < 0.01) in Group D) than Group (A). Also the proportion of transferable embryos was lower in Group (D) in comparison to all the other treatments (P < 0.01). Group A gave the best production of embryos (7.3/ewe; 89.0% transferable). In Experiment II, combined mating plus AI improved fertilization rate (80.3%) compared to both mating (P < 0.01) and AI (P < 0.02) alone. PMID:15763116

  18. Follicle Stimulating Hormone (FSH) Dosage Based on Body Weight Enhances Ovulatory Responses and Subsequent Embryo Production in Goats

    PubMed Central

    Rahman, M. R.; Rahman, M. M.; Wan Khadijah, W. E.; Abdullah, R. B.

    2014-01-01

    An experiment was conducted to evaluate the efficacy of porcine follicle stimulating hormone (pFSH) dosage based on body weight (BW) on ovarian responses of crossbred does. Thirty donor does were divided into 3 groups getting pFSH dosages of 3, 5, and 8 mg pFSH per kg BW, respectively, and were named as pFSH-3, pFSH-5 and pFSH-8, respectively. Estrus was synchronized by inserting a controlled internal drug release (CIDR) device and a single injection of prostaglandin F2α (PGF2α). The pFSH treatments were administered twice a day through 6 decreasing dosages (25, 25, 15, 15, 10, and 10% of total pFSH amount; decreasing daily). Ovarian responses were evaluated on Day 7 after CIDR removal. After CIDR removal, estrus was observed 3 times in a day and pFSH treatments were initiated at 2 days before the CIDR removal. All does in pFSH-5 and pFSH-8 showed estrus signs while half of the does in pFSH-3 showed estrus signs. No differences (p>0.05) were observed on the corpus luteum and total ovarian stimulation among the treatment groups, while total and transferable embryos were higher (p<0.05) in pFSH-5 (7.00 and 6.71) than pFSH-3 (3.00 and 2.80) and pFSH-8 (2.00 and 1.50), respectively. In conclusion, 5 mg pFSH per kg BW dosage gave a higher number of embryos than 3 and 8 mg pFSH per kg BW dosages. The results indicated that the dosage of pFSH based on BW is an important consideration for superovulation in goats. PMID:25178370

  19. Endocrine control of spermatogenesis: Role of FSH and LH/ testosterone

    PubMed Central

    Ramaswamy, Suresh; Weinbauer, Gerhard F

    2014-01-01

    Evaluation of testicular functions (production of sperm and androgens) is an important aspect of preclinical safety assessment and testicular toxicity is comparatively far more common than ovarian toxicity. This chapter focuses (1) on the histological sequelae of disturbed reproductive endocrinology in rat, dog and nonhuman primates and (2) provides a review of our current understanding of the roles of gonadotropins and androgens. The response of the rodent testis to endocrine disturbances is clearly different from that of dog and primates with different germ cell types and spermatogenic stages being affected initially and also that the end-stage spermatogenic involution is more pronounced in dog and primates compared to rodents. Luteinizing hormone (LH)/testosterone and follicle-stimulating hormone (FSH) are the pivotal endocrine factors controlling testicular functions. The relative importance of either hormone is somewhat different between rodents and primates. Generally, however, both LH/testosterone and FSH are necessary for quantitatively normal spermatogenesis, at least in non-seasonal species. PMID:26413400

  20. Enhancement of FSH bioactivity in vivo using site-specific antisera.

    PubMed

    Ferasin, L; Gabai, G; Beattie, J; Bono, G; Holder, A T

    1997-03-01

    The ability of site-specific antipeptide antisera to enhance the biological activity of ovine FSH (oFSH) in vivo was investigated using hypopituitary Snell dwarf mice. These animals were shown to respond to increasing doses of oFSH (3.3-90 micrograms/day), administered in two daily injections over a 5-day treatment period, in a highly significant dose-dependent fashion. The responses measured were increases in uterine weight, ovarian weight and the index of keratinisation in vaginal smears. The dose-dependent response to oFSH confirmed the suitability of this animal model for these investigations and suggested the suboptimal dose of oFSH (20 micrograms/day) for use in enhancement studies. Five peptides derived from the beta subunit of bovine FSH (bFSH) (A, residues 33-47; B, 40-51; C, 69-80; D, 83-94; E, 27-39) were used to generate polyclonal antipeptide antisera. Of these peptides, only A and B produced an antiserum (raised in sheep) capable of recognising 125I-bFSH in a liquid phase RIA. Antisera prepared against peptide A or peptide B were found to significantly enhance the biological activity of 20 micrograms oFSH/day over a 5-day treatment period. The response to antipeptide antisera alone did not differ significantly from that observed in PBS-injected control animals, neither did the response to FSH alone differ from that observed in animals treated with FSH plus preimmune serum. Thus the enhanced responses are dependent upon the presence of FSH plus antipeptide antiserum. Peptides A and B are located in a region thought to be involved in receptor recognition, this may have implications for the mechanism underlying this phenomenon and/or the structure/function relationships of FSH. That FSH-enhancing antisera can be generated by immunisation of animals with peptides A and B suggests that it may be possible to develop these peptides as vaccines capable of increasing reproductive performance, such as ovulation rate. The high degree of sequence homology between

  1. Characterization of FSH signalling networks in bovine cumulus cells: a perspective on oocyte competence acquisition.

    PubMed

    Khan, D R; Guillemette, C; Sirard, M A; Richard, F J

    2015-09-01

    Understanding the mechanisms regulating oocyte developmental competence is essential to enhance the clinical efficiency of assisted reproduction. FSH orchestrates the acquisition of oocyte competence, both in vivo and in vitro. Multiple pathways are implicated in FSH signalling; however, their precise coordination remains unresolved. A robust system to investigate FSH signalling is oocyte in vitro maturation (IVM) and we have previously demonstrated better bovine embryo development after FSH addition for the first 6 h during IVM. Using this model, we investigated FSH signalling in cumulus through transcriptomic and pharmacological tools. We demonstrate modulation of cumulus transcriptome by FSH mainly through protein kinase A (PKA) and epidermal growth factor (EGF) pathways. Differentially expressed transcripts were implicated in cumulus expansion, steroidogenesis, cell metabolism and oocyte competence. FSH required rouse-sarcoma oncogene (SRC) for EGF receptor transactivation. PKA and EGF pathway crosstalk was investigated using extracellular signal-regulated kinases (ERK1/2) phosphorylation as the functional end-point. FSH enhanced ERK1/2 activation by the EGF pathway with a simultaneous diminution through PKA. More specifically, FSH increased dual specific phosphatase (DUSP1) transcripts via PKA although DUSP1 protein did not change since EGF was required to prevent degradation. Our findings implicate FSH in PKA and EGF pathway activation, which interact to maintain appropriate levels of ERK1/2 phosphorylation and eventually cumulus expansion, metabolism and steroidogenesis. Moreover, considering the implication of the EGF pathway in GDF9 and BMP15 actions, our findings suggest that FSH may have a role in modulation of the cumulus response to oocyte-secreted factors. This information has implications for improvement of IVM and hence oocyte developmental competence. PMID:26113519

  2. 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. PMID:25449660

  3. Some effects of adding p-LH in defined amounts to purified p-FSH to modify FSH/LH ratios during the superovulatory treatment of anestrous ewes.

    PubMed

    D'Alessandro, A; Martemucci, G; Colonna, M A; Cafueri, C; Toteda, F

    1997-05-01

    Nonlactating Leccese ewes (n = 61) were used during seasonal anestrus to investigate the effects on ovarian response and embryo production of adding defined amounts of p-LH to purified p-FSH as well as decreasing the FSH/LH ratio during treatment. The ewes were synchronized with FGA-impregnated intravaginal pessaries for 9 days and prostaglandin F2 alpha (Cloprostenol) injected on the seventh day. They were divided into six treatment groups in a 3 x 2 factorial design: three amounts of purified p-LH (100, 50 or 25% equivalent to 525, 262 or 131 IU p-LH) x 2 regimen of p-FSH and p-LH administration (constant or decreasing FSH/LH ratio). Each ewe received a total of 525 IU p-FSH at a decreasing dose, twice daily over a 3-day period. Group I (n = 11), Group II (n = 10) and Group III (n = 10) were treated with p-FSH supplemented with p-LH at 100%, 50% and 25%, respectively, of p-FSH dose and a constant FSH/LH ratio throughout the treatment period. Group IV (n = 10), Group V (n = 10) and Group VI (n = 10) were treated with p-FSH supplemented with p-LH at 100%, 50% and 25%, respectively, of p-FSH dose but with a decreasing FSH/LH ratio over the 3 days of the treatment: 1.7-0.86-0.43 for Group IV; 3.4-1.7-0.86 for Group V; 6-3-1.5 for Group VI. Embryos were flushed surgically on Day 6 after estrus. The ovulation rate did not differ among the groups (8-12.8). Superovulation with 100% p-LH and decreasing the FSH/LH ratio (Group IV) resulted in: (i) the highest ova recovery (9.8 +/- 1.7), and this was significantly different (P < 0.05) from the 25% p-LH treated group (Group VI; 5.0 +/- 1.7), (ii) the highest fertilization rate (90.6 +/- 9.2%), with a significant (P < 0.01) difference compared with the constant ratio regimen (Group I; 62.6 +/- 8.3%); (iii) the highest transferable embryo yield (6.4 +/- 1.1), differing significantly (P < 0.01) from Group VI (2.2 +/- 1.1) and Group I (2.7 +/- 1.0). It is concluded that decreasing the amount of p-LH added to purified p-FSH did

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  6. Synthetic peptides corresponding to human follicle-stimulating hormone (hFSH)-beta-(1-15) and hFSH-beta-(51-65) induce uptake of 45Ca++ by liposomes: evidence for calcium-conducting transmembrane channel formation

    SciTech Connect

    Grasso, P.; Santa-Coloma, T.A.; Reichert, L.E. Jr. )

    1991-06-01

    We have previously described FSH receptor-mediated influx of 45Ca++ in cultured Sertoli cells from immature rats and receptor-enriched proteoliposomes via activation of voltage-sensitive and voltage-independent calcium channels. We have further shown that this effect of FSH does not require cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding protein or activation of adenylate cyclase. In the present study, we have identified regions of human FSH-beta-subunit which appear to be involved in mediating calcium influx. We screened 11 overlapping peptide amides representing the entire primary structure of hFSH-beta-subunit for their effects on 45Ca++ flux in FSH receptor-enriched proteoliposomes. hFSH-beta-(1-15) and hFSH-beta-(51-65) induced uptake of 45Ca++ in a concentration-related manner. This effect of hFSH-beta-(1-15) and hFSH-beta-(51-65) was also observed in liposomes lacking incorporated FSH receptor. Reducing membrane fluidity by incubating liposomes (containing no receptor) with hFSH-beta-(1-15) or hFSH-beta-(51-65) at temperatures lower than the transition temperatures of their constituent phospholipids resulted in no significant (P greater than 0.05) difference in 45Ca++ uptake. The effectiveness of the calcium ionophore A23187, however, was abolished. Ruthenium red, a voltage-independent calcium channel antagonist, was able to completely block uptake of 45Ca++ induced by hFSH-beta-(1-15) and hFSH-beta-(51-65) whereas nifedipine, a calcium channel blocker specific for L-type voltage-sensitive calcium channels, was without effect. These results suggest that in addition to its effect on voltage-sensitive calcium channel activity, interaction of FSH with its receptor may induce formation of transmembrane aqueous channels which also facilitate influx of extracellular calcium.

  7. FSH treatment of male idiopathic infertility improves pregnancy rate: a meta-analysis

    PubMed Central

    Santi, D; Granata, A R M; Simoni, M

    2015-01-01

    Introduction The aim of this study is to comprehensively evaluate whether FSH administration to the male partner of infertile couples improves pregnancy rate, spontaneously and/or after assisted reproductive techniques (ART). Methods Meta-analysis of controlled clinical trials in which FSH was administered for male idiopathic infertility, compared with placebo or no treatment. Randomization was not considered as an inclusion criterion. Results We found 15 controlled clinical studies (614 men treated with FSH and 661 treated with placebo or untreated). Concerning the type of FSH, eight studies used recombinant FSH, whereas seven studies used purified FSH. Nine studies evaluated spontaneous pregnancy rate, resulting in an overall odds ratio (OR) of about 4.5 (CI: 2.17–9.33). Eight studies evaluated pregnancy rate after ART, showing a significant OR of 1.60 (CI: 1.08–2.37). Sub-dividing studies according to the FSH preparations (purified/recombinant), pregnancy rate improvement remained significant for each preparation. Eleven studies considered sperm quality after FSH treatment, finding a significant improvement of sperm concentration (2.66×106/ml, CI: 0.47–4.84), but not of concentration of sperm with progressive motility (1.22×106/ml, CI: −0.07 to 2.52). Three trials evaluated testicular volume, showing a non-significant increase in men treated (1.35 ml, CI: −0.44 to 3.14). Conclusion The results of controlled clinical trials available in the literature indicate an improvement of pregnancy rate after FSH administration to the male partner of infertile couples, both spontaneously and after ART. However, the heterogeneity of studies, the high risk of bias and the lack of precise criteria to guide FSH administration limit the strength of these results. Future studies should be designed to identify the markers of FSH response which are helpful in the decision-making process. Meanwhile, the use of FSH in the treatment of male infertility should be cautious

  8. An Investigation on a Novel Anti-tumor Fusion Peptide of FSH33-53-IIKK

    PubMed Central

    Yang, Runlin; Liu, Ping; Pan, Donghui; zhang, Pengjun; Bai, Zhicheng; Xu, Yuping; Wang, Lizhen; Yan, Junjie; Yan, Yongjun; Liu, Xingdang; Yang, Min

    2016-01-01

    A novel fusion peptide FSH33-53-IIKK was designed and expected to combine the follicle stimulating hormone receptor (FSHR) targeting and tumor toxicity. In vitro and in vivo study showed the anti-tumor activity of FSH33-53-IIKK was enhanced compared to that of IIKK only. FSH33-53-IIKK could inhibit the growth of tumor via apoptosis and autophagy pathways. In summary, combining the tumor marker-target peptide and anti-tumor peptide together may be an efficient way to search for better anti-tumor candidates. PMID:27313792

  9. An Investigation on a Novel Anti-tumor Fusion Peptide of FSH33-53-IIKK.

    PubMed

    Yang, Runlin; Liu, Ping; Pan, Donghui; Zhang, Pengjun; Bai, Zhicheng; Xu, Yuping; Wang, Lizhen; Yan, Junjie; Yan, Yongjun; Liu, Xingdang; Yang, Min

    2016-01-01

    A novel fusion peptide FSH33-53-IIKK was designed and expected to combine the follicle stimulating hormone receptor (FSHR) targeting and tumor toxicity. In vitro and in vivo study showed the anti-tumor activity of FSH33-53-IIKK was enhanced compared to that of IIKK only. FSH33-53-IIKK could inhibit the growth of tumor via apoptosis and autophagy pathways. In summary, combining the tumor marker-target peptide and anti-tumor peptide together may be an efficient way to search for better anti-tumor candidates. PMID:27313792

  10. Greater amberjack Fsh, Lh, and their receptors: Plasma and mRNA profiles during ovarian development.

    PubMed

    Nyuji, Mitsuo; Kazeto, Yukinori; Izumida, Daisuke; Tani, Kosuke; Suzuki, Hiroshi; Hamada, Kazuhisa; Mekuchi, Miyuki; Gen, Koichiro; Soyano, Kiyoshi; Okuzawa, Koichi

    2016-01-01

    To understand the endocrine regulation of ovarian development in a multiple spawning fish, the relationship between gonadotropins (Gths; follicle-stimulating hormone [Fsh] and luteinizing hormone [Lh]) and their receptors (Gthrs; Fshr and Lhr) were investigated in greater amberjack (Seriola dumerili). cDNAs encoding the Gth subunits (Fshβ, Lhβ, and glycoprotein α [Gpα]) and Gthrs were cloned. The in vitro reporter gene assay using recombinant hormones revealed that greater amberjack Fshr and Lhr responded strongly to their own ligands. Competitive enzyme-linked immunosorbent assays (ELISAs) were developed for measuring greater amberjack Fsh and Lh. Anti-Fsh and anti-Lh antibodies were raised against recombinant chimeric single-chain Gths consisting of greater amberjack Fshβ (or Lhβ) with rabbit GPα. The validation study showed that the ELISAs were precise (intra- and inter-assay coefficient of variation, <10%) and sensitive (detection limit of 0.2ng/ml for Fsh and 0.8ng/ml for Lh) with low cross-reactivity. A good parallelism between the standard curve and serial dilutions of greater amberjack plasma and pituitary extract were obtained. In female greater amberjack, pituitary fshb, ovarian fshr, and plasma E2 gradually increased during ovarian development, and plasma Fsh significantly increased during the post-spawning period. This suggests that Fsh plays a role throughout ovarian development and during the post-spawning period. Pituitary lhb, ovarian lhr, and plasma Lh were high during the spawning period, suggesting that the synthesis and secretion of Lh, and Lhr expression are upregulated to induce final oocyte maturation and ovulation. PMID:26519759

  11. FSH Regulates mRNA Translation in Mouse Oocytes and Promotes Developmental Competence.

    PubMed

    Franciosi, Federica; Manandhar, Shila; Conti, Marco

    2016-02-01

    A major challenge in assisted reproductive technology is to develop conditions for in vitro oocyte maturation yielding high-quality eggs. Efforts are underway to assess whether known hormonal and local factors play a role in oocyte developmental competence and to identify the molecular mechanism involved. Here we have tested the hypothesis that FSH improves oocyte developmental competence by regulating the translational program in the oocyte. Accumulation of oocyte proteins (targeting protein for the Xenopus kinesin xklp2 and IL-7) associated with improved oocyte quality is increased when cumulus-oocyte complexes are incubated with FSH. This increase is due to enhanced translation of the corresponding mRNAs, as indicated by microinjection of constructs in which the 3' untranslated region of the Tpx2 or Il7 transcripts is fused to the luciferase reporter. A transient activation of the phosphatidyl-inositol 3-phosphate/AKT cascade in the oocyte preceded the increase in translation. When the epidermal growth factor (EGF) receptor is down-regulated in follicular cells, the FSH-induced rate of maternal mRNA translation and AKT activation were lost, demonstrating that the effects of FSH are indirect and require EGF receptor signaling in the somatic compartment. Using Pten(fl/fl):Zp3cre oocytes in which the AKT is constitutively activated, translation of reporters was increased and was no longer sensitive to FSH stimulation. More importantly, the oocytes lacking the phosphate and tensin homolog gene showed increased developmental competence, even when cultured in the absence of FSH or growth factors. Thus, we demonstrate that FSH intersects with the follicular EGF network to activate the phosphatidyl-inositol 3-phosphate/AKT cascade in the oocyte to control translation and developmental competence. These findings provide a molecular rationale for the use of FSH to improve egg quality. PMID:26653334

  12. Expression of FSH receptor in the hamster ovary during perinatal development

    PubMed Central

    Chakraborty, Prabuddha; Roy, Shyamal K.

    2014-01-01

    FSH plays an important role in ovarian follicular development, and it functions via the G-protein coupled FSH receptor. The objectives of the present study were to determine if full-length FSHR mRNA and corresponding protein were expressed in fetal through postnatal hamster ovaries to explain the FSH-induced primordial follicle formation, and if FSH or estrogen (E) would affect the expression. A full-length and two alternately spliced FSHR transcripts were expressed from E14 through P20. The level of the full-length FSHR mRNA increased markedly through P7 before stabilizing at a lower level with the formation and activation of primordial follicles. A predicted 87kDa FSHR protein band was detected in fetal through P4 ovaries, but additional bands appeared as ovary developed. FSHR immunosignal was present in undifferentiated somatic cells and oocytes in early postnatal ovaries, but was granulosa cells specific after follicles formed. Both eCG and E significantly up-regulated full-length FSHR mRNA levels. Therefore, FSHR is expressed in the hamster ovary from the fetal life to account for FSH-induced primordial follicle formation and cAMP production. Further, FSH or E regulates the receptor expression. PMID:25462586

  13. Blocking antibody to the β-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis

    PubMed Central

    Zhu, Ling-Ling; Blair, Harry; Cao, Jay; Yuen, Tony; Latif, Rauf; Guo, Lida; Tourkova, Irina L.; Li, Jianhua; Davies, Terry F.; Sun, Li; Bian, Zhuan; Rosen, Clifford; Zallone, Alberta; New, Maria I.; Zaidi, Mone

    2012-01-01

    Low estrogen levels undoubtedly underlie menopausal bone thinning. However, rapid and profuse bone loss begins 3 y before the last menstrual period, when serum estrogen is relatively normal. We have shown that the pituitary hormone FSH, the levels of which are high during late perimenopause, directly stimulates bone resorption by osteoclasts. Here, we generated and characterized a polyclonal antibody to a 13-amino-acid-long peptide sequence within the receptor-binding domain of the FSH β-subunit. We show that the FSH antibody binds FSH specifically and blocks its action on osteoclast formation in vitro. When injected into ovariectomized mice, the FSH antibody attenuates bone loss significantly not only by inhibiting bone resorption, but also by stimulating bone formation, a yet uncharacterized action of FSH that we report herein. Mesenchymal cells isolated from mice treated with the FSH antibody show greater osteoblast precursor colony counts, similarly to mesenchymal cells isolated from FSH receptor (FSHR)−/− mice. This suggests that FSH negatively regulates osteoblast number. We confirm that this action is mediated by signaling-efficient FSHRs present on mesenchymal stem cells. Overall, the data prompt the future development of an FSH-blocking agent as a means of uncoupling bone formation and bone resorption to a therapeutic advantage in humans. PMID:22908268

  14. Pre-diagnostic circulating follicle stimulating hormone (FSH) concentrations and ovarian cancer risk

    PubMed Central

    McSorley, MA; Alberg, AJ; Allen, DS; Allen, NE; Brinton, LA; Dorgan, JF; Kaaks, R; Rinaldi, S; Helzlsouer, KJ

    2009-01-01

    Gonadotropins have been indicted in ovarian carcinogenesis but direct evidence has been limited and inconsistent. The aim of this study was to determine the association between pre-diagnostic levels of follicle stimulating hormone (FSH) and subsequent development of invasive epithelial ovarian cancer. A nested case-control study was conducted using cases and controls drawn from three cohorts: CLUE I and CLUE II of Washington County, MD, and the Island of Guernsey Study, UK. In total, 67 incident invasive epithelial ovarian cancer cases were each matched to one to two controls on age, menopausal status, time since last menstrual period, current hormone use, and other relevant factors. FSH concentrations were classified into ranked thirds of low, medium, or high based on the distribution among controls. Conditional logistic regression was used to estimate the odds ratio (OR) across increasing thirds of FSH concentrations. Results of the analysis showed that ovarian cancer risk decreased with higher FSH concentrations (p-trend =0.005). Compared to the lowest third of FSH concentrations, the odds ratio among those in the middle and highest thirds were 0.45 (95% Confidence Interval (CI) 0.20– 1.00) and 0.26 (95% CI 0.10–0.70), respectively. Associations persisted after excluding cases diagnosed within five years of follow-up. In conclusion, a reduction in subsequent risk of invasive epithelial ovarian cancer was observed among women with higher circulating FSH concentrations. These findings contradict the hypothesized role of FSH as a risk factor in ovarian carcinogenesis. PMID:19444906

  15. In Estimated Good Prognosis Patients Could Unexpected "Hyporesponse" to Controlled Ovarian Stimulation be Related to Genetic Polymorphisms of FSH Receptor?

    PubMed

    Alviggi, Carlo; Conforti, Alessandro; Caprio, Francesca; Gizzo, Salvatore; Noventa, Marco; Strina, Ida; Pagano, Tiziana; De Rosa, Pasquale; Carbone, Floriana; Colacurci, Nicola; De Placido, Giuseppe

    2016-08-01

    It has been reported that 10% to 15% of young normogonadotrophic women show suboptimal response to standard gonadotropin-releasing hormone-a long protocol. These patients require higher doses of exogenous follicle-stimulating hormone (FSH). This phenomenon could be associated with genetic characteristics. In this study, FSH receptor polymorphism was retrospectively evaluated in 42 normoresponder young women undergoing an in vitro fertilization/intracytoplasmic sperm injection cycle; patients were stratified according to recombinant human FSH (r-hFSH) consumption. We selected 17 normoresponder young patients who required a cumulative dose of recombinant FSH (rFSH) >2500 UI (group A). A control group was randomly selected among patients who required a cumulative dose of rFSH <2500 UI (group B). Follicle-stimulating hormone receptor (FSH-R) 307Ala and 680Ser variants were analyzed in all our patients. Our results show that the mean number of rFSH vials (36.3 ± 7.5 vs 28.6 ± 4.5, P = .0001) and days of stimulation (12.7 ± 2.4 vs 10.8 ± 2.8, P = .03) were significantly lower in group B, whereas the number of oocytes retrieved (7.1 ± 1.5 vs 9.6 ± 2.4; P = .0005) and the average number of embryos transferred (2.1 ± 0.7 vs 2.7 ± 0.4; P = .001) were significantly lower in group A. Estradiol serum levels on the human chorionic gonadotrophin day were significantly lower in group A (997.8 ± 384.9 pg/mL vs 1749.1 ± 644.4; P = .0001). The incidence of the Ser/Ser genotype was higher in patients with higher r-hFSH consumption (group A; P = .02). Based on our results, we hypothesize an association between the FSH-R polymorphisms and a "hyporesponse" to exogenous FSH. PMID:26902430

  16. Addition of low dose hCG to rFSh benefits older women during ovarian stimulation for IVF

    PubMed Central

    2012-01-01

    Background To compare the outcome of IVF cycles in women receiving controlled ovarian stimulation with recFSH or recFSH plus low dose hCG. Methods A retrospective case control study, performed at a private practice affiliated with an academic institute. Patients were infertile women who were treated with IVF/ICSI and controlled ovarian stimulation in a long GnRH agonist protocol using either low dose hCG in addition to recFSH [N = 88] or recFSH alone [N = 99]. Primary outcomes were mean FSH dose, number of mature eggs, number of fertilized eggs, and serum levels of estradiol. Secondary outcomes were endometrial thickness, cycle cancellations and pregnancy rates. Results A significant increase in number of mature and fertilized eggs was observed in women over 40 years of age using low dose hCG in addition to recFSH. The estradiol level was significantly higher on the day of hCG administration and the serum level of FSH on cycle day 7 and on the day of hCG administration were lower. Conclusion Addition of low dose hCG to recFSH compared with recFSH alone significantly modified cycle characteristics in patients >/= 40 years and could be of potential benefit for IVF cycles in older infertile women. PMID:22866896

  17. Androgen and FSH synergistically stimulate lipoprotein degradation and utilization by ovary granulosa cells

    SciTech Connect

    Schreiber, J.R.; Nakamura, K.; Schmit, V.; Weinstein, D.B.

    1984-01-01

    Androgen can directly modulate the induction of steroidogenic enzymes by FSH (follicle stimulating hormone) in ovary granulosa cells. In studies of its mechanism of action, the authors examined the androgen effect on granulosa cell interaction with lipoproteins, the physiologic source of cholesterol. After granulosa cells were cultured for 48 hours with and without androgen and/or FSH, the cells were incubated for 24 hours with /sup 125/I-lipoproteins (human high density lipoprotein (HDL), rat HDL, or human low density lipoprotein (LDL)). The media were then analyzed for lipoprotein protein coat degradation products (mainly /sup 125/I-monoiodotyrosine) and progestin (mainly 20 alpha-dihydroprogesterone (20 alpha-DHP)). In the absence of FSH and androgen, 2 X 10(5) granulosa cells degraded basal levels of all three lipoproteins, but produced no measurable 20 alpha-DHP. The addition of 10(-7) M androstenedione (A), testosterone (T), or 5 alpha-dihydrotestosterone (DHT) had no effect on lipoprotein protein degradation or 20 alpha-DHP production. FSH alone stimulated lipoprotein protein degradation by 50 to 300% while the addition of androgen synergistically augmented the FSH-stimulated 20 alpha-DHP production as well as protein coat degradation of all three lipoproteins. DHT and T were both effective, indicating that androgens themselves, and not estrogen products, were responsible for the effect on lipoprotein protein degradation and 20 alpha-DHP production.

  18. Synthesis and characterization of biologically active recombinant elk and horse FSH.

    PubMed

    Fachal, María Victoria; Furlan, Mike; Clark, Rena; Card, Claire E; Chedrese, P Jorge

    2010-02-01

    The objective of this investigation was to clone and express the elk and horse common alpha-subunit and FSH beta-subunit cDNAs, and to produce recombinant FSH from both species in vitro. The RNAs extracted from elk and horse pituitary glands were reverse-transcribed and amplified by polymerase chain reaction. The cDNAs corresponding to both subunits of elk and horse were cloned into the expression vector pBudCE4.1 and transfected into CRL-9096 cells. Expression of both genes was determined in the transfected cells by Northern and Western blot analysis. Recombinant elk and horse FSH secreted in culture media were characterized by an in vitro bioassay and RIA. When the recombinant products were assessed as activity over mass of FSH measured by RIA, the horse product was 5.6 times more potent than the elk product. The recombinant products injected to immature female Wistar rats stimulated ovarian growth. The results suggest that the products obtained correspond to recombinant versions of the native elk and horse FSH. The availability of these recombinant products may aid in the development of more predictable and efficient techniques of ovarian stimulation in cervids, equids, and other species as well. PMID:19500922

  19. Follicular development and embryo recovery following 3 versus 8 FSH injections in heifers.

    PubMed

    Purwantara, B; Schmidt, M; Callesen, H; Greve, T

    1994-01-01

    Ovarian follicular dynamics and embryo yield were studied during 2 different FSH regimens for superovulation of cattle. Twenty heifers were given intramuscular injections of FSH (total of 35 mg NIH) either once daily for 3 days (Group 3x1) or twice daily for 4 days (Group 4x2). At 72 h after the first FSH injection, each animal was injected with 0.75 mg cloprostenol. Inseminations were performed at 12 h and 24 h after the onset of heat. Transrectal ultrasonography was performed on the day of the first FSH injection, the day of cloprostenol injection, the day of insemination and finally on the day of embryo recovery (day 6 or 7 after heat). The numbers of small (2-4 mm), medium (5-9 mm) and large (> 10 mm) size follicles were recorded. The total number of corpora lutea, eggs and transferable embryos were recorded on the day of embryo recovery. No differences were found between the 2 groups in either of the parameters studied (p > 0.05). It can be concluded that treatment with this FSH preparation once daily for 3 days gives a folliculogenic and superovulatory response similar to a treatment regimen where it is given twice daily for 4 days. PMID:8209824

  20. FSH in vitro versus LH in vivo: similar genomic effects on the cumulus

    PubMed Central

    2013-01-01

    The use of gonadotropins to trigger oocyte maturation both in vivo and in vitro has provided precious and powerful knowledge that has significantly increased our understanding of the ovarian function. Moreover, the efficacy of most assisted reproductive technologies (ART) used in both humans and livestock species relies on gonadotropin input, mainly FSH and LH. Despite the significant progress achieved and the huge impact of gonadotropins, the exact molecular pathways of the two pituitary hormones, FSH and LH, still remain poorly understood. Moreover, these pathways may not be the same when moving from the in vivo to the in vitro context. This misunderstanding of the intricate synergy between these two hormones leads to a lack of consensus about their use mainly in vitro or in ovulation induction schedules in vivo. In order to optimize their use, additional work is thus required with a special focus on comparing the in vitro versus the in vivo effects. In this context, this overview will briefly summarize the downstream gene expression pathways induced by both FSH in vitro and LH in vivo in the cumulus compartment. Based on recent microarray comparative analysis, we are reporting that in vitro FSH stimulation on cumulus cells appears to achieve at least part of the gene expression activity after in vivo LH stimulation. We are then proposing that the in vitro FSH-response of cumulus cells have similitudes with the in vivo LH-response. PMID:24066945

  1. Pubertal Onset in Girls is Strongly Influenced by Genetic Variation Affecting FSH Action

    PubMed Central

    Hagen, Casper P.; Sørensen, Kaspar; Aksglaede, Lise; Mouritsen, Annette; Mieritz, Mikkel G.; Tinggaard, Jeanette; Wohlfart-Veje, Christine; Petersen, Jørgen Holm; Main, Katharina M.; Meyts, Ewa Rajpert-De; Almstrup, Kristian; Juul, Anders

    2014-01-01

    Age at pubertal onset varies substantially in healthy girls. Although genetic factors are responsible for more than half of the phenotypic variation, only a small part has been attributed to specific genetic polymorphisms identified so far. Follicle-stimulating hormone (FSH) stimulates ovarian follicle maturation and estradiol synthesis which is responsible for breast development. We assessed the effect of three polymorphisms influencing FSH action on age at breast deveopment in a population-based cohort of 964 healthy girls. Girls homozygous for FSHR -29AA (reduced FSH receptor expression) entered puberty 7.4 (2.5–12.4) months later than carriers of the common variants FSHR -29GG+GA, p = 0.003. To our knowledge, this is the strongest genetic effect on age at pubertal onset in girls published to date. PMID:25231187

  2. Ultrastructure of Sheep Primordial Follicles Cultured in the Presence of Indol Acetic Acid, EGF, and FSH

    PubMed Central

    Andrade, Evelyn Rabelo; Maddox-Hyttel, Poul; Landim-Alvarenga, Fernanda Da Cruz; Viana Silva, José Roberto; Alfieri, Amauri Alcindo; Seneda, Marcelo Marcondes; Figueiredo, José Ricardo; Toniolli, Ricardo

    2011-01-01

    The aim of this study was to investigate the ultrastructural characteristics of primordial follicles after culturing of sheep ovarian cortical slices in the presence of indol acetic acid (IAA), Epidermal Growth Factor (EGF), and FSH. To evaluate ultrastructure of primordial follicles cultured in MEM (control) or in MEM containing IAA, EGF, and FSH, fragments of cultured tissue were processes for transmission electron microscopy. Except in the control, primordial follicles cultured in supplemented media for 6 d were ultrastructurally normal. They had oocyte with intact nucleus and the cytoplasm contained heterogeneous-sized lipid droplets and numerous round or elongated mitochondria with intact parallel cristae were observed. Rough endoplasmic reticulum (RER) was rarely found. The granulosa cells cytoplasm contained a great number of mitochondria and abundant RER. In conclusion, the presence of IAA, EGF, and FSH helped to maintain ultrastructural integrity of sheep primordial follicles cultured in vitro. PMID:21188166

  3. Fsh and Lh direct conserved and specific pathways during flatfish semicystic spermatogenesis.

    PubMed

    Chauvigné, François; Zapater, Cinta; Crespo, Diego; Planas, Josep V; Cerdà, Joan

    2014-10-01

    The current view of the control of spermatogenesis by Fsh and Lh in non-mammalian vertebrates is largely based on studies carried out in teleosts with cystic and cyclic spermatogenesis. Much less is known concerning the specific actions of gonadotropins during semicystic germ cell development, a type of spermatogenesis in which germ cells are released into the tubular lumen where they transform into spermatozoa. In this study, using homologous gonadotropins and a candidate gene approach, for which the genes' testicular cell-type-specific expression was established, we investigated the regulatory effects of Fsh and Lh on gene expression during spermatogenesis in Senegalese sole (Solea senegalensis), a flatfish with asynchronous and semicystic germ cell development. During early spermatogenesis, Fsh and Lh upregulated steroidogenesis-related genes and nuclear steroid receptors, expressed in both somatic and germ cells, through steroid-dependent pathways, although Lh preferentially stimulated the expression of downstream genes involved in androgen and progestin syntheses. In addition, Lh specifically promoted the expression of spermatid-specific genes encoding spermatozoan flagellar proteins through direct interaction with the Lh receptor in these cells. Interestingly, at this spermatogenic stage, Fsh primarily regulated genes encoding Sertoli cell growth factors with potentially antagonistic effects on germ cell proliferation and differentiation through steroid mediation. During late spermatogenesis, fewer genes were regulated by Fsh or Lh, which was associated with a translational and posttranslational downregulation of the Fsh receptor in different testicular compartments. These results reveal that conserved and specialized gonadotropic pathways regulate semicystic spermatogenesis in flatfish, which may spatially adjust cell germ development to maintain a continuous reservoir of spermatids in the testis. PMID:25024405

  4. Fsh Stimulates Spermatogonial Proliferation and Differentiation in Zebrafish via Igf3.

    PubMed

    Nóbrega, Rafael Henrique; Morais, Roberto Daltro Vidal de Souza; Crespo, Diego; de Waal, Paul P; de França, Luiz Renato; Schulz, Rüdiger W; Bogerd, Jan

    2015-10-01

    Growth factors modulate germ line stem cell self-renewal and differentiation behavior. We investigate the effects of Igf3, a fish-specific member of the igf family. Fsh increased in a steroid-independent manner the number and mitotic index of single type A undifferentiated spermatogonia and of clones of type A differentiating spermatogonia in adult zebrafish testis. All 4 igf gene family members in zebrafish are expressed in the testis but in tissue culture only igf3 transcript levels increased in response to recombinant zebrafish Fsh. This occurred in a cAMP/protein kinase A-dependent manner, in line with the results of studies on the igf3 gene promoter. Igf3 protein was detected in Sertoli cells. Recombinant zebrafish Igf3 increased the mitotic index of type A undifferentiated and type A differentiating spermatogonia and up-regulated the expression of genes related to spermatogonial differentiation and entry into meiosis, but Igf3 did not modulate testicular androgen release. An Igf receptor inhibitor blocked these effects of Igf3. Importantly, the Igf receptor inhibitor also blocked Fsh-induced spermatogonial proliferation. We conclude that Fsh stimulated Sertoli cell production of Igf3, which promoted via Igf receptor signaling spermatogonial proliferation and differentiation and their entry into meiosis. Because previous work showed that Fsh also released spermatogonia from an inhibitory signal by down-regulating anti-Müllerian hormone and by stimulating androgen production, we can now present a model, in which Fsh orchestrates the activity of stimulatory (Igf3, androgens) and inhibitory (anti-Müllerian hormone) signals to promote spermatogenesis. PMID:26207345

  5. FSH and LH plasma levels in bitches with differences in risk for urinary incontinence.

    PubMed

    Reichler, Iris Margaret; Hung, Elisabeth; Jöchle, Wolfgang; Piché, Claude A; Roos, Malgorzata; Hubler, Madeleine; Arnold, Susi

    2005-05-01

    To determine whether the height of the plasma gonadotropin levels after spaying is associated with urinary incontinence, the concentrations of plasma follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined once in 191 intact and 308 spayed bitches. The bitches were grouped according to their risk for urinary incontinence and the medians of their respective gonadotropin levels were compared. For intact anestrous bitches, the FSH- and LH-plasma concentrations were 5.2 (4, 8) ng/mL (median (Q1, Q3)) and 0.5 (0.5-0.5) ng/mL, respectively. In the first year after spaying, the gonadotropin concentrations rose significantly, then stabilised at a level around 10 times those of intact bitches (FSH 62.5 (44, 91) ng/mL; LH 6.1(4, 11) ng/mL). The plasma gonadotropin concentrations of long-term spayed (>12 months) continent bitches (n=209) were higher (FSH 66.8 (46, 104) ng/mL; LH 6.5 (4, 11) ng/mL) than in spayed incontinent bitches (n=60) (FSH 51.5 (38, 74) ng/mL; LH 5.5 (3, 8) ng/mL), the latter also had a higher body weight. Multiple regression analysis showed that the FSH-plasma concentration and not the body weight was decisive for the occurrence of urinary incontinence. The results of this study suggest that levels of gonadotropins are associated, directly or indirectly in the pathophysiology of urinary incontinence after spaying. PMID:15826681

  6. FSH and bFGF regulate the expression of genes involved in Sertoli cell energetic metabolism.

    PubMed

    Regueira, Mariana; Riera, María Fernanda; Galardo, María Noel; Camberos, María Del Carmen; Pellizzari, Eliana Herminia; Cigorraga, Selva Beatriz; Meroni, Silvina Beatriz

    2015-10-01

    The purpose of this study was to investigate if FSH and bFGF regulate fatty acid (FA) metabolism and mitochondrial biogenesis in Sertoli cells (SC). SC cultures obtained from 20-day-old rats were incubated with 100ng/ml FSH or 30ng/ml bFGF for 6, 12, 24 and 48h. The expression of genes involved in transport and metabolism of FA such as: fatty acid transporter CD36 (FAT/CD36), carnitine-palmitoyltransferase 1 (CPT1), long- and medium-chain 3-hydroxyacyl-CoA dehydrogenases (LCAD, MCAD), and of genes involved in mitochondrial biogenesis such as: nuclear respiratory factors 1 and 2 (NRF1, NRF2) and transcription factor A (Tfam), was analyzed. FSH stimulated FAT/CD36, CPT1, MCAD, NRF1, NRF2 and Tfam mRNA levels while bFGF only stimulated CPT1 expression. A possible participation of PPARβ/δ activation in the regulation of gene expression and lactate production was then evaluated. SC cultures were incubated with FSH or bFGF in the presence of the PPARβ/δ antagonist GSK3787 (GSK; 20μM). bFGF stimulation of CPT1 expression and lactate production were inhibited by GSK. On the other hand, FSH effects were not inhibited by GSK indicating that FSH regulates the expression of genes involved in FA transport and metabolism and in mitochondrial biogenesis, independently of PPARβ/δ activation. FA oxidation and mitochondrial biogenesis as well as lactate production are essential for the energetic metabolism of the seminiferous tubule. The fact that these processes are regulated by hormones in a different way reflects the multifarious regulation of molecular mechanisms involved in Sertoli cell function. PMID:26315388

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

    PubMed Central

    2013-01-01

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

  8. Effects of oestradiol on LH, FSH and prolactin in ovariectomized ewes.

    PubMed

    Rozell, T G; Keisler, D H

    1990-03-01

    This study was conducted to test the hypothesis that the rate (dose/time) at which oestradiol-17 beta (oestradiol) is presented to the hypothalamo-pituitary axis influences secretion of LH, FSH and prolactin. A computer-controlled infusion system was used to produce linearly increasing serum concentrations of oestradiol in ovariectomized ewes over a period of 60 h. Serum samples were collected from ewes every 2 h from 8 h before to 92 h after start of infusion, and assayed for oestradiol, LH, FSH and prolactin. Rates of oestradiol increase were categorized into high (0.61-1.78 pg/h), medium (0.13-0.60 pg/h) and low (0.01-0.12 pg/h). Ewes receiving high rates of oestradiol (N = 11) responded with a surge of LH 12.7 +/- 2.0 h after oestradiol began to increase, whereas ewes receiving medium (N = 15) and low (N = 11) rates of oestradiol responded with a surge of LH at 19.4 +/- 1.7 and 30.9 +/- 2.0 h, respectively. None of the surges of LH was accompanied by a surge of FSH. Serum concentrations of FSH decreased and prolactin increased in ewes receiving high and medium rates of oestradiol, when compared to saline-infused ewes (N = 8; P less than 0.05). We conclude that rate of increase in serum concentrations of oestradiol controls the time of the surge of LH and secretion of prolactin and FSH in ovariectomized ewes. We also suggest that the mechanism by which oestradiol induces a surge of LH may be different from the mechanism by which oestradiol induces a surge of FSH. PMID:2109071

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

    PubMed

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

    2016-09-15

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

  10. Balance of insulin and FSH concentrations improves the in vitro development of isolated goat preantral follicles in medium containing GH.

    PubMed

    Ferreira, A C A; Maside, C; Sá, N A R; Guerreiro, D D; Correia, H H V; Leiva-Revilla, J; Lobo, C H; Araújo, V R; Apgar, G A; Brandão, F Z; Figueiredo, J R; Campello, C C

    2016-02-01

    The aim of this study was to evaluate the effect of different combinations of insulin and FSH concentrations in culture media containing GH on the in vitro follicle morphology, antrum formation, growth rates, estradiol (E2) production, oocyte viability and maturation as well as gene expression for FSHR, GHR, INSR, CYP19A1, CYP17, 3ßHSD. Secondary follicles were individually cultured for 18 days in a basic medium containing 50ng/mL GH supplemented with low insulin concentration (INS-LW: 10ng/mL) or high insulin concentration (INS-HG: 10μg/mL) alone or with a fixed FSH concentration (FSH100: 100ng/mL) or with increasing FSH concentrations (FSH-SEQ: 100ng/mL, days 0-6; 500ng/mL, days 6-12; 1000ng/mL days 12-18). In the INS-LW treatment was observed a higher (P<0.05) incidence of normal follicles at day 18 of culture. However, overall higher (P<0.05) follicular growth, oocyte diameter and meiotic resumption rates were obtained using INS-HG+FSH 100. The INS-HG and INS-HG+FSH100 treatments showed higher E2 production and mRNA levels for CYP19A1, CYP17, 3βHSD when compared to INS-LW and INS-LW+FSH100. However, the addition of increasing FSH concentration, regardless of insulin concentration, did not improve the follicular growth, meotic resumption, E2 production or gene expression of steroidogenic enzymes when compared with INS-HG+FSH100. In conclusion, in presence of GH, a basic medium supplemented with 10μg/mL insulin and 100μg/mL FSH throughout the culture period, improves follicular and oocyte growth, oocyte meiotic resumption and E2 production from isolated preantral caprine follicles cultured in vitro. PMID:26723481

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

    PubMed

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

    2016-03-15

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

  12. IGF-I Signaling Is Essential for FSH Stimulation of AKT and Steroidogenic Genes in Granulosa Cells

    PubMed Central

    Zhou, Ping; Baumgarten, Sarah C.; Wu, Yanguang; Bennett, Jill; Winston, Nicola; Hirshfeld-Cytron, Jennifer

    2013-01-01

    FSH and IGF-I synergistically stimulate gonadal steroid production; conversely, silencing the FSH or the IGF-I genes leads to infertility and hypogonadism. To determine the molecular link between these hormones, we examined the signaling cross talk downstream of their receptors. In human and rodent granulosa cells (GCs), IGF-I potentiated the stimulatory effects of FSH and cAMP on the expression of steroidogenic genes. In contrast, inhibition of IGF-I receptor (IGF-IR) activity or expression using pharmacological, genetic, or biochemical approaches prevented the FSH- and cAMP-induced expression of steroidogenic genes and estradiol production. In vivo experiments demonstrated that IGF-IR inactivation reduces the stimulation of steroidogenic genes and follicle growth by gonadotropins. FSH or IGF-I alone stimulated protein kinase B (PKB), which is also known as AKT and in combination synergistically increased AKT phosphorylation. Remarkably, blocking IGF-IR expression or activity decreased AKT basal activity and abolished AKT activation by FSH. In GCs lacking IGF-IR activity, FSH stimulation of Cyp19 expression was rescued by overexpression of constitutively active AKT. Our findings demonstrate, for the first time, that in human, mouse, and rat GCs, the well-known stimulatory effect of FSH on Cyp19 and AKT depends on IGF-I and on the expression and activation of the IGF-IR. PMID:23340251

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

    PubMed

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

    2015-10-01

    The effect of high concentrations of testosterone on ovarian follicle development was investigated. Primary follicles and granulosa cells were cultured in vitro in media supplemented with a testosterone concentration gradient. The combined effects of testosterone and follicle-stimulating hormone (FSH) on follicular growth and granulosa cell gonadotropin receptor mRNA expression were also investigated. Follicle growth in the presence of high testosterone concentrations was promoted at early stages (days 1-7), but inhibited at later stage (days 7-14) of in vitro culture. Interestingly, testosterone-induced follicle development arrest was rescued by treatment with high concentrations of FSH (400 mIU/mL). In addition, in cultured granulosa cells, high testosterone concentrations induced cell proliferation, and increased the mRNA expression level of FSH receptor (FSHR), and luteinized hormone/choriogonadotropin receptor. It was concluded that high concentrations of testosterone inhibited follicle development, most likely through regulation of the FSH signaling pathway, although independently from FSHR downregulation. These findings are an important step in further understanding the pathogenesis of polycystic ovary syndrome. PMID:26489629

  14. A FSH-Secreting Pituitary Macroadenoma Causing A Testosterone Deficiency Syndrome.

    PubMed

    Wang, Xiong; Ge, Li; Cui, Yuanqing; Lang, Cuihong; Hao, Cuifang

    2014-04-01

    FSH-secreting pituitary adenomas can affect sexual and reproductive function. In this article, we have reported the case of a 32-year-old male with secondary infertility. The patient had sexual and reproductive disturbances. The test results of the blood samples indicated obviously decreased testosterone (T) and estradiol (E2) levels. Based on previous hormonal results, the patient received pituitary stimulation and human chorionic gonadotropin (hCG) tests. Both follicle stimulating hormone (FSH) and luteinizing hormone (LH) showed low response during the pituitary stimulation test. The results of the hCG test indicated that T/E2 could recover to a normal level. In addition, this patient was diagnosed with pituitary macroadenoma, which was supported by the pituitary MRI. The man's sexual and reproductive functions recovered following surgery. The pathological results confirmed that the tumor tissue was an FSH-secreting pituitary adenoma by immunohistochemical staining. The purpose of this report was to review the relative literature and discuss the influence of FSH-secreting pituitary adenomas on hormones through the hypothalamus-pituitary-testis axis. PMID:24696774

  15. Effect of sialylation and complexity of FSH oligosaccharides on inhibin production by granulosa cells.

    PubMed

    Loreti, Nazareth; Ambao, Verónica; Andreone, Luz; Trigo, Romina; Bussmann, Ursula; Campo, Stella

    2013-02-01

    Granulosa cell (GC) inhibin A and B production is regulated by FSH and gonadal factors. This gonadotrophin is released as a mixture of glycoforms, which induce different biological responses in vivo and in vitro. Our aim was to determine the effect of recombinant human FSH (rhFSH) glycosylation variants on inhibin A and B production by rat GCs. Preparative isoelectro focusing was used to isolate more acidic/sialylated (pH <4.00) and less acidic/sialylated (pH >5.00) rhFSH charge analogues. Concanavalin A was used to isolate unbound and firmly bound rhFSH glycoforms on the basis of their oligosaccharide complexity. GCs, obtained from oestrogen-primed immature rats, were cultured with either native rhFSH or its glycosylation variants. Inhibin A and B were determined using specific ELISAs. Results were expressed as mean±s.e.m. Under basal conditions, inhibin A was the predominant dimer produced (inhibin A: 673±55; inhibin B: 80±4  pg/ml). More acidic/sialylated charge analogues stimulated inhibin B production when compared to inhibin A at all doses studied; by contrast, less acidic/sialylated charge analogues stimulated inhibin A production and elicited no effect on inhibin B. Glycoforms bearing complex oligosaccharides showed a potent stimulatory effect on inhibin B when compared to inhibin A production (i.e. dose 1  ng/ml: 4.9±0.5 vs 0.9±0.1-fold stimulation, P<0.001). Glycoforms bearing hybrid-type oligosaccharides favoured inhibin A production (i.e. dose 4  ng/ml 2.9±0.1 vs 1.6±0.1-fold stimulation, P<0.05). These results show that the sialylation degree as well as the complexity of oligosaccharides present in the rhFSH molecule may be considered additional factors that differentially regulate dimeric inhibin production by rat GCs. PMID:23166369

  16. Cumulus expansion, nuclear maturation and connexin 43, cyclooxygenase-2 and FSH receptor mRNA expression in equine cumulus-oocyte complexes cultured in vitro in the presence of FSH and precursors for hyaluronic acid synthesis

    PubMed Central

    Dell'Aquila, Maria Elena; Caillaud, Maud; Maritato, Filippo; Martoriati, Alain; Gérard, Nadine; Aiudi, Giulio; Minoia, Paolo; Goudet, Ghylène

    2004-01-01

    The aim of this study was to investigate cumulus expansion, nuclear maturation and expression of connexin 43, cyclooxygenase-2 and FSH receptor transcripts in equine cumuli oophori during in vivo and in vitro maturation in the presence of equine FSH (eFSH) and precursors for hyaluronic acid synthesis. Equine cumulus-oocyte complexes (COC) were cultured in a control defined medium supplemented with eFSH (0 to 5 micrograms/ml), Fetal Calf Serum (FCS), precursors for hyaluronic acid synthesis or glutamine according to the experiments. After in vitro maturation, the cumulus expansion rate was increased with 1 microgram/ml eFSH, and was the highest with 20% FCS. It was not influenced by precursors for hyaluronic acid synthesis or glutamine. The expression of transcripts related to cumulus expansion was analyzed in equine cumulus cells before maturation, and after in vivo and in vitro maturation, by using reverse transcription-polymerase chain reaction (RT-PCR) with specific primers. Connexin 43, cyclooxygenase-2 (COX-2) and FSH receptor (FSHr) mRNA were detected in equine cumulus cells before and after maturation. Their level did not vary during in vivo or in vitro maturation and was influenced neither by FSH nor by precursors for hyaluronic acid synthesis. Results indicate that previously reported regulation of connexin 43 and COX-2 proteins during equine COC maturation may involve post-transcriptional mechanisms. PMID:15212696

  17. Lack of FSH support enhances LIF-STAT3 signaling in granulosa cells of atretic follicles in cattle.

    PubMed

    Ilha, Gustavo Freitas; Rovani, Monique T; Gasperin, Bernardo G; Antoniazzi, Alfredo Quites; Gonçalves, Paulo Bayard Dias; Bordignon, Vilceu; Duggavathi, Raj

    2015-10-01

    Subordinate follicles (SFs) of bovine follicular waves undergo atresia due to declining FSH concentrations; however, the signalling mechanisms have not been fully deciphered. We used an FSH-induced co-dominance model to determine the effect of FSH on signalling pathways in granulosa cells of the second-largest follicles (SF in control cows and co-dominant follicle (co-DF2) in FSH-treated cows). The SF was smaller than DF in control cows while diameters of co-DF1 and co-DF2 in FSH-treated cows were similar. The presence of cleaved CASP3 protein confirmed that granulosa cells of SFs, but not of DFs and co-DFs, were apoptotic. To determine the effect of FSH on molecular characteristics of the second-largest follicles, we generated relative variables for the second largest follicle in each cow. For this, variables of SF or co-DF2 were divided by the variables of the largest follicle DF or co-DF1 in each cow. There was higher transcript abundance of MAPK1/3 and AKT1/2/3 but lower abundance of phosphorylated MAPK3/1 in SF than co-DF2 granulosa cells. Abundance of mRNA and phosphorylated protein of STAT3 was higher in granulosa cells of control SF than FSH-treated co-DF2. SF granulosa cells had higher levels of LIFR and IL6ST transcripts, the two receptors involved in STAT3 activation. Further, lower transcript abundance of interleukin 6 receptor (IL6R), another receptor involved in STAT3 activation, indicated that STAT3 activation in SF granulosa cells could be mainly due to leukemia inhibitory factor (LIF) signalling. These results indicate that atresia due to lack of FSH is associated with activated LIF-STAT3 signalling in SF granulosa cells, as FSH treatment reversed such activation. PMID:26336147

  18. FSHB promoter polymorphism within evolutionary conserved element is associated with serum FSH level in men

    PubMed Central

    Grigorova, Marina; Punab, Margus; Ausmees, Kristo; Laan, Maris

    2008-01-01

    BACKGROUND No polymorphisms affecting serum FSH levels have been described in the human FSHB gene. We have identified a potential regulatory single nucleotide polymorphism (SNP, rs10835638; G/T) 211 bp upstream from the FSHB mRNA transcription start-site, located within a highly conserved region among placental mammals. We aimed to determine the correlation of carrier status of rs10835638 alternative alleles with serum FSH level in men, and testicular and hormonal parameters. METHODS A quantitative genetic association study using a cohort of healthy men (n = 554; age 19.2 ± 1.7 years) visiting the Centre of Andrology, Tartu University Hospital, Estonia. RESULTS Rs10835638 (allele frequencies: G 87.6%, T 12.4%) was significantly associated with serum FSH level (analysis of variance: F = 13.0, P = 0.0016, df = 1; regression testing for a linear trend: P = 0.0003). Subjects with the GG genotype exhibited higher FSH levels (3.37 ± 1.79 IU/l, n = 423) compared with heterozygotes (2.84 ± 1.54 IU/l, n = 125) (P = 0.0005), the group of T-allele carriers (GT+TT, 2.78 ± 1.51 IU/l, n = 131) (P = 0.0005) and TT-homozygotes (2.02 ± 0.81 IU/L, n = 6) (P = 0.031). Rs10835638 was also associated with significant (P < 0.05) reduction in free testosterone index and testes volume, but increased semen volume, sex hormone-binding globulin, serum testosterone and estradiol. LH and inhibin-B levels did not differ significantly between groups. CONCLUSIONS The identification of a regulatory SNP in FSHB promoter paves the way to study the effect of constitutively low FSH on male health and fertility. As FSH contributes to follicular development and sex steroid production in women, the role of this FSHB variant in female reproductive success is still to be addressed. PMID:18567894

  19. Regulation of Sertoli-Germ Cell Adhesion and Sperm Release by FSH and Nonclassical Testosterone Signaling

    PubMed Central

    Shupe, John; Cheng, Jing; Puri, Pawan; Kostereva, Nataliya

    2011-01-01

    Testosterone and FSH act in synergy to produce the factors required to maximize the production of spermatozoa and male fertility. However, the molecular mechanisms by which these hormones support spermatogenesis are not well established. Recently, we identified a nonclassical mechanism of testosterone signaling in cultured rat Sertoli cells. We found that testosterone binding to the androgen receptor recruits and activates Src tyrosine kinase. Src then causes the activation of the epidermal growth factor receptor, which results in the phosphorylation and activation of the ERK MAPK and the cAMP response element-binding protein transcription factor. In this report, we find that FSH inhibits testosterone-mediated activation of ERK and the MAPK pathway in Sertoli cells via the protein kinase A-mediated inhibition of Raf kinase. In addition, FSH, as well as inhibitors of Src and ERK kinase activity, reduced germ cell attachment to Sertoli cells in culture. Using pathway-specific androgen receptor mutants we found that the nonclassical pathway is required for testosterone-mediated increases in germ cell attachment to Sertoli cells. Studies of seminiferous tubule explants determined that Src kinase, but not ERK kinase, activity is required for the release of sperm from seminiferous tubule explants. These findings suggest the nonclassical testosterone-signaling pathway acts via Src and ERK kinases to facilitate the adhesion of immature germ cells to Sertoli cells and through Src to permit the release of mature spermatozoa. In contrast, FSH acts to limit testosterone-mediated ERK kinase activity and germ cell attachment. PMID:21177760

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

    ERIC Educational Resources Information Center

    Suwa, Seizo; And Others

    1974-01-01

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

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

    PubMed

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

    2014-10-01

    Many pregnant Muslim women fast during Ramadan. Leptin has an important role in the reproductive system and hormones. In this study, FSH, LH, oestrogen, progesterone and leptin were measured in the first, second and fourth week of Ramadan and the second week post-Ramadan, in 30 fasting pregnant women. Data were analysed using repeated measures ANOVA by SPSS. The weight and BMI did not change during the study. A significant change in FSH, oestrogen, progesterone and leptin was observed (p < 0.05). The lowest value of FSH was in the second week of Ramadan. Progesterone increased at the end of Ramadan and the second week after. Oestrogen increased significantly during Ramadan and decreased after Ramadan. A decreasing trend was seen in LH during the Ramadan and 2 weeks after (p < 0.1). Leptin decreased significantly 2 weeks after Ramadan. We found poor weight gain and hypoleptinaemia in pregnant fasted women during the study. Food restriction in pregnant fasted women during Ramadan may induce poor weight gain during pregnancy. These data confirm that Ramadan fasting by pregnant women may have potential risks during pregnancy. We recommend further study to evaluate long-term effects of Ramadan fasting during pregnancy in different countries with different food habits and traditions, to obtain reliable and documented data. PMID:24914688

  2. FSHR polymorphism p.N680S mediates different responses to FSH in vitro.

    PubMed

    Casarini, Livio; Moriondo, Valeria; Marino, Marco; Adversi, Francesca; Capodanno, Francesco; Grisolia, Chiarina; La Marca, Antonio; La Sala, Giovanni Battista; Simoni, Manuela

    2014-08-01

    The single nucleotide polymorphism p.N680S of the follicle-stimulating hormone (FSH) receptor (FSHR) is a discrete marker of ovarian response but previous in vitro studies failed to demonstrate differences in the response to FSH between N and S carrier cells. Here we demonstrate that p.N680S mediates different kinetics of the response to FSH in vitro. Intracellular cAMP production is faster in p.N680S N than in S homozygous human granulosa cells (45 versus 90 min to achieve the plateau, respectively; Mann-Whitney's U-test; p < 0.005; n = 4). Reflecting the cAMP kinetics, phospho-ERK1/2 and -CREB activation, AREG and STARD1 gene expressions and progesterone production were qualitatively and quantitatively different in N versus S homozygous cells. Finally, the blockade of ERK pathway by U0126 abolishes the genotype-mediated different effects on gene expression and progesterone production (Mann-Whitney's U-test; p ≥ 0.005; n = 3). PMID:24970684

  3. Pituitary sensitivity to 50 micro g LH/FSH-RH in subjects with anorexia nervosa in acute and recovery stages.

    PubMed Central

    Palmer, R L; Crisp, A H; Mackinnoh, P C; Franklin, M; Bonnar, J; Wheeler, M

    1975-01-01

    Gonadotrophic output was measured in response to a 50-mug dose of luteinizing hormone/follicle stimulating hormone-releasing hormone (LH/FSH-RH) in subjects with anorexia nervosa. A diminished response was found in subjects of low body weight, and in some a response occurred with increments of plasma FSH greater than those of LH. With restoration of body weight the response to the releasing factor was similar to that usually observed in healthy men and women. PMID:1089445

  4. Urinary hMG (Meropur) versus recombinant FSH plus recombinant LH (Pergoveris) in IVF: a multicenter, prospective, randomized controlled trial.

    PubMed

    Pacchiarotti, Alessandro; Sbracia, Marco; Frega, Antonio; Selman, Helmy; Rinaldi, Leonardo; Pacchiarotti, Arianna

    2010-11-01

    To compare IVF outcome in ovarian stimulation protocols with recombinant FSH plus recombinant LH versus hMG, 122 patients were randomized into two study groups: group A, patients treated with urinary hMG, and group B, patients treated with rFSH plus rLH. The two groups proved to be comparable to the main IVF outcome (pregnancy rate, implantation rate, oocytes, and embryos quality), with an increasing risk of ovarian hyperstimulation in the Pergoveris group. PMID:20537626

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

    PubMed

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

    2016-04-01

    This study investigated the effect of adding different concentrations of bovine recombinant follicle-stimulating hormone on the IVC of equine preantral follicles enclosed in ovarian tissue fragments. Randomized ovarian fragments were fixed immediately (fresh noncultured control) or cultured for 1 or 7 days in α-MEM(+) supplemented with 0, 10, 50, and 100 ng/mL FSH and subsequently analyzed by classical histology. Culture media collected on Day 1 or Day 7 and were analyzed for steroids (estradiol and progesterone) and reactive oxygen species (ROS). After Day 1 and Day 7 of culture, 50-ng/mL FSH treatment had a greater (P < 0.05) percentage of morphologically normal follicles when compared to the other groups, except the 10-ng/mL FSH treatment at Day 1 of culture. The percentage of developing follicles (transition, primary, and secondary), and follicular and oocyte diameters were higher (P < 0.05) in the 50-ng/mL FSH treatment compared to the other groups after Day 7 of culture. Furthermore, estradiol secretion and ROS production were maintained (P > 0.05) throughout the culture in the 50-ng/mL FSH treatment. In conclusion, the addition of 50 ng/mL of FSH promoted activation of primordial follicles to developing follicles, improved survival of preantral follicles, and maintained estradiol and ROS production of equine ovarian tissue after 7 days of culture. PMID:26723132

  6. Selective effects of charge on G protein activation by FSH-receptor residues 551-555 and 650-653.

    PubMed

    Grasso, P; Deziel, M R; Reichert, L E

    1995-01-01

    Two cytosolic regions of the rat testicular FSH receptor (FSHR), residues 533-555 and 645-653, have been identified as G protein-coupling domains. We localized the activity in these domains to their C-terminal sequences, residues 551-555 (KIAKR, net charge +3) and 650-653 (RKSH, net charge +3), and examined the effects of charge on G protein activation by the C-terminal peptides, using synthetic analogs containing additions, through alanine (A) linkages, of arginine (R, +), histidine (H, +) or both. RA-KIAKR (net charge +4) mimicked the effect of FSHR-(551-555) on guanine nucleotide exchange in rat testis membranes, but reduced its ability to inhibit FSH-stimulated estradiol biosynthesis in cultured rat Sertoli cells. Further increasing net charge by the addition of H (HARA-KIAKR, net charge +5) increased guanosine 5'-triphosphate (GTP) binding, but eliminated FSHR-(551-555) effects on FSH-stimulated steroidogenesis. HA-RKSH (net charge +4) significantly inhibited guanine nucleotide exchange in rat testis membranes, but stimulated basal and potentiated FSH-induced estradiol biosynthesis in cultured rat Sertoli cells. Addition of two H residues (HAHA-RKSH, net charge +5) restored GTP binding and further potentiated basal and FSH-stimulated steroidogenesis. These results suggest that positive charges in G protein-coupling domains of the FSHR play a role in modulating G protein activation and postbinding effects of FSH, such as steroidogenesis. PMID:8589550

  7. Elevated basal FSH levels, if it is under 15 IU/L, will not reflect poor ART outcomes

    PubMed Central

    Nakagawa, Koji; Nakashima, Akira; Horikawa, Takashi; Ohgi, Shirei; Saito, Hidekazu

    2008-01-01

    Purpose For this study, the impact of basal FSH levels on ART outcomes was assessed. Methods From June 2003 to May 2006, 191 ART cycles were performed in our hospital. All cases were treated with GnRH-a long protocol. The patients were classified according to their basal FSH level as follows: group A: FSH < 10 IU/l, group B: 10 ≦ FSH < 15 IU/l, and group C: 15 IU/l ≦ FSH. ART outcomes were compared among the three groups. Results The number of retrieved oocytes in group A was significantly higher than in group B, but fertilized oocytes and the pregnancy rates were comparable. The pregnancy rate in group C was not significantly lower than those found in either group A or B, but the trend was lower. Conclusion Oocytes retrieved from the patients who showed basal FSH levels below 15 IU/l were found to possess significant pregnancy potential. PMID:18228128

  8. Genetically Determined Dosage of Follicle-Stimulating Hormone (FSH) Affects Male Reproductive Parameters

    PubMed Central

    Grigorova, Marina; Punab, Margus; Ẑilaitienė, Birutė; Erenpreiss, Juris; Ausmees, Kristo; Matuleviĉius, Valentinas; Tsarev, Igor; Jørgensen, Niels

    2011-01-01

    Context: The detailed role of FSH in contributing to male testicular function and fertility has been debated. We have previously identified the association between the T-allele of the FSHB promoter polymorphism (rs10835638; G/T, −211 bp from the mRNA start) and significantly reduced male serum FSH. Objective: In the current study, the T-allele carriers of the FSHB −211 G/T single nucleotide polymorphism represented a natural model for documenting downstream phenotypic consequences of insufficient FSH action. Design and Subjects: We genotyped rs10835638 in the population-based Baltic cohort of young men (n = 1054; GG carriers, n = 796; GT carriers, n = 244; TT carriers, n = 14) recruited by Andrology Centres in Tartu, Estonia; Riga, Latvia; and Kaunas, Lithuania. Marker-trait association testing was performed using linear regression (additive, recessive models) adjusted by age, body mass index, smoking, and recruitment center. Results: Serum hormones directly correlated with the T-allele dosage of rs10835638 included FSH (additive model, P = 1.11 × 10−6; T-allele effect, −0.41 IU/liter), inhibin-B (P = 2.16 × 10−3; T-allele effect, −14.67 pg/ml), and total testosterone (P = 9.30 × 10−3; T-allele effect, −1.46 nmol/liter). Parameters altered only among TT homozygotes were reduced testicular volume (recessive model, P = 1.19 × 10−4; TT genotype effect, −9.47 ml) and increased serum LH (P = 2.25 × 10−2; TT genotype effect, 1.07 IU/liter). The carrier status of rs10835638 alternative genotypes did not affect sperm motility and morphology, calculated free testosterone, serum SHBG, and estradiol concentrations. Conclusion: We showed for the first time that genetically determined low FSH may have wider downstream effects on the male reproductive system, including impaired testes development, altered testicular hormone levels (inhibin-B, total testosterone, LH), and affected male reproductive potential. PMID:21733993

  9. Comparison of marmoset and human FSH using synthetic peptides of the β-subunit L2 loop region and anti-peptide antibodies.

    PubMed

    Kutteyil, Susha S; Kulkarni, Bhalchandra J; Mojidra, Rahul; Joseph, Shaini; Pathak, Bhakti R; Mahale, Smita D

    2016-06-01

    Follicle stimulating hormone (FSH) is a glycoprotein hormone required for female and male gametogenesis in vertebrates. Common marmoset (Callithrix jacchus) is a New World primate monkey, used as animal model in biomedical research. Observations like, requirement of extremely high dose of human FSH in marmosets for superovulation compared to other primates and generation of antibodies in marmoset against human FSH after repeated superovulation cycles, point towards the possibility that FSH-FSH receptor (FSHR) interaction in marmosets might be different than in the humans. In this study we attempted to understand some of these structural differences using FSH peptides and anti-peptide antibody approach. Based on sequence alignment, in silico modeling and docking studies, L2 loop of FSH β-subunit (L2β) was found to be different between marmoset and human. Hence, peptides corresponding to region 32-50 of marmoset and human L2β loop were synthesized, purified and characterized. The peptides displayed dissimilarity in terms of molecular mass, predicted isoelectric point, predicted charge and in the ability to inhibit hormone-receptor interaction. Polyclonal antibodies generated against both the peptides were found to exhibit specific binding for the corresponding peptide and parent FSH in ELISA and Western blotting respectively and exhibited negligible reactivity to cross-species peptide and FSH in ELISA. The anti-peptide antibody against marmoset FSH was also able to detect native FSH in marmoset plasma samples and pituitary sections. In summary, the L2β loop of marmoset and human FSH has distinct receptor interaction ability and immunoreactivity indicating possibility of subtle conformational and biochemical differences between the two regions which may affect the FSH-FSHR interaction in these two primates. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID:27282136

  10. Differential thermal stability of human, bovine and ovine Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) quaternary structures.

    PubMed

    Haj Hassan, Maya; Cahoreau, Claire; Jégot, Gwenhael; Jouanny, Camille; Mariot, Julie; Lecompte, François; Klett, Danièle; Combarnous, Yves

    2015-02-01

    Quaternary structure of human, bovine and ovine Follicle-Stimulating Hormones (hFSH, bFSH and oFSH) and Luteinizing Hormone was assessed in sandwich ELISAs using monoclonal anti-oFSHβ or anti-oLHβ antibodies, respectively, for capture and a biotinylated anti-hFSHα (α4 epitope) for detection. Neither free subunit gave any signal in this assay so that it was possible to measure the residual heterodimeric fraction after thermal treatment of the gonadotropins under study. The hormones were subjected to 5-min heating between 37 and 90 °C before rapid cooling in melting ice before ELISA. The data show half-dissociation of natural and recombinant human and ovine FSH preparations between 68 and 74 °C whereas bovine FSH preparations exhibited lower stability in these conditions with half-dissociation between 61 and 64 °C. Moreover, whereas all human and bovine as well as most ovine FSH preparations were fully dissociated at temperatures above 80 °C, one natural oFSH and one recombinant hLH preparations contained an important fraction that resisted dissociation even at 93 °C and retained in vitro bioactivity. This suggests the existence of gonadotropin αβ heterodimer with covalently linked subunits. Similarly, about 20% of the recombinant hLH preparation was also found withstand heat denaturation and also probably to have cross-linked subunits. The origin and chemical nature of these inter-subunit bonds remain to be determined. PMID:24732063

  11. Level of nutrition modulates the dynamics of oestradiol feedback on plasma FSH in ovariectomized ewes.

    PubMed

    Adams, N R; Briegel, J R; Sanders, M R; Blackberry, M A; Martin, G B

    1997-05-01

    The frequency of multiple ovulations in mature, cyclic ewes is strongly influenced by the level of nutrition, but it is difficult to demonstrate concurrent changes in plasma concentrations of gonadotropins. The failure to do so might be a consequence of rapid compensation by the homeostatic feedback mechanism linking secretion by the hypothalamus/pituitary gland and ovarian hormones. Most experimental models have examined the components of the homeostatic feedback system after steady state relationships had been established. We hypothesised that the effects of nutrition might be observed more readily if the system were disrupted and then examined while equilibrium was being re-established. This hypothesis was tested in three experiments in Merino ewes by allowing gonadotropin secretion to escape feedback for 5 days after ovariectomy and then replacing ovarian hormones and examining effects of feeding regimen on the return of plasma concentrations of FSH to baseline values. In all three experiments, oestrogen replacement caused plasma concentrations of FSH to decline more rapidly (P < 0.05) in ewes fed at 0.5x maintenance, than in ewes fed at 1.4x maintenance, with groups fed at maintenance being intermediate. No effect of diet was observed on plasma FSH concentrations in the absence of oestradiol, and neither progesterone nor charcoal-treated bovine follicular fluid influenced the effect of nutrition. Plasma concentrations of oestradiol were 9.8% lower on average (NS) in ewes fed above maintenance than in the sheep fed below maintenance over the three experiments, suggesting that there may have been a reduced clearance of oestradiol which contributed to the result. We conclude that feeding regimen affects the secretion or clearance of gonadotropins in mature ewes, as in the mature ram, and that this is one mechanism by which ovulation rate may be affected. PMID:9233506

  12. Development of specific enzyme-linked immunosorbent assay for determining LH and FSH levels in tilapia, using recombinant gonadotropins.

    PubMed

    Aizen, Joseph; Kasuto, Harel; Levavi-Sivan, Berta

    2007-01-01

    We recently produced Oreochromis niloticus recombinant LH and FSH as single-chain polypeptides in the methylotrophic yeast Pichia pastoris. Glycoprotein subunit alpha was joined with tilapia (t) LHbeta or tFSHbeta mature protein-coding sequences to form a fusion gene that encodes a ;;tethered" polypeptide, in which the gonadotropin beta-subunit forms the N-terminal part and the alpha-subunit forms the C-terminal part. Recombinant (r) gonadotropins were used to develop specific and homologous competitive ELISAs for measurements of FSH and LH in the plasma and pituitary of tilapia, using primary antibodies against rtLHbeta or rtFSHbeta, respectively, and rtLHbetaalpha or rtFSHbetaalpha for the standard curves. The wells were coated with either rtLHbeta (2ng/ml) or rtFSHbeta (0.5ng/well), and the final concentrations of the antisera were 1:5000 (for tLH) or 1:50,000 (for tFSH). The sensitivity of the assay was 15.84pg/ml for tLH and 0.24pg/ml for tFSH measurements in the plasma, whereas for the measurements in the pituitary, the sensitivity was 2.43ng/ml and 1.52ng/ml for tLH and tFSH, respectively. The standard curves for tFSH and tLH paralleled those of serially diluted pituitary extracts of other cichlids, as well as of serially diluted pituitary extract of seabream, European seabass and hybrid bass. We examined plasma tFSH and tLH levels in the course of one reproductive cycle, between two successive spawnings, in three individual tilapia females. Plasma levels of both FSH and LH increased during the second day after the eggs had been removed, probably related to the vitellogenic phase. LH levels increased toward spawning, which occurred on the 11th day. FSH levels also increased on day of cycle, probably due to recruitment of a new generation of follicles for the successive spawning. The development of specific ELISAs using recombinant gonadotropins is expected to advance the study of the distinct functions of each of these important hormones. PMID:17507016

  13. Mink aging is associated with a reduction in ovarian hormone release and the response to FSH and ghrelin.

    PubMed

    Sirotkin, Alexander V; Mertin, Dušan; Süvegová, Karina; Lauričik, Jozef; Morovič, Martin; Harrath, Abdel Halim; Kotwica, Jan

    2016-09-15

    The endocrine mechanisms of mink ovarian hormones release and reproductive aging are poorly investigated. The aims of our study were to: (1) identify hormones produced by mink ovaries (the steroids progesterone [P] and estradiol [E], the peptide hormone oxytocin [OT], and the prostaglandin F [PGF] and prostaglandin E [PGE]); (2) examine the effect of FSH and ghrelin on the release of the hormones listed previously; and (3) understand whether these hormones can be involved in the control of mink reproductive aging, i.e., whether aging can be associated with changes (a) in the basal release of P, E, OT, PGF, or PGE and (b) their response to FSH and ghrelin. Fragments of ovaries of young (yearlings) and old (3-5 years of age) minks were cultured with and without FSH and ghrelin (0, 1, 10, or 100 ng/mL), and the release of hormones was analyzed by EIA/RIA. We found that isolated ovaries were able to release P, E, OT, PGF, and PGE, and the levels of P produced in the ovaries of old animals were lower than those produced in the ovaries of young animals, whereas the levels of other hormones did not differ. FSH was able to stimulate P and E and suppress OT and PGF and did not affect PGE release. Aging was associated with the inhibition of the effect of FSH on ovarian P and E, the appearance of the inhibitory action of FSH on OT, and the disappearance of this action on ovarian PGF. PGE was not affected by FSH, irrespective of animal age. Ghrelin was able to promote E (but not P) and suppress OT, PGF, and PGE output. Aging was associated with the appearance of an inhibitory influence of ghrelin on ovarian OT and PGE and with the disappearance of this influence on PGF output. Aging did not affect the action of ghrelin on ovarian P and E. Our observations (1) confirm the production of P and E and show that OT, PGF, and PGE are released from mink ovaries, (2) confirm the involvement of FSH and demonstrate the involvement of ghrelin in the control of mink ovarian hormone

  14. FSH regulates fat accumulation and redistribution in aging through the Gαi/Ca2+/CREB pathway

    PubMed Central

    Liu, Xin-Mei; Chan, Hsiao Chang; Ding, Guo-Lian; Cai, Jie; Song, Yang; Wang, Ting-Ting; Zhang, Dan; Chen, Hui; Yu, Mei Kuen; Wu, Yan-Ting; Qu, Fan; Liu, Ye; Lu, Yong-Chao; Adashi, Eli Y; Sheng, Jian-Zhong; Huang, He-Feng

    2015-01-01

    Increased fat mass and fat redistribution are commonly observed in aging populations worldwide. Although decreased circulating levels of sex hormones, androgens and oestrogens have been observed, the exact mechanism of fat accumulation and redistribution during aging remains obscure. In this study, the receptor of follicle-stimulating hormone (FSH), a gonadotropin that increases sharply and persistently with aging in both males and females, is functionally expressed in human and mouse fat tissues and adipocytes. Follicle-stimulating hormone was found to promote lipid biosynthesis and lipid droplet formation; FSH could also alter the secretion of leptin and adiponectin, but not hyperplasia, in vitro and in vivo. The effects of FSH are mediated by FSH receptors coupled to the Gαi protein; as a result, Ca2+ influx is stimulated, cAMP-response-element-binding protein is phosphorylated, and an array of genes involved in lipid biosynthesis is activated. The present findings depict the potential of FSH receptor-mediated lipodystrophy of adipose tissues in aging. Our results also reveal the mechanism of fat accumulation and redistribution during aging of males and females. PMID:25754247

  15. Characteristics and functions of a minor FSH surge near the end of an interovulatory interval in Bos taurus heifers.

    PubMed

    Ginther, O J; Baldrighi, J M; Siddiqui, M A R; Wolf, C A

    2016-07-01

    The apparent function of a minor FSH surge based on temporality with follicular events was studied in 10 heifers with 2 follicular waves per interovulatory interval. Individual follicles were tracked from their emergence at 2 mm until their outcome was known, and a blood sample was collected for FSH and LH assay every 12 h from day -14 (day 0 = ovulation) to day 4. A minor FSH surge occurred in each heifer (peak, day -4.6 ± 0.2). Concentration of LH increased (P < 0.05) during the FSH increase of the minor surge but did not decrease during the FSH decrease. A minor follicular wave with 8.2 ± 2.0 follicles occurred in 6 of 10 heifers. The maximal diameter (mean, 3.4 ± 0.9 mm) of 77% of the minor-wave follicles occurred in synchrony on day -4.4 ± 0.4. Most (59%) of minor-wave follicles regressed before ovulation and 41% decreased and then increased in diameter (recovered) on day -1.9 ± 0.3 to become part of the subsequent wave 1. A mean of 3.7 ± 0.9 regressing subordinate follicles from wave 2 recovered on the day before or at the peak of the minor FSH surge. The growth rate of the preovulatory follicle decreased (P < 0.02) for 3 d before the peak of the minor FSH surge and then increased (P < 0.03). Concentration of LH increased slightly but significantly temporally with the resurgence in growth rate of the preovulatory follicle. A minor LH surge peaked (P < 0.0002) on day 3 at the expected deviation in growth rates between the future dominant and subordinate follicles. Results indicated on a temporal basis that the recovery of some regressing subordinate follicles of wave 2 was attributable to the minor FSH surge. The hypothesis was supported that some regressing follicles from the minor follicular wave recover to become part of wave 1. PMID:27131335

  16. Effect of FSH and LH hormones on oocyte maturation of buffalo and gene expression analysis of their receptors and Cx43 in maturing oocytes.

    PubMed

    Pandey, Alok; Gupta, S C; Gupta, Neelam

    2010-08-01

    Follicle stimulating hormone (FSH) and luteinizing hormone (LH) are commonly added to maturation media to improve cumulus expansion known to be a predictor of oocyte maturation. Therefore, effects of various concentrations of FSH (1000 ng/ml), LH (1000 ng/ml) and FSH + LH (1000 ng/ml each) in comparison with control (without FSH + LH) cultured oocytes were investigated. FSH and LH (1000 ng/ml each) induced significantly more cumulus expansion and polar body numbers, as compared with control and treatments of 1000 ng/ml FSH and 1000 ng/ml LH alone. Expression of FSH receptor (r), LHr and Cx43 mRNAs was determined by real-time PCR in cumulus-oocyte complexes (COCs) and denuded oocytes at different maturation times. Expression of all three genes was higher in COCs compared with denuded oocytes, confirming the importance of cumulus cells in oocyte maturation. FSHr and connexin 43 (Cx43) mRNA abundance in both COCs and denuded oocytes was highest at 0-6 h of maturation and decreased subsequently. However, LHr mRNA abundance increased from 6 h up to 24 h of maturation. The study concluded that FSH, LH receptors and Cx43 gene expression regulation is an index related to oocyte maturation. PMID:20128947

  17. The effect of increased dietary intake on superovulatory response to FSH in heifers.

    PubMed

    Gong, J G; Armstrong, D G; Baxter, G; Hogg, C O; Garnsworthy, P C; Webb, R

    2002-04-01

    We have previously shown that the number of ovarian follicles <4 mm in diameter can be increased by enhanced dietary intake in heifers. This study investigated the effect of the same dietary treatment on superovulatory response. The estrous cycles of 24 mature Hereford x Friesian heifers were synchronized by a standard progesterone plus prostaglandin protocol. The animals were fed with either 100% (group M, n = 12) or 200% (group 2M, n = 12) maintenance requirements for a 3-week period. Starting from day 4 of the synchronized estrous cycle, all the animals were superovulated using a standard 4-day FSH regime followed by an injection of GnRH analogue (GnRHa) to induce ovulation. Rectal ultrasound scanning was carried out to assess ovarian follicular populations at the start of FSH treatment and on the day of GnRHa injection, and to determine the number of corpora lutea 5 days after GnRHa injection. The body weight (BW) and body condition score (BCS) were recorded weekly and plasma samples were collected throughout the experimental period. There were no differences in either BW or BCS between two groups at the start of the experiment. The BW and BCS were maintained during the experiment in the group M, whilst animals in the group 2M showed a non-significant (P > 0.05) increase in BW and BCS. Circulating concentrations of insulin were significantly (P < 0.01) higher in heifers from the group 2M throughout the controlled feeding period. The group 2M had significantly (P < 0.05) more follicles 2-4 mm in diameter at the start of FSH treatment and more (P < 0.01) follicles >9 mm in diameter on the day of GnRHa injection, when compared with the group M. Similarly, 5 days after GnRHa injection there were significantly (P < 0.01) more corpora lutea in the group 2M (18.1+/-2.2) than in the group M (10.6+/-3.0). In addition, plasma progesterone concentrations following GnRHa injection were significantly (P < 0.01) higher in heifers from the group 2M. In conclusion, these

  18. Influence of hormonal contraceptives on the pituitary response to LH/FSH-releasing hormone.

    PubMed

    Carol, W; Lauterbach, H; Klinger, G; Möller, R

    1978-03-01

    In the pre-ovulatory phase the absolute and relative LH increase was much greater than during the luteal phase and less pronounced in the early follicular phase of the normal cycle. FSH release was affected only during the pre-ovulatory period, where a retarded, 3- or 4-fold increase compared to basal levels was recorded. In the women taking oral contraceptives of the conventional type the first LH-RH test showed gonadotropin responses similar to those obtained during the luteal phase of the controls. The second test brought a significantly lower LH response, suggesting an increasing exogenous steroid inhibition at the pituitary level in the course of the therapeutic cycle. This inhibition seems to be reversed during the monthly tablet-free interval. A particularly small and retarded gonadotropin response was observed in patients taking Deposiston. These results are discussed as to their clinical significance. PMID:357145

  19. Novel FSH receptor mutation in a case of spontaneous ovarian hyperstimulation syndrome with successful pregnancy outcome

    PubMed Central

    Chauhan, Anahita R.; Prasad, Madhva; Chamariya, Sumit; Achrekar, Swati; Mahale, Smita D.; Mittal, Kartik

    2015-01-01

    The objective is to study the FSH receptor (FSHR) for mutations in a case of spontaneous ovarian hyperstimulation syndrome (sOHSS). This is a single case study and it examined patient who presented with spontaneous critical OHSS in early pregnancy and had successful good obstetric outcome. Intervention of this study was analysis of blood for genetic analysis of FSHR postdelivery. The main outcome measure noted was FSHR mutation. The study resulted in a novel, here though unreported, heterozygous mutation in FSHR gene at nucleotide position 1346 (AC1346T to AAT) in exon 10 yielding a threonine to asparagine (Thr449Asn) substitution in the transmembrane domain helix 3 of the FSHR. To conclude FSHR gene analysis can add to our understanding of sOHSS. PMID:26752859

  20. Blocking antibody to the beta-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low estrogen levels undoubtedly underlie menopausal bone thinning. However, rapid and profuse bone loss begins three years prior to the last menstrual period, when serum estrogen is relatively normal. We have shown that the pituitary hormone FSH, the levels of which are high during the late peri-men...

  1. Body Mass Index and Gonadotropin Hormones (LH & FSH) Associate With Clinical Symptoms Among Women With Polycystic Ovary Syndrome

    PubMed Central

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

    2015-01-01

    To evaluate the relevance of body mass index (BMI), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and LH/FSH ratio with clinical symptoms in polycystic ovary syndrome (PCOS) women. Methods: We reviewed the medical records of all women visited in the PCOS Clinic of Babol (Iran) from 2008 to 2012. A retrospective cross-sectional study was conducted on 175 PCOS women; aged 18–38 years diagnosed based on the Rotterdam criteria. Among the PCOs women, the prevalence of oligomenorrhea, acne, and hirsutism were found to be 92.0%, 31.4%, and 78.9%, respectively. Positive finding of polycystic ovaries was observed in 89.1% of PCOS women with by using sonography. A total of 69.2% overweight/obesity patients had polycystic ovary morphology on ultrasound image. Compared with non- overweight/obesity, the adjusted OR of PCOS women for sonographic view of polycystic ovaries was 4.33 (95% CI, 1.42-13.15, p=0.001), Nevertheless, the adjusted odds ratio (OR) showed no significant associations between LH, FSH, and LH/FSH ratio with clinical symptoms in these women. The findings of this study indicated that the overweight/obese women with PCOS are at an increased risk for sonographic view of polycystic ovaries. Therefore, it is suggested that successful weight loss is the most effective method of restoring ovulation, menstruation that should be used as major advice in obese PCOS patients. PMID:25716399

  2. Disruption of periovulatory FSH and LH surges during induced anovulation by an inhibitor of prostaglandin synthesis in mares.

    PubMed

    Ginther, O J; Cuervo-Arango, J; Beg, M A

    2011-06-01

    The role of passage of follicular fluid into the peritoneal cavity during ovulation in the transient disruption in the periovulatory FSH and LH surges was studied in ovulatory mares (n=7) and in mares with blockage of ovulation by treatment with an inhibitor of prostaglandin synthesis (n=8). Mares were pretreated with hCG when the largest follicle was ≥32 mm (Hour 0). Ultrasonic scanning was done at Hours 24 and 30 and every 2h thereafter until ovulation or ultrasonic signs of anovulation. Blood samples were collected at Hours 24, 30, 32, 34, 36, 38, 48, and 60. Ovulation in the ovulatory group occurred at Hours 38 (five mares), 40, and 44. Until Hour 36, diameter of the follicle and concentrations of FSH, LH, and estradiol-17β (estradiol) were similar between groups. Between Hours 34 and 36, a novel transient increase in estradiol occurred in each group, and color-Doppler signals of blood flow in the follicular wall decreased in the ovulatory group and increased in the anovulatory group. In each group, FSH and LH periovulatory surges were disrupted by a decrease or plateau between Hours 38 and 48 and an increase between Hours 48 and 60. The discharge of hormone-laden follicular fluid into the peritoneal cavity at ovulation was not an adequate sole explanation for the temporally associated transient depression in FSH and LH. Other routes from follicle to circulation for gonadotropin inhibitors played a role, based on similar depression in the ovulatory and anovulatory groups. PMID:21571458

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

    SciTech Connect

    Bruheim, Kjersti Svartberg, Johan; Carlsen, Erik; Dueland, Svein; Haug, Egil; Skovlund, Eva; Tveit, Kjell Magne; Guren, Marianne G.

    2008-03-01

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

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

    PubMed

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

    2015-02-01

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

  5. The subunit structure of the follitropin (FSH) receptor. Photoaffinity labeling of the membrane-bound receptor follitropin complex in situ.

    PubMed

    Smith, R A; Branca, A A; Reichert, L E

    1985-11-15

    Human follicle-stimulating hormone (hFSH) was acylated with N-hydroxysuccinimidyl-4-azidobenzoate (HSAB) and radioiodinated (55 microCi/micrograms) for use as a photoaffinity probe to investigate the subunit structure of the FSH receptor in calf testis. After incubation with the photoaffinity probe and photolysis with UV light, the cross-linked hormone-receptor complex was solubilized from the membrane and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence and absence of the reducing agent dithiothreitol. Autoradiography of the polyacrylamide gels revealed two major bands, 64 kDa and 84 kDa. These were equivalent in molecular mass to those observed in a previous study (Branca, A. A., Sluss, P. M., Smith, A. A., and Reichert, L. E., Jr. (1985) J. Biol. Chem. 260, 9988-9993) in which performed hormone-receptor complexes were solubilized with detergent prior to formation of covalent cross-linkages through the use of homobifunctional cross-linking reagents. Reduction with dithiothreitol resulted in the loss of radioactivity from the 84-kDa band with a concomitant increase in the intensity of the 64-kDa band. Since dithiothreitol increases the dissociation of intact radioiodinated azidobenzoyl-FSH into subunits, it is suggested that the conversion of the 84-kDa band to the 64-kDa band by dithiothreitol is due to the loss of non-cross-linked hFSH subunit from the 84-kDa band and that the two bands observed after photoaffinity labeling arise from covalent bond formation between hFSH and a receptor subunit having a relative molecular weight (Mr) of 48,000. In addition to the predominant photolabeling of the receptor to yield the 64-kDa and 84-kDa bands, several other, less intense bands (54 kDa, 76 kDa, 97 kDa, and 116 kDa) were also consistently observed on autoradiographs. The appearance of all bands, however, was inhibited by the inclusion of unlabeled hFSH in the initial binding incubation mixtures. The results of this study indicate

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

    PubMed

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

    2016-09-15

    The effects of Amburana cearensis ethanolic extract, with or without addition of a mix of supplements associated or not with FSH, on in vitro morphology and development of caprine secondary follicles were evaluated. In experiment 1, isolated follicles (250 μm in diameter) were cultured for 12 days in alpha-modified minimal essential medium (α-MEM) alone (control) or in medium composed of different concentrations of A. cearensis extract (Amb 0.1; 0.2, or 0.4 mg/mL). In experiment 2, culture media were α-MEM or Amb 0.2 mg/mL (both without supplements), or these same media supplemented with BSA, insulin, transferrin, selenium, glutamine, hypoxanthine, and ascorbic acid (referred as α-MEM(+) and Amb 0.2(+), respectively), or these last groups also supplemented with sequential FSH (100 ng/mL from Day 0 to Day 6; 500 ng/mL from Day 6 to Day 12), constituting groups α-MEM(+) + FSH and Amb 0.2(+) + FSH. At the end of culture in experiment 1, control medium (α-MEM) and Amb 0.2 mg/mL had higher percentages (P < 0.05) of morphologically normal follicles and percentage of fully grown oocytes, i.e., oocyte greater than 110 μm, compared to the other A. cearensis extract concentrations. In experiment 2, all supplemented media had higher percentages (P < 0.05) of normal follicles and antrum formation than nonsupplemented media. In addition, follicles cultured in Amb 0.2(+) + FSH showed an average increase in diameter higher (P < 0.05) than the other treatments. Oocytes cultured in both treatments supplemented with FSH showed greater glutathione and active mitochondria levels than nonsupplemented media but similar to the other treatments. In conclusion, A. cearensis extract (0.2 mg/mL) added by supplements and FSH improves follicular growth. Therefore, it can be an alternative culture medium for goat preantral follicle development. PMID:27287468

  7. Treatment with recombinant equine follicle stimulating hormone (reFSH) followed by recombinant equine luteinizing hormone (reLH) increases embryo recovery in superovulated mares.

    PubMed

    Meyers-Brown, G; Bidstrup, L A; Famula, T R; Colgin, M; Roser, J F

    2011-10-01

    The dynamics of ovarian follicular development depend on a timely interaction of gonadotropins and gonadal feedback in the mare. The development and efficacy of genetically cloned recombinant equine gonadotropins (reFSH and reLH) increase follicular activity and induce ovulation, respectively, but an optimum embryo recovery regimen in superovulated mares has not been established. The objective of this study was to determine if treatment with reFSH followed by reLH would increase the embryo per ovulation ratio and the number of embryos recovered after superovulation in mares. Sixteen estrous cycling mares of light horse breeds (4-12 years) were randomly assigned to one of two groups: Group 1; reFSH (0.65mg)/PBS (n=8) and Group 2; reFSH (0.65mg)/reLH (1.5mg) (n=8). On the day of a 22-25mm follicle post-ovulation mares were injected IV twice daily with reFSH for 3 days (PGF(2α) given IM on the second day of treatment) and once per day thereafter until a follicle or cohort of follicles reached 29mm after which either PBS or reLH was added and both groups injected IV twice daily until the presence of a 32mm follicles, when reFSH was discontinued. Thereafter, mares were injected three times daily IV with only PBS or reLH until a majority of follicles reached 35-38mm when treatment was discontinued. Mares were given hCG IV (2500IU) to induce ovulation and bred. Embryo recovery was performed on day 8 day post-treatment ovulation. Daily jugular blood samples were collected from the time of first ovulation until 8 days post-treatment ovulation. Blood samples were analyzed for LH, FSH, estradiol, progesterone and inhibin by validated RIA. Duration of treatment to a ≥35mm follicle(s) and number of ovulatory size follicles were similar between reFSH/reLH and reFSH/PBS treated mares. The number of ovulations was greater (P<0.01) in the reFSH/reLH group, while the number of anovulatory follicles was less (P<0.05) compared to the reFSH/PBS group. Number of total embryos

  8. Genetic evidence that lower circulating FSH levels lengthen menstrual cycle, increase age at menopause and impact female reproductive health

    PubMed Central

    Ruth, Katherine S.; Beaumont, Robin N.; Tyrrell, Jessica; Jones, Samuel E.; Tuke, Marcus A.; Yaghootkar, Hanieh; Wood, Andrew R.; Freathy, Rachel M.; Weedon, Michael N.; Frayling, Timothy M.; Murray, Anna

    2016-01-01

    STUDY QUESTION How does a genetic variant in the FSHB promoter, known to alter FSH levels, impact female reproductive health? SUMMARY ANSWER The T allele of the FSHB promoter polymorphism (rs10835638; c.-211G>T) results in longer menstrual cycles and later menopause and, while having detrimental effects on fertility, is protective against endometriosis. WHAT IS KNOWN ALREADY The FSHB promoter polymorphism (rs10835638; c.-211G>T) affects levels of FSHB transcription and, as a result, circulating levels of FSH. FSH is required for normal fertility and genetic variants at the FSHB locus are associated with age at menopause and polycystic ovary syndrome (PCOS). STUDY DESIGN, SIZE, DURATION We used cross-sectional data from the UK Biobank to look at associations between the FSHB promoter polymorphism and reproductive traits, and performed a genome-wide association study (GWAS) for length of menstrual cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS We included white British individuals aged 40–69 years in 2006–2010, in the May 2015 release of genetic data from UK Biobank. We tested the FSH-lowering T allele of the FSHB promoter polymorphism (rs10835638; c.-211G>T) for associations with 29, mainly female, reproductive phenotypes in up to 63 350 women and 56 608 men. We conducted a GWAS in 9534 individuals to identify genetic variants associated with length of menstrual cycle. MAIN RESULTS AND THE ROLE OF CHANCE The FSH-lowering T allele of the FSHB promoter polymorphism (rs10835638; MAF 0.16) was associated with longer menstrual cycles [0.16 SD (c. 1 day) per minor allele; 95% confidence interval (CI) 0.12–0.20; P = 6 × 10−16], later age at menopause (0.13 years per minor allele; 95% CI 0.04–0.22; P = 5.7 × 10−3), greater female nulliparity [odds ratio (OR) = 1.06; 95% CI 1.02–1.11; P = 4.8 × 10−3] and lower risk of endometriosis (OR = 0.79; 95% CI 0.69–0.90; P = 4.1 × 10−4). The FSH-lowering T allele was not associated with other female

  9. Pueraria tuberosa DC Extract Improves Androgenesis and Sexual Behavior via FSH LH Cascade

    PubMed Central

    Chauhan, Nagendra Singh; Sharma, Vikas; Christine Helena Frankland Sawaya, Alexandra; Dixit, V. K.

    2013-01-01

    The aim of this study was to investigate the effects of ethanolic extract of Pueraria tuberosa (PT) on sexual behaviour and androgenic activity. Male albino rats were divided into four groups of six animals each: control group 1 (2% acacia solution), PT-treated group 2 (50 mg/Kg), PT-treated group 3 (100 mg/Kg), and PT-treated group 4 (150 mg/Kg). Sexual behavior of male rats in the presence of a female rat was recorded. The treated groups were evaluated for sexual parameters. The extract was characterized using LC-MS. The effect of treatment on anabolic and weight of secondary sexual organs was determined. The histological changes in section of testis and epididymis after treatment were observed. Sperm count in epididymis and fructose content in seminal vesicles were also measured. Levels of hormones like FSH, LH, and T were determined. A dose-dependent increase in sexual behaviors was evidenced in the animals of extract treated groups. Increase in testis weight was recorded in PT. At the highest dose PT also affects the hormones level. The four compounds namely puerarin, daidzein, biochanin-A and formononetin were identified in ethanolic extract using LC-MS. It concluded that PT extract possesses androgenic effect and it significantly increased the sexual behaviour and hormones level. PMID:24489512

  10. Photoperiod-gonadotropin mismatches induced by treatment with acyline or FSH in Siberian hamsters: impacts on ovarian structure and function.

    PubMed

    Zysling, D A; Park, S-U; McMillan, E L; Place, N J

    2012-11-01

    Many seasonal breeders time their reproductive efforts to specific times of the year to ensure adequate resources for the production and care of young. For long-day (LD) breeders, females born before the summer solstice (LDs) reach sexual maturity quickly and often breed that same year, whereas females born after the summer solstice (short days (SDs)) may delay reproductive development to the following spring when environmental conditions are favorable for reproduction. In Siberian hamsters, development in SD is associated with structural and functional differences in the ovary compared with females held in LD, including a greater number of primordial follicles and an abundance of hypertrophied granulosa cells (HGCs), which are immunoreactive for anti-Müllerian hormone. The goal of this study was to determine whether SD-induced gonadotropin suppression is responsible for these phenotypic differences. Gonadotropin levels were suppressed in LD hamsters using the GNRH antagonist acyline. Conversely, to determine whether the SD ovarian phenotype is completely reversed by gonadotropin stimulation, recombinant human FSH (rhFSH) was administered. Our treatments were successful in mimicking FSH concentrations of the opposite photoperiod, but they did not produce a comparable change in the ovarian phenotype. Most notable was the lack of HGCs in the ovaries of acyline-treated LD females. Similarly, HGCs were maintained in the ovaries of SD females treated with rhFSH. Our data suggest that gonadotropins alone do not account for the SD ovarian phenotype. Future studies will determine whether SD-induced changes in other factors underlie these phenotypic changes. PMID:22936286

  11. [Dependence of serum hormones (T, FSH, LH) on morphometric testicular findings after chemo- and radiotherapy in patients with malignant testicular tumors].

    PubMed

    Barth, V; Schönfelder, M

    1990-01-01

    Correlations which exist between morphometric parameters of remaining testicular tissue, on the one hand, and serum hormones on the other (testosterone = T, follicle-stimulating hormone = FSH, luteinising hormone = LH), depending on therapeutic action taken on patients for malignant testicular tumours, seem to suggest that decline in epithelial thickness together with increase in wall thickness leads to rise in FSH. No unambiguous relations, on the other hand, were found to exist between testosterone or luteotrophic hormone and morphometric findings. Hence, FSH seems to characterise the severity of damage to germ epithelium and thus the degree of impairment to spermatogenesis. FSH may be accepted as a criterion for fertility disorders in sexually active men. PMID:2122615

  12. Superovulation in heifers given FSH initiated either at day 2 or day 10 of the estrous cycle.

    PubMed

    Goulding, D; Williams, D H; Duffy, P; Boland, M P; Roche, J F

    1990-10-01

    The aim of this study was to determine if initiation of superovulation in heifers during the time of development of the first dominant follicle (Days 2 to 6) would give equivalent ovulation and embryo production rates as treatment initiated at mid-cycle. Estrus was synchronized in 60 beef heifers using luprostiol (PG) and they were randomly allocated to treatment with 4.5, 3.5, 2.5 and 1.5 mg of porcine follicle stimulating hormone (FSH) administered twice daily, either on Days 2, 4, 5 and 6 (Day-2 group), respectively, or with similar doses at four consecutive days during mid-cycle (Day-10 group, initiation on Day 9 to 11). All heifers received 500 mug cloprostenol at the fifth FSH injection and 250 mug at the sixth injection. Blood samples for progesterone determination were collected at the time of FSH injections. Heifers were slaughtered 7 d post estrus, and the number of ovulations and large follicles (>/=10mm) were determined on visual inspection of the ovary. Following flushing of the uterine horns the quality of embryos and the fertilization rate were determined. Significant differences between treatments were determined using a two-sided t-test, and frequency distributions were compared using Chi-square tests. The mean number (+/-SEM) of ovulations for heifers in the Day-10 group was 12.9+/-1.0, and 8.5+/-0.9 embryos were recovered. Both the number of ovulations (6.7+/-0.8) and embryos recovered (4.1+/-0.6) were lower (P=0.0001) in heifers in the Day-2 group. Following grading based on a morphological basis, a higher number (P=0.002) of embryos was categorized as Grades 1 and 2 (4.1+/-0.6) and Grade 3 (2.1+/-0.4) in Day-10 heifers than in the Day-2 group (Grade 1 and 2, 1.9+/-0.3; Grade 3, 0.7+/-0.2). The number of Grade 4 and 5 embryos (Day 10, 1.6+/-0.2; Day 2, 1.4+/-0.2) and the number of unfertilized ova (Day 10, 0.7+/-0.4; Day 2, 0.2+/-0.1) did not differ between treatments. Progesterone concentrations were lower (P=0.0001) in Day-2 heifers at FSH

  13. Regulation of expression of ovarian mRNA encoding steroidogenic enzymes and gonadotrophin receptors by FSH and GH in hypogonadotrophic cattle.

    PubMed

    Garverick, H A; Baxter, G; Gong, J; Armstrong, D G; Campbell, B K; Gutierrez, C G; Webb, R

    2002-05-01

    A study was conducted to determine the effects of FSH and bovine somatotrophin on the expression of mRNA encoding the gonadotrophin receptors and steroidogenic enzymes in ovarian follicles of cattle rendered hypogonadotrophic by treatment with a GnRH agonist. Hereford x Friesian heifers were allotted into two pretreatment groups: controls (n = 10) and GnRH agonist-treated (n = 20). Ovaries of control cows were removed on day 2 of the first follicular wave after synchronized oestrus. GnRH agonist-treated heifers were given either FSH or no FSH. FSH was infused at 50 microg h(-1) for 48 h. Ovaries in GnRH agonist-treated heifers were removed at the end of exogenous hormone treatment. The control, GnRH agonist and GnRH agonist plus FSH treatment groups were divided further into bovine somatotrophin or no bovine somatotrophin treatments (n = 5 per treatment). Bovine somatotrophin (25 mg day(-1) by s.c. injection) was administered for 3 days. Ovaries were scanned once a day by ultrasonography. Blood samples for hormone measurements were collected three times a day from oestrus until the time of removal of ovaries. Expression of mRNAs for the FSH and LH receptors and cytochrome P450 side-chain cleavage (P450scc), cytochrome P450 17alpha-hydroxylase (P450c17) and cytochrome P450 aromatase (P450arom) enzymes was localized by in situ hybridization and quantified by image analysis. Ovarian follicular growth was arrested at < or = 4.5 mm in diameter in GnRH agonist-treated heifers. There was no effect of bovine somatotrophin on follicular dynamics, gonadotrophin secretion or expression of mRNA for either the gonadotrophin receptors or steroidogenic enzymes. Infusion of FSH to GnRH agonist-treated heifers increased FSH concentrations in serum to the physiological concentrations observed in controls and stimulated growth of follicles to a size similar (5.5-8.0 mm in diameter) to recruited follicles in control cows. FSH induced mRNA expression of P450scc and P450arom in

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

    PubMed

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

    2008-06-01

    The goal of the present study was to compare the ovarian response, oocyte yields per animal, and the morphological quality of oocytes collected by ultrasound guided follicular aspiration from Holstein cows treated either with FSH or eCG. Twenty four normal cyclic, German Holstein cows were randomly divided into two groups. Fourteen cows received 3000 IU eCG on day-4 prior to ovum pick-up (OPU) (day 0), 2 days later (day-2), 625 microg cloprostenol was administered. On day-1 GnRH was administered i.m. and 24h later OPU (day 0) was performed. In ten cows a total dose of 500 IU follicle stimulating hormone (Pluset) was administered intramuscularly in a constant dosage for 4 days with intervals of 12h, starting on day-5. Luteolysis was induced by application of 625 microg cloprostenol on day-2. On day-1 (24h after the last FSH treatment) GnRH was administered i.m. and 24h later OPU (day 0) was performed. Ovarian follicles were visualized on the ultrasound monitor, counted and recorded. All visible antral follicles were punctured. Recovered oocytes were graded morphologically based on the cumulus investment. Average follicle number in ovaries was higher in FSH group than eCG group (p<0.05). Oocyte yields per animal did not differ between FSH and eCG groups. The proportion of grade A oocytes was higher in the FSH group in the than eCG group (p<0.05). Likewise, rate of grade C oocytes in FSH group were lower than eCG group (p<0.05). In conclusion, these results suggest that ovarian response, follicle number in ovaries and oocyte quality are affected by the type of gonadotropin and FSH is better alternative than eCG for OPU treatment. PMID:18294785

  15. Induction of Cyclin D2 in Rat Granulosa Cells Requires FSH-dependent Relief from FOXO1 Repression Coupled with Positive Signals from Smad*

    PubMed Central

    Park, Youngkyu; Maizels, Evelyn T.; Feiger, Zachary J.; Alam, Hena; Peters, Carl A.; Woodruff, Teresa K.; Unterman, Terry G.; Lee, Eun Jig; Jameson, J. Larry; Hunzicker-Dunn, Mary

    2006-01-01

    Ovarian follicles undergo exponential growth in response to follicle-stimulating hormone (FSH), largely as a result of the proliferation of granulosa cells (GCs). In vitro under serum-free conditions, rat GCs differentiate in response to FSH but do not proliferate unless activin is also present. In the presence of FSH plus activin, GCs exhibit enhanced expression of cyclin D2 as well as inhibin-α, aromatase, steroidogenic factor-1 (SF-1), cholesterol side chain (SCC), and epiregulin. In this report we sought to identify the signaling pathways by which FSH and activin promote GC proliferation and differentiation. Our results show that these responses are associated with prolonged Akt phosphorylation relative to time-matched controls and are dependent on phosphati-dylinositol 3-kinase (PI 3-kinase) and Smad2/3 signaling, based on the ability of the PI 3-kinase inhibitor LY294002 or infection with adenoviral dominant negative Smad3 (DN-Smad3) mutant to attenuate induction of cyclin D2, inhibin-α, aromatase, SCC, SF-1, and epiregulin. The DN-Smad3 mutant also abolished prolonged Akt phosphorylation stimulated by FSH plus activin 24 h post-treatment. Infection with the adenoviral constitutively active forkhead box-containing protein, O subfamily (FOXO)1 mutant suppressed induction of cyclin D2, aromatase, inhibin-α, SF-1, and epiregulin. Transient transfections of GCs with constitutively active FOXO1 mutant also suppressed cyclin D2, inhibin-α, and epiregulin promoter-reporter activities. Chromatin immunoprecipitation results demonstrate in vivo the association of FOXO1 with the cyclin D2 promoter in untreated GCs and release of FOXO1 from the cyclin D2 promoter upon addition of FSH plus activin. These results suggest that proliferation and differentiation of GCs in response to FSH plus activin requires both removal of FOXO1-dependent repression and positive signaling from Smad2/3. PMID:15613482

  16. Estrus response and follicular development in Boer does synchronized with flugestone acetate and PGF2α or their combination with eCG or FSH.

    PubMed

    Bukar, Muhammad Modu; Yusoff, Rosnina; Haron, Abd Wahid; Dhaliwal, Gurmeet Kaur; Khan, Mohd Azam Goriman; Omar, Mohammed Ariff

    2012-10-01

    The effects of different estrus synchronization techniques on follicular development and estrus response were studied in 81 nulliparous Boer does. The does were divided into nine groups. Eight of the nine groups were synchronized with prostaglandin F2-alpha (PGF(2α)) or flugestone acetate (FGA) or their combinations, and the ninth group was a control group. In addition to the above combinations, four of the eight synchronized groups were given 5 mg follicle-stimulating hormone (FSH) and the remaining four groups were administered 300 IU equine chorionic gonadotrophin (eCG). Posttreatment follicular development was monitored until ovulation occurred using a real-time B-mode ultrasound scanner (Aloka, 500 SSD, Japan), with a 7.5-MHz transrectal linear probe. All the does from the synchronized groups that were given eCG exhibited oestrus while only 88.9% of the does synchronized with FSH showed estrus. The estrus response was observed to be the least among the does synchronized with PGF(2α) + FSH (33.3%) combination followed closely by the FGA + FSH (42.9%) combinations. It was observed that the combinations of FGA + PGF(2α) + FSH resulted in increased percentage of estrus response, duration of estrus, and ovulation. The number of follicles was higher (P < 0.05) in FSH-synchronized groups than the eCG-synchronized groups. It was concluded that the best estrus synchronization protocol in goats is the FGA + eCG with or without PGF(2α). However, the PGF(2α) + FGA + FSH method of estrus synchronization is the most promising combination for further development as a better alternative to estrus synchronization with eCG in does. PMID:22461200

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

    PubMed Central

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

    2011-01-01

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

  18. Effects of different batches of /sup 125/iodine on properties of /sup 125/I-hFSH and characteristics of radioligand-receptor assays

    SciTech Connect

    Melson, B.E.; Sluss, P.M.; Reichert, L.E. Jr.

    1987-02-01

    Radioiodination of highly purified human follicle-stimulating hormone (hFSH) (4000 IU/mg) was performed every other week for 23 weeks using 2 mCI carrier free Na/sup 125/I (Amersham Corp., 15 mCi/micrograms I2) in the presence of lactoperoxidase. Incorporation of /sup 125/I into hFSH was determined by the method of R. C. Greenwood, W. M. Hunter, and J. S. Grover (1963) Biochem. J. 89, 114). Hormone binding was studied in vitro under steady-state conditions (16 h, 20 degrees C) using different calf testis membrane preparations having similar receptor characteristics. Each /sup 125/I-hFSH preparation was characterized for maximum bindability, specific activity of bindable radioligand as determined by self-displacement analysis, and by determination of Ka and Rt. Incorporation of /sup 125/I into FSH was relatively constant over the large number of experiments (62.4 +/- 6.4 microCi/micrograms; n = 23). By comparison, however, specific radioactivity of the receptor bindable fraction of /sup 125/I-hFSH was related to the lot of /sup 125/I utilized, and was significantly (P less than or equal to 0.01) lower and more variable (28.7 +/- 10.5 microCi/micrograms). Maximum bindability of /sup 125/I-hFSH was not correlated to specific activity (r = 0.06) but was negatively correlated to hFSH /sup 125/I incorporation (r = -0.47; P less than or equal to 0.05). These observations demonstrate the need to assess the quality of each batch of radioligand before undertaking radioligand-receptor assays and suggest that differences in Na/sup 125/I lots affect specific radioactivity of the radioligand and its receptor binding characteristics.

  19. Follicle-stimulating hormone receptor (FSHR) alternative skipping of exon 2 or 3 affects ovarian response to FSH

    PubMed Central

    Karakaya, Cengiz; Guzeloglu-Kayisli, Ozlem; Hobbs, Rebecca J.; Gerasimova, Tsilya; Uyar, Asli; Erdem, Mehmet; Oktem, Mesut; Erdem, Ahmet; Gumuslu, Seyhan; Ercan, Deniz; Sakkas, Denny; Comizzoli, Pierre; Seli, Emre; Lalioti, Maria D.

    2014-01-01

    Genes critical for fertility are highly conserved in mammals. Interspecies DNA sequence variation, resulting in amino acid substitutions and post-transcriptional modifications, including alternative splicing, are a result of evolution and speciation. The mammalian follicle-stimulating hormone receptor (FSHR) gene encodes distinct species-specific forms by alternative splicing. Skipping of exon 2 of the human FSHR was reported in women of North American origin and correlated with low response to ovarian stimulation with exogenous follicle-stimulating hormone (FSH). To determine whether this variant correlated with low response in women of different genetic backgrounds, we performed a blinded retrospective observational study in a Turkish cohort. Ovarian response was determined as low, intermediate or high according to retrieved oocyte numbers after classifying patients in four age groups (<35, 35–37, 38–40, >40). Cumulus cells collected from 96 women undergoing IVF/ICSI following controlled ovarian hyperstimulation revealed four alternatively spliced FSHR products in seven patients (8%): exon 2 deletion in four patients; exon 3 and exons 2 + 3 deletion in one patient each, and a retention of an intron 1 fragment in one patient. In all others (92%) splicing was intact. Alternative skipping of exons 2, 3 or 2 + 3 were exclusive to low responders and was independent of the use of agonist or antagonist. Interestingly, skipping of exon 3 occurs naturally in the ovaries of domestic cats—a good comparative model for human fertility. We tested the signaling potential of human and cat variants after transfection in HEK293 cells and FSH stimulation. None of the splicing variants initiated cAMP signaling despite high FSH doses, unlike full-length proteins. These data substantiate the occurrence of FSHR exon skipping in a subgroup of low responders and suggest that species-specific regulation of FSHR splicing plays diverse roles in mammalian ovarian function. PMID

  20. Effects of paint thinner exposure on serum LH, FSH and testosterone levels and hypothalamic catecholamine contents in the male rat.

    PubMed

    Yilmaz, B; Kutlu, S; Canpolat, S; Sandal, S; Ayar, A; Mogulkoc, R; Kelestimur, H

    2001-02-01

    We have investigated the effects of thinner inhalation on serum LH, FSH and testosterone levels together with changes in hypothalamic catecholaminergic system in the male rat. A control group inhaled normal air ventilation. The remaining animals were divided into two groups and exposed to paint thinner in a glassy cage for 15 or 30 d. Toluene concentration (the largest constituent in thinner, 66%) was set at 3000 ppm in the inhalation air. At the end, all animals were decapitated and blood samples obtained. Serum LH and FSH levels were measured by RIA and testosterone by enzyme immunoassay. Following removal of brains on dry ice, medial preoptic area, suprachiasmatic nucleus, median eminence and arcuate nucleus were isolated by micropunch technique. Noradrenaline, 3,4-dihydroxyphenylglycol (DHPG) and dopamine concentrations of these hypothalamic areas were determined by HPLC-ECD. Fifteen-day thinner inhalation significantly suppressed serum LH and testosterone levels in parallel (p<0.001) compared to control group values (LH: 0.77+/-0.07; testosterone: 2.67+/-0.39). Thirty-day exposure markedly decreased LH levels (p<0.001), but surprisingly had no significant effect on testosterone. Serum FSH levels were not significantly altered in either group. Thinner inhalation for 15 or 30 d did not cause any significant change in noradrenaline, DHPG or dopamine concentrations in the hypothalamic regions examined (except in the arcuate nucleus). These results suggest that paint thinner has an anti-gonadotropic effect and may cause long-term endocrine disturbances in the male. It is thought that the hypothalamic catecholaminergic system is not involved in thinner inhibition of LH and testosterone secretion. PMID:11217085

  1. Superovulation in ewes by a single injection of pFSH dissolved in polyvinylpyrrolidone (PVP): effects of PVP molecular weight, concentration and schedule of treatment.

    PubMed

    D'Alessandro, A G; Martemucci, G; Colonna, M A; Borghese, A; Terzano, M G; Bellitti, A

    2001-03-30

    Three experiments were carried out to evaluate induction in ewes of superovulation and embryo production by a single injection of a porcine pituitary extract (pFSH) dissolved in polyvinylpyrrolidone (PVP), investigating the effects of PVP molecular weight and its concentration (Experiment I), time and method of treatment (Experiments II and III). All ewes were synchronized for estrus by vaginal sponges impregnated with fluorogestone acetate (FGA; 30 mg, 9 days) plus PGF(2alpha) (Cloprostenol, 50 microg, 48h before sponge removal - s.r.), and superovulated by 250 IU pFSH. In Experiment I, 60 Gentile di Puglia ewes were subdivided into five experimental groups (n = 12): Group A, the control, received six decreasing intramuscular (i.m.) doses of pFSH, 12 h apart, beginning 48h before s.r.; Groups B and C were given 48 h before s.r. a single i.m. injection of pFSH dissolved in PVP with MW = 10,000, respectively, at concentrations of 15 and 30% w/v; Groups D and E received the same treatments as for B and C using PVP with MW = 40,000. None of the pFSH-PVP treatments were effective in inducing superovulation. In Experiment II, 22 Leccese ewes were subdivided into two groups (n = 11): Group A, control received i.m. four decreasing doses of pFSH, beginning 24 h before s.r., 12h apart; Group B was given a single i.m. injection of pFSH dissolved in PVP (MW = 40,000 at 30% w/v), 24 h before s.r. The pFSH-PVP treatment provided an ovulation rate similar to the control and tended to enhance embryo yield (4.4 versus 2.4, P>0.05). In Experiment III, 60 Leccese ewes were subdivided into six treatment groups (n = 10). Groups A and D served as controls and received i.m. 12 h apart, six doses (from 48 h before s.r.) and four doses (from 24h before s.r.) of pFSH, respectively. Groups B and C were treated by a single injection of pFSH in PVP (MW = 10,000; 30% w/v) 48 h before s.r., respectively by i.m. or subcutaneous (s.c.) administration. Groups E and F received the same treatments

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

    SciTech Connect

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

    2013-07-01

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

  3. Impact of infertility regimens on breast cancer cells: FSH and LH lack a direct effect on breast cell proliferation in vitro

    PubMed Central

    Boukaidi, Samir Alexandre; Cooley, Anne; Hardy, Ashley; Matthews, Laura; Zelivianski, Stanislav; Jeruss, Jacqueline S.

    2011-01-01

    OBJECTIVE To examine the impact of hormones used for controlled ovarian hyperstimulation (COH) on normal and malignant breast cell growth and proliferation. DESIGN In vitro study of cultured normal and malignant breast cell lines. SETTING Academic medical center INTERVENTIONS Normal and malignant breast cell lines were cultured in two- (2D) and three-dimensional (3D) systems and treated with follicle-stimulating hormone (FSH), luteinizing hormone (LH), or FSH with LH or human chorionic gonadotropin (hCG). MAIN OUTCOME MEASURES Effects of treatment on cell proliferation in 2D culture using the MTS assay and on colony growth in 3D culture. RESULTS Compared with untreated cells, normal MCF-10A cells showed a decrease in proliferation and colony size when exposed to a combination of FSH and hCG. HCC 1937 cells treated with FSH and LH also showed a decrease in colony growth but no change in proliferation. None of the treatments had an effect on the proliferation or colony size of the MCF-7 cells. CONCLUSION FSH, LH, and hCG do not appear to cause an increase in cell proliferation or colony growth in either normal or malignant mammary epithelial cell lines. The potential risk for mammary cell transformation associated with these agents may be related to indirect endocrine effects on breast cell physiology. PMID:22188984

  4. An unbalanced translocation unmasks a recessive mutation in the follicle-stimulating hormone receptor (FSHR) gene and causes FSH resistance

    PubMed Central

    Kuechler, Amla; Hauffa, Berthold P; Köninger, Angela; Kleinau, Gunnar; Albrecht, Beate; Horsthemke, Bernhard; Gromoll, Jörg

    2010-01-01

    Follicle-stimulating hormone (FSH) mediated by its receptor (FSHR) is pivotal for normal gametogenesis. Inactivating FSHR mutations are known to cause hypergonadotropic hypogonadism with disturbed follicular maturation in females. So far, only very few recessive point mutations have been described. We report on a 17-year-old female with primary amenorrhea, hypergonadotropic hypogonadism and disturbed folliculogenesis. Chromosome analysis detected a seemingly balanced translocation 46,XX,t(2;8)(p16.3or21;p23.1)mat. FSHR sequence analysis revealed a novel non-synonymous point mutation in exon 10 (c.1760C>A, p.Pro587His), but no wild-type allele. The mutation was also found in the father, but not in the mother. Furthermore, molecular-cytogenetic analyses of the breakpoint region on chromosome 2 showed the translocation to be unbalanced, containing a deletion with one breakpoint within the FSHR gene. The deletion size was narrowed down by array analysis to approximately 163 kb, involving exons 9 and 10 of the FSHR gene. Functional studies of the mutation revealed the complete lack of signal transduction presumably caused by a changed conformational structure of transmembrane helix 6. To our knowledge, this is the first description of a compound heterozygosity of an inactivating FSHR point mutation unmasked by a partial deletion. This coincidence of two rare changes caused clinical signs consistent with FSH resistance. PMID:20087398

  5. Novel Action of FSH on Stem Cells in Adult Mammalian Ovary Induces Postnatal Oogenesis and Primordial Follicle Assembly.

    PubMed

    Bhartiya, Deepa; Parte, Seema; Patel, Hiren; Sriraman, Kalpana; Zaveri, Kusum; Hinduja, Indira

    2016-01-01

    Adult mammalian ovary has been under the scanner for more than a decade now since it was proposed to harbor stem cells that undergo postnatal oogenesis during reproductive period like spermatogenesis in testis. Stem cells are located in the ovary surface epithelium and exist in adult and menopausal ovary as well as in ovary with premature failure. Stem cells comprise two distinct populations including spherical, very small embryonic-like stem cells (VSELs which express nuclear OCT-4 and other pluripotent and primordial germ cells specific markers) and slightly bigger ovarian germ stem cells (OGSCs with cytoplasmic OCT-4 which are equivalent to spermatogonial stem cells in the testes). These stem cells have the ability to spontaneously differentiate into oocyte-like structures in vitro and on exposure to a younger healthy niche. Bone marrow may be an alternative source of these stem cells. The stem cells express FSHR and respond to FSH by undergoing self-renewal, clonal expansion, and initiating neo-oogenesis and primordial follicle assembly. VSELs are relatively quiescent and were recently reported to survive chemotherapy and initiate oogenesis in mice when exposed to FSH. This emerging understanding and further research in the field will help evolving novel strategies to manage ovarian pathologies and also towards oncofertility. PMID:26635884

  6. Novel Action of FSH on Stem Cells in Adult Mammalian Ovary Induces Postnatal Oogenesis and Primordial Follicle Assembly

    PubMed Central

    Bhartiya, Deepa; Parte, Seema; Patel, Hiren; Sriraman, Kalpana; Zaveri, Kusum; Hinduja, Indira

    2016-01-01

    Adult mammalian ovary has been under the scanner for more than a decade now since it was proposed to harbor stem cells that undergo postnatal oogenesis during reproductive period like spermatogenesis in testis. Stem cells are located in the ovary surface epithelium and exist in adult and menopausal ovary as well as in ovary with premature failure. Stem cells comprise two distinct populations including spherical, very small embryonic-like stem cells (VSELs which express nuclear OCT-4 and other pluripotent and primordial germ cells specific markers) and slightly bigger ovarian germ stem cells (OGSCs with cytoplasmic OCT-4 which are equivalent to spermatogonial stem cells in the testes). These stem cells have the ability to spontaneously differentiate into oocyte-like structures in vitro and on exposure to a younger healthy niche. Bone marrow may be an alternative source of these stem cells. The stem cells express FSHR and respond to FSH by undergoing self-renewal, clonal expansion, and initiating neo-oogenesis and primordial follicle assembly. VSELs are relatively quiescent and were recently reported to survive chemotherapy and initiate oogenesis in mice when exposed to FSH. This emerging understanding and further research in the field will help evolving novel strategies to manage ovarian pathologies and also towards oncofertility. PMID:26635884

  7. Differences between follicular waves 1 and 2 in patterns of emergence of 2-mm follicles, associated FSH surges, and ovarian vascular perfusion in heifers.

    PubMed

    Ginther, O J; Siddiqui, M A R; Baldrighi, J M; Wolf, C A; Greene, J M

    2015-10-01

    The emergence (first detection) of 2-mm follicles, FSH surges, and ovarian vascular perfusion for follicular wave 1 and surge 1 (n = 26) and wave 2 and surge 2 (n = 25) were studied daily in heifers. The day the future dominant follicle was closest to 5.5 mm was designated Day 0 for each wave. In wave 1, many 2-mm follicles (41%) emerged on Days -5 to -3, whereas FSH surge 1 did not begin until Day -3. Concentration of FSH increased abruptly in 1 day to a peak on the day of maximal number of emerging 2-mm follicles, although the day of maximal number relative to Day 0 differed among individuals. The first emergence of 2-mm follicles in wave 2 occurred concurrently with the first increase in the FSH of surge 2. In wave 1, ovarian resistance to vascular perfusion was negatively correlated (r = -0.48, P < 0.05) with a number of 2-mm follicles on Days -4 to -1 for ovaries that did not contain the preovulatory follicle; vascular perfusion increased with an increase in the number of small follicles. The following hypotheses were supported for wave 1 but not for wave 2: (1) an increase in the number of emerging 2-mm follicles of a follicular wave occurs before the beginning of an increase in FSH, (2) the day of maximal number of emerging 2-mm follicles occurs concurrently with an abrupt FSH increase on different days among individuals, and (3) the association between the number of emerging 2-mm follicles and the extent of ovarian vascular perfusion is positive. PMID:26159090

  8. Effects of ovum pick-up frequency and FSH stimulation: a retrospective study on seven years of beef cattle in vitro embryo production.

    PubMed

    De Roover, R; Feugang, J M N; Bols, P E J; Genicot, G; Hanzen, Ch

    2008-04-01

    The aim of this retrospective study was to compare the number of follicles, cumulus oocyte complexes (COCs) and cultured In Vitro Produced (IVP) embryos obtained from 1396 non-stimulated Ovum Pick-up (OPU) sessions on 81 donor animals in a twice weekly OPU scheme. Results were obtained from 640 sessions following FSH-LH superstimulation, on 112 donors subjected to OPU once every 2 weeks. The stimulation protocol started with the insertion of an ear implant containing 3 mg norgestomet (Crestar, Intervet, Belgium) 8 days before puncture (day -8). The dominant follicle was ablated by ultrasound-guided follicle puncture on day -6. On day -3 and day -2, cows were injected with FSH (Ovagen, ICP) twice daily (8 am to 8 pm), i.e. a total dose of 160 mug FSH and 40 mug LG per donor per stimulation cycle. Animals were punctured 48 h after the last FSH injection (day 0). Progesterone implants were removed the next day. Stimulated donor cows were treated with this protocol at 14-day intervals. Follicles were visualized with a Dynamic Imaging ultrasound scanner, equipped with a 6.5 MHz sectorial probe. Follicles were punctured with 55 cm long, 18 gauge needles at an aspiration pressure corresponding to a flow rate of 15 ml/min. Cumulus oocyte complexes were recovered and processed in a routine IVF set-up. Results demonstrate that, expressed per session, FSH stimulation prior to OPU increases production efficiency with significantly more follicles punctured and oocytes retrieved. However, when overall results during comparable 2-week periods are considered (four non-stimulated sessions vs one stimulated), more follicles are punctured and more oocytes are retrieved using the non-stimulated protocol. No significant differences in the number of cultured embryos could be detected, indicating that FSH/LH stimulation prior to OPU might have a positive effect on in vitro oocyte developmental competence as more embryos are cultured with less, presumably better-quality, oocytes. PMID

  9. Effects of 31 kDa bovine inhibin on FSH and LH in rat pituitary cells in vitro: antagonism of gonadotrophin-releasing hormone agonists.

    PubMed

    Farnworth, P G; Robertson, D M; de Kretser, D M; Burger, H G

    1988-11-01

    The effects of 31 kDa bovine inhibin on the release of FSH and LH stimulated by gonadotrophin-releasing hormone (GnRH) or its agonist analogue buserelin have been studied using 5-day-old cultures of pituitary cells prepared from adult male Sprague-Dawley rats. Exposure of cultures to increasing concentrations of inhibin for 3 days before and during a 4-h stimulation with GnRH resulted in the progressive suppression of both basal and stimulated gonadotrophin release. At the highest inhibin concentrations FSH release was abolished (inhibin median inhibitory concentration (IC50) = 0.15 U/ml) whereas LH release was suppressed by 75% (IC50 = 0.93 U/ml). To correct for the reduced size of the FSH pool resulting from inhibin pretreatment, the amount of FSH or LH released by an agonist was expressed as a proportion of the total hormone available for release in each case. Following this adjustment, concentrations of inhibin producing maximal effects increased the GnRH median effective concentration for FSH release 4.1-fold and that for LH release 2.2-fold, with inhibin IC50 values of 0.45 and 0.32 U/ml respectively. Inhibin also suppressed the maximum proportion of both FSH and LH that excess GnRH released in 4 h by 36%, with IC50 values of 0.53 and 0.76 U/ml respectively. These effects were not changed by reduction of the inhibin pretreatment period from 3 days to 1 day or by exclusion of inhibin during the stimulation period. After a 3-day pretreatment, inhibin inhibited gonadotrophin release by buserelin less effectively than that by GnRH, but the pattern of antagonism was the same.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3143796

  10. Peroxisome Proliferator–Activated Receptor-γ Mediates Bisphenol A Inhibition of FSH-Stimulated IGF-1, Aromatase, and Estradiol in Human Granulosa Cells

    PubMed Central

    Kwintkiewicz, Jakub; Nishi, Yoshihiro; Yanase, Toshihiko; Giudice, Linda C.

    2010-01-01

    Background Bisphenol A (BPA), a chemical used as a plasticizer, is a potent endocrine disruptor that, even in low concentrations, disturbs normal development and functions of reproductive organs in different species. Objectives We investigated whether BPA affects human ovarian granulosa cell function. Methods We treated KGN granulosa cells and granulosa cells from subjects undergoing in vitro fertilization (IVF) with follicle-stimulating hormone (FSH), BPA, or BPA plus FSH in a dose- and time-dependent manner. We then evaluated expression of insulin-like growth factor 1 (IGF-1), aromatase, and transcription factors known to mediate aromatase induction by FSH [including steroidogenic factor-1 (SF-1), GATA4, cAMP response element binding protein-1 (CREB-1), and peroxisome proliferator–activated receptor-γ (PPARγ)], as well as 17β-estradiol (E2) secretion. KGN cells were transfected with a PPARγ-containing vector, followed by assessment of aromatase and IGF-I expression. Results BPA reduced FSH-induced IGF-1 and aromatase expression and E2 secretion in a dose-dependent fashion. Similar effects on aromatase were observed in IVF granulosa cells. SF-1 and GATA4, but not CREB-1, were reduced after BPA treatment, although PPARγ, an inhibitor of aromatase, was significantly up-regulated by BPA in a dose-dependent manner, with simultaneous decrease of aromatase. Overexpression of PPARγ in KGN cells reduced FSH-stimulated aromatase and IGF-1 mRNAs, with increasing concentrations of the transfected expression vector, mimicking BPA action. Also, BPA reduced granulosa cell DNA synthesis without changing DNA fragmentation, suggesting that BPA does not induce apoptosis. Conclusions Overall, the data demonstrate that BPA induces PPARγ, which mediates down-regulation of FSH-stimulated IGF-1, SF-1, GATA4, aromatase, and E2 in human granulosa cells. These observations support a potential role of altered steroidogenesis and proliferation within the ovarian follicular

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  13. Interaction of seasonal and ovarian factors in the regulation of LH and FSH secretion in the mare.

    PubMed

    Garcia, M C; Freedman, L J; Ginther, O J

    1979-01-01

    A working hypothesis for the regulation of LH secretion in the mare is postulated which involves the following two components: (1) a primary central nervous system (CNS)-pituitary component which is responsible for a basal circannual LH rhythm, entrained to an environmental 'Zeitgeber' (most probably photoperiod) and independent of ovarian influences, and (2) a secondary ovarian (steroidal) component which modifies the primary rhythm during the ovulatory season. This hypothesis does not seem to apply in its entirety to FSH secretion; the CNS-pituitary component is demonstrable within the first year after ovariectomy in mares and then seems to disappear, and the ovarian component probably involves factors other than steroids on the basis of present evidence. PMID:289780

  14. Comparison of recombinant human follicle stimulating hormone (rhFSH), human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) on semen parameters after varicocelectomy: a randomized clinical trial

    PubMed Central

    Amirzargar, Mohammad Ali; Yavangi, Mahnaz; Basiri, Abbass; Hosseini Moghaddam, Sayyed Mahdi; Babbolhavaeji, Hooshang; Amirzargar, Nasibeh; Amirzargar, Hossein; Moadabshoar, Leila

    2012-01-01

    Background: The most frequent physical finding in infertile men is varicocele, in which one of the mechanisms that can affect seminal parameters is oxidative stress. Objective: Our study aimed, for the first time, to compare the efficacy of recombinant human follicle-stimulating hormone (rhFSH), human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) on sperm parameters and fertility after varicocelectomy. Materials and Methods: 113 infertile men with varicocele were divided into four groups. Group A received HCG 5000 IU weekly, group B received HMG 75 IU three times a week, group C received rhFSH 75 IU three times a week and group D received no medical treatment after varicocelectomy. Results: After three months, in group A sperm morphology improved (p=0.007), causing a 32% pregnancy rate. In group B, sperm motility (p=0.023) and morphology (p=0.014) improved, causing a 57% pregnancy rate. In group C, all of the investigated semen parameters increased (p<0.05), causing a 62.5% pregnancy rate. Only rhFSH improved sperm concentrations to >20×106 mL (p=0.027). In group D, sperm morphology increased (p=0.038), but other parameters remained unchanged and no pregnancies occurred. Conclusion: It can be concluded that drugs can reduce induction time for spermatogenesis and fertility in comparison with varicocelectomy alone. For these purposes, rhFSH is more effective than other drugs. PMID:25246910

  15. Stimulation of LH, FSH, and luteal blood flow by GnRH during the luteal phase in mares.

    PubMed

    Castro, T; Oliveira, F A; Siddiqui, M A R; Baldrighi, J M; Wolf, C A; Ginther, O J

    2016-03-01

    A study was performed on the effect of a single dose per mare of 0 (n = 9), 100 (n = 8), or 300 (n = 9) of GnRH on Day 10 (Day 0 = ovulation) on concentrations of LH, FSH, and progesterone (P4) and blood flow to the CL ovary. Hormone concentration and blood flow measurements were performed at hours 0 (hour of treatment), 0.25, 0.5, 1, 2, 3, 4, and 6. Blood flow was assessed by spectral Doppler ultrasonography for resistance to blood flow in an ovarian artery before entry into the CL ovary. The percentage of the CL with color Doppler signals of blood flow was estimated from videotapes of real-time color Doppler imaging by an operator who was unaware of mare identity, hour, or treatment dose. Concentrations of LH and FSH increased (P < 0.05) at hour 0.25 and decreased (P < 0.05) over hours 1 to 6; P4 concentration was not altered by treatment. Blood flow resistance decreased between hours 0 and 1, but the decrease was greater (P < 0.05) for the 100-μg dose than for the 300-μg dose. The percentage of CL with blood flow signals increased (P < 0.05) between hours 0 and 1 with no significant difference between the 100- and 300-μg doses. The results supported the hypothesis that GnRH increases LH concentration, vascular perfusion of the CL ovary, and CL blood flow during the luteal phase; however, P4 concentration was not affected. PMID:26600292

  16. Superovulatory response to gonadotrophin FSH/LH treatment and effect of progestin supplement to recipients on survival of transferred vitrified embryos in goats.

    PubMed

    D'Alessandro, Angela Gabriella; Martemucci, Giovanni

    2016-01-15

    Two experiments were carried out in goats to evaluate the effects of the FSH/LH ratio during treatment on ovarian response and embryo production (experiment 1) and the efficiency of progestin supplementation on pregnancy and the survival of vitrified embryos (experiment 2). In experiment 1, 30 goats were synchronized and allocated to 2 groups (n = 15) corresponding to the following superovulatory treatments with p-FSH (250 IU, over 3 days) having different doses of purified FSH and LH: (group A) control, FSH/LH ratio of 1, kept constant during treatment; (group B) FSH/LH ratio of 2 and daily FSH/LH ratio of 5.0:1.0:0.3 for the first, second, and third days of treatment, respectively. Ovarian response and embryo production were assessed 7.5 days after estrus. In experiment 2, 46 vitrified blastocysts from p-FSH-superovulated donors were transferred to 26 recipients (2 blastocysts per goat) 7.5 days after estrus. The recipients were synchronized with donors and allocated to 2 experimental groups (n = 13). Group C received progestin supplement as fluorgestone acetate (FGA) inserted into the vagina at the time of embryo transfer, replaced with a new one 16 days later, and maintained until the 45th day of pregnancy; group D, no treatment (control). Pregnancy was diagnosed by transrectal ultrasound scanning on Days 30 and 45 after estrus and followed to term. The results indicated that the increase in FSH/LH ratio from 1 to 2 with decreasing daily FSH/LH (treatment B) did not improve the superovulatory response. Superovulatory treatment A (control) advanced (P < 0.05) the onset of estrus and showed a higher ovulation rate compared to group B (14.9 vs. 10.9; P < 0.05). Fertilization rate, embryo yield, and mean number of transferable embryos in group A (7.5) were higher (P < 0.05) than those in group B (3.2). Recipient goats receiving progestin supplementation (group C) showed a higher (P < 0.05) pregnancy rate and embryo survival (kids born per embryos

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

    PubMed

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

    2015-04-01

    Follicle-stimulating hormone (FSH) and triiodothyronine (T3) are known regulatory factors of spermatogenesis initiation. Hyperstimulation of both hormones evokes regressional changes in connexin 43 expression and the seminiferous epithelium in young rats during testicular maturation. However, separate treatments with T3 reduce Sertoli cell number, which seems to be closely connected with the maturation of connexin 43 gap junctions. FSH elevates Sertoli cell number and function, but this effect may take place regardless of the presence of connexin 43-dependent intercellular communication. The aim of the study was to evaluate the later effects of such treatments. Newborn, male Wistar rats were divided randomly into experimental groups receiving daily subcutaneous injections of either 7.5 IU/animal FSH, or 100 mg/kg b.w. T3, or both substances or the same volume of vehicle (control group) until day 15 of life. The animals were sacrificed on day 50. Morphometric analysis and immunohistochemical reactions were performed using antibodies against Vimentin, Proliferating Cell Nuclear Antigen and Connexin 43 in the testis. Sertoli cell count, efficiency of spermatogenesis, and hormonal pattern were examined. Disturbances in the connexin 43 expression reduced the number of Sertoli cells, the efficiency of spermatogenesis and impaired endocrine function of testes in adult rats treated with FSH and T3 during puberty. Stimulation with FSH alone increased Sertoli cell number, but was associated with a negative effect on cell-to-cell connexin 43-dependent communication, with a consequential reduction of spermatogenesis efficiency. J. Exp. Zool. 323A: 256-265, 2015. © 2015 Wiley Periodicals, Inc. PMID:25739512

  18. Seasonal patterns of basal and GnRH-induced LH, FSH and testosterone secretion in Eld's deer stags (Cervus eldi thamin).

    PubMed

    Monfort, S L; Brown, J L; Wood, T C; Wemmer, C; Vargas, A; Williamson, L R; Wildt, D E

    1993-07-01

    Plasma LH, FSH and testosterone were measured in blood samples collected via remote catheterization from six adult Eld's deer stags every 10 min for 8 h before and 2 h after GnRH (1 microgram kg-1, i.v.) administration. Blood samples were collected within 2 weeks of the summer solstice (21 June), autumn equinox (22 September), winter solstice (21 December) and spring equinox (20 March). Marked seasonal variations in basal LH, FSH and testosterone concentrations were observed. From autumn, well-defined LH pulses were temporally associated with small, but detectable pulses in testosterone. During the winter transition into the breeding season, episodic LH pulses were also temporally associated with corresponding testosterone surges that lasted 2-3 h. High amplitude, low frequency testosterone surges were also observed during the spring, but often in the absence of detectable LH pulses. Basal LH and testosterone concentrations decreased during the summer and, although LH pulses were detected, associated testosterone pulses were absent. Only 37% of LH pulses occurred coincidentally with FSH pulses, and FSH pulses were generally less prominent. The increases in LH and FSH above basal concentrations after GnRH treatment were significant (P < 0.05) for all seasons. Increases in testosterone after GnRH treatment were greatest during the winter and spring, but testosterone also increased to a lesser extent during the autumn (P < 0.05). In contrast, testosterone concentrations were not different before and after GnRH treatment during summer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8410814

  19. A Preliminary Report of A Low-Dose Step-Up Regimen of Recombinant Human FSH for Young Women Undergoing Ovulation Induction with IUI

    PubMed Central

    Lu, Hsin-Fen; Peng, Fu-Shiang; Chen, Shee-Uan; Chiu, Bao-Chu; Yeh, Szu-Hsing; Hsiao, Sheng-Mou

    2016-01-01

    Background The aim of this study was to evaluate the efficacy and safety of a recombinant human follicle stimulating hormone (r-FSH) low-dose step-up regimen for controlled ovarian hyperstimulation in patients undergoing ovulation induction (OI) with intrauterine insemination (IUI). Materials and Methods The study was conducted in the Department of Obstetrics and Gynecology, Far Eastern Memorial Hospital, New Taipei, Taiwan. In this prospective, observational study, consecutive infertile women (20-35 years) with regular menstrual cycles and a normal baseline FSH level were prospectively enrolled between January 2010 and September 2010. A starting dose of 112.5 IU/day r-FSH was administered on day 3 and increased by 37.5 IU/day every 2 days until a follicle ≥11 mm in diameter was present. Recombinant human chorionic gonadotropin (r-hCG) was administered when a follicle ≥18 mm was noted. Monifollicular development was defined as only one follicle with a diameter ≥16 mm. Clinical pregnancy was defined as a pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs. Results A total of 29 women and 30 cycles were included. The mean daily dose of r-FSH to achieve a follicle of ≥11 mm in diameter was 131.3 ± 23.6 IU and the mean total dose was 1030.0 ± 383.2 IU. Approximately 41% of the cycles were monofollicular. Clinical pregnancy was observed in 9 (30.0%) cycles, and a fetal heart beat was observed in 7 (23.3%). There were no multiple pregnancies. Mild ovarian hyperstimulation syndrome, which was resolved with conservative management, was observed in 3 (10.0%) cycles. Conclusion This r-FSH low-dose step-up regimen seems to be a feasible and practical method for OI in younger infertile women undergoing IUI. PMID:26985331

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

    PubMed

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

    2016-03-01

    Women of advanced maternal age (AMA) (age ≥ 35) have increased rates of infertility, miscarriages, and trisomic pregnancies. Collectively these conditions are called "egg infertility." A root cause of egg infertility is increased rates of oocyte aneuploidy with age. AMA women often have elevated endogenous FSH. Female senescence-accelerated mouse-prone-8 (SAMP8) has increased rates of oocyte spindle aberrations, diminished fertility, and rising endogenous FSH with age. We hypothesize that elevated FSH during the oocyte's FSH-responsive growth period is a cause of abnormalities in the meiotic spindle. We report that eggs from SAMP8 mice treated with equine chorionic gonadotropin (eCG) for the period of oocyte growth have increased chromosome and spindle misalignments. Activin is a molecule that raises FSH, and ActRIIB:Fc is an activin decoy receptor that binds and sequesters activin. We report that ActRIIB:Fc treatment of midlife SAMP8 mice for the duration of oocyte growth lowers FSH, prevents egg chromosome and spindle misalignments, and increases litter sizes. AMA patients can also have poor responsiveness to FSH stimulation. We report that although eCG lowers yields of viable oocytes, ActRIIB:Fc increases yields of viable oocytes. ActRIIB:Fc and eCG cotreatment markedly reduces yields of viable oocytes. These data are consistent with the hypothesis that elevated FSH contributes to egg aneuploidy, declining fertility, and poor ovarian response and that ActRIIB:Fc can prevent egg aneuploidy, increase fertility, and improve ovarian response. Future studies will continue to examine whether ActRIIB:Fc works via FSH and/or other pathways and whether ActRIIB:Fc can prevent aneuploidy, increase fertility, and improve stimulation responsiveness in AMA women. PMID:26713784

  1. Ultrasonographic determination of caput epididymis diameter is strongly predictive of obstruction in the genital tract in azoospermic men with normal serum FSH.

    PubMed

    Pezzella, A; Barbonetti, A; Micillo, A; D'Andrea, S; Necozione, S; Gandini, L; Lenzi, A; Francavilla, F; Francavilla, S

    2013-01-01

    The relationship between epididymis ultrasonography (US) and infertility is poorly defined probably owing to lack of objective and reproducible criteria of US evaluation. Here, we evaluated US size of testes, caput and of corpus epididymis in infertile men: 165 with total sperm count ≥39 × 10(6) , 187 with total sperm count <39 × 10(6) and 75 azoospermic men. Blood levels of follicle stimulating hormone (FSH) and of total testosterone were also evaluated. US measures obtained using a high-frequency (12 MHz) linear array transducer, included the mean value of bilateral testicular volumes (mL) (Testes-M), of bilateral longitudinal diameter of caput epididymis (mm) (Caput-M) and of the bilateral antero-posterior diameter of the corpus measured on a longitudinal scan (mm) (Corpus-M). Testicular histology of azoospermic men was obtained and the percentage of seminiferous tubules with elongated spermatids (%T) was used to classify cases with normal spermatogenesis (obstructive azoospermia) (n = 17; %T ≥ 80), or with deranged spermatogenesis (n = 58; %T ≤ 33). Caput-M was correlated with Testes-M (p = 0.0003; r = 0.17) and with FSH serum levels (p = 0.024; r = -0.14) but not with semen parameters. Caput-M but not Corpus-M values resulted greater in obstructive azoospermia compared with other groups, but difference was not significant. Cut-off values of Testes-M, Caput-M and of FSH correctly classified cases of obstructive azoospermia (AUC > 0.5). A patient with FSH < 7.8 IU/mL had a 63.6% chance (CI 40.1-83.2%) of being affected by obstructive azoospermia. US Caput-M ≥10.85 mm, which represented the cut-off value with the highest combination of sensitivity (58.8%, CI 32.9-81.6%) and specificity (91.4%, CI 81.0-97.1%) applied in cases with FSH < 7.8 IU/mL increased the probability for obstructive azoospermia from 63.6% up to 92.3% (CI 76.5-98.8%). US evaluation of the caput epididymis diameter helped in predicting the obstructive origin

  2. Influence of FSH and hCG on the resumption of meiosis of bovine oocytes surrounded by cumulus cells connected to membrana granulosa.

    PubMed

    van Tol, H T; van Eijk, M J; Mummery, C L; van den Hurk, R; Bevers, M M

    1996-10-01

    Cumulus oocyte complexes (COCs) and cumulus oocyte complexes connected to a piece of the membrane granulosa (COCGs) were isolated from bovine antral follicles with a diameter of 2 to 8 mm. After culture of COCGs without gonadotrophic hormones for 22 hr approximately 50% of the oocytes were still in the germinal vesicle (GV) stage. Histology of the COCGs showed that the pieces of the membrana granulosa were free of thecal cells and parts of the basal membrane. This indicates that the membrana granulosa solely inhibits the progression of meiosis. To investigate the effect of gonadotropins on the resumption of meiosis of oocytes from small and medium sized antral follicles, COCs and COCGs were cultured with or without rec-hFSH or hCG. Addition of 0.05 IU rec-hFSH to the culture medium of COCGs resulted in germinal vesicle breakdown in 97.8% of the oocytes compared to 46% in the control group, and an increase of the diameter of the COCs (479 microns vs. 240 microns in the control group). Addition of 0.05 IU hCG to the culture medium had no effect on nuclear maturation (47.2% GV vs. 48.5% GV in the control group) nor on cumulus expansion (246 microns vs. 240 microns in the control group). RT-PCR on cDNA of the follicular wall, cumulus cells, granulosa cells, COCs, and oocytes revealed that mRNA for FSH receptor was present in all cell types except oocytes. mRNA of the LH receptor was detected exclusively in thecal cells. Nucleotide sequence analysis and alignment of the cloned PCR products showed the presence of two isoforms of the FSH receptor mRNA and two isoforms of the LH receptor mRNA. It is concluded that, in vitro, resumption of meiosis of oocytes, originating from small and medium sized antral follicles and meiotically arrested by the membrana granulosa, is triggered by FSH and not by LH. This is supported by the fact that receptors for FSH, but not for LH, are transcribed in the cumulus and granulosa cells of these follicles. PMID:8914080

  3. Expression of Bone Morphogenetic Protein Receptor (BMPR) during Perinatal Ovary Development and Primordial Follicle Formation in the Hamster: Possible Regulation by FSH

    PubMed Central

    Wang, Cheng; Roy, Shyamal K.

    2009-01-01

    To understand whether bone morphogenetic protein plays any role in the formation of primordial follicles in the hamster, we examined the temporal and spatial expression of bone morphogenetic protein receptor (BMPR) mRNA and protein in embryonic (E) 13 through postnatal day (P) 15 ovarian cells and a possible regulation by FSH during the formation of primordial follicles on P8. BMPRIA and BMPRII mRNA levels were significantly higher than that of BMPR1B throughout ovary development. BMPRIA and BMPRII mRNA levels increased significantly on E14 and declined by P5 through P6. Whereas BMPRII mRNA increased again by P7, BMPRIA mRNA levels increased through P8 concurrent with primordial follicle formation. In contrast, BMPRIB mRNA levels increased greater than 10-fold on P7-9, with a further 3-fold increase by P10. BMPR proteins were low in the somatic cells and oocytes on E13 but increased progressively during postnatal development. BMPR expression in somatic cells increased markedly on P8. Whereas BMPRII expression declined by P10 and remained steady thereafter, BMPRIA protein expression fluctuated until P15 when it became low and steady. Overall, BMPRIB immunoreactivity also declined by P10 and then remained low in the interstitial cells through P15. FSH antiserum treatment on E12 significantly attenuated receptor mRNA and protein levels by P8, but equine chorionic gonadotropin replacement on P1 reversed the inhibition. Furthermore, FSH in vitro up-regulated BMPR levels in P4 ovaries. This unique pattern of BMPR expression in the oocytes and somatic cells during perinatal ovary development suggests that BMP may play a regulatory role in primordial follicle formation. Furthermore, FSH may regulate BMP action by modulating the expression of its receptors. PMID:19074578

  4. Oocytes lacking O-glycans alter follicle development and increase fertility by increasing follicle FSH sensitivity, decreasing apoptosis, and modifying GDF9:BMP15 expression.

    PubMed

    Grasa, Patricia; Ploutarchou, Panayiota; Williams, Suzannah A

    2015-02-01

    The number of eggs ovulated varies within and between species and is influenced by many variables. However, the regulatory mechanisms remain poorly understood. We previously demonstrated a key role for the oocyte because mice generating oocytes deficient in core 1-derived O-glycans ovulate ∼40-50% more eggs than Controls. Here we analyze the basis of this phenotype using Mutant [core 1 β1,3-galactosyltransferase 1 (C1galt1)(FF):zona pellucida glycoprotein 3 Cre (ZP3Cre)] and Control (C1galt1(FF)) female mice. In culture, Mutant follicles exhibited delayed antrum formation [indicative of follicle stimulant hormone (FSH) dependence] and increased sensitivity to FSH. Although the Mutant estrous cycle was extended, comprehensive endocrine changes were not observed; rather FSH, LH, inhibin B, and anti-Mullerian hormone were temporally altered, revealing estrous cycle stage-specific modifications to the hypothalamic-pituitary-gonadal axis. At proestrus, when FSH levels were decreased in Mutants, ovaries contained more, smaller, preantral follicles. Mutant follicles exhibited reduced levels of apoptosis, and both B-cell lymphoma 2 (Bcl-2) and BCL-2-associated X protein (Bax) were altered compared with Controls. Mutant ovaries also had an increase in the expression ratio of growth differentiation factor 9 (GDF9):bone morphogenetic protein 15 (BMP15) at diestrus. On the basis of these data, we propose that modified oocyte glycoproteins alter GDF9:BMP15 expression modifying follicle development resulting in the generation of more follicles. Thus, the oocyte is a key regulator of follicle development and has a crucial role in determining ovulation rate. PMID:25416550

  5. Recombinant FSH Compared to Clomiphene Citrate as the First-Line in Ovulation Induction in Polycystic Ovary Syndrome Using Newly Designed Pens: A Randomized Controlled Trial

    PubMed Central

    Hossein-Rashidi, Batool; Khandzad, Bahareh; Shahrokh-Tehraninejad, Ensieh; Bagheri, Maryam; Gorginzadeh, Mansoureh

    2016-01-01

    Objective: Since there is still controversy regarding the best first-line choice for ovulation induction (OI) other than clomiphene citrate (CC) in infertile women diagnosed with polycystic ovary syndrome (PCOS), the aim of the present study was to compare recombinant human FSH with CC as the first course of OI in these women. Materials and methods: In this pilot randomized controlled trial, 104 infertile women diagnosed with PCOS were randomized in two groups to receive either CC with the dose of 100mg per day from day 3 of a spontaneous or progestin-induced menstruation for 5 days or rFSH with the starting dose of 50 IU daily {and weekly dose increment of as low as 12.5 IU}, on the day4 of the cycle. They were assessed during a single OI course. The pregnancy rate (PR) and live birth rate (LBR) were the primary outcomes. The follicular response, endometrial thickness, cancellation of the cycles and ovarian hyper stimulation (OHSS) rate were the secondary outcomes. Results: Analyzing data of 96 patients using Chi2 and Fischer’s Exact test (44 in rFSH group and 52 in CC group), both PR and LBR were comparable in the two groups {13.6% vs. 9.6% and 11.4% vs. 9.6% respectively}, with the difference not to be significant (p > 0.05). No cases of OHSS or multiple gestations happened during the treatment course. Conclusion: It seems that rFSH is as efficacious as CC while not with more complications for the first-line OI in infertile women with PCOS. However, due to the limitations of the present study including the small population and the single cycle of treatment, our results did not come out to prove this and more studies with larger study population are needed to compare the cumulative PR and LBR. PMID:27385973

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

    PubMed

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

    2010-01-01

    The gonadal function of patients with Turner syndrome (TS) is variable. Individuals with mosaicism characterized by 45,X/46,XX or 45,X/47,XXX are more likely to experience spontaneous menarche compared with other karyotypes. Prepubertal gonadotropins of TS patients with spontaneous menarche are reportedly normal or significantly lower than those of patients with induced menarche. The present study investigated an index of spontaneous and cyclical menstruation at 10-12 years old in TS. Subjects comprised 50 patients with TS, divided into three groups: Group A (n=7), with spontaneous menarche before 16 years old and regular menstruation for at least 1 year and 6 months; Group B (n=6), with irregular menstruation since menarche leading to secondary amenorrhea despite spontaneous menarche before 16 years old; and Group C (n=37), without spontaneous breast budding before 14 years old or without spontaneous menarche before 16 years old. Karyotype, LH and FSH concentrations at 10 and 12 years old were analyzed retrospectively. Spontaneous and cyclical menstruation was more frequently observed in TS with mosaicism characterized by 45,X/46,XX or 45,X/47,XXX than in TS with other karyotypes, as previously described. Spontaneous and cyclical menstruation in TS was observed when serum FSH level was <10 mIU/mL at 12 years old, suggesting this FSH level as an index of spontaneous and cyclical menstruation in TS. PMID:20798475

  7. Extracellular Signal-regulated Kinase (ERK)-dependent Phosphorylation of Y-Box-binding Protein 1 (YB-1) Enhances Gene Expression in Granulosa Cells in Response to Follicle-stimulating Hormone (FSH).

    PubMed

    Donaubauer, Elyse M; Hunzicker-Dunn, Mary E

    2016-06-01

    Within the ovarian follicle, immature oocytes are surrounded and supported by granulosa cells (GCs). Stimulation of GCs by FSH leads to their proliferation and differentiation, events that are necessary for fertility. FSH activates multiple signaling pathways to regulate genes necessary for follicular maturation. Herein, we investigated the role of Y-box-binding protein-1 (YB-1) within GCs. YB-1 is a nucleic acid binding protein that regulates transcription and translation. Our results show that FSH promotes an increase in the phosphorylation of YB-1 on Ser(102) within 15 min that is maintained at significantly increased levels until ∼8 h post treatment. FSH-stimulated phosphorylation of YB-1(Ser(102)) is prevented by pretreatment of GCs with the PKA-selective inhibitor PKA inhibitor (PKI), the MEK inhibitor PD98059, or the ribosomal S6 kinase-2 (RSK-2) inhibitor BI-D1870. Thus, phosphorylation of YB-1 on Ser(102) is PKA-, ERK-, and RSK-2-dependent. However, pretreatment of GCs with the protein phosphatase 1 (PP1) inhibitor tautomycin increased phosphorylation of YB-1(Ser(102)) in the absence of FSH; FSH did not further increase YB-1(Ser(102)) phosphorylation. This result suggests that the major effect of RSK-2 is to inhibit PP1 rather than to directly phosphorylate YB-1 on Ser(102) YB-1 coimmunoprecipitated with PP1β catalytic subunit and RSK-2. Transduction of GCs with the dephospho-adenoviral-YB-1(S102A) mutant prevented the induction by FSH of Egfr, Cyp19a1, Inha, Lhcgr, Cyp11a1, Hsd17b1, and Pappa mRNAs and estradiol-17β production. Collectively, our results reveal that phosphorylation of YB-1 on Ser(102) via the ERK/RSK-2 signaling pathway is necessary for FSH-mediated expression of target genes required for maturation of follicles to a preovulatory phenotype. PMID:27080258

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

    PubMed Central

    2014-01-01

    Background The competence for embryonic development after IVF is low in the yak, therefore, we investigated the effects of supplementation of FSH, LH and the proteasome inhibitor MG132 in IVM media on yak oocyte competence for development after IVF. Methods In Experiment 1, yak cumulus-oocyte complexes (COCs) were in vitro matured (IVM) in TCM-199 with 20% fetal calf serum (FCS), 1 microg/mL estradiol-17beta, and different combinations of LH (50 or 100 IU/mL) and FSH (0, 1, 5, 10 microg/mL) at 38.6 degrees C, 5% CO2 in air for 24 h. Matured oocytes were exposed to frozen–thawed, heparin-capacitated yak sperm. Presumptive zygotes were cultured in SOF medium containing 6 mg/ml BSA, 0.5 mg/mL myoinositol, 3% (v/v) essential amino acids, 1% nonessential amino acids and 100 μg/mL L-glutamine (48 h, 38.5 degrees C, 5% CO2, 5% O2, and 90% N2). In Experiment 2, cumulus cells were collected at the end of IVM to determine FSHR and LHR mRNA expression by real-time PCR. In Experiment 3 and 4, COCs were cultured in the presence or absence of the proteasomal inhibitor MG132 from either 0–6 h or 18–24 h after initiation of maturation. Results The optimum concentration of FSH and LH in IVM media was 5 microg/mL FSH and 50 IU/mL LH which resulted in the greatest cleavage (79.1%) and blastocyst rates (16.1%). Both FSHR and LHR mRNA were detected in yak cumulus cells after IVM. Treatment with MG132 early in maturation reduced (P < 0.05) cleavage and blastocyst rates. Conversely, treatment with MG132 late in maturation improved (P < 0.05) blastocyst rate. Optimal results with MG132 were achieved at a concentration of 10 microM. Conclusions An optimum concentration of FSH and LH in IVM medium, and treatment with MG132 late in maturation can improve yak oocytes competence for development after IVF. PMID:24754924

  9. Toward gene therapy of premature ovarian failure: intraovarian injection of adenovirus expressing human FSH receptor restores folliculogenesis in FSHR(−/−) FORKO mice

    PubMed Central

    Ghadami, M.; El-Demerdash, E.; Salama, S.A.; Binhazim, A.A.; Archibong, A.E.; Chen, X.; Ballard, B.R.; Sairam, M.R.; Al-Hendy, A.

    2010-01-01

    A homozygous missense mutation, C566T, in the follicle stimulation hormone receptor (FSHR) gene has been linked to premature ovarian failure. The disease leads to infertility in a normal karyotype female with an elevated follicle stimulating hormone (FSH) and decreased serum estrogen level. Female mice carrying mutated FSHR gene, called follitropin receptor knockout (FORKO), display similar phenotype and are sterile because of a folliculogenesis block at a primary stage. We investigated the effects of bilateral intra-ovarian injection of an adenovirus expressing a normal copy of human FSHR on the reproductive system of 6–10 weeks female FORKO mice. Ad-LacZ was injected directly into each ovary of the control group. Animals were sacrificed at 2, 4, 8 and 12 weeks post-injection and tissues collected for evaluation. Treated mice showed estrogenic changes in daily vaginal smear whereas control animals remained fixated in the diestrus stage. Histological evaluation showed on average 26 ± 4 follicles/ovary in treated group with 8 ± 2 follicles at the antral stage compared with only 5 ± 2 with zero follicles at antral stage in Ad-LacZ control mice. There was no significant change in serum level of progesterone, however, estrogen level increased 2–3-fold (P < 0.02) and FSH decreased by up to 50% (P < 0.04) in treated animals. FSHR mRNA was detected in the ovaries of the treated group. In conclusion, intra-ovarian injection of an adenovirus expressing human FSHR gene is able to restore FSH responsiveness and reinitiate ovarian folliculogenesis as well as resume estrogen production in female FORKO mice. Ad-LacZ injections indicate the absence of systemic viral dissemination or germ line transmission of adenovirus DNA to offspring. PMID:20086006

  10. Genetic Polymorphisms Influence the Ovarian Response to rFSH Stimulation in Patients Undergoing In Vitro Fertilization Programs with ICSI

    PubMed Central

    Boudjenah, Radia; Molina-Gomes, Denise; Torre, Antoine; Bergere, Marianne; Bailly, Marc; Boitrelle, Florence; Taieb, Stéphane; Wainer, Robert; Benahmed, Mohamed; de Mazancourt, Philippe; Selva, Jacqueline; Vialard, François

    2012-01-01

    Introduction Obtaining an adequate number of high-quality oocytes is a major challenge in controlled ovarian hyperstimulation (COH). To date, a range of hormonal and clinical parameters have been used to optimize COH but none have significant predictive value. This variability could be due to the genetic predispositions of single-nucleotide polymorphisms (SNPs). Here, we assessed the individual and combined impacts of thirteen SNPs that reportedly influence the outcome of in vitro fertilisation (IVF) on the ovarian response to rFSH stimulation for patients undergoing intracytoplasmic sperm injection program (ICSI). Results Univariate analysis revealed that only FSHR, ESR2 and p53 SNPs influenced the number of mature oocytes. The association was statistically significant for FSHR (p=0.0047) and ESR2 (0.0017) in the overall study population and for FSHR (p=0.0009) and p53 (p=0.0048) in subgroup that was more homogeneous in terms of clinical variables. After Bonferroni correction and a multivariate analysis, only the differences for FSHR and ESR2 polymorphisms were still statistically significant. In a multilocus analysis, only the FSHR and AMH SNP combination significantly influenced oocyte numbers in both population (p<0.01). Discussion We confirmed the impact of FSHR and ESR2 polymorphisms on the IVF outcome. Furthermore, we showed for the first time that a p53 polymorphism (which is already known to impact embryo implantation) could influence the ovarian response. However, given that this result lost its statistical significance after multivariate analysis, more data are needed to draw firm conclusions. Only the FSHR and AMH polymorphism combination appears to influence mature oocyte numbers but this finding also needs to be confirmed. Materials and Methods A 13 gene polymorphisms: FSHR(Asn680Ser), p53(Arg72Pro), AMH(Ile49Ser), ESR2(+1730G>A), ESR1(−397T>C), BMP15(−9C>G), MTHFR1(677C>T), MTHFR2(1298A>C), HLA-G(−725C>G), VEGF(+405G>C), TNFα(−308A>G), AMHR

  11. Gdnf-Gfra1 pathway is expressed in a spermatogenetic-dependent manner and is regulated by Fsh in a fish testis.

    PubMed

    Bellaïche, Johanna; Goupil, Anne-Sophie; Sambroni, Elisabeth; Lareyre, Jean-Jacques; Le Gac, Florence

    2014-10-01

    What makes the spermatogonial stem cells (SSCs) self-renew or differentiate to produce spermatozoa is barely understood, in particular in nonmammalian species. Our research explores possible regulations of the SSC niche in teleost, locally by paracrine factors and peripherally by hormonal regulation. In the present study, we focus on the Gdnf-Gfra1 pathway that plays a major role in the regulation of SSC self-renewal in mammals. We describe a complex evolution of the genes encoding for Gdnf and Gfra1 proteins in trout with the emergence of three gdnf and two gfra1 paralogs. Using quantitative PCR measurements in isolated testicular cell populations, the gdnfb paralog was found expressed in A-spermatogonia and probably in another testicular cell type. In contrast, the transcript of gfra1a, the Gdnf receptor, was preferentially expressed in a population of undifferentiated A-spermatogonia (und A-Spg) separated by centrifugal elutriation. These und A-Spg also demonstrated high stemness potential in transplantation studies and preferentially expressed nanos2, a putative SSC marker in trout (Bellaiche et al., Biol Reprod 2014; 90:79). Flow cytometer experiments demonstrate that only a subfraction of und A-Spg express Gfra1. In trout, spermatogenesis develops along a strict annual cycle, and gdnfb and its receptor were expressed in a spermatogenetic activity-dependent manner. In particular, a dramatic increase of the gdnfb transcript coincided with the progressive cessation of rapid spermatogonial proliferation and of meiosis toward the end of the reproductive cycle. Together these results suggest that, in trout, Gdnfb is involved in the repression of und A-Spg differentiation. Fsh is an endocrine regulator of SSCs self-renewal through the up-regulation of Gdnf in rodents. We demonstrate that in trout, in vitro Fsh treatment stimulated the expression of the gfra1a1 but not of its ligand, gdnfb. Fsh treatment also stimulated the proliferation of und A-Spg cocultured with

  12. Effects of chronic treatment with a gonadotrophin-releasing hormone agonist on peripheral concentrations of FSH and LH, and ovarian function in heifers.

    PubMed

    Gong, J G; Bramley, T A; Gutierrez, C G; Peters, A R; Webb, R

    1995-11-01

    The effect of chronic treatment with a gonadotrophin-releasing hormone agonist (GnRHa) on ovarian function in cattle was investigated by injecting heifers i.m. twice a day with saline, 5 micrograms GnRHa (Buserelin) or 10 micrograms GnRHa (n = 7) for 21 days. Blood samples were taken twice a day during the treatment period, and then three times a day for 7 days and once daily for a further 4 days. Frequent samples were also collected on day 1, day 10 and day 21 of treatment. The ovaries of all heifers were examined daily using real-time ultrasonography throughout the experimental period. No significant differences in the response were observed between two doses of GnRHa. The first GnRHa injection produced a large LH and FSH surge and this acute response was still present by day 21 of treatment, but both the magnitude and duration of response were significantly attenuated (P < 0.01). After an initial increase, LH returned to the basal concentration, which was maintained until the termination of treatment, when concentrations increased significantly, with a preovulatory surge occurring approximately 6 days later. Peripheral FSH concentrations during the oestrous cycle in control animals displayed a pattern of three waves, each of which closely preceded a wave of follicular development. Concentrations of FSH in GnRHa-treated heifers showed a normal pattern for the first wave after the start of treatment. During the next wave, concentrations increased and remained at the peak values until about 4 days after the end of treatment. An additional ovulation was induced in 11 of 14 GnRHa-treated heifers within 2-3 days of the start of treatment, and a significant (P < 0.05) increase in serum progesterone concentrations was detected 2 days later. All GnRHa-treated heifers then showed a normal follicular wave, with the development and regression of a dominant follicle. The dominant follicles from the next wave grew to only 7-9 mm in diameter and remained at this size until the

  13. Somatic environment and germinal differentiation in antral follicle: The effect of FSH withdrawal and basal LH on oocyte competence acquisition in cattle.

    PubMed

    Sirard, Marc-André

    2016-07-01

    In most mammals, the ovarian follicle interacts with the oocyte during all the steps of folliculogenesis, but in large mono-ovulating species such as cows, the full competence of oocytes to become a viable embryo is mainly acquired in the last few days before ovulation in large follicles. Although some embryos after IVM and IVF of oocytes obtained from nondominant follicles can produce blastocysts, these are less competent (rate and quality) than the ones from dominant or preovulatory follicles. Therefore, the last few days of folliculogenesis are crucial for the final oocyte maturation before ovulation resulting in optimal gamete preparation for fertilization and post-fertilization events. In a natural cycle, this period is characterized by a low amount of circulating FSH and LH. This low LH or basal LH level is nonetheless sufficient to maintain follicular growth and differentiation leading to the conditions triggering the LH surge and ovulation. This article provides a review of the different concepts correlated to oocyte competence acquisition including FSH depletion and exposes the results of different transcriptomic experiments offering a novel perspective of the different elements important to adequate granulosa cells development during the exceptional low LH window. PMID:27158126

  14. Urodynamic parameters and plasma LH/FSH in spayed Beagle bitches before and 8 weeks after GnRH depot analogue treatment.

    PubMed

    Reichler, Iris Margaret; Barth, Andrea; Piché, Claude A; Jöchle, Wolfgang; Roos, Malgorzata; Hubler, Madeleine; Arnold, Susi

    2006-12-01

    The pathophysiology of urinary incontinence due to spaying remains unknown. Incontinent bitches can be treated successfully with depot preparations of GnRH-analogues and there are differences in plasma gonadotropin levels between continent and incontinent spayed bitches. It is therefore assumed that the supraordinated hormones, GnRH, FSH, and/or LH, have an effect on the urodynamic parameters. In this study, the potential influence of these hormones on the lower urinary tract was investigated by measuring urethral pressure profiles and cystometry. Simultaneously, plasma concentrations in 10 spayed Beagle bitches were determined 5 weeks prior to and 8 weeks after treatment with the GnRH analogue leuprolide. Within 1 week of GnRH analogue administration, plasma FSH and LH levels decreased from 72.5 and 7.7 to 7.75 and 0.72ng/mL, respectively. These plasma gonadotropin levels correspond with those of intact bitches during anoestrus. Urethral pressure profiles indicated that the treatment had no significant effect on maximum urethral closure pressure, functional and total length of the urethra, or area of the closure pressure curve. The data obtained by cystometry regarding mean bladder threshold volume showed a significant increase from 109 to 172mL. The improvement in bladder function after the application of GnRH-application is presumably a direct effect of the GnRH as a relationship between the plasma gonadotropin levels and the urodynamic parameters could not demonstrated. PMID:16876857

  15. Immunohistochemical localization and quantitative assessment of GnRH-, FSH-, and LH-receptor mRNA Expression in canine skin: a powerful tool to study the pathogenesis of side effects after spaying.

    PubMed

    Welle, Monika M; Reichler, Iris M; Barth, Andrea; Forster, Ursula; Sattler, Ursula; Arnold, Susi

    2006-11-01

    It has been proposed that gonadotropins and/or gonadotropin releasing hormone (GnRH) could be involved in the pathophysiology of the side effects after spaying in bitches, such as urinary incontinence and an increased production of a woolly undercoat. In order to provide tools to investigate the role of these hormones in dogs we developed immunohistochemical techniques and real-time RT-PCR to study whether GnRH-, LH-, and FSH-receptors exist in canine skin and urinary bladder. Tissue samples from the skin of the flank region and the ventral midline of the urinary bladder from euthanised dogs were examined. We were able to quantify mRNA expression of GnRH-, FSH-, and LH-receptors in canine skin and bladder biopsies with a high primer efficacy. Immunohistochemical studies showed that GnRH-, FSH-, and LH-receptors are expressed in vessel walls, the epidermis, the hair follicle and in sebaceous and sweat glands in canine skin and in transitional epithelium, and smooth muscle tissue in the urinary bladder. Our data provide the fundamentals to examine the distribution of FSH-, LH-, and GnRH-receptors in canine skin and urinary bladder and to assess gene activity at the transcriptional level by real-time RT-PCR. PMID:16715322

  16. Comparisons of mRNA expression for aromatase, FSH receptor, and IGF-I in the granulosa of small ovarian follicles between cattle selected and unselected for twin ovulations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-term selection of cattle for the production of twin ovulations and births has enhanced the development of preantral and antral ovarian follicles and increased the frequency of twin or triplet ovulations to greater than 60%. However, these differences have not been linked to differences in FSH s...

  17. FSH-induced p38-MAPK-mediated dephosphorylation at serine 727 of the signal transducer and activator of transcription 1 decreases Cyp1b1 expression in mouse granulosa cells.

    PubMed

    Du, Xue-Hai; Zhou, Xiao-Long; Cao, Rui; Xiao, Peng; Teng, Yun; Ning, Cai-Bo; Liu, Hong-Lin

    2015-01-01

    Most mammalian follicles undergo atresia at various stages before ovulation, and granulosa cell apoptosis is a major cause of antral follicular atresia. Estradiol is an essential mitogen for granulosa cell proliferation in vivo and inhibition of apoptosis. The estradiol-producing capacity and metabolism levels are important for follicle health, and sufficient estradiol is necessary for follicle development and ovulation. Cyp1b1, a member of the cytochrome P450 1 subfamily, is responsible for the metabolism of a wide variety of halogenated and polycyclic aromatic hydrocarbons in diverse tissues. In mouse follicles, Cyp1b1 converts estradiol to 4-hydroxyestradiol. We investigated mouse granulosa cells (MGCs) in vivo and in vitro and found that Cyp1b1 played a crucial role in estradiol metabolism in dominant follicles. Follicle-stimulating hormone (FSH) decreased estrogen metabolism by reducing Cyp1b1 mRNA and protein levels in MGCs. Furthermore, FSH regulated signal transducer and activator of transcription 1 (STAT1), a significant transcription factor of Cyp1b1, by mediating the dephosphorylation of STAT1 on serine 727 (Ser(727)) in MGCs. p38 mitogen-activated protein kinase (MAPK) may be involved in the FSH-induced dephosphorylation of STAT1 on Ser(727) in MGCs. These results suggested that FSH functions via p38 MAPK-induced dephosphorylation at Ser(727) of STAT1 to downregulate Cyp1b1 expression and maintain the estradiol levels in mouse dominant follicles. PMID:25315223

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

    PubMed

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

    2016-07-01

    Hormonal ovarian stimulation may affect transcripts in somatic cells of cumulus-oocyte complexes (COCs) and affect the resulting oocyte quality. Here, in parallel with morphological classification and in vitro maturation (IVM) rate analysis, we investigated the expression of hyaluronan synthase 2 (HAS2), gonadotropic receptors (FSHR and LHR) and connexin 43 (GJA1) in cumulus cells (CCs) from goat COCs after multi-dose FSH (MD) or one-shot FSH/eCG (OS) treatments, using bovine COCs as control groups. The MD treatment produced more large follicles, and the resulting COCs had a better morphology and IVM rate than were obtained with OS. The OS treatment produced COCs with increased HAS2, FSHR, LHR and GJA1 expression. This gene expression pattern was also observed in the CCs of COCs that showed poor morphological characteristics. On the other hand, the mRNA levels were more similar between groups after IVM; FSHR and LHR were the main genes that showed decreased expression. Some events that occurred in bovine CCs during IVM, such as cell expansion, increased HAS2 expression and decreased GJA1 expression, were less evident or did not occur in goat COCs. In conclusion, increasing HAS2, FSHR, LHR and GJA1 expression in goat COCs does not confer greater meiotic competence to oocytes. Instead, it may result from poor regulation of gene expression in CCs by lower quality oocytes. Finally, cumulus expansion, together with HAS2 upregulation and GJA1 downregulation, seems to be more important for bovine COCs than for goat COCs. Additional studies are needed to investigate the importance of other HAS isoforms and connexins in goat COCs. PMID:27072623

  19. Involvement of microRNA Mir15a in control of human ovarian granulosa cell proliferation, apoptosis, steroidogenesis, and response to FSH.

    PubMed

    Sirotkin, Alexander V; Kisová, Gabriela; Brenaut, Pauline; Ovcharenko, Dmitriy; Grossmann, Roland; Mlyncek, Milos

    2014-01-01

    Our study aimed to examine the role of micro RNA Mir15a in control of basic ovarian cell functions: proliferation, apoptosis, and secretory activity. In the first series of experiments, primary human ovarian granulosa cells were transfected with antisense construct blocking Mir15a (anti-Mir15a) and cultured without hormonal treatments. Accumulation of markers of proliferation (MAPK/ERK1,2 and PCNA) and apoptosis (caspase 3 and bax), and release of steroid hormones (progesterone, testosterone, and estradiol) were evaluated by immunocytochemical analysis and by enzyme immunoassay. In the second series of experiments, granulosa cells were transfected with gene construct encoding Mir15a precursor (pre-Mir15a) and cultured with and without follicle-stimulating hormone (FSH; 0, 1, 10, and 100 ng/ml). Expression of markers of proliferation (MAPK/ERK1,2) apoptosis (caspase 3), and steroidogenesis (release of progesterone, testosterone, and estradiol) were evaluated. Transfection of cells with anti-Mir15a resulted in a significant increase in accumulation of both proliferation and apoptosis markers, a reduction in progesterone and testosterone release, and an increase in estradiol release. Transfection of cells with pre-Mir15a had an opposite effect: it reduced accumulation of proliferation- and apoptosis-related proteins MAPK/ERK1,2 and caspase 3, and promoted release of progesterone and testosterone, but not estradiol. Moreover, pre-Mir15a reversed the effect of FSH on caspase 3, progesterone, and testosterone, but not on MAPK/ERK1,2 and estradiol. Our observations demonstrate involvement of Mir15a in control of multiple ovarian functions: proliferation, apoptosis, release of progesterone, androgen, and estrogen, and response to gonadotropin. Moreover, this is the first demonstration that miRNAs can affect response of cells to hormonal regulators. We propose that Mir15 could potentially be used for control of different reproductive processes. PMID:25069510

  20. Reproductive Physiology in Young Men Is Cumulatively Affected by FSH-Action Modulating Genetic Variants: FSHR -29G/A and c.2039 A/G, FSHB -211G/T

    PubMed Central

    Grigorova, Marina; Punab, Margus; Punab, Anna Maria; Poolamets, Olev; Vihljajev, Vladimir; Žilaitienė, Birutė; Erenpreiss, Juris; Matulevičius, Valentinas; Laan, Maris

    2014-01-01

    Follicle-Stimulating Hormone Receptor (FSHR) -29G/A polymorphism (rs1394205) was reported to modulate gene expression and reproductive parameters in women, but data in men is limited. We aimed to bring evidence to the effect of FSHR -29G/A variants in men. In Baltic young male cohort (n = 982; Estonians, Latvians, Lithuanians; aged 20.2±2.0 years), the FSHR -29 A-allele was significantly associated with higher serum FSH (linear regression: effect 0.27 IU/L; P = 0.0019, resistant to Bonferroni correction for multiple testing) and showed a non-significant trend for association with higher LH (0.19 IU/L) and total testosterone (0.93 nmol/L), but reduced Inhibin B (−7.84 pg/mL) and total testes volume (effect −1.00 mL). Next, we extended the study and tested the effect of FSHR gene haplotypes determined by the allelic combination of FSHR -29G/A and a well-studied variant c.2039 A/G (Asn680Ser, exon 10). Among the FSHR -29A/2039G haplotype carriers (A-Ser; haplotype-based linear regression), this genetic effect was enhanced for FSH (effect 0.40 IU/L), Inhibin B (−16.57 pg/mL) and total testes volume (−2.34 mL). Finally, we estimated the total contribution of three known FSH-action modulating SNPs (FSHB -211G/T; FSHR -29G/A, c.2039 A/G) to phenotypic variance in reproductive parameters among young men. The major FSH-action modulating SNPs explained together 2.3%, 1.4%, 1.0 and 1.1% of the measured variance in serum FSH, Inhibin B, testosterone and total testes volume, respectively. In contrast to the young male cohort, neither FSHR -29G/A nor FSHR haplotypes appeared to systematically modulate the reproductive physiology of oligozoospermic idiopathic infertile patients (n = 641, Estonians; aged 31.5±6.0 years). In summary, this is the first study showing the significant effect of FSHR -29G/A on male serum FSH level. To account for the genetic effect of known common polymorphisms modulating FSH-action, we suggest haplotype-based analysis of FSHR SNPs

  1. Data in support of FSH induction of IRS-2 in human granulosa cells: Mapping the transcription factor binding sites in human IRS-2 promoter

    PubMed Central

    Kaur, Surleen; Anjali, G.; Bhardwaj, Priya; Taneja, Jyoti; Singh, Rita

    2015-01-01

    Insulin receptor substrate-2 (IRS-2) plays critical role in the regulation of various metabolic processes by insulin and IGF-1. The defects in its expression and/or function are linked to diseases like polycystic ovary syndrome (PCOS), insulin resistance and cancer. To predict the transcription factors (TFs) responsible for the regulation of human IRS-2 gene expression, the transcription factor binding sites (TFBS) and the corresponding TFs were investigated by analysis of IRS-2 promoter sequence using MatInspector Genomatix software (Cartharius et al., 2005 [1]). The ibid data is part of author׳s publication (Anjali et al., 2015 [2]) that explains Follicle stimulating hormone (FSH) mediated IRS-2 promoter activation in human granulosa cells and its importance in the pathophysiology of PCOS. Further analysis was carried out for binary interactions of TF regulatory genes in IRS-2 network using Cytoscape software tool and R-code. In this manuscript, we describe the methodology used for the identification of TFBSs in human IRS-2 promoter region and provide details on experimental procedures, analysis method, validation of data and also the raw files. The purpose of this article is to provide the data on all TFBSs in the promoter region of human IRS-2 gene as it has the potential for prediction of the regulation of IRS-2 gene in normal or diseased cells from patients with metabolic disorders and cancer. PMID:26858982

  2. The effect of androgens on ovarian follicle maturation: Dihydrotestosterone suppress FSH-stimulated granulosa cell proliferation by upregulating PPARγ-dependent PTEN expression.

    PubMed Central

    Chen, Mei-Jou; Chou, Chia-Hung; Chen, Shee-Uan; Yang, Wei-Shiung; Yang, Yu-Shih; Ho, Hong-Nerng

    2015-01-01

    Intraovarian hyperandrogenism is one of the determining factors of follicular arrest in women with polycystic ovary syndrome (PCOS). Using androgenized rat models, we investigated the effects of androgens on metabolism, as well as on factors involved in follicular arrest and the reduced number of estrus cycles. The dihydrotestosterone (DHT)-treated rats had fewer estrus cycles, higher numbers of large arrested follicles and an increased in body weight gain compared with the dehydroepiandrostenedione (DHEA)- and placebo-treated rats. In cultured rat granulosa cells, DHT suppressed follicle stimulating hormone (FSH)-induced granulosa cell proliferation and increased the accumulation of cells in the G2/M phase. DHT decreased phosphorylated Akt (p-Akt) and cyclin D1 levels through increasing PTEN. DHT-promoted PTEN expression was regulated by peroxisome proliferator-activated receptor gamma (PPARγ) in granulosa cells. Meanwhile, in the large follicles of the DHT-treated rats, the expressions of PPARγ and PTEN were higher, but the expression of p-Akt and proliferating cell nuclear antigen (PCNA) were lower. Conclusively, DHT and DHEA produced differential effects on metabolism in prepubertal female rats like clinical manifestations of women with PCOS. DHT treatment may affect ovarian follicular maturation by altering granulosa cell proliferation through the regulation of enhancing PPARγ dependent PTEN/p-Akt expression in the granulosa cells. PMID:26674985

  3. Kiss2 as a Regulator of Lh and Fsh Secretion via Paracrine/Autocrine Signaling in the Teleost Fish European Sea Bass (Dicentrarchus labrax).

    PubMed

    Espigares, Felipe; Zanuy, Silvia; Gómez, Ana

    2015-11-01

    Kisspeptins are key players in the neuroendocrine control of puberty and other reproductive processes in mammals. Several studies have demonstrated that the KISS/GPR54 system is expressed by gonadotrophs, but in vitro studies assessing the direct stimulatory effects of kisspeptin on gonadotropin secretion in the pituitary have provided conflicting results. In this study, we investigated whether kisspeptin directly influences the reproductive function of sea bass pituitary. First, the highly active peptides Kiss1-15 and Kiss2-12 were used to stimulate dispersed sea bass pituitary cells obtained from mature males. Our results show that, first, Kiss2-12 induced luteinizing hormone (Lh) and follicle-stimulating hormone (Fsh) release, whereas Kiss1-15 had no effect on gonadotropin secretion at full spermiation stage. Second, the distribution and nature of Kiss2 and its potential interactions with the gonadotropin-releasing hormone 1 (Gnrh1) system in the pituitary were analyzed using dual fluorescence immunohistochemistry. Kiss2 cells were found in the proximal pars distalis and colocalized with gonadotropin-immunoreactive cells. In summary, our results provide, for the first time in a teleost species, functional and neuroanatomical evidence that Kiss2 may act through different routes to directly modulate the activity of gonadotrophs, either as a hypophysiotropic neuropeptide or as an autocrine/paracrine factor. PMID:26400402

  4. Data in support of FSH induction of IRS-2 in human granulosa cells: Mapping the transcription factor binding sites in human IRS-2 promoter.

    PubMed

    Kaur, Surleen; Anjali, G; Bhardwaj, Priya; Taneja, Jyoti; Singh, Rita

    2016-03-01

    Insulin receptor substrate-2 (IRS-2) plays critical role in the regulation of various metabolic processes by insulin and IGF-1. The defects in its expression and/or function are linked to diseases like polycystic ovary syndrome (PCOS), insulin resistance and cancer. To predict the transcription factors (TFs) responsible for the regulation of human IRS-2 gene expression, the transcription factor binding sites (TFBS) and the corresponding TFs were investigated by analysis of IRS-2 promoter sequence using MatInspector Genomatix software (Cartharius et al., 2005 [1]). The ibid data is part of author׳s publication (Anjali et al., 2015 [2]) that explains Follicle stimulating hormone (FSH) mediated IRS-2 promoter activation in human granulosa cells and its importance in the pathophysiology of PCOS. Further analysis was carried out for binary interactions of TF regulatory genes in IRS-2 network using Cytoscape software tool and R-code. In this manuscript, we describe the methodology used for the identification of TFBSs in human IRS-2 promoter region and provide details on experimental procedures, analysis method, validation of data and also the raw files. The purpose of this article is to provide the data on all TFBSs in the promoter region of human IRS-2 gene as it has the potential for prediction of the regulation of IRS-2 gene in normal or diseased cells from patients with metabolic disorders and cancer. PMID:26858982

  5. Effect of cow age on the in vitro developmental competence of oocytes obtained after FSH stimulation and coasting treatments.

    PubMed

    Landry, David A; Bellefleur, Anne-Marie; Labrecque, Rémi; Grand, François-Xavier; Vigneault, Christian; Blondin, Patrick; Sirard, Marc-André

    2016-09-15

    The use of oocytes obtained from younger donors for IVF followed by embryo transfer represents an opportunity to accelerate genetic gain by reducing generation time. In this study, we investigated the relationship between donor age and the in vitro developmental competence of oocytes obtained from Holstein females (aged 5-18 months) after FSH stimulation and coasting. The follicle size patterns showed a significantly higher total number of small follicles (5-6 mm) from donors aged 5 to 10 months and a higher total number of medium-sized follicles (7-10 mm) in donors aged 6 to 7 months. Our analysis also revealed that the total number of follicles was significantly higher (P < 0.05) in donors aged 5 to 8 months and tended to be higher (P = 0.053) in nine-month-old donors. However, oocytes obtained from donors aged 5 to 10 months yielded fewer embryos reaching the morula and blastocyst stages. In summary, our results demonstrate that a higher number of oocytes can be obtained from younger animals but lower developmental competence negates this gain. PMID:27215669

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

    PubMed

    Kawai, Tomoko; Yanaka, Noriyuki; Richards, JoAnne S; Shimada, Masayuki

    2016-05-01

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

  7. Effects of diets containing free gossypol on follicular development, embryo recovery and corpus luteum function in Brangus heifers treated with bFSH.

    PubMed

    Randel, R D; Willard, S T; Wyse, S J; French, L N

    1996-04-01

    Thirty 2 yr old Brangus heifers were randomly assigned to 1 of 3 dietary treatments: Control, 0 g of free gossypol (FG) per head per day (FGHD) from corn and soybean meal (SBM); 5 g of FGHD from cottonseed meal (CSM); and 15 g of FGHD from whole cottonseed (WCS). Blood samples were collected weekly for serum progesterone (P(4)) and later quantified by RIA. Whole blood was collected on Days 1, 28, 42, 56 and 70 for erythrocyte fragility (EF) analysis. Following 65 d on dietary treatments and estrus detection, the heifers received bovine-FSH (bFSH) once daily on Days 10, 11 and 12 postestrus, and PGF(2alpha) on Day 12 postestrus. Fifteen of the thirty heifers were randomly selected, and 12 h following PGF(2alpha), the ovaries were removed and follicular diameters, ovarian weight and stromal weights were recorded. Follicular fluid was analyzed for steroid content by RIA. The remaining fifteen heifers were artificially inseminated. Embryos were recovered non-surgically on Day 7 postestrus and graded, and the recovery efficiencies were calculated. Following embryo collection, both ovaries were removed, the number of CLs was recorded, and CL P(4) content was determined by RIA. By Day 42 of treatment, heifers receiving CSM had elevated (P < 0.04) EF compared with the Controls, and remained elevated above that of Controls throughout the study. At Day 70, the CSM heifers tended to have higher (P < 0.07) EF than the WCS group, which in turn tended to be higher (P < 0.06) than the Controls. The Control and CSM heifers gained weight during the 70 d treatment period, while heifers consuming WCS lost weight (P < 0.05). Ovarian and stromal weights did not differ (P > 0.10) among treatment groups. Heifers receiving CSM had fewer (P < 0.05) follicles > 5 mm than WCS or Control heifers. Follicular fluid weights and steroid content did not differ (P > 0.10) among treatments. Both CL weight and the number of CLs per heifer were similar (P > 0.10) among treatments. Heifers receiving

  8. Leptin receptor null mice with reexpression of LepR in GnRHR expressing cells display elevated FSH levels but remain in a prepubertal state.

    PubMed

    Allen, Susan J; Garcia-Galiano, David; Borges, Beatriz C; Burger, Laura L; Boehm, Ulrich; Elias, Carol F

    2016-06-01

    Leptin signals energy sufficiency to the reproductive hypothalamic-pituitary-gonadal (HPG) axis. Studies using genetic models have demonstrated that hypothalamic neurons are major players mediating these effects. Leptin receptor (LepR) is also expressed in the pituitary gland and in the gonads, but the physiological effects of leptin in these sites are still unclear. Female mice with selective deletion of LepR in a subset of gonadotropes show normal pubertal development but impaired fertility. Conditional deletion approaches, however, often result in redundancy or developmental adaptations, which may compromise the assessment of leptin's action in gonadotropes for pubertal maturation. To circumvent these issues, we adopted a complementary genetic approach and assessed if selective reexpression of LepR only in gonadotropes is sufficient to enable puberty and improve fertility of LepR null female mice. We initially assessed the colocalization of gonadotropin-releasing hormone receptor (GnRHR) and LepR in the HPG axis using GnRHR-IRES-Cre (GRIC) and LepR-Cre reporter (tdTomato or enhanced green fluorescent protein) mice. We found that GRIC and leptin-induced phosphorylation of STAT3 are expressed in distinct hypothalamic neurons. Whereas LepR-Cre was observed in theca cells, GRIC expression was rarely found in the ovarian parenchyma. In contrast, a subpopulation of gonadotropes expressed the LepR-Cre reporter gene (tdTomato). We then crossed the GRIC mice with the LepR null reactivable (LepR(loxTB)) mice. These mice showed an increase in FSH levels, but they remained in a prepubertal state. Together with previous findings, our data indicate that leptin-selective action in gonadotropes serves a role in adult reproductive physiology but is not sufficient to allow pubertal maturation in mice. PMID:27101301

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

    PubMed

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

    2016-03-15

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

  10. Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol

    PubMed Central

    Griesinger, Georg; Verweij, Pierre J. M.; Gates, Davis; Devroey, Paul; Gordon, Keith; Stegmann, Barbara J.; Tarlatzis, Basil C.

    2016-01-01

    Study Question What is the threshold for the prediction of moderate to severe or severe ovarian hyperstimulation syndrome (OHSS) based on the number of growing follicles ≥ 11 mm and/or estradiol (E2) levels? Summary Answer The optimal threshold of follicles ≥11 mm on the day of hCG to identify those at risk was 19 for both moderate to severe OHSS and for severe OHSS. Estradiol (E2) levels were less prognostic of OHSS than the number of follicles ≥ 11 mm. What Is Known Already In comparison to long gonadotropin-releasing hormone (GnRH) agonist protocols, the risk of severe OHSS is reduced by approximately 50% in a GnRH antagonist protocol for ovarian stimulation prior to in vitro fertilisation (IVF), while the two protocols provide equal chances of pregnancy per initiated cycle. Nevertheless, moderate to severe OHSS may still occur in GnRH antagonist protocols if human chorionic gonadotropin (hCG) is administered to trigger final oocyte maturation, especially in high responder patients. Severe OHSS following hCG trigger may occur with an incidence of 1–2% in a relatively young (aged 18 to 36 years) IVF population treated in a GnRH-antagonist protocol. Study Design, Size, Duration From the Engage, Ensure and Trust trials, in total, 2,433 women who received hCG for oocyte maturation and for whom the number of follicles ≥ 11 mm and the level of E2 on the day of hCG administration were known were included in the analyses. Participants/Materials, Setting, Methods The threshold for OHSS prediction of moderate and severe OHSS was assessed in women treated with corifollitropin alfa or daily recombinant follicle stimulation hormone (rFSH) in a gonadotropin-releasing hormone (GnRH)-antagonist protocol. Receiver operating characteristics curve analyses for moderate to severe OHSS and severe OHSS were performed on the combined dataset and the sensitivity and specificity for the optimal threshold of number of follicles ≥ 11 mm, E2 levels on the day of (hCG), and a

  11. A systematic immunohistochemical survey of the distribution patterns of GH, prolactin, somatolactin, beta-TSH, beta-FSH, beta-LH, ACTH, and alpha-MSH in the adenohypophysis of Oreochromis niloticus, the Nile tilapia.

    PubMed

    Kasper, Romano Silvio; Shved, Natallia; Takahashi, Akiyoshi; Reinecke, Manfred; Eppler, Elisabeth

    2006-08-01

    Fish pituitary plays a central role in the control of growth, development, reproduction and adaptation to the environment. Several types of hormone-secreting adenohypophyseal cells have been characterised and localised in diverse teleost species. The results suggest a similar distribution pattern among the species investigated. However, most studies deal with a single hormone or hormone family. Thus, we studied adjacent sections of the pituitary of Oreochromis niloticus, the tilapia, by conventional staining and immunohistochemistry with specific antisera directed against growth hormone (GH), prolactin (PRL), somatolactin (SL), thyrotropin (beta-TSH), follicle-stimulating hormone (beta-FSH), luteinising hormone (beta-LH), adrenocorticotropic hormone (ACTH) and melanocyte-stimulating hormone (alpha-MSH). The pituitary was characterised by a close interdigitating neighbourhood of neurohypophysis (PN) and adenohypophysis. PRL-immunoreactive and ACTH-immunoreactive cells were detected in the rostral pars distalis. GH-immunoreactive cells were present in the proximal pars distalis (PPD). A small region of the PPD contained beta-TSH-immunoreactive cells, and beta-LH-immunoreactive cells covered approximately the remaining parts. Centrally, beta-FSH-immunoreactive cells were detected in the vicinity of the GH-containing cells. Some of these cells also displayed beta-LH immunoreactivity. The pars intermedia was characterised by branches of the PN surrounded by SL-containing and alpha-MSH-immunoreactive cells. The ACTH and alpha-MSH antisera were observed to cross-react with the respective antigens. This cross-reactivity was abolished by pre-absorption. We present a complete map of the distinct localisation sites for the classical pituitary hormones, thereby providing a solid basis for future research on teleost pituitary. PMID:16552525

  12. Follicle-stimulating hormone (FSH) blood test

    MedlinePlus

    ... Parts of the brain (the pituitary gland or hypothalamus ) not producing normal amounts of some or all ... parts of the brain (the pituitary gland or hypothalamus) do not produce normal amounts of some or ...

  13. Facioscapulohumeral dystrophy: a distinct regional myopathy with a novel molecular pathogenesis. FSH Consortium.

    PubMed

    Tawil, R; Figlewicz, D A; Griggs, R C; Weiffenbach, B

    1998-03-01

    Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common inherited diseases of muscle. Until recently, FSHD had received little attention because of its relatively benign course and the perception that it represented a syndrome rather than a distinct myopathy. Research interest into this disease was reignited with the demonstration of linkage of FSHD to chromosome 4q35 in 1990. Clinical and molecular genetic research in FSHD has since helped define it as a distinct clinical entity, outlined its natural history, and defined the primary molecular defect associated with the condition. FSHD is now known to be associated with large deletions of variable size on chromosome 4q35. These deletions, however, do not appear to disrupt a transcribed gene but are thought to interfere with the expression of a gene or genes located proximal to the deletions. These observations complicate the search for the FSHD gene but also imply the presence of a potentially novel molecular pathogenesis. PMID:9506542

  14. Granulosa Cell Apoptosis Induced by a Novel FSH Binding Inhibitory Peptide From Human Ovarian Follicular Fluid

    PubMed Central

    Chitnis, Swati S.; Navlakhe, Rajshri M.; Shinde, Gayatri C.; Barve, Sharmila J.; D'Souza, Serena; Mahale, Smita D.; Nandedkar, Tarala D.

    2008-01-01

    Pituitary gonadotropins, follicle-stimulating hormone and luteinizing hormone, are the key regulators of ovarian folliculogenesis; these are known to be directly or indirectly modulated by many intraovarian factors. Our group has identified and studied one such novel peptide from human ovarian follicular fluid. Its partial N-terminal eight amino acid sequence has been deduced, referred to as octapeptide (OP). OP induces follicular atresia in mice and interferes with normal ovarian function in non-human primates, this action being similar to the native peptide. Thus, in this study, an attempt has been made to elucidate the mechanism of action of the synthetic OP by studying the pathway of follicular atresia in mouse ovary. Changes in granulosa cells were studied using various apoptotic markers by flow cytometry and immunohistochemistry. An increase in apoptotic cell population in atretic- and peptide-treated groups was observed compared with normal controls. Interestingly, both these groups exhibited differences in the apoptotic pathway. Results showed that the mitochondrial pathway was predominant in the atretic group, whereas the Fas-FasL pathway was predominant in the peptide-treated groups. The ultrastructural study also showed apoptotic changes in the OP-treated and atretic groups; the pattern of apoptosis differed at the subcellular level. (J Histochem Cytochem 56:961–968, 2008) PMID:18645207

  15. Umatilla River Basin Anadromous Fsh Habitat Enhancement Project : 2000 Annual Report.

    SciTech Connect

    Shaw, R. Todd

    2001-12-31

    The Umatilla River Basin Anadromous Fish Habitat Enhancement Project continued to identify impacted stream reaches throughout the Umatilla River Basin for habitat improvements during the 2000 project period. Public outreach efforts, biological and physical monitoring, and continued development of a Umatilla River Basin Watershed Assessment assisted the project in fostering public cooperation, targeting habitat deficiencies and determining habitat recovery measures. Habitat enhancement projects continued to be maintained on 44 private properties, four riparian easements and one in-stream enhancement agreement were secured, two new projects implemented and two existing projects improved to enhance anadromous fish habitat and natural fisheries production capabilities in the Umatilla River Basin. New project locations included sites on the mid Umatilla River and Buckaroo Creek. Improvements were implemented at existing project sites on the upper Umatilla River and Wildhorse Creek. A stream bank stabilization project was implemented at approximately River Mile 37.4 Umatilla River to stabilize 760 feet of eroding stream bank and improve in-stream habitat diversity. Habitat enhancements at this site included construction of six rock barbs with one large conifer root wad incorporated into each barb, stinging approximately 10,000 native willow cuttings, planting 195 tubling willows and 1,800 basin wildrye grass plugs, and seeding 40 pounds of native grass seed. Staff time to assist in development of a subcontract and fence materials were provided to establish eight spring sites for off-stream watering and to protect wetlands within the Buckaroo Creek Watershed. A gravel bar was moved and incorporated into an adjacent point bar to reduce stream energy and stream channel confinement within the existing project area at River Mile 85 Umatilla River. Approximately 10,000 native willow cuttings were stung and trenched into the stream channel margins and stream banks, and 360 basin wildrye grass plugs planted and 190 pounds of native grass seed broadcast on terraces between River Mile 10 and 12.5 within the existing Wildhorse Creek Project Area. Approximately 70 pounds of native grasses were seeded in the existing McKay Creek Project Area at approximately River Mile 21.5. Financial and in-kind cost share assistance was provided by the Confederated Tribes of the Umatilla Indian Reservation, U.S. Bureau of Indian Affairs, U.S. Department of Agriculture, U.S. Fish and Wildlife Service, National Fish and Wildlife Federation and the Umatilla National Forest for the enhancements at River Mile 37.4 Umatilla River and within the Buckaroo Creek Watershed. Monitoring continued to quantify effects of habitat enhancements in the upper basin. Maximum, minimum and average daily stream temperatures were collected from June through September at 22 sites. Suspended sediment samples were obtained at three gage stations to arrive at daily sediment load estimates. Photographs were taken at 94 existing and two newly established photo points to document habitat recovery. Umatilla Basin Watershed Assessment efforts were continued under a subcontract with Washington State University. This endeavor involves compiling existing information, identifying data gaps, determining habitat-limiting factors and recommending actions to improve anadromous fisheries habitat. This watershed assessment document and working databases will be completed in fiscal year 2002 and made available to assist project personnel with sub-watershed prioritization of habitat needs.

  16. Molecular cloning and functional analysis of the FSH receptor gene promoter from the volcano mouse (Neotomodon alstoni alstoni).

    PubMed

    Pérez-Solis, Marco Allán; Macías, Héctor; Acosta-MontesdeOca, Adriana; Pasapera, Ana María; Fierro, Reyna; Ulloa-Aguirre, Alfredo; Gutiérrez-Sagal, Rubén

    2010-02-01

    To gain further insights on the genetic divergence and the species-specific characteristics of the follicle-stimulating hormone receptor (FSHR), we cloned 946 bp of the 5'-flanking region of the FSHR gene from the volcano mouse (Neotomodon alstoni alstoni), and compared its features with those from other mammalian species. The sequence of neotomodon FSHR (nFSHR) gene from the translation initiation site to -946 is 74, 71, 64, and 59% homologous to rat, mouse (129/J), human, and sheep, respectively. The nFSHR 5'-flanking region exhibits new interesting putative cis-regulatory elements including those for the SRY transcription factor, which had not been previously related to the FSHR gene. The transcriptional regulation properties of nFSHR gene were studied in mouse Sertoli (MSC-1) and non-Sertoli (H441) cell lines, and compared with those obtained with similar 129/J constructs. All constructs tested were more active in H441 than in MSC-1 cells. The low transcription levels detected in MSC-1 cells probably reflect the recruitment of Sertoli cells-specific nuclear factors that repress transcription of the FSHR gene. In H441 cells, 129/J constructs were more active than their neotomodon counterparts, indicating important species-specific differences in their transcription pattern. Functional analysis of a series of progressive 5'-deletion mutants identified regions involved in positive and negative transcriptional regulation as well as the strongest minimal promoter spanning 260 bp upstream the translation initiation site. The identification of inhibitory nuclear transcription factors, which are apparently expressed in MSC-1 cells, may contribute to a better understanding of the transcriptional regulation of the FSHR gene. PMID:19862645

  17. A Proteomic Analysis of Human Follicular Fluid: Comparison between Younger and Older Women with Normal FSH Levels

    PubMed Central

    Hashemitabar, Mahmoud; Bahmanzadeh, Maryam; Mostafaie, Ali; Orazizadeh, Mahmoud; Farimani, Marzieh; Nikbakht, Roshan

    2014-01-01

    The follicular fluid (FF) is produced during folliculogenesis and contains a variety of proteins that play important roles in follicle development and oocyte maturation. Age-related infertility is usually considered as a problem that can be solved by assisted reproduction technology. Therefore, the identification of novel biomarkers that are linked to reproductive aging is the subject of this study. FF was obtained from healthy younger (20–32 years old) and older (38–42 years old) women undergoing intracytoplasmic sperm injection (ICSI) due to male factor infertility. The FF was analyzed by two-dimensional gel electrophoresis (2-DE). The power of two-dimensional gel electrophoresis and the identification of proteins were exploited using matrix-assisted laser desorption-ionization time-of-flight/time-of-flight (MALDI-TOF-TOF) mass spectrometry. Twenty three protein spots showed reproducible and significant changes in the aged compared to the young group. Of these, 19 protein spots could be identified using MALDI-TOF-TOF-MS. As a result of MASCOT search, five unique downregulated proteins were identified in the older group. These were identified as serotransferrin, hemopexin precursor, complement C3, C4 and kininogen. A number of protein markers were found that may help develop diagnostic methods of infertility. PMID:25268621

  18. Archive of side scan sonar and bathymetry data collected during USGS Cruise 06FSH01 offshore of Siesta Key, Florida, May 2006

    USGS Publications Warehouse

    Ciembronowicz, Katherine T.; Flocks, James G.; Wiese, Dana S.; DeWitt, Nancy T.; Ferina, Nick F.; Robbins, Lisa L.; Harrison, Arnell S.

    2007-01-01

    This DVD publication was prepared by an agency of the United States Government. Although these data have been processed successfully on a computer system at the U.S. Geological Survey, no warranty expressed or implied is made regarding the display or utility of the data on any other system, or for general or scientific purposes, nor shall the act of distribution imply any such warranty. The U.S. Geological Survey shall not be held liable for improper or incorrect use of the data described and (or) contained herein. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof.

  19. Archive of digital boomer and CHIRP seismic reflection data collected during USGS cruise 06FSH03 offshore of Fort Lauderdale, Florida, September 2006

    USGS Publications Warehouse

    Harrison, Arnell S.; Dadisman, Shawn V.; Reich, Christopher D.; Wiese, Dana S.; Greenwood, Jason W.; Swarzenski, Peter W.

    2007-01-01

    In September of 2006, the U.S. Geological Survey conducted geophysical surveys offshore of Fort Lauderdale, FL. This report serves as an archive of unprocessed digital boomer and CHIRP seismic reflection data, trackline maps, navigation files, GIS information, Field Activity Collection System (FACS) logs, observer's logbook, and formal FGDC metadata. Filtered and gained digital images of the seismic profiles are also provided. The archived trace data are in standard Society of Exploration Geophysicists (SEG) SEG-Y format (Barry and others, 1975) and may be downloaded and processed with commercial or public domain software such as Seismic Unix (SU). Example SU processing scripts and USGS software for viewing the SEG-Y files (Zihlman, 1992) are also provided.

  20. Archive of digital CHIRP seismic reflection data collected during USGS cruise 06FSH01 offshore of Siesta Key, Florida, May 2006

    USGS Publications Warehouse

    Harrison, Arnell S.; Dadisman, Shawn V.; Flocks, James G.; Wiese, Dana S.; Robbins, Lisa L.

    2007-01-01

    In May of 2006, the U.S. Geological Survey conducted geophysical surveys offshore of Siesta Key, Florida. This report serves as an archive of unprocessed digital chirp seismic reflection data, trackline maps, navigation files, GIS information, Field Activity Collection System (FACS) logs, observer's logbook, and formal FGDC metadata. Gained digital images of the seismic profiles are also provided. The archived trace data are in standard Society of Exploration Geophysicists (SEG) SEG-Y format (Barry and others, 1975) and may be downloaded and processed with commercial or public domain software such as Seismic Unix (SU). Example SU processing scripts and USGS software for viewing the SEG-Y files (Zihlman, 1992) are also provided.

  1. A prospective, quantitative study of the natural history of facioscapulohumeral muscular dystrophy (FSHD): implications for therapeutic trials. The FSH-DY Group.

    PubMed

    1997-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder localized to 4q35. Neither the gene nor the gene product has been identified. There is presently no established treatment for FSHD. Prospective data on the natural history of this disorder are essential for the effective design of therapeutic trials. We systematically followed 81 well defined FSHD patients for up to 3 years using a standardized protocol that included manual muscle testing (MMT), maximum voluntary isometric contraction testing (MVICT), and functional testing. Muscle strength was strongly associated with measures of muscle mass, age at onset, and duration of disease. Decline in strength over time was slow but detectable with both MVICT and MMT. The magnitude of decline was not associated with either age, gender, age at onset, or duration of disease. This study establishes reliable and valid measures of disease state and progression for use as outcome variables in clinical trials in FSHD, and also provides guidelines for determining sample size and duration of follow-up. A two-armed clinical trial involving 160 patients per group and 1 year of follow-up would provide 80% power to detect complete arrest of the progression of the disease. Trials with fewer patients would thus have adequate power to detect only improvements in strength, unless follow-up duration were extended well beyond 1 year. PMID:9008491

  2. A case of ovarian torsion in a patient carrier of a FSH receptor gene mutation previously affected by spontaneous ovarian hyperstimulation syndrome.

    PubMed

    Di Carlo, C; Savoia, F; Fabozzi, A; Gargano, V; Nappi, C

    2015-02-01

    We here report a case of ovarian torsion in a patient with an history of two previous episodes of spontaneous ovarian hyperstimulation syndrome during her two pregnancies. A mutation of follicle-stimulating hormone receptor (FSHr) gene was identified in this patient and in other members of the family. Two years after her successful second pregnancy, the patient showed signs of severe thyroiditis during administration of oral contraceptive, with suppressed TSH and increased thyreoglobulin, in the absence of any abnormalities of the auto-antibodies. In few days, she developed severe pelvic pain and ultrasonographic evidence of increased ovarian volume. She underwent laparoscopy with unilateral adnexectomy for ovarian ischemic necrosis due to adnexal torsion. Our experience suggests that patients' carrier of a mutation of FSHr gene are at risk of ovarian pathologies also when non-pregnant and in the presence of low TSH levels. Further investigations are needed for an appropriate knowledge of typical and atypical manifestations of spontaneous ovarian hyperstimulation syndrome. PMID:25495063

  3. CRISPR/dCas9-mediated Transcriptional Inhibition Ameliorates the Epigenetic Dysregulation at D4Z4 and Represses DUX4-fl in FSH Muscular Dystrophy.

    PubMed

    Himeda, Charis L; Jones, Takako I; Jones, Peter L

    2016-03-01

    Facioscapulohumeral muscular dystrophy (FSHD) is one of the most prevalent myopathies, affecting males and females of all ages. Both forms of the disease are linked by epigenetic derepression of the D4Z4 macrosatellite repeat array at chromosome 4q35, leading to aberrant expression of D4Z4-encoded RNAs in skeletal muscle. Production of full-length DUX4 (DUX4-fl) mRNA from the derepressed D4Z4 array results in misexpression of DUX4-FL protein and its transcriptional targets, and apoptosis, ultimately leading to accumulated muscle pathology. Returning the chromatin at the FSHD locus to its nonpathogenic, epigenetically repressed state would simultaneously affect all D4Z4 RNAs, inhibiting downstream pathogenic pathways, and is thus an attractive therapeutic strategy. Advances in CRISPR/Cas9-based genome editing make it possible to target epigenetic modifiers to an endogenous disease locus, although reports to date have focused on more typical genomic regions. Here, we demonstrate that a CRISPR/dCas9 transcriptional inhibitor can be specifically targeted to the highly repetitive FSHD macrosatellite array and alter the chromatin to repress expression of DUX4-fl in primary FSHD myocytes. These results implicate the promoter and exon 1 of DUX4 as potential therapeutic targets and demonstrate the utility of CRISPR technology for correction of the epigenetic dysregulation in FSHD. PMID:26527377

  4. Follicle-Stimulating Hormone: A Review of Form and Function in the Treatment of Infertility.

    PubMed

    Smitz, Johan; Wolfenson, Claudio; Chappel, Scott; Ruman, Jane

    2016-06-01

    The use of gonadotropin therapy, including follicle-stimulating hormone (FSH), represents an indispensable part of fertility treatment. There are a number of FSH preparations commercially available or in development, including both urinary-derived products (urinary-derived FSH [uFSH]) and FSH produced through recombinant techniques (recombinant FSH [rFSH]). Differences in the glycosylation patterns of FSH give rise to a number of naturally occurring isoforms that may differ functionally. The relative concentrations of these isoforms vary over the course of the menstrual cycle and the lifetime, indicating that these differences in glycosylation may have physiologic relevance. Although both uFSH and rFSH contain human FSH, there are differences in the glycosylation patterns, which may give rise to differences in biologic activity between products. Current FSH products have been shown to have high purity and to exhibit consistent, favorable efficacy and safety profiles for the treatment of infertility, regardless of urinary or recombinant origin. PMID:26446000

  5. Effect of recombinant-LH and hCG in the absence of FSH on in vitro maturation (IVM) fertilization and early embryonic development of mouse germinal vesicle (GV)-stage oocytes.

    PubMed

    Dinopoulou, Vasiliki; Drakakis, Peter; Kefala, Stella; Kiapekou, Erasmia; Bletsa, Ritsa; Anagnostou, Elli; Kallianidis, Konstantinos; Loutradis, Dimitrios

    2016-06-01

    During in vitro maturation (IVM), intrinsic and extrinsic factors must co-operate properly in order to ensure cytoplasmic and nuclear maturation. We examined the possible effect of LH/hCG in the process of oocyte maturation in mice with the addition of recombinant LH (r-LH) and hCG in our IVM cultures of mouse germinal vesicle (GV)-stage oocytes. Moreover, the effects of these hormones on fertilization, early embryonic development and the expression of LH/hCG receptor were examined. Nuclear maturation of GV-stage oocytes was evaluated after culture in the presence of r-LH or hCG. Fertilization rates and embryonic development were assessed after 24h. Total RNA was isolated from oocytes of different stages of maturation and from zygotes and embryos of different stages of development in order to examine the expression of LH/hCG receptor, using RT-PCR. The in vitro nuclear maturation rate of GV-stage oocytes that received hCG was significantly higher compared to the control group. Early embryonic development was increased in the hCG and LH cultures of GV oocytes when LH was further added. The LH/hCG receptor was expressed in all stages of in vitro matured mouse oocytes and in every stage of early embryonic development. Addition of hCG in IVM cultures of mouse GV oocytes increased maturation rates significantly. LH, however, was more beneficial to early embryonic development than hCG. This suggests a promising new technique in basic science research or in clinical reproductive medicine. PMID:27288338

  6. Effect of a long acting GnRH analogue or placebo on plasma LH/FSH, urethral pressure profiles and clinical signs of urinary incontinence due to Sphincter mechanism incompetence in bitches.

    PubMed

    Reichler, Iris Margaret; Jöchle, Wolfgang; Piché, Claude A; Roos, Malgorzata; Arnold, Susi

    2006-09-15

    In 23 bitches with urinary incontinence due to spaying, the effect of treatment with a long-acting formulation of leuprolide acetate on frequency of incontinence, plasma gonadotropin levels and urodynamic parameters was evaluated. In addition, the clinical effect was compared with that of treatment with alpha-adrenergics. Before treatment, the dogs' incontinent episodes occurred, on average, 4 times per day on up to 6 days per week. In the pre-trial after therapy with phenylpropanolamine (n=23) the episodes of incontinence decreased by 92%, in the double-blind study 5 weeks after GnRH-analogue (n=11) by 71%; and by 28% after the placebo (n=12). By the end of the study, nine of twenty-two leuprolide treated bitches responded completely to treatment and were continent for periods lasting 70-575 days after treatment. In another 10 dogs, response to therapy was partial and the frequency of incontinence was reduced by at least 50%. After therapy with placebo, one bitch had no episodes of incontinence for 412 days. Treatment with the GnRH-analogue significantly decreased the plasma gonadotropin levels but there was no correlation between the effect on gonadotropin levels and response to treatment. Treatment with leuprolide or placebo had no effect on urethral closure pressure regardless of the response to treatment. The hypothesis that the change of the plasma gonadotropin levels after spaying is the cause of reduced urethral closure function was not supported by the results of this study. A possible direct effect of GnRH-analogues on the bladder is discussed. Long acting GnRH analogues appear to be a well-tolerated alternative for urinary incontinence treatment, but they appear to be less effective than the alpha-adrenergics. PMID:16672159

  7. Assembly and structural characterization of an authentic complex between human follicle stimulating hormone and a hormone-binding ectodomain of its receptor

    PubMed Central

    Fan, Qing R.; Hendrickson, Wayne A.

    2007-01-01

    Follicle stimulating hormone (FSH) is secreted from the pituitary gland to regulate reproduction in vertebrates. FSH signals through a G-protein coupled receptor (FSHR) on the target cell surface. We describe here the strategy to produce a soluble FSH-FSHR complex that involves the co-secretion of a truncated FSHR ectodomain (FSHRHB) and a covalently-linked FSHαβ heterodimer from baculovirus-infected insect cells. FSH binds to FSHRHB with a high affinity comparable to that for the full-length receptor. The crystal structure of the FSH-FSHRHB complex provides explanations for the high affinity and specificity of FSH interaction with FSHR, and it shows an unexpected dimerization of these complexes. Here we also compare the crystal structure with theoretical models of the FSH-FSHR binding mode. We conclude that the FSH-FSHRHB structure gives an authentic representation of FSH binding to intact FSHR. PMID:17045735

  8. Blood Test: Testosterone

    MedlinePlus

    ... secretes two hormones (luteinizing hormone, or LH; and follicle-stimulating hormone, or FSH) that work together to ... TOPIC Blood Test: Luteinizing Hormone (LH) Blood Test: Follicle Stimulating Hormone (FSH) Blood Test: Estradiol Precocious Puberty ...

  9. Genetics Home Reference: fragile X-associated primary ovarian insufficiency

    MedlinePlus

    ... and elevated levels of a hormone known as follicle stimulating hormone (FSH). FSH is produced in both males and females and helps regulate the development of reproductive cells (eggs in females and sperm ...

  10. Macro- and Micro-heterogeneity in Pituitary and Urinary Follicle-Stimulating Hormone Glycosylation

    PubMed Central

    Bousfield, George R.; Butnev, Vladimir Y.; Rueda-Santos, Monica A.; Brown, Alan; Hall, Aaron Smalter; Harvey, David J.

    2015-01-01

    FSH glycosylation macroheterogeneity in pituitary and urinary hFSH samples was evaluated by Western blotting. Microheterogeneity in two highly purified urinary and pituitary hFSH preparations was evaluated by nano-electrospray mass spectrometry of peptide-N-glycanase-released oligosaccharides. An age-related loss of hypo-glycosylated hFSH in individual female pituitaries was indicated by progressively reduced abundance of hFSH21 relative to hFSH24. Urinary hFSH was evaluated as a potentially non-invasive indicator of glycoform abundance, as the only way for pituitary FSH to reach the urine is through the blood. Both highly purified and crude postmenopausal urinary hFSH preparations possessed the same amount of hFSH21 as postmenopausal pituitary gland FSH. Considerable microheterogeneity was encountered in both pituitary and urinary hFSH glycan populations, as 84 pituitary hFSH glycan ions were observed as compared with 68 urinary hFSH glycans. The biggest quantitative differences between the two populations were reduced abundance of bisecting GlcNAc-containing and fucosylated glycans, along with sulfated glycans in the urinary hFSH glycan population. The relative abundance of sialic acid and glycan antenna did not rationalize the retarded electrophoretic mobilities of the urinary hFSHβ21- and α-subunit bands relative to the corresponding pituitary hFSH bands, as the most abundant glycans in the former possessed only 2 more branches and the same sialic content as in the latter. Site-specific glycosylation information will probably be necessary. PMID:25722940

  11. 36 CFR 215.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... statement (EIS) nor an environmental assessment (EA) is required (40 CFR 1508.4; FSH 1909.15, Chapter 30... follow CEQ procedures for notice and comment (40 CFR parts 1503 and 1506.10; FSH 1909.15, Chapter 20... environmental assessment and a Finding of No Significant Impact (FONSI) (40 CFR 1508.13; FSH 1909.15, Chapter...

  12. 36 CFR 215.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... an environmental assessment (EA) is required (40 CFR 1508.4; FSH 1909.15, Chapter 30). Comment period... procedures for notice and comment (40 CFR parts 1503 and 1506.10; FSH 1909.15, Chapter 20). The time period... assessment and a Finding of No Significant Impact (FONSI) (40 CFR 1508.13; FSH 1909.15, Chapter...

  13. 36 CFR 215.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... statement (EIS) nor an environmental assessment (EA) is required (40 CFR 1508.4; FSH 1909.15, Chapter 30... follow CEQ procedures for notice and comment (40 CFR parts 1503 and 1506.10; FSH 1909.15, Chapter 20... environmental assessment and a Finding of No Significant Impact (FONSI) (40 CFR 1508.13; FSH 1909.15, Chapter...

  14. 36 CFR 215.2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... an environmental assessment (EA) is required (40 CFR 1508.4; FSH 1909.15, Chapter 30). Comment period... procedures for notice and comment (40 CFR parts 1503 and 1506.10; FSH 1909.15, Chapter 20). The time period... assessment and a Finding of No Significant Impact (FONSI) (40 CFR 1508.13; FSH 1909.15, Chapter...

  15. Immunocytochemical localization and ultrastructural study of gonadotroph cells in the female desert lizard Uromastyx acanthinura.

    PubMed

    Hammouche, S; Gernigon, T; Exbrayat, J M

    2007-02-01

    The pars distalis from the pituitary gland of adult female desert lizards (Uromastyx acanthinura), captured during vitellogenesis (late may) and hivernal period, was studied with immunocytochemical methods using specific antisera against human FSH (hFSH) and LH (hLH). The immunostaining with anti-hLH and anti-hFSH allowed the identification of only FSH-like containing cells. The FSH-like immunoreactive cells were affected differently by a physiological stage and showed some heterogenous cytological characteristics. During vitellogenesis, four aspects of rostral FSH-like immunoreactive cells could be recognized. The expression of FSH-like in mainly immunoreactive cells was parallel to an intense synthetic activity and to the presence of ultrastructural features indicating an intense release of the hormone. This release was considerably altered in winter, the immunoreactive cells stored an important amount of secretion granules which increased in size and undergo a crinophagic process. PMID:17098269

  16. Effect of duration of the growing phase of ovulatory follicles on oocyte competence in superstimulated cattle.

    PubMed

    Dias, F C F; Costa, E; Adams, G P; Mapletoft, R J; Kastelic, J; Dochi, O; Singh, J

    2013-01-01

    In the present study, we tested the hypotheses that oocyte competence is compromised by a longer duration of follicular growth and that it is not affected by FSH starvation. Cows were allocated to short FSH (n=14), FSH starvation (n=13) and long FSH (n=13) groups. The first two groups were given eight doses of FSH, whereas the third group was given 14 doses of FSH, starting from the day of wave emergence (Day 0). A progesterone-releasing device (controlled internal drug release; CIDR) was placed intravaginally at the start of the experiment in all groups. The short FSH group was given prostaglandin (PG) F2α on Day 3, whereas the two other groups received PGF2α on Day 6. In all cows, the CIDR was removed at the time of PGF treatment; porcine (p) LH was given 24h after CIDR removal and cows were inseminated 24 and 36 h later. Reproductive tracts were collected 4 days after insemination and ova and/or embryos were cultured for ≥6 days. The FSH starvation group had fewer ovulations (P=0.001), and ova and/or embryos (P<0.05). No difference in embryo quality was detected between long and short FSH groups at 7, 9 or 10 days after artificial insemination. In conclusion, oocyte competence was not altered by the duration of the follicular growth phase in superstimulated cows, whereas FSH starvation substantially reduced the ability of superstimulated follicles to ovulate. PMID:23464499

  17. Positive feedback effect of oestradiol in superovulated women.

    PubMed

    Messinis, I E; Mademtzis, I; Zikopoulos, K; Tsahalina, E; Seferiadis, K; Tsolas, O; Templeton, A A

    1992-04-01

    To investigate the mechanism of blockage of the luteinizing hormone (LH) surge in superovulated women, six normally ovulating women were studied in three cycles: a spontaneous cycle treated with exogenous oestrogen (oestradiol benzoate cycle), a cycle treated with follicle stimulating hormone (FSH; 225 IU/day; FSH cycle) and a cycle treated with FSH plus exogenous oestrogen (FSH + oestradiol benzoate cycle). Oestradiol benzoate was injected i.m. on cycle days 4 (0800 and 2000 h), 5 (0800 h) and 6 (0800 h) at doses of 0.5, 1.0, 2.0 and 2.5 mg respectively to achieve supraphysiological levels of serum oestradiol. Exogenous oestrogen (supraphysiological oestradiol levels) induced an LH surge in all six women in the oestradiol benzoate cycles, but failed to stimulate an LH surge in three of the six patients during treatment with FSH. In three patients treated with FSH, an LH surge was stimulated both by supraphysiological (FSH + oestradiol benzoate cycles) and 'high normal' oestradiol levels (FSH cycles), while in three patients treated with FSH only, the LH surge was blocked, although the threshold level for the positive feedback effect had been exceeded by cycle day 9. We conclude that in women, supraphysiological concentrations of oestradiol exert a positive feedback effect on LH secretion. It is suggested that the occurrence of an LH surge in cycles superovulated with FSH is not dependent on serum oestradiol concentrations, but mainly on the strength of ovarian inhibitory substances. PMID:1522187

  18. The M-OVIN study: does switching treatment to FSH and / or IUI lead to higher pregnancy rates in a subset of women with world health organization type II anovulation not conceiving after six ovulatory cycles with clomiphene citrate – a randomised controlled trial

    PubMed Central

    2013-01-01

    Background Clomiphene citrate (CC) is first line treatment in women with World Health Organization (WHO) type II anovulation and polycystic ovary syndrome (PCOS). Whereas 60% to 85% of these women will ovulate on CC, only about one half will have conceived after six cycles. If women do not conceive, treatment can be continued with gonadotropins or intra-uterine insemination (IUI). At present, it is unclear for how many cycles ovulation induction with CC should be repeated, and when to switch to ovulation induction with gonadotropins and/or IUI. Methods/Design We started a multicenter randomised controlled trial in the Netherlands comparing six cycles of CC plus intercourse or six cycles of gonadotrophins plus intercourse or six cycles of CC plus IUI or six cycles of gonadotrophins plus IUI. Women with WHO type II anovulation who ovulate but did not conceive after six ovulatory cycles of CC with a maximum of 150 mg daily for five days will be included. Our primary outcome is birth of a healthy child resulting from a pregnancy that was established in the first eight months after randomisation. Secondary outcomes are clinical pregnancy, miscarriage, multiple pregnancy and treatment costs. The analysis will be performed according to the intention to treat principle. Two comparisons will be made, one in which CC is compared to gonadotrophins and one in which the addition of IUI is compared to ovulation induction only. Assuming a live birth rate of 40% after CC, 55% after addition of IUI and 55% after ovulation induction with gonadotrophins, with an alpha of 5% and a power of 80%, we need to recruit 200 women per arm (800 women in total). An independent Data and Safety Monitoring Committee has criticized the data of the first 150 women and concluded that a sample size re-estimation should be performed after including 320 patients (i.e. 80 per arm). Discussion The trial will provide evidence on the most effective, safest and most cost effective treatment in women with WHO type II anovulation who do not conceive after six ovulatory cycles with CC with a maximum of 150 mg daily for five days. This evidence could imply the need for changing our guidelines, which may cause a shift in large practice variation to evidence based primary treatment for these women. Trial registration number Netherlands Trial register NTR1449 PMID:24160333

  19. Sertoli Cell-specific Expression of Metastasis-associated Protein 2 (MTA2) Is Required for Transcriptional Regulation of the Follicle-stimulating Hormone Receptor (FSHR) Gene during Spermatogenesis*

    PubMed Central

    Zhang, Shun; Li, Wei; Zhu, Chuchao; Wang, Xiaohong; Li, Zhen; Zhang, Jinshan; Zhao, Jie; Hu, Jing; Li, Teng; Zhang, Yuanqiang

    2012-01-01

    The effect of follicle-stimulating hormone (FSH) on spermatogenesis is modulated at a fundamental level by controlling the number of competent receptors present at the surface of Sertoli cells (SCs). One underlying mechanism is the down-regulation of the expression levels of the FSH receptor (FSHR) gene after exposure to FSH. Here we report that metastasis-associated protein 2 (MTA2), a component of histone deacetylase and nucleosome-remodeling complexes, as a gene product induced directly by testosterone or indirectly by FSH, is exclusively expressed in SCs. Stimulation of SCs with FSH is accompanied by up-regulation of MTA2 expression and enhancement of deacetylase activity. This effect requires the integrity of functional androgen receptor. Furthermore, MTA2 is a potent corepressor of FSHR transcription, because it can recruit histone deacetylase-1 onto the FSHR promoter and participates in the down-regulation of FSHR expression upon FSH treatment. Abolishment of endogenous MTA2 by siRNA treatment disrupted the desensitization of the FSH response and thereafter impaired the FSH-dependent secretory function of SCs. From a clinical standpoint, deregulated expression of MTA2 in SCs of human pathological testes negatively correlates to the deregulated level of serum FSH. Overall, our present results provide the first evidence that the FSH/androgen receptor/MTA2 cascade may serve as an indispensable negative feedback mechanism to modulate the transduction events of SCs in response to FSH. These data also underscore an unexpected reproductive facet of MTA2, which may operate as a novel integrator linking synergistic actions of FSH and androgen signaling in SCs. PMID:23086931

  20. Studies on the structure of the follicle-stimulating hormone receptor using photoaffinity labeling procedures

    SciTech Connect

    Smith, R.A.

    1985-01-01

    The general objective of this project was to study the structure of the follicle stimulating hormone (FSH) receptor using affinity labeling methods. A low density fraction derived from homogenates of bovine testis was found to contain high affinity and low capacity receptors specific for FSH. Electron microscopic examination of the fraction revealed structure resembling multilamellar membranous vesicles (MV). For photoaffinity labeling of the FSH receptors in MV, an azidobenzoyl-/sup 125/I-analog of human FSH was prepared (/sup 125/I-AB-hFSH) and binding of specific FSH receptors was studied. /sup 125/I-AB-hFSH binding of receptors was inhibited in a dose dependent manner by unlabeled hFSH, and binding was not prevented by structurally-related human chorionic gonadotropin (hCG). The formation of photocrosslinked protein of relative molecular mass (M/sub r/) 54,000, 64,000, 76,000, 84,000, 97,000 and 116,000 was found to be inhibited by unlabeled hFSH in a dose related manner, and to be dependent on photoactivation of the FSH derivative. The interpretation of the photoaffinity labeling experiments was that three proteins associated with the FSH receptor were photoaffinity labeled. Analysis by indirect means suggested that the three proteins were assembled to form oligomeric complexes, and based on the intensities and composition of the oligomeric species, spatial relationships of the polypeptides with respect to each other on the membrane surface were deduced. The results of photoaffinity labeling suggest the FSH receptor is composed of three subunits of M/sub r/ 38,000, 48,000, and 81,000 and exists in the membrane in part as a M/sub r/ 330,000 dimer.

  1. Chicken lutropin acts like follitropin in rat ovarian follitropin receptor: an isoelectric focusing study.

    PubMed

    Iwasawa, A; Hattori, M; Fukuhara, Y; Kawashima, M; Wakabayashi, K; Kamiyoshi, M

    1998-07-01

    This study investigates whether chicken lutropin (LH) specifically binds to rat ovarian follitropin (FSH) receptor and exerts FSH-like bioactivity. Glycoprotein fraction, prepared from the chicken anterior pituitary gland, was fractionated using isoelectric focusing within a pH range of 3.5-11. Analysis of the focused fractions, by a radioreceptor assay (RRA) specific for FSH in rats using rat ovarian homogenate as receptor source, and 125I-labeled rat FSH as radioligand, detected a large component having an isoelectric point of 10.25. This focusing profile obtained by RRA was quite similar to that obtained by a specific radioimmunoassay (RIA) for chicken LH, but clearly different from that obtained by a specific RIA for chicken FSH, indicating this RRA specifically recognizes chicken LH. Chicken LH fraction prepared from the electrofocused material was used for further studies. The chicken LH preparation was three times more potent than rat FSH in the RRA in displacing the radioligand bound to rat ovarian receptor, while chicken LH facilitated an 8-fold less production of estradiol in dispersed rat granulosa cells than rat FSH. These results suggest that chicken LH acts like rat FSH in rat ovarian FSH receptor, but receptor-binding activity is much higher than biological activity. PMID:9827020

  2. Blood Test: Estradiol

    MedlinePlus

    ... Testosterone Blood Test: Luteinizing Hormone (LH) Blood Test: Follicle Stimulating Hormone (FSH) Understanding Early Sexual Development Precocious Puberty Understanding Puberty Endocrine System Getting a ...

  3. Abdominal mesotherapy injection extended the absorption of follicle-stimulating hormone.

    PubMed

    Hsu, Chao-Chin; Kuo, Hsin-Chih; Hsu, Chao-Tien; Gu, Qing

    2011-05-01

    Abdominal mesotherapy injection of recombinant human FSH (rhFSH) was well tolerated with increased net absorption (AUC0-∞ 4,655.3 IU·h/L and t1/2 247.6 h) up to 360 hours compared with those of 120 hours (AUC0-∞ 1,915.7 IU·h/L and t1/2 101.8 h). The extended absorption of rhFSH suggests that abdominal mesotherapy injection mode be considered for future administration of rhFSH in controlled ovarian hyperstimulation. PMID:21208615

  4. Follicular characteristics and luteal development after follicle-stimulating hormone induced multiple ovulations in heifers.

    PubMed

    Glick, G; Hogeg, M; Moallem, U; Lavon, Y; Wolfenson, D

    2013-01-01

    A protocol based on small doses of FSH was examined for the induction of double or triple (multiple) ovulations in cattle. Ovulation rate, follicular characteristics, and luteal responses were determined. In Exp. 1, three groups of estrous-synchronized, cyclic Holstein heifers were treated once daily, on d 3 to 6 of the cycle, with a FSH product (Folltropin-V): large FSH dose (total of 150 mg; n=18), medium FSH dose (total of 130 mg, n=12), and small FSH dose (total of 80 mg; n=7). Controls received saline (n=6). Prostaglandin F(2α) was injected on d 6, ultrasound-guided aspiration of surplus follicles (if needed) was performed on d 7, and GnRH was injected on d 8 to induce ovulation. The large FSH dose induced growth of more (2.6±0.3, P<0.05) large follicles than controls on d 8; medium and small FSH doses insufficiently stimulated growth of <2 large follicles. Ovulation rates were determined in subgroups of heifers (n=10, 13, 4, and 6, respectively). The large FSH dose induced greater rates (P<0.01) of mostly double and triple ovulations (90% multiple ovulations, 70% double ovulations), most of which (89%) were bilateral, with only 2 out of 10 heifers requiring aspiration of surplus follicles. Medium and small FSH doses induced fewer multiple ovulations (38% and 25%, respectively). Estradiol concentrations on d 8 did not differ among treatments, but the concentration per large follicle in controls was greater (P<0.05) than in FSH treatments. Mean corpus luteum (CL) volume in single-ovulation controls was greater (P<0.05) than that of multiple ovulations in the large FSH group and total CL volume and progesterone concentrations were numerically greater in multiple ovulations. In Exp. 2, the characteristics of follicles aspirated on d 7 from large FSH (n=11) and control heifers (n=10) were compared. Based on estradiol-to-progesterone ratio, 57% of the large FSH-treated follicles were classified as codominant/healthy follicles and 43% as subordinate/early atretic

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

    SciTech Connect

    Geng, Wenxin; Yan, Xingrong; Du, Huicong; Cui, Jihong; Li, Liwen Chen, Fulin

    2013-05-03

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

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

    PubMed Central

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

    2015-01-01

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

  7. Follicle-stimulating hormone increases the intramuscular fat content and expression of lipid biosynthesis genes in chicken breast muscle*

    PubMed Central

    Cui, Xiao-yan; Li, Ying-ying; Liu, Ran-ran; Zhao, Gui-ping; Zheng, Mai-qing; Li, Qing-he; Wen, Jie

    2016-01-01

    Intramuscular fat (IMF) is a crucial factor in the quality of chicken meat. The genetic basis underlying it is complex. Follicle-stimulating hormone (FSH), well-known as an effector in reproductive tissues, was recently discovered to stimulate abdominal fat accumulation in chicken. The effect of FSH on IMF accumulation and the underlying molecular regulatory mechanisms controlling both IMF and abdominal fat deposition in vivo are largely unknown. In this study, two groups of chickens were treated with chicken FSH or a placebo. The lipid content of breast muscle, abdominal fat volume, and serum concentrations of FSH were examined. Related genes implicated in breast muscle and abdominal fat accumulation were also investigated. Compared to the control group, the triglyceride (TG) content of breast muscle and the percentage of abdominal fat in FSH-treated chickens were significantly increased by 64.9% and 56.5% (P<0.01), respectively. The FSH content in the serum of FSH-treated chickens was 2.1 times than that of control chickens (P<0.01). Results from quantitative real-time polymerase chain reaction (qRT-PCR) assays showed that relative expression levels of fatty acid synthase (FAS), lipoprotein lipase (LPL), diacylglycerol acyltransferase 2 (DGAT2), adipocyte fatty acid binding protein (A-FABP), and peroxisome proliferator-activated receptor γ (PPARγ) were significantly upregulated in breast muscle following FSH treatment (P<0.01). Treatment with FSH also significantly increased relative expression levels of FAS, LPL, DGAT2, A-FABP, and PPARγ in abdominal fat tissue (P<0.05). The results of principal component analysis (PCA) for gene expression (breast muscle and abdominal fat) showed that the control and FSH treatment groups were well separated, which indicated the reliability of the data. This study demonstrates that FSH plays an important role in IMF accumulation in female chickens, which likely involves the regulation of biosynthesis genes related to lipid

  8. Characterization of human follicle-stimulating hormone binding to human granulosa cells by an immunoenzymological method.

    PubMed

    Perrotin, F; Royere, D; Roussie, M; Combarnous, Y; Lansac, J; Müh, J P

    1992-04-01

    An original, nonradiometric method has been developed for studying the binding parameters of native follicle-stimulating hormone (FSH) to its specific receptors in human ovarian granulosa cells. After binding and washing of the cells, hFSH was desorbed from its receptors and quantitatively measured by a specific enzyme immunoassay (EIA) in which nonspecific binding was estimated in the presence of an excess of equine chorionic gonadotropin (eCG/PMSG), which binds to human FSH receptors but does not interfere in the hFSH EIA. This method makes use of native nonmodified hFSH molecules (in contrast to radiometric methods) and permits direct estimation of the binding parameters (Kd and total number of sites). The Kd of hFSH for its human granulosa receptors measured by this technique (4.8 +/- 0.3 x 10(-10) M) is close to that determined by other methods. However, we found a total number of specific FSH receptors per granulosa cell (1 to 6 x 10(4) higher than that reported by others by Scatchard analysis of competition dose-response curves in radioreceptor assays. The method is also sensitive enough to measure the in vivo occupancy of receptors by endogenous hFSH, which was found to be less than 6% in women undergoing hormonal treatment for in vitro fertilization. PMID:1621987

  9. Protein Kinase A: A Master Kinase of Granulosa Cell Differentiation

    PubMed Central

    Puri, Pawan; Little-Ihrig, Lynda; Chandran, Uma; Law, Nathan C.; Hunzicker-Dunn, Mary; Zeleznik, Anthony J.

    2016-01-01

    Activation of protein kinase A (PKA) by follicle stimulating hormone (FSH) transduces the signal that drives differentiation of ovarian granulosa cells (GCs). An unresolved question is whether PKA is sufficient to initiate the complex program of GC responses to FSH. We compared signaling pathways and gene expression profiles of GCs stimulated with FSH or expressing PKA-CQR, a constitutively active mutant of PKA. Both FSH and PKA-CQR stimulated the phosphorylation of proteins known to be involved in GC differentiation including CREB, ß-catenin, AKT, p42/44 MAPK, GAB2, GSK-3ß, FOXO1, and YAP. In contrast, FSH stimulated the phosphorylation of p38 MAP kinase but PKA-CQR did not. Microarray analysis revealed that 85% of transcripts that were up-regulated by FSH were increased to a comparable extent by PKA-CQR and of the transcripts that were down-regulated by FSH, 76% were also down-regulated by PKA-CQR. Transcripts regulated similarly by FSH and PKA-CQR are involved in steroidogenesis and differentiation, while transcripts more robustly up-regulated by PKA-CQR are involved in ovulation. Thus, PKA, under the conditions of our experimental approach appears to function as a master upstream kinase that is sufficient to initiate the complex pattern of intracellular signaling pathway and gene expression profiles that accompany GC differentiation. PMID:27324437

  10. 36 CFR 218.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... reduction project: A hazardous fuel reduction project authorized by the Healthy Forests Restoration Act of... CFR 1508.13; Forest Service Handbook (FSH) 1909.15, chapter 40). Environmental assessment (EA): A... of a statement when one is necessary (40 CFR 1508.9; FSH 1909.15, Chapter 40). Environmental...

  11. 36 CFR 218.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... reduction project: A hazardous fuel reduction project authorized by the Healthy Forests Restoration Act of... CFR 1508.13; Forest Service Handbook (FSH) 1909.15, chapter 40). Environmental assessment (EA): A... of a statement when one is necessary (40 CFR 1508.9; FSH 1909.15, Chapter 40). Environmental...

  12. 36 CFR 218.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... reduction project: A hazardous fuel reduction project authorized by the Healthy Forests Restoration Act of... CFR 1508.13; Forest Service Handbook (FSH) 1909.15, chapter 40). Environmental assessment (EA): A... of a statement when one is necessary (40 CFR 1508.9; FSH 1909.15, Chapter 40). Environmental...

  13. Comparative glycomics of the glycoprotein follicle stimulating hormone: glycopeptide analysis of isolates from two mammalian species.

    PubMed

    Dalpathado, Dilusha S; Irungu, Janet; Go, Eden P; Butnev, Vladimir Y; Norton, Katie; Bousfield, George R; Desaire, Heather

    2006-07-18

    Follicle stimulating hormone (FSH) is one of the important hormones that regulate gonadal functions. This hormone is glycosylated, and the glycans greatly influence the biological properties. In the present study the negatively charged glycopeptides of equine and human pituitary follicle stimulating hormone (eFSH and hFSH) have been characterized in a glycosylation site-specific manner using FT-ICR-MS and Edman sequencing. The characteristic pattern of glycan distribution at each glycosylation site has been deduced and compared between horse and human FSH preparations. The data suggest that site-specific differences exist between glycoforms of human and equine FSH. For instance, except for one site in the beta subunit (Asn7) of hFSH all other sites in both species have sulfated glycoforms. Also, glycoforms at Asn52 of hFSH are all complex type, whereas in eFSH, both complex and hybrid structures exist at this site. There is also a higher percentage of sulfated glycans in the latter site compared to the former. This is the first study that characterizes the glycans from this hormone in a glycosylation site-specific manner, and these data can be used to begin correlative studies between glycosylation structure and hormone function. PMID:16834341

  14. Discrepancies between Antimullerian Hormone and Follicle Stimulating Hormone in Assisted Reproduction

    PubMed Central

    Cahill, David; Gordon, Uma

    2013-01-01

    Data from 107 women undergoing their first IVF/ICSI were analyzed. Relationships between antimullerian hormone (AMH) and follicle stimulating hormone (FSH) were analyzed after dividing patients into four groups according to AMH/FSH levels. Concordance was noted in 57% of women (both AMH/FSH either normal or abnormal) while 43%of women had discordant values (AMH/FSH one hormone normal and the other abnormal). Group 1 (AMH and FSH in normal range) and group 2 (normal AMH and high FSH) were younger compared to group 3 (low AMH and normal FSH) and group 4 (both AMH/FSH abnormal). Group 1 showing the best oocyte yield was compared to the remaining three groups. Groups 3 and 4 required higher dose of gonadotrophins for controlled ovarian hyperstimulation showing their low ovarian reserve. There was no difference in cycle cancellation, clinical pregnancy, and live birth/ongoing pregnancy rate in all groups. These tests are useful to predict ovarian response but whether AMH is a substantially better predictor is not yet established. PMID:24454387

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

    EPA Science Inventory

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

  16. Sex hormones, sexual activity and plasma anticonvulsant levels in male epileptics.

    PubMed Central

    Toone, B K; Wheeler, M; Nanjee, M; Fenwick, P; Grant, R

    1983-01-01

    Testosterone, LH, FSH, PRL, and sex hormone binding globulin (SHBG) were measured in 72 male epileptic patients on chronic anticonvulsant drug regimes. Sexual activity was estimated and plasma anticonvulsants measured. Total testosterone (TT), LH, FSH, PRL, and SHBG were increased; free testosterone (FT) was decreased. Sexual activity appeared diminished particularly in relation to reduced FT. PMID:6413659

  17. Comparison of Follicle-Stimulating Hormone Glycosylation Microheterogenity by Quantitative Negative Mode Nano-Electrospray Mass Spectrometry of Peptide-N Glycanase-Released Oligosaccharides

    PubMed Central

    Bousfield, George R.; Butnev, Vladimir Y.; White, William K.; Hall, Aaron Smalter; Harvey, David J.

    2015-01-01

    Glycans from six highly purified hFSH preparations were released by peptide-N-glycanase digestion and analyzed by negative mode nano-ESI mass spectrometry before and after neuraminidase digestion. Pituitary glycan structures were mainly high-mannose, di-, tri-, and tetra-antennary, and their abundance largely paralleled that reported by other investigators using different approaches. For most of the FSH preparations, the differences in glycosylation appeared to be restricted to relative abundances of the major glycan families, as defined by their neutral core oligosaccharide structures. Qualitative differences between glycan populations were largely relegated to those species that were lowest in abundance. Significant qualitative differences were noted in two cases. Recombinant GH3-hFSH triantennary glycans appeared to have the third antenna exclusively on the mannose6-branch, in contrast to all pituitary and urinary hFSH triantennary glycans, in which this antenna was exclusively attached to the mannose3-branch. The hypo-glycosylated hFSH preparation isolated from purified hLH was decorated with high mannose glycans that accounted for over 40% of the total in this population. As this preparation was found to be consistently 20-fold more active than hFSH24 in FSH receptor-binding assays, it appears that both macroheterogeneity and microheterogeneity in FSH preparations need to be taken into account. PMID:25960929

  18. Data on the characterization of follicle-stimulating hormone monoclonal antibodies and localization in Japanese eel pituitary.

    PubMed

    Kim, Dae-Jung; Park, Chae-Won; Byambaragchaa, Munkhzaya; Kim, Shin-Kwon; Lee, Bae-Ik; Hwang, Hyung-Kyu; Myeong, Jeong-In; Hong, Sun-Mee; Kang, Myung-Hwa; Min, Kwan-Sik

    2016-09-01

    Monoclonal antibodies were generated against recombinant follicle-stimulating hormone (rec-FSH) from Japanese eel Anguilla japonica; rec-FSH was produced in Escherichia coli and purified using Ni-NTA Sepharose column chromatography. In support of our recent publication, "Production and characterization of monoclonal antibodies against recombinant tethered follicle-stimulating hormone from Japanese eel Anguilla japonica" [1], it was important to characterize the specificity of eel follicle-stimulating hormone antibodies. Here, the production and ELISA system of these monoclonal antibodies are presented. The affinity-purified monoclonal antibodies specifically detected eel rec-FSH in ELISA and on western blots of rec-FSH produced from CHO cells. Immunohistochemical analysis revealed that FSH staining was specifically localized in the eel pituitary. PMID:27331121

  19. Luteinizing hormone and follicle stimulating hormone synergy: A review of role in controlled ovarian hyper-stimulation

    PubMed Central

    Raju, Gottumukkala Achyuta Rama; Chavan, Rahul; Deenadayal, Mamata; Gunasheela, Devika; Gutgutia, Rohit; Haripriya, Geetha; Govindarajan, Mirudhubashini; Patel, Nayana Hitesh; Patki, Ameet Shashikant

    2013-01-01

    Luteinizing hormone (LH) in synergy with follicle stimulating hormone (FSH) stimulates normal follicular growth and ovulation. FSH is frequently used in assisted reproductive technology (ART). Recent studies have facilitated better understanding on the complementary role of the LH to FSH in regulation of the follicle; however, role of LH in stimulation of follicle, optimal dosage of LH in stimulation and its importance in advanced aged patients has been a topic of discussion among medical fraternity. Though the administration of exogenous LH with FSH is obligatory for controlled ovarian stimulation in patients with hypogonadotropic hypogonadism, there is still a paucity of information of its usage in other patient population. In this review we looked in to the multiple roles that LH plays complementary to FSH to better understand the LH requirement in patients undergoing ART. PMID:24672160

  20. Pharmacologic profiling of corifollitropin alfa, the first developed sustained follicle stimulant.

    PubMed

    Verbost, Pieter; Sloot, Willem N; Rose, Ursula M; de Leeuw, Renato; Hanssen, Rob G J M; Verheijden, Gijs F M

    2011-01-25

    Corifollitropin alfa (Elonva®, MSD, previously N.V. Organon or Schering-Plough Oss, The Netherlands) is a newly developed sustained follicle stimulant composed of the α subunit of human follicle-stimulating hormone (FSH) and a hybrid β subunit formed by fusion of the human chorionic gonadotropin β subunit carboxy terminal peptide with the β subunit of human FSH. Binding characteristics of corifollitropin alfa at the rat FSH receptor and transactivation properties at the rat FSH receptor, human luteinizing hormone (LH) receptor, and human thyroid-stimulating hormone receptor (TSH receptor) were assessed in vitro. Bioactivity of corifollitropin alfa in rats was also assessed. Serum corifollitropin alfa levels in rats and dogs were used to derive the main pharmacokinetic parameters of corifollitropin alfa. Binding and transactivation profile of corifollitropin alfa to rat FSH receptor was specific and comparable to that of recombinant human FSH, with no intrinsic TSH receptor or LH receptor activation. From pharmacokinetic studies, circulating half-life of corifollitropin alfa was calculated to be 17.3h in rats and 46.9h in dogs, 1.5- to 2-fold longer than recombinant FSH. Corifollitropin alfa demonstrated a 2- to 4-fold increase in bioactivity (ovarian weight, serum estradiol and progesterone, ovulated ova) over recombinant FSH across all in vivo parameters assessed. These data demonstrate that corifollitropin alfa is a specific ligand with high affinity for FSH receptor, lacking intrinsic activity for LH receptor and TSH receptor. By virtue of its increased in vivo half-life, corifollitropin alfa can be a valuable alternative to FSH by acting as a sustained follicle stimulant. PMID:21115001

  1. Conversion of human choriogonadotropin into a follitropin by protein engineering.

    PubMed

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

    1991-02-01

    Human reproduction is dependent upon the actions of follicle-stimulating hormone (hFSH), luteinizing hormone (hLH), and chorionic gonadotropin (hCG). While the alpha subunits of these heterodimeric proteins can be interchanged without effect on receptor-binding specificity, their beta subunits differ and direct hormone binding to either LH/CG or FSH receptors. Previous studies employing chemical modifications of the hormones, monoclonal antibodies, or synthetic peptides have implicated hCG beta-subunit residues between Cys-38 and Cys-57 and corresponding regions of hLH beta and hFSH beta in receptor recognition and activation. Since the beta subunits of hCG or hLH and hFSH exhibit very little sequence similarity in this region, we postulated that these residues might contribute to hormone specificity. To test this hypothesis we constructed chimeric hCG/hFSH beta subunits, coexpressed them with the human alpha subunit, and examined their ability to interact with LH and FSH receptors and hormone-specific monoclonal antibodies. Surprisingly, substitution of hFSH beta residues 33-52 for hCG beta residues 39-58 had no effect on receptor binding or stimulation. However, substitution of hFSH beta residues 88-108 in place of the carboxyl terminus of hCG beta (residues 94-145) resulted in a hormone analog identical to hFSH in its ability to bind and stimulate FSH receptors. The altered binding specificity displayed by this analog is not attributable solely to the replacement of hCG beta residues 108-145 or substitution of residues in the "determinant loop" located between hCG beta residues 93 and 100. PMID:1899483

  2. Conversion of human choriogonadotropin into a follitropin by protein engineering

    SciTech Connect

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

    1991-02-01

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

  3. Rescue from dominant follicle atresia by follicle-stimulating hormone in mice.

    PubMed

    Zhou, X L; Teng, Y; Cao, R; Fu, H; Xiong, K; Sun, W X; Zhu, C C; Huang, X J; Xiao, P; Liu, H L

    2013-01-01

    We investigated the effects of follicle-stimulating hormone (FSH) on atresia of the dominant follicle and changes in relevant apoptosis genes in granulosa cells of dominant follicles regulated by FSH in vivo. Four-week-old mice were administered FSH by intraperitoneal injection to induce follicular maturation. Granulosa cells of dominant follicles were collected at 48, 72, and 96 h after the first FSH injection. Phosphate-buffered saline was injected as a control. The mRNA levels of relevant granulosa cell apoptosis genes were examined by real-time quantitative polymerase chain reaction, and apoptosis of granulosa cells in dominant ovarian follicles was determined by the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Apoptosis in granulosa cells of dominant follicles was almost TUNEL-negative at 48, 72-66, 72, and 96-90 h after the first FSH injection, but granulosa cell apoptosis in dominant follicles was clearly detected at 96, 102, and 102-96 h by TUNEL. The BIM, caspase-3, and caspase-9 mRNA expression levels were significantly lower after FSH treatment at 72-66 and 96-90 h, compared with that at 72 and 96 h (P < 0.05). Caspase-8 and FasL mRNA expressions did not respond to FSH. FSH rescued granulosa cells from apoptosis when the relevant apoptosis genes were upregulated in early atretic follicles. FSH did not rescue granulosa cells from apoptosis if the DNA was cut into fragments by endonucleases. Thus, the rescue by FSH of granulosa cells from apoptosis and dominant follicle atresia may be accomplished by inhibition of apoptosis in mitochondria. PMID:24065650

  4. Conversion of human choriogonadotropin into a follitropin by protein engineering.

    PubMed Central

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

    1991-01-01

    Human reproduction is dependent upon the actions of follicle-stimulating hormone (hFSH), luteinizing hormone (hLH), and chorionic gonadotropin (hCG). While the alpha subunits of these heterodimeric proteins can be interchanged without effect on receptor-binding specificity, their beta subunits differ and direct hormone binding to either LH/CG or FSH receptors. Previous studies employing chemical modifications of the hormones, monoclonal antibodies, or synthetic peptides have implicated hCG beta-subunit residues between Cys-38 and Cys-57 and corresponding regions of hLH beta and hFSH beta in receptor recognition and activation. Since the beta subunits of hCG or hLH and hFSH exhibit very little sequence similarity in this region, we postulated that these residues might contribute to hormone specificity. To test this hypothesis we constructed chimeric hCG/hFSH beta subunits, coexpressed them with the human alpha subunit, and examined their ability to interact with LH and FSH receptors and hormone-specific monoclonal antibodies. Surprisingly, substitution of hFSH beta residues 33-52 for hCG beta residues 39-58 had no effect on receptor binding or stimulation. However, substitution of hFSH beta residues 88-108 in place of the carboxyl terminus of hCG beta (residues 94-145) resulted in a hormone analog identical to hFSH in its ability to bind and stimulate FSH receptors. The altered binding specificity displayed by this analog is not attributable solely to the replacement of hCG beta residues 108-145 or substitution of residues in the "determinant loop" located between hCG beta residues 93 and 100. PMID:1899483

  5. Properties of follicle-stimulating-hormone receptor in cell membranes of bovine testis.

    PubMed Central

    Cheng, K W

    1975-01-01

    A simple method for preparing plasma membranes from bovine testes is described. Bovine testicular receptor has a high affinity and specificity for 125I-labelled human FSH (follicle-stimulating hormone). The specific binding of 125I-labelled human FSH to the plasma membranes is a saturable process with respect to the amounts of receptor protein and FSH added. The association and dissociation of 125I-labelled human FSH are time- and temperature-dependent, and the binding of labelled human FSH to bovine testicular receptor is strong and not readily reversible. Scatchard [Ann. N.Y. Acad. Sci. (1949) 51, 660-672] analysis indicates a dissociation constant, Kd, of 9.8 X10(-11)M, and 5.9 X 10(-14)mol of binding sites/mg of membrane protein. The testicular membrane receptor is heat-labile. Preheating at 40 degrees C for 15 min destroyed 30% of the binding activity. Specific binding is pH-dependent, with an optimum between pH 7.0 and 7.5. Brief exposure to extremes of pH caused irreversible damage to the receptors. The ionic strength of the incubation medium markedly affects the association of 125I-labelled human FSH with its testicular receptor. Various cations at concentrations of 0.1M inhibit almost completely the binding of 125I-labelled human FSH. Nuclectides and steroid hormones at concentrations of 1mM and 5mu/ml respectively have no effect on the binding of FSH to its receptor. Incubation of membranes with and chymotrypsin resulted in an almost complete loss of binding activity, suggesting that protein moieties are essential for the binding of 125I-labelled human FSH. Binding of 125I-labelled human FSH to bovine testicular receptor does not result in destruction or degradation of the hormone. PMID:242318

  6. Decreased bone mineral density in rats rendered follicle-deplete by an ovotoxic chemical correlates with changes in follicle-stimulating hormone and inhibin A.

    PubMed

    Lukefahr, A L; Frye, J B; Wright, L E; Marion, S L; Hoyer, P B; Funk, J L

    2012-03-01

    Bone loss during perimenopause, an estrogen-sufficient period, correlates with elevated serum follicle-stimulating hormone (FSH) and decreased inhibins A and B. Utilizing a recently described ovotoxin-induced animal model of perimenopause characterized by a prolonged estrogen-replete period of elevated FSH, we examined longitudinal changes in bone mineral density (BMD) and their association with FSH. Additionally, serum inhibin levels were assessed to determine whether elevated FSH occurred secondary to decreased ovarian inhibin production and, if so, whether inhibins also correlated with BMD. BMD of the distal femur was assessed using dual-energy X-ray absorptiometry (DXA) over 19 months in Sprague-Dawley rats treated at 1 month with vehicle or 4-vinylcyclohexene diepoxide (VCD, 80 or 160 mg/kg daily). Serum FSH, inhibins A and B, and 17-ß estradiol (E(2)) were assayed and estrus cyclicity was assessed. VCD caused dose-dependent increases in FSH that exceeded values occurring with natural senescence, hastening the onset and prolonging the duration of persistent estrus, an acyclic but E(2)-replete period. VCD decreased serum inhibins A and B, which were inversely correlated with FSH (r(2) = 0.30 and 0.12, respectively). In VCD rats, significant decreases in BMD (5-13%) occurred during periods of increased FSH and decreased inhibins, while BMD was unchanged in controls. In skeletally mature rats, FSH (r(2) = 0.13) and inhibin A (r(2) = 0.15) correlated with BMD, while inhibin B and E(2) did not. Thus, for the first time, both the hormonal milieu of perimenopause and the association of dynamic perimenopausal changes in FSH and inhibin A with decreased BMD have been reproduced in an animal model. PMID:22249524

  7. Decreased Bone Mineral Density in Rats Rendered Follicle-Deplete by an Ovotoxic Chemical Correlates with Changes in Follicle-Stimulating Hormone and Inhibin A

    PubMed Central

    Lukefahr, A. L.; Frye, J. B.; Wright, L. E.; Marion, S. L.; Hoyer, P. B.; Funk, J. L.

    2012-01-01

    Bone loss during perimenopause, an estrogen-sufficient period, correlates with elevated serum follicle-stimulating hormone (FSH) and decreased inhibins A and B. Utilizing a recently described ovotoxin-induced animal model of perimenopause characterized by a prolonged estrogen-replete period of elevated FSH, we examined longitudinal changes in bone mineral density (BMD) and their association with FSH. Additionally, serum inhibin levels were assessed to determine whether elevated FSH occurred secondary to decreased ovarian inhibin production and, if so, whether inhibins also correlated with BMD. BMD of the distal femur was assessed using dual-energy X-ray absorptiometry (DXA) over 19 months in Sprague-Dawley rats treated at 1 month with vehicle or 4-vinylcyclohexene diepoxide (VCD, 80 or 160 mg/kg daily). Serum FSH, inhibins A and B, and 17-ß estradiol (E2) were assayed and estrus cyclicity was assessed. VCD caused dose-dependent increases in FSH that exceeded values occurring with natural senescence, hastening the onset and prolonging the duration of persistent estrus, an acyclic but E2-replete period. VCD decreased serum inhibins A and B, which were inversely correlated with FSH (r2 = 0.30 and 0.12, respectively). In VCD rats, significant decreases in BMD (5–13%) occurred during periods of increased FSH and decreased inhibins, while BMD was unchanged in controls. In skeletally mature rats, FSH (r2 = 0.13) and inhibin A (r2 = 0.15) correlated with BMD, while inhibin B and E2 did not. Thus, for the first time, both the hormonal milieu of perimenopause and the association of dynamic perimenopausal changes in FSH and inhibin A with decreased BMD have been reproduced in an animal model. PMID:22249524

  8. Trajectory Clustering of Estradiol and Follicle-Stimulating Hormone during the Menopausal Transition among Women in the Study of Women's Health across the Nation (SWAN)

    PubMed Central

    Randolph, John F.; McConnell, Daniel S.; Crawford, Sybil L.; El Khoudary, Samar R.; Joffe, Hadine; Gold, Ellen B.; Zheng, Huiyong; Bromberger, Joyce T.; Sutton-Tyrrell, Kim

    2012-01-01

    Context: Variability in the pattern of change in estradiol (E2) and FSH levels over the menopause transition has not been well defined. Objective: The current study aimed to determine whether different trajectories of E2 and FSH could be identified and whether race/ethnicity and body mass index were related to the different trajectories. Design: The Study of Women's Health Across the Nation is a longitudinal observational study of the menopausal transition. Setting: Women aged 42–52 yr from seven participating sites were recruited and underwent up to 11 annual visits. Participants: Postmenopausal women with 12 or more months of amenorrhea that was not due to hysterectomy/oophorectomy and who were not using hormone therapy before the final menstrual period participated in the study. Main Outcome Measures: Annual serum E2 and FSH levels anchored to final menstrual period were measured. Results: Four distinct E2 trajectories and three distinct FSH trajectories were identified. The E2 trajectories were: slow decline (26.9%), flat (28.6%), rise/slow decline (13.1%), and rise/steep decline (31.5%). The FSH trajectories were: low (10.6%), medium (48.7%), and high (41.7%) rising patterns. Obesity increased the likelihood of a flat E2 and low FSH trajectory for all race/ethnic groups. Normal-weight Caucasian and African-American women tended to follow the rise/steep decline E2 and high FSH trajectories. Normal-weight Chinese/Japanese women tended to follow the slow decline E2 and the high/medium FSH trajectories. Conclusions: E2 and FSH trajectories over the menopausal transition are not uniform across the population of women. Race/ethnicity and body mass index affect the trajectory of both E2 and FSH change over the menopausal transition. PMID:22659249

  9. Differential effects of follicle-stimulating and luteinizing hormones on testosterone production by mouse testes.

    PubMed

    Dalterio, S L; Suter, D E; Schwartz, N B; Mayfield, D; Rettori, V B

    1986-07-01

    In adult mice, direct intratesticular injection of ovine follicle-stimulating hormone (o-FSH-13; AFP 2846-C, from NIAMDD, less than 1% LH contamination) at 10, 100 or 1000 ng significantly elevated concentrations of testosterone (T) within the testis. These effects were rapid, with peak values attained by 15 min, and transient, with return to values comparable to that in the contralateral, saline-injected testis within 90 min. Intratesticular injection of FSH (1 microgram) significantly increased testicular T levels in 15- and 60-day old mice. This contrasted with the effects of intratesticular administration of human chorionic gonadotropin (hCG), which stimulated T production significantly at 30 days of age through adulthood. In adult mice, the equivalent LH to the possible contamination in the FSH preparation (1 ng) had no effect. Intratesticular injection of 10 ng LH produced comparable stimulation to that by 100 ng FSH (approximately 7-fold). Systemic pre-treatment with a charcoal-treated porcine follicular fluid (PFF) extract for 2 days reduced plasma FSH levels [86 +/- 17 (5) vs 700 +/- 8 (6); P less than 0.05], but had no effect on plasma LH. Twenty-four hours after the last treatment, the response to intratesticular injection of hCG (2.5 mIU), FSH (100 ng) or LH (10 ng) was also significantly attenuated in these mice. Intratesticular injection of PFF had no direct effect on testicular T levels. In vitro T production in the presence of hCG, LH or FSH were differentially affected by the concentrations of calcium (Ca2+) or magnesium (Mg2+) in the incubation media. The stimulatory effects of FSH were apparent at significantly lower levels of Ca2+ or Mg2+, than were those of LH or hCG. The results of these studies indicate that FSH is capable of stimulating testicular T production. Furthermore, the responsiveness to FSH is qualitatively different than that to LH/hCG in terms of the age pattern, as well as the dependence on Ca2+ or Mg2+. In addition, plasma FSH

  10. Serum follicle-stimulating hormone levels predict time to development of castration-resistant prostate cancer

    PubMed Central

    Hoare, Dylan; Skinner, Thomas A.A.; Black, Angela; Robert Siemens, D.

    2015-01-01

    Introduction: Treatment of advancing prostate cancer focuses on blocking the activation of the androgen receptor with resultant prolonged perturbation of the hypothalamic-pituitary-gonadal axis. Androgen deprivation therapy (ADT) is marked, however, by eventual progression to castration- resistant prostate cancer (CRPC). Emerging evidence has postulated that follicle-stimulating hormone (FSH) may lead to proliferative and mutagenic responses of prostate cancer. We investigated the association of serum FSH and time to castration resistance. Methods: This was a single-centre retrospective study assessing serum FSH levels of patients undergoing ADT for advancing prostate cancer. The primary outcome was time of ADT initiation to the development of CRPC. For each patient on treatment and with castrate levels of testosterone, the maximum FSH value between ADT commencement and CRPC was identified and recorded. FSH was analyzed as a continuous and categorical variable. Cox multivariate regression in a step-wise fashion was used to explore the association between FSH levels and time to CRPC. Results: From a database of 323 prostate cancer patients actively managed with ADT, 103 men had a documented FSH value while castrate, with 45 men progressing to CRPC. The mean ± standard deviation maximum FSH value of these patients was 6.66 ± 4.22 mIU/mL (range: 1.5–28.1). The mean duration from ADT commencement to CRPC was 3.03 ± 0.34 years (range: 0.36–9.71). Univariate analysis suggested a trend of a negative correlation between FSH values and time to castrate resistance. A FSH value of less than or equal to the lowest tertile (4.8 mIU/mL) was associated with a longer time to CRPC (hazard ratio 0.46; p = 0.006). In the Cox regression analysis, elevated FSH was associated with a shorter duration time to CRPC (p = 0.03). Conclusions: This retrospective, single-centre study would suggest there may be an association between serum FSH levels and time to CRPC for men treated

  11. Corifollitropin alfa: a new option to treat female infertility.

    PubMed

    de Lartigue, Jane

    2011-08-01

    Corifollitropin alfa (Elonva®) is the first hybrid follicle-stimulating hormone (FSH) molecule with demonstrated sustained follicle-stimulating activity. The β subunit of this molecule contains the carboxy-terminal peptide of human chorionic gonadotropin, which alters the pharmacokinetic profile of the molecule. It demonstrates a longer circulation half-life and extended time to peak levels when compared with recombinant FSH (rFSH). Like rFSH, it lacks luteinizing hormone activity and binds specifically to the FSH receptor in vitro. Clinical trials show that corifollitropin alfa is able to sustain multiple follicular growth for a week, with a similar ovarian response and safety profile as rFSH. A single injection of corifollitropin alfa can replace 7 daily injections of rFSH during the first week of ovarian stimulation in gonadotropin-releasing hormone antagonist protocols. Therefore, corifollitropin alfa addresses the need for a simplified treatment approach to lessen the burden of multiple daily injections for in vitro fertilization. PMID:21850281

  12. Prediagnostic circulating follicle stimulating hormone concentrations and ovarian cancer risk.

    PubMed

    McSorley, Meghan A; Alberg, Anthony J; Allen, Diane S; Allen, Naomi E; Brinton, Louise A; Dorgan, Joanne F; Kaaks, Rudolf; Rinaldi, Sabina; Helzlsouer, Kathy J

    2009-08-01

    Gonadotropins have been indicted in ovarian carcinogenesis but direct evidence has been limited and inconsistent. The aim of this study was to determine the association between prediagnostic levels of follicle stimulating hormone (FSH) and subsequent development of invasive epithelial ovarian cancer. A nested case-control study was conducted using cases and controls drawn from three cohorts: CLUE I and CLUE II of Washington County, MD, and the Island of Guernsey Study, United Kingdom. In total, 67 incident invasive epithelial ovarian cancer cases were each matched to 1 to 2 controls on age, menopausal status, time since last menstrual period, current hormone use and other relevant factors. FSH concentrations were classified into ranked thirds of low, medium or high based on the distribution among controls. Conditional logistic regression was used to estimate the odds ratio (OR) across increasing thirds of FSH concentrations. Results of the analysis showed that ovarian cancer risk decreased with higher FSH concentrations (p-trend = 0.005). Compared with the lowest third of FSH concentrations, the OR among those in the middle and highest thirds were 0.45 [95% Confidence Interval (CI): 0.20-1.00] and 0.26 (95% CI: 0.10-0.70), respectively. Associations persisted after excluding cases diagnosed within 5 years of follow-up. In conclusion, a reduction in subsequent risk of invasive epithelial ovarian cancer was observed among women with higher circulating FSH concentrations. These findings contradict the hypothesized role of FSH as a risk factor in ovarian carcinogenesis. PMID:19444906

  13. CREB coactivator CRTC2/TORC2 and its regulator calcineurin crucially mediate follicle-stimulating hormone and transforming growth factor β1 upregulation of steroidogenesis.

    PubMed

    Fang, Wei-Ling; Lee, Ming-Ting; Wu, Leang-Shin; Chen, Yun-Ju; Mason, Jian; Ke, Ferng-Chun; Hwang, Jiuan-Jiuan

    2012-06-01

    In vitro and in vivo studies implicate that follicle-stimulating hormone (FSH) and transforming growth factor β1 (TGFβ1) play crucial physiological roles in regulating ovarian granulosa cell function essential to fertility control in females. FSH induces cAMP and calcium signaling, thereby activating transcription factor CREB to upregulate steroidogenic gene expression, and TGFβ1 greatly enhances FSH-stimulated steroidogenesis. A CREB coactivator CRTC2/TORC2 was identified to function as a cAMP and calcium-sensitive coincidence sensor. This led us to explore the role of CRTC2 and its regulator calcineurin in FSH and TGFβ1-stimulated steroidogenesis. Primary culture of granulosa cells from gonadotropin-primed immature rats was used. Immunoblotting analysis shows that FSH rapidly and transiently induced dephosphorylation/activation of CRTC2, and FSH + TGFβ1 additionally induced late-phase CRTC2 dephosphorylation. Immunofluorescence analysis further confirms FSH ± TGFβ1 promoted CRTC2 nuclear translocation. Using selective inhibitors, we demonstrate that FSH activated CRTC2 in a PKA- and calcineurin-dependent manner, and TGFβ1 acting through its type I receptor (TGFβRI)-modulated FSH action in a calcineurin-mediated and PKA-independent fashion. Next, we investigated the involvement of calcineurin and CRTC2 in FSH and TGFβ1-stimulated steroidogenesis. Calcineurin and TGFβRI inhibitor dramatically reduced the FSH ± TGFβ1-increased progesterone synthesis and protein levels of StAR, P450scc, and 3β-HSD enzyme. Furthermore, chromatin-immunoprecipitation and immunoprecipitation analyses demonstrate that FSH ± TGFβ1 differentially increased CRTC2, CREB, and CBP binding to these steroidogenic genes, and CREB nuclear association with CRTC2 and CBP. In all, this study reveals for the first time that CRTC2 and calcineurin are critical signaling mediators in FSH and TGFβ1-stimulated steroidogenesis in ovarian granulosa cells. PMID:21826657

  14. Electrophoretic purification of radioiodinated follicle-stimulating hormone for radioligand receptor assay and radioimmunoassay

    SciTech Connect

    Schneyer, A.L.; Sluss, P.M.; Bosukonda, D.; Reichert, L.E. Jr.

    1986-10-01

    A method is described for electrophoretic purification of (/sup 125/I)human (h) FSH after radioiodination that improves radioligand binding to FSH membrane receptors. Lactoperoxidase-iodinated hFSH was separated from reaction products by electrophoresis on 7.5% polyacrylamide tube gels (PAGE). Material eluted from 3-mm gel slices was analyzed for incorporation of /sup 125/I and binding to antibody (RIA) or receptor (RRA), and by sodium dodecyl sulfate-PAGE for protein composition. Sodium dodecyl sulfate-PAGE analysis of individual PAGE fractions demonstrated that iodinated proteins, both higher and lower in apparent mol wt than intact FSH, were separated by PAGE, but not by gel filtration chromatography (Sephadex G-25). PAGE purification of radioligand resulted in significantly greater (compared to gel filtration) RRA sensitivity and specificity. Maximum binding of PAGE-purified (/sup 125/I)hFSH to excess calf tests membrane receptors was 45%, with a specific activity of approximately 26 microCi/micrograms, as determined by the method of self-displacement. Maximum binding to excess hFSH antisera (NIH anti-hFSH 4) was 80-85%. This allowed a useful final dilution of 1:120,000, thereby facilitating development of a sensitive and specific RIA with this antiserum. These data indicate that PAGE separation of intact (/sup 125/I)hFSH from other iodinated proteins results in improved radioligand binding, assay sensitivity, and assay specificity. In addition, PAGE-purified lactoperoxidase-iodinated hFSH is suitable for use in both RIA and RRA.

  15. Modulation of cultured porcine granulosa cell responsiveness to follicle stimulating hormone and epidermal growth factor

    SciTech Connect

    Buck, P.A.

    1986-01-01

    Ovarian follicular development is dependent upon the coordinated growth and differentiation of the granulosa cells which line the follicle. Follicle stimulating hormone (FSH) induces granulosa cell differentiation both in vivo and in vitro. Epidermal growth factor (EGF) stimulates granulosa cell proliferation in vitro. The interaction of these two effectors upon selected parameters of growth and differentiation was examined in monolayer cultures of porcine granulose cells. Analysis of the EGF receptor by /sup 125/I-EGF binding revealed that the receptor was of high affinity with an apparent dissociation constant of 4-6 x 10/sup -10/ M. The average number of receptors per cell varied with the state of differentiation both in vivo and in vitro; highly differentiated cells bound two-fold less /sup 125/I-EGF and this effect was at least partially induced by FSH in vitro. EGF receptor function was examined by assessing EGF effects on cell number and /sup 3/H-thymidine incorporation. EGF stimulated thymidine incorporation in both serum-free and serum-supplemented culture, but only in serum-supplemented conditions was cell number increased. EGF receptor function was inversely related to the state of differentiation and was attenuated by FSH. The FSH receptor was examined by /sup 125/I-FSH binding. EGF increased FSH receptor number, and lowered the affinity of the receptor. The function of these receptors was assessed by /sup 125/I-hCG binding and progesterone radioimmunoassay. If EGF was present continuously in the cultures. FSH receptor function was attenuated regardless of FSH receptor number. A preliminary effort to examine the mechanism of this interaction was performed by analyzing hormonally controlled protein synthesis with /sup 35/S-methionine labeling, SDS polyacrylamide gel electrophoresis and fluorography. FSH promoted the expression of a 27,000 dalton protein. This effect was attenuated by EGF.

  16. Accelerated follicle growth during the culture of isolated caprine preantral follicles is detrimental to follicular survival and oocyte meiotic resumption.

    PubMed

    Apolloni, Livia Brunetti; Bruno, Jamily Bezerra; Alves, Benner Geraldo; Ferreira, Anna Clara Accioly; Paes, Victor Macêdo; Moreno, Jesus de Los Reyes Cadenas; de Aguiar, Francisco Léo Nascimento; Brandão, Felipe Zandonadi; Smitz, Johan; Apgar, Gary; de Figueiredo, José Ricardo

    2016-10-01

    This study investigated the effect of androstenedione (A4) alone or in association with different concentrations of bovine recombinant FSH on the IVC of isolated goat preantral follicles. Follicles were mechanically isolated from ovarian tissue and cultured for 18 days in α-minimum essential medium supplemented or not with A4 (10 ng/mL) alone or in association with fixed (A4 + FixFSH: 100 ng/mL) or sequential (A4 + SeqFSH: Day 0, 100 ng/mL; Day 6, 500 ng/mL; Day 12, 1000 ng/mL) concentrations of FSH. After 18 days, the oocytes were recovered for IVM and fluorescence analysis. At Day 18 of culture, only A4 + SeqFSH treatment showed a lower (P < 0.05) rate of intact follicles, survival probability, and meiotic resumption, as well as higher (P < 0.05) percentage of degeneration and/or extrusion after antrum formation. Taken together, these results reported a positive correlation between fast-growing follicles and follicles that degenerated and/or extruded after antrum formation. When compared with control, the addition of A4 alone or in association of FSH did not increase (P > 0.05) the estradiol production or androstenedione levels on Day 6. However, on Day 18, the androstenedione levels were significantly lower in A4 + SeqFSH treatment when compared with A4 alone or to A4 + FixFSH treatments, whereas the estradiol production did not differ (P > 0.05). In summary, this study found that accelerated follicle growth negatively impacted the morphology of caprine preantral follicle cultured in vitro. In addition, the association of androstenedione with increasing concentration of FSH was detrimental to follicular survival and oocyte meiotic resumption. PMID:27371972

  17. Evidence to Incorporate Inclusive Reproductive Health Measures in Guidelines for Childhood and Adolescent Cancer Survivors

    PubMed Central

    Salih, Sana. M.; Elsarrag, Sarah Z.; Prange, Elizabeth; Contreras, Karli; Osman, Radya G; Eikoff, Jens; Puccetti, Diane

    2014-01-01

    Objective Female childhood cancer survivors are at an increased risk of reproductive health impairment. We compared reproductive health outcomes with the recommended standard in a cohort of childhood cancer survivors. Study Design and Participants A retrospective chart review of 222 female childhood cancer survivors aged 21 years or younger that presented to a tertiary referral center between 1997-2008 was initiated. The main outcome measures were the abidance with the American Society of Clinical Oncology (ASCO) guidelines for childhood cancer survivor management of reproductive health. In particular, we evaluated menstrual cycle regularity, fertility preservation counseling, and endocrine profile, as defined by FSH and AMH levels as surrogate markers for ovarian reserve. Secondary outcomes were to study the contribution of survivor clinics in enforcing these guidelines. Results Of 136 patients older than 13 years at their last visit, 58 patients (43%) had FSH data available and none had AMH data. Patients were stratified into three groups according to FSH levels. 40 of 58 patients (69%) have normal ovarian reserve (FSH level <10), 10 of 58 patients (17%) have decreased ovarian reserve (FSH levels 10 – 40), and 8 of 58 patients (14%) have premature menopause, defined as FSH>40. Most patients with amenorrhea have elevated FSH levels indicating primary ovarian insufficiency, while 3 patients (2.2%) have low FSH levels consistent with hypothalamic amenorrhea. None of the patients were counseled on fertility preservation. Conclusions Reproductive health follow-up in children with cancer, including FSH and AMH measurement when indicated, should be established and strictly adhered. PMID:25850590

  18. Follicle-Stimulating Hormone and Estradiol Interact to Stimulate Glutathione Synthesis in Rat Ovarian Follicles and Granulosa Cells1

    PubMed Central

    Hoang, Yvonne D.; Nakamura, Brooke N.; Luderer, Ulrike

    2009-01-01

    Glutathione (GSH), the most abundant intracellular nonprotein thiol, is critical for many cellular functions. The rate-limiting step in GSH synthesis is catalyzed by glutamate cysteine ligase (GCL), a heterodimer composed of a catalytic (GCLC) and a modifier (GCLM) subunit. The tissue-specific regulation of GSH synthesis is poorly understood. We showed previously that gonadotropin hormones regulate ovarian GSH synthesis. In the present study, we sought to clarify the ovarian cell type-specific effects of follicle-stimulating hormone (FSH) and estradiol on GSH synthesis. Immature female rats were treated with estradiol to stimulate development of small antral follicles. Granulosa cells (GCs) from these follicles or whole follicles were cultured in serum-free media, with or without FSH and 17beta-estradiol. The GSH and GCLC protein and mRNA levels increased in GCs treated with FSH alone. The effects of FSH on GCLC and GCLM protein and mRNA levels, GCL enzymatic activity, and GSH concentrations in GCs were significantly enhanced by the addition of estradiol. Estradiol alone had no effects on GSH. Dibromo-cAMP mimicked and protein kinase A (PKA) inhibitors prevented FSH stimulation of GCL subunit protein levels. In cultured small antral follicles, FSH stimulated estradiol synthesis and robustly increased GCL subunit mRNA and protein levels and GSH concentrations. The GCL subunit mRNA expression increased in both the granulosa cells and theca cells of follicles with FSH stimulation. These data demonstrate that maximal stimulation of GSH synthesis by FSH in granulosa cells and follicles requires estradiol. Without estradiol, FSH causes lesser increases in GCL subunit expression via a PKA-dependent pathway. PMID:19516019

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

    SciTech Connect

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

    1990-08-01

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

  20. In vitro fertilization and development of bovine oocytes matured in serum-free medium.

    PubMed

    Saeki, K; Hoshi, M; Leibfried-Rutledge, M L; First, N L

    1991-02-01

    This study was undertaken to investigate the effects of supplementation of serum (fetal calf serum), gonadotropins (LH, FSH, prolactin) and estradiol-17 beta (E2) to culture medium during in vitro maturation of bovine cumulus oocyte complexes on subsequent fertilization and development to the blastocyst stage in vitro. Serum supplementation during bovine oocyte maturation was not required but hormonal supplementation, gonadotropins (LH + FSH) and E2, enhanced the fertilizability and developmental ability of bovine oocytes matured in vitro. The addition of prolactin to maturation medium containing LH, FSH, and E2 did not further enhance frequencies of fertilization and development. PMID:2009327

  1. Ovarian function in female patients with multibacillary leprosy.

    PubMed

    Neena, Khanna; Ammini, A C; Singh, Manjula; Pandhi, Ravindra Kumar

    2003-06-01

    Eighty six adult female patients with multibacillary leprosy were included to study the sex hormone profile LH, FSH, and prolactin, as well as their gynecological events like menstrual function and fertility status. A third of the patients gave a history of irregularity of periods. The mean levels of LH and FSH were significantly higher in patients with multibacilary leprosy vis-à-vis the controls. Of the 24 married women with irregularity of periods, 12 (50%) were infertile. Seven of these patients had elevated levels of FSH and LH, almost reaching castration levels. PMID:12914132

  2. Chronic spinal muscular atrophy of facioscapulohumeral type.

    PubMed Central

    Furukawa, T; Toyokura, Y

    1976-01-01

    Chronic spinal muscular atrophy of FSH type affecting a mother and her son and daughter is reported. The relevant literature is reviewed and the relation between this conditon and Kugelberg-Welander (K-W) disease is discussed. Chronic spinal muscular atrophy of FSH type is considered to be a different entity from the eponymous K-W disease. Each type of muscular dystrophy, e.g. limb-girdle, FSH, distal, ocular, or oculopharyngeal type, has its counterpart of nuclear origin. A classification of the chronic spinal muscular atrophies is suggested following the classification of muscular dystrophy. Images PMID:957378

  3. A rapid solid-phase radioimmunoassay for human plasma follicle-stimulating hormone.

    PubMed

    Lovesey, A C

    1980-01-01

    The measurement of plasma levels of human follicle-stimulating hormone (FSH) has proved to be of value for the study of the hypothalamic-hypophyseal-gonadal axis, greatly facilitating the diagnosis and mangement of problems relating to the menopause and infertility. In the present work a solid-phase radioimmunoassay for human FSH has been developed. This system is characterised by high precision, is economical, and is considerably faster to operate than conventional double antibody systems used in the hospital assay service. Reference values for plasma FSH in various endocrine states are recorded and discussed. PMID:6769381

  4. Improvement of embryo production by the replacement of the last two doses of porcine follicle-stimulating hormone with equine chorionic gonadotropin in Sindhi donors.

    PubMed

    Mattos, M C C; Bastos, M R; Guardieiro, M M; Carvalho, J O; Franco, M M; Mourão, G B; Barros, C M; Sartori, R

    2011-05-01

    The aim of this study was to evaluate the superovulatory (SOV) response of Sindhi (Bos indicus) donors submitted to an ovarian follicular superstimulatory protocol replacing the last two doses of pFSH by eCG. Forty-eight SOV treatments were performed in a crossover design in 19 nulliparous and primiparous females that were randomly divided into two groups: FSH (n=24), which consisted of eight pFSH injections, or FSH/eCG (n=24), which consisted of six pFSH injections followed by two eCG injections. Each female underwent two or three SOV treatments that consisted of an i.m. injection of 2mg estradiol benzoate and the insertion of an intravaginal progesterone-releasing device on Day 0. On Day 4, superstimulatory treatments were initiated and 100mg pFSH was divided into twice daily decreasing doses over a 4-day period. In the FSH/eCG group, the last two doses of pFSH were replaced by two doses of eCG (150 IU eCG each). At the time of the fifth and sixth injections of FSH, 0.150 mg PGF(2α) was injected i.m. The intravaginal progesterone-releasing device was removed at the time of the last FSH or eCG injection and ovulation was induced with 0.2 mg GnRH 18 h later. All females were artificially inseminated with frozen-thawed semen from the same bull 6 and 18 h after GnRH treatment. Seven days after GnRH treatment, embryos/ova were recovered and classified. Follicular superstimulatory (number of follicles ≥6mm at the time of the last FSH or eCG injection) and SOV (CL number) responses were determined by transrectal ultrasonography. Data were analyzed using generalized linear models and results were presented as least squares means±standard error. The FSH/eCG group had higher superstimulatory (33.8±3.9 compared to 23.8±2.6 follicles; P=0.03) and SOV (16.8±2.9 compared to 10.8±2.1 CL; P=0.10) responses. Although the number of total ova/embryos was not different between groups (8.2±1.8 compared to 5.9±1.4 for FSH/eCG and FSH groups, respectively; P=0.25), the number

  5. Birth control pill - series (image)

    MedlinePlus

    ... to produce a successful pregnancy. To prevent pregnancy, birth control pills affect how these organs normally function. ... The lower levels of estrogen in birth control pills suppress FSH ... woman is pregnant. Ovulation will then not occur, which prevents ...

  6. Androgen insensitivity syndrome

    MedlinePlus

    ... check levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) Genetic testing (karyotype) to determine ... KJ, Bloom SL, et al. Fetal growth and development. In: Cunningham F, Leveno KJ, Bloom SL, et ...

  7. What Are Common Treatments for Problems of Puberty?

    MedlinePlus

    ... injected, suppress production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Delayed Puberty With delayed puberty ... News and Spotlights Exploring Factors That Influence Child Development Picture This: NICHD Support for Neuroscience Research Division ...

  8. Ovulation

    MedlinePlus Videos and Cool Tools

    Ovulation occurs though a sequence of hormonal responses. Located deep within the brain, the pituitary gland releases the hormones FSH and LH, which ... ovaries. These hormones signal the development and release a single egg cell from one of the ovaries. ...

  9. Hypogonadotropic hypogonadism

    MedlinePlus

    ... levels such as FSH, LH, and TSH, prolactin, testosterone and estradiol LH response to GnRH MRI of ... of the problem, but may involve: Injections of testosterone (in males) Slow-release testosterone skin patch (in ...

  10. Hypogonadism

    MedlinePlus

    ... Estrogen level (women) FSH level and LH level Testosterone level (men) Other tests may include: Blood tests ... the form of a pill or skin patch. Testosterone is used for boys and men. The medicine ...

  11. Testicular failure

    MedlinePlus

    ... Blood tests may show a low level of testosterone and high levels of prolactin, FSH , and LH . ... testes will be ordered. Testicular failure and low testosterone level may be hard to diagnose in older ...

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

    SciTech Connect

    Gallagher, Carolyn M.; Moonga, Baljit S.; Kovach, John S.

    2010-01-15

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

  13. Evaluation of an immunoenzymometric assay (IEMA) using automated system for determination of luteinizing hormone and follicle stimulating hormone.

    PubMed

    Fonseca, E; Mason, M; Galván, R E; Pascoe, D; Ochoa, R; Hernández, M; Zárate, A

    1997-01-01

    It has been proposed that automated systems for immunoenzymometric assay (IEMA) may substitute traditional radioimmunoassay (RIA) for measurement of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in blood due to the advantage of being more rapid, higher sensitivity, lower cost and not requiring radioactive reagents. The study was designed to evaluate both systems using serum samples to determine luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations. The automatic system (ES-300) for IEMA utilized two monoclonal antibodies, one of them on the solid phase was the specific extractant for the antigen, and the other was a peroxidase labeled antibody which recognizes a different epitope in the antigen molecule, specifically bound in linear proportion to the antigen concentration. Blood samples were obtained from patients who were treated at the hospital for various clinical problems ("problem group") as well as blood samples from patients in whom FSH and LH concentrations were already known ("high", "medium" and "low" levels) by previous RIA ("control group"). IEMA showed a higher sensitivity, 0.42 and 0.96 mIU/ml for FSH and LH, respectively, whereas RIA was 1.95 mIU/ml for both hormones. Intra- and interassay coefficient of variation were below 10% within the range of 15-150 mIU/ml for FSH and 5-100 mIU/ml for LH; however, the coefficient of variation was 15-25% at lower concentrations of FSH and LH. Accuracy of IEMA was evaluated by recovery percentage, thus when high and medium concentrations of FSH and LH were analyzed the recovery was between 99-104%. On the other hand, the recovery was 110% when low levels of FSH and LH were used. In conclusion, IEMA resulted reliable when FSH and LH concentrations are in the middle and high range; likewise, the detection limit of IEMA was lower than RIA, particularly for FSH. On the bases of these results, IEMA showed several advantages over RIA, but its reliability diminishes when serum

  14. Biopotency in vitro and metabolic clearance rates of five pituitary preparations of follicle stimulating hormone.

    PubMed

    Phillips, D J; Hudson, N L; Lun, S; Condell, L A; McNatty, K P

    1993-01-01

    Five pituitary preparations of follicle stimulating hormone (FSH), namely NIDDK-oFSH-17, Bioscan oFSH, Ovagen, Folltropin-V and F.S.H.-P., were examined for biological activity in terms of their potency in an in vitro bioassay, receptor assay and heterologous radioimmunoassay and in terms of their metabolic clearance rates. In the three assays, Bioscan oFSH was the most potent (P < 0.05) (3- to 5-fold the potency of NIDDK-oFSH-17), with Ovagen being 25-50% the potency of the NIDDK standard (P < 0.05). Folltropin-V and F.S.H.-P. had the lowest potencies in all three assays. For each preparation, the ratio of activities between the assays was not consistent, suggesting that the preparations behaved differently in each assay. In 9 of 10 cases, potency estimates in the heterologous radioimmunoassay were greater than those in the in vitro bioassay or receptor assay. Polyacrylamide gel electrophoresis of the preparations showed banding consistent with the molecular weight of FSH, but also indicated that the preparations were contaminated with other proteins to varying extents. The half-lives of these preparations when injected into the bloodstream of mature female mice were 28.0, 8.6, 13.4, 11.6 and 17.4 min for NIDDK-oFSH-17, Bioscan oFSH, Ovagen, Folltropin-V and F.S.H.-P. respectively. The slopes of the decay rates were significantly different from each other (P < 0.05) except between Ovagen and Folltropin-V. The results of these studies show that a number of widely available FSH preparations have differing biopotencies. Moreover, the biopotency of a preparation in vitro is not related to its metabolic clearance rate, and not all FSH preparations behave identically in different assays. Measures of biopotency in vitro combined with those of metabolic clearance rate may provide useful information on the properties of FSH preparations used for research purposes and for superovulation of farmed livestock. PMID:8265802

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

    PubMed Central

    Wex, Jaro; Abou-Setta, Ahmed M

    2013-01-01

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

  16. Follitropin receptors contain cryptic ligand binding sites.

    PubMed

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

    2007-01-01

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

  17. Trial of Recombinant Follicle-Stimulating Hormone Pretreatment for GnRH-Induced Fertility in Patients with Congenital Hypogonadotropic Hypogonadism

    PubMed Central

    Dwyer, Andrew A.; Sykiotis, Gerasimos P.; Hayes, Frances J.; Boepple, Paul A.; Lee, Hang; Loughlin, Kevin R.; Dym, Martin; Sluss, Patrick M.; Crowley, William F.

    2013-01-01

    Context and Objective: The optimal strategy for inducing fertility in men with congenital hypogonadotropic hypogonadism (CHH) is equivocal. Albeit a biologically plausible approach, pretreatment with recombinant FSH (rFSH) before GnRH/human chorionic gonadotropin administration has not been sufficiently assessed. The objective of the study was to test this method. Design and Setting: This was a randomized, open-label treatment protocol at an academic medical center. Patients and Interventions: GnRH-deficient men (CHH) with prepubertal testes (<4 mL), no cryptorchidism, and no prior gonadotropin therapy were randomly assigned to either 24 months of pulsatile GnRH therapy alone (inducing endogenous LH and FSH release) or 4 months of rFSH pretreatment followed by 24 months of GnRH therapy. Patients underwent serial testicular biopsies, ultrasound assessments of testicular volume, serum hormone measurements, and seminal fluid analyses. Results: rFSH treatment increased inhibin B levels into the normal range (from 29 ± 9 to 107 ± 41 pg/mL, P < .05) and doubled testicular volume (from 1.1 ± 0.2 to 2.2 ± 0.3 mL, P < .005). Histological analysis showed proliferation of both Sertoli cells (SCs) and spermatogonia, a decreased SC to germ cell ratio (from 0.74 to 0.35), and SC cytoskeletal rearrangements. With pulsatile GnRH, the groups had similar hormonal responses and exhibited significant testicular growth. All men receiving rFSH pretreatment developed sperm in their ejaculate (7 of 7 vs 4 of 6 in the GnRH-only group) and showed trends toward higher maximal sperm counts. Conclusions: rFSH pretreatment followed by GnRH is successful in inducing testicular growth and fertility in men with CHH with prepubertal testes. rFSH not only appears to maximize the SC population but also induces morphologic changes, suggesting broader developmental roles. PMID:24037890

  18. Testicular function in patients with differentiated thyroid carcinoma treated with radioiodine

    SciTech Connect

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

    1994-09-01

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

  19. Effects of starvation and refeeding on gonadotropin and thyrotropin subunit mRNAs in male Japanese quail.

    PubMed

    Kobayashi, Masaki; Cockrem, John F; Ishii, Susumu

    2002-04-01

    The contents of mRNAs encoding LH beta-, FSH beta-, TSH beta- and common alpha-subunit precursor molecules were measured in food-deprived and subsequently re-fed male Japanese quail. Pituitary LH beta, FSH beta and common alpha mRNA levels were decreased by starvation, and increased to the control levels by re-feeding. The rates of decreases of LH beta and common alpha mRNA levels were greater the corresponding rate for FSH beta levels. Pituitary TSH beta mRNA levels were not decreased by starvation, but increased transitorily by re-feeding. Plasma LH and triiodothyronine levels were decreased by starvation, and then increased to control levels by re-feeding, while plasma FSH and thyroxine levels did not show significant changes. Plasma LH and FSH levels showed positive correlations with pituitary common alpha and FSH beta mRNA levels, respectively, while plasma thyroxine levels showed a negative correlation with TSH beta mRNA levels. Hepatic weight was decreased slightly but significantly by starvation, and then showed a remarkable rebound after re-feeding was started. These results suggest that LH synthesis and secretion are more sensitive to starvation than FSH synthesis and secretion in Japanese quail, and that LH production recovered to initial levels within several days when birds were fully fed. Also, there is a possibility that the synthesis of TSH is accelerated transitorily by re-feeding. Furthermore, these results showed that there are different relationships between the plasma levels of LH, FSH, and TSH and the various hormone subunit mRNA levels. The remarkable change in hepatic weight leads us to assume that hepatic thyroid hormone metabolism is affected by starvation and re-feeding. PMID:12130823

  20. Oocyte and cumulus cell transcripts from cultured mouse follicles are induced to deviate from normal in vivo conditions by combinations of insulin, follicle-stimulating hormone, and human chorionic gonadotropin.

    PubMed

    Sánchez, Flor; Romero, Sergio; Smitz, Johan

    2011-09-01

    Gonadotropins and insulin are major regulators of cell proliferation, differentiation, and survival in cultured mouse ovarian follicles. Applications of variable doses of insulin in combination with follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were studied at the gene expression level in oocytes and cumulus cells. Early preantral follicles grown over 9 days were sequentially exposed to combinations of doses of insulin, FSH, and human chorionic gonadotropin (hCG). From culture Day 1 to 6 (preantral stage), two insulin concentrations (5 ng/ml and 5 μg/ml) were combined with 10 mIU/ml FSH. From Days 6 to 9 (antral stage), the three variable gonadotropin treatments set under each insulin condition were 10 mIU/ml FSH, 25 mIU/ml FSH, and 25 mIU/ml FSH plus 3 mIU/ml hCG. The Gdf9, Bmp15, Fgf8, Dazl, Pou5f1, and Pik3ca mRNA transcripts were quantified in oocytes, and the Amh, Lhcgr, Hsd3b1, Vegfa, and Insig1 mRNA transcripts were quantified in cumulus cells. In vivo controls were unprimed and eCG (equine chorionic gonadotropin)-primed prepubertal female mice. During the preantral stage, none except the Amh transcripts was regulated by insulin. Oocyte transcripts were not affected by the variable gonadotropin treatments on the last culture day but were upregulated in the combination of high insulin plus 25 mIU/ml FSH. Under low insulin conditions, high FSH levels increased levels of Lhcgr and Vegfa expression, and hCG abated this effect. However, under high insulin conditions, hCG upregulated levels of Lhcgr, Vegfa, and Insig1 mRNA. High insulin concentrations upregulated Hsd3b1 transcripts. These results demonstrate that in an in vitro follicle culture, a near physiological insulin background yields oocyte and cumulus cell transcript levels that are more similar to those in vivo. PMID:21565993

  1. Forkhead box O member FOXO1 regulates the majority of follicle-stimulating hormone responsive genes in ovarian granulosa cells.

    PubMed

    Herndon, Maria K; Law, Nathan C; Donaubauer, Elyse M; Kyriss, Brandon; Hunzicker-Dunn, Mary

    2016-10-15

    FSH promotes maturation of ovarian follicles. One pathway activated by FSH in granulosa cells (GCs) is phosphatidylinositol-3 kinase/AKT. The AKT target FOXO1 is reported to function primarily as a repressor of FSH genes, including Ccnd2 and Inha. Based on its broad functions in other tissues, we hypothesized that FOXO1 may regulate many more GC genes. We transduced GCs with empty adenovirus or constitutively active FOXO1 followed by treatment with FSH for 24 h, and conducted RNA deep sequencing. Results show that FSH regulates 3772 genes ≥2.0-fold; 60% of these genes are activated or repressed by FOXO1. Pathway Studio Analysis revealed enrichment of genes repressed by FOXO1 in metabolism, signaling, transport, development, and activated by FOXO1 in signaling, cytoskeletal functions, and apoptosis. Gene regulation was verified by q-PCR (eight genes) and ChIP analysis (two genes). We conclude that FOXO1 regulates the majority of FSH target genes in GCs. PMID:27328024

  2. Effective Mobilization of Very Small Embryonic-Like Stem Cells and Hematopoietic Stem/Progenitor Cells but Not Endothelial Progenitor Cells by Follicle-Stimulating Hormone Therapy

    PubMed Central

    Zbucka-Kretowska, Monika; Eljaszewicz, Andrzej; Lipinska, Danuta; Grubczak, Kamil; Rusak, Malgorzata; Mrugacz, Grzegorz; Dabrowska, Milena; Ratajczak, Mariusz Z.; Moniuszko, Marcin

    2016-01-01

    Recently, murine hematopoietic progenitor stem cells (HSCs) and very small embryonic-like stem cells (VSELs) were demonstrated to express receptors for sex hormones including follicle-stimulating hormone (FSH). This raised the question of whether FSH therapy at clinically applied doses can mobilize stem/progenitor cells in humans. Here we assessed frequencies of VSELs (referred to as Lin−CD235a−CD45−CD133+ cells), HSPCs (referred to as Lin−CD235a−CD45+CD133+ cells), and endothelial progenitor cells (EPCs, identified as CD34+CD144+, CD34+CD133+, and CD34+CD309+CD133+ cells) in fifteen female patients subjected to the FSH therapy. We demonstrated that FSH therapy resulted in statistically significant enhancement in peripheral blood (PB) number of both VSELs and HSPCs. In contrast, the pattern of responses of EPCs delineated by different cell phenotypes was not uniform and we did not observe any significant changes in EPC numbers following hormone therapy. Our data indicate that FSH therapy mobilizes VSELs and HSPCs into peripheral blood that on one hand supports their developmental origin from germ lineage, and on the other hand FSH can become a promising candidate tool for mobilizing HSCs and stem cells with VSEL phenotype in clinical settings. PMID:26635885

  3. Effective Mobilization of Very Small Embryonic-Like Stem Cells and Hematopoietic Stem/Progenitor Cells but Not Endothelial Progenitor Cells by Follicle-Stimulating Hormone Therapy.

    PubMed

    Zbucka-Kretowska, Monika; Eljaszewicz, Andrzej; Lipinska, Danuta; Grubczak, Kamil; Rusak, Malgorzata; Mrugacz, Grzegorz; Dabrowska, Milena; Ratajczak, Mariusz Z; Moniuszko, Marcin

    2016-01-01

    Recently, murine hematopoietic progenitor stem cells (HSCs) and very small embryonic-like stem cells (VSELs) were demonstrated to express receptors for sex hormones including follicle-stimulating hormone (FSH). This raised the question of whether FSH therapy at clinically applied doses can mobilize stem/progenitor cells in humans. Here we assessed frequencies of VSELs (referred to as Lin(-)CD235a(-)CD45(-)CD133(+) cells), HSPCs (referred to as Lin(-)CD235a(-)CD45(+)CD133(+) cells), and endothelial progenitor cells (EPCs, identified as CD34(+)CD144(+), CD34(+)CD133(+), and CD34(+)CD309(+)CD133(+) cells) in fifteen female patients subjected to the FSH therapy. We demonstrated that FSH therapy resulted in statistically significant enhancement in peripheral blood (PB) number of both VSELs and HSPCs. In contrast, the pattern of responses of EPCs delineated by different cell phenotypes was not uniform and we did not observe any significant changes in EPC numbers following hormone therapy. Our data indicate that FSH therapy mobilizes VSELs and HSPCs into peripheral blood that on one hand supports their developmental origin from germ lineage, and on the other hand FSH can become a promising candidate tool for mobilizing HSCs and stem cells with VSEL phenotype in clinical settings. PMID:26635885

  4. Role of follicle-stimulating hormone on biliary cyst growth in autosomal dominant polycystic kidney disease

    PubMed Central

    Onori, Paolo; Mancinelli, Romina; Franchitto, Antonio; Carpino, Guido; Renzi, Anastasia; Brozzetti, Stefania; Venter, Julie; Francis, Heather; Glaser, Shannon; Jefferson, Douglas M.; Alpini, Gianfranco; Gaudio, Eugenio

    2014-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder characterized by the progressive development of renal and hepatic cysts. Follicle-stimulating hormone (FSH) has been demonstrated to be a trophic factor for biliary cells in normal rats and experimental cholestasis induced by bile duct ligation (BDL). Aims To assess the effect of FSH on cholangiocyte proliferation during ADPKD using both in vivo and in vitro models. Methods Evaluation of FSH receptor (FSHR), FSH, phospho-extracellular-regulated kinase (pERK) and c-myc expression in liver fragments from normal patients and patients with ADPKD. In vitro, we studied proliferating cell nuclear antigen (PCNA) and cAMP levels in a human immortalized, non-malignant cholangiocyte cell line (H69) and in an immortalized cell line obtained from the epithelium lining the hepatic cysts from the patients with ADPKD (LCDE) with or without transient silencing of the FSH gene. Results Follicle-stimulating hormone is linked to the active proliferation of the cystic wall and to the localization of p-ERK and c-myc. This hormone sustains the biliary growth by activation of the cAMP/ERK signalling pathway. Conclusion These results showed that FSH has an important function in cystic growth acting on the cAMP pathway, demonstrating that it provides a target for medical therapy of hepatic cysts during ADPKD. PMID:23617956

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

    PubMed Central

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

    2015-01-01

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

  6. The effects of postoperative adjuvant chemotherapy and radiotherapy on testicular function in men undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Rosenberg, S.A.

    1981-05-15

    Testicular function was studied in 26 men with sarcoma who received adjuvant treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate (with or without radiotherapy). Testicular size, sperm output, and serum FSH, LH and testosterone levels were assessed after treatment. Five of 17 men who received chemotherapy or chemotherapy with radiotherapy to the neck, arm, chest, or leg, had normal testicular function. Eight of the remaining 12 men who provided ejaculates were oligospermic or azoospermic and serum FSH was increased threefold and LH twofold; testosterone levels were normal. In the five men with normal testicular function, FSH was increased fourfold during therapy but returned to normal six to 21 months after treatment. In men less than 40 years old, the mean FSH was less than that of men over 40 years of age (P . to 0.05), suggesting that recovery from the injury was age-related. By contrast, all nine men who received chemotherapy plus radiotherapy to the abdomen or thigh had decreased testicular size, azoospermia, fourfold increase in FSH, and twofold increase in LH levels; but testosterone concentration was normal. These data increase in FSH, and reversible testicular injury occurs after treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate; recovery is age-related. However, these agents in combination with use of adjuvant radiotherapy to the thigh or abdomen may produce permanent testicular injury even in young patients.

  7. Weight loss results in a small decrease in follicle stimulating hormone in overweight glucose-intolerant postmenopausal women

    PubMed Central

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

    2014-01-01

    Structured Abstract Objective To examine the impact of a weight loss intervention upon follicle stimulating hormone (FSH) levels in postmenopause. Design and Methods Participants were postmenopausal, overweight, glucose-intolerant women not using exogenous estrogen (n=382) in the Diabetes Prevention Program. Women were randomized to intensive lifestyle change (ILS) with the goals of weight reduction of at least 7% of initial weight and 150 minutes per week of moderate intensity exercise, metformin 850 mg, or placebo administered twice a day. Results Randomization to ILS led to small increases in FSH between baseline and 1-year follow-up vs. placebo (2.3 IU/l vs. -0.81 IU/l, p<0.01). Increases in FSH were correlated with decreases in weight (r=-0.165, p<0.01) and E2 (r=-0.464, p<0.0001) after adjustment for age, race/ethnicity, and randomization arm. Changes in FSH were still significantly associated with changes in weight even after adjustment for E2 levels. Metformin users had reductions in weight but non-significant changes in FSH and E2 levels vs. placebo. Conclusions Weight loss leads to small increases in FSH among overweight, postmenopausal women, potentially through pathways mediated by endogenous estrogen as well as other pathways. PMID:25294746

  8. Follicle stimulating hormone increases spermatogonial stem cell colonization during in vitro co-culture.

    PubMed

    Narenji Sani, Reza; Tajik, Parviz; Yousefi, Mohammad Hassan; Movahedin, Mansoureh; Qasemi-Panahi, Babak; Shafiei, Shiva; Ahmadi Hamedani, Mahmood

    2013-01-01

    The complex process of spermatogenesis is regulated by various factors. Studies on spermatogonial stem cells (SCCs) have provided very important tool to improve herd genetic and different field. 0.2 to 0.3 percent of total cells of seminiferous tubules is consist of spermatogonial stem cells. To investigate and biomanipulation of these cells, proliferation and viability rate of cells should be increased in vitro, at first. Follicle stimulating hormone (FSH) has been suggested to play a determinant role in the survival of germ cells in addition to increasing spermatogonial proliferation. In this study, the in vitro effects of FSH on spermatogonial cell colony formation were investigated. Sertoli and spermatogonial cells were isolated from 3-5 months old calves. The identity of the Sertoli cells and spermatogonial stem cells were confirmed through immunocytochemistry and colony morphology, respectively. Co-cultured Sertoli and spermatogonial cells were treated with FSH in different dose of 10, 20 and 40 IU mL(-1) FSH, before colony assay. Results indicated that, FSH increased in vitro colonization of spermatogonial cells in comparison with control group. In conclusion, using FSH provided proper bovine spermatogonial stem cell culture medium for in vitro study of these cells. PMID:25593684

  9. Follicle stimulating hormone increases spermatogonial stem cell colonization during in vitro co-culture

    PubMed Central

    Narenji Sani, Reza; Tajik, Parviz; Yousefi, Mohammad Hassan; Movahedin, Mansoureh; Qasemi-Panahi, Babak; Shafiei, Shiva; Ahmadi Hamedani, Mahmood

    2013-01-01

    The complex process of spermatogenesis is regulated by various factors. Studies on spermatogonial stem cells (SCCs) have provided very important tool to improve herd genetic and different field. 0.2 to 0.3 percent of total cells of seminiferous tubules is consist of spermatogonial stem cells. To investigate and biomanipulation of these cells, proliferation and viability rate of cells should be increased in vitro, at first. Follicle stimulating hormone (FSH) has been suggested to play a determinant role in the survival of germ cells in addition to increasing spermatogonial proliferation. In this study, the in vitro effects of FSH on spermatogonial cell colony formation were investigated. Sertoli and spermatogonial cells were isolated from 3-5 months old calves. The identity of the Sertoli cells and spermatogonial stem cells were confirmed through immunocytochemistry and colony morphology, respectively. Co-cultured Sertoli and spermatogonial cells were treated with FSH in different dose of 10, 20 and 40 IU mL-1 FSH, before colony assay. Results indicated that, FSH increased in vitro colonization of spermatogonial cells in comparison with control group. In conclusion, using FSH provided proper bovine spermatogonial stem cell culture medium for in vitro study of these cells. PMID:25593684

  10. Experimental and computational study of inter- and intra- species specificity of gonadotropins for various gonadotropin receptors.

    PubMed

    Aizen, Joseph; Kowalsman, Noga; Kobayashi, Makito; Hollander, Lian; Sohn, Young Chang; Yoshizaki, Goro; Niv, Masha Y; Levavi-Sivan, Berta

    2012-11-25

    The gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and their receptors play critical roles in vertebrate reproduction. In order to study intra- and interspecies ligand promiscuity of gonadotropins, COS-7 cells were transiently transfected with one of the gonadotropin receptor genes, FSHR or LHR, and tested for activation by gonadotropins from representative fish orders: Aquilliformes (eel; e), Salmoniformes (trout; tr), and Perciformes (tilapia; ta), and of mammalian origin: porcine (p), bovine (b) and human (h). The study reveals complex relations between the gonadotropin hormones and their receptors. Each gonadotropin activated its own cognate receptor. However, taLHR was also activated by hCG and eLHR was activated by hFSH, hCG, and trFSH. For FSHR, the only cross-reactivity detected was for hFSHR, which was activated by pFSH and bFSH. These findings are of great interest and applicability in the context of activation of various GTHRs by their ligands and by ligands from other vertebrates. Analysis of the three-dimensional models of the structures highlights the importance of residues outside of the currently established hormone-receptor interface region. In addition, the interface residues in taFSHR and the effect of exon duplication, which causes an insert in the LRR domain, are suggested to affect the interaction and binding of taFSH. PMID:22954681

  11. Protection from radiation-induced damage of spermatogenesis in the rhesus monkey (Macaca mulatta) by follicle-stimulating hormone

    SciTech Connect

    van Alphen, M.M.; van de Kant, H.J.; de Rooij, D.G.

    1989-02-01

    In adult rhesus monkeys a two- to threefold increase in the number of spermatogonia was found at Day 75 after 1 Gy of X-irradiation when the animals were pretreated with two intramuscular injections of follicle-stimulating hormone (FSH) each day. Also the percentage of cross-sections of seminiferous tubules showing spermatogonia (repopulation index) was much higher when FSH was given before irradiation. At 75 days postirradiation the repopulation index was 39 +/- 10% after irradiation alone and 81 +/- 11% when FSH pretreatment was applied. The pretreatment with two injections of FSH each day during 16 days caused an increase in the number of proliferating A spermatogonia. In view of earlier results in the mouse, where proliferating spermatogonial stem cells appeared more radioresistant than quiescent ones, it is suggested that the protective effects of FSH treatment are caused by the increase in the proliferative activity of the A spermatogonia and consequently of the spermatogonial stem cells. The results indicate that in the rhesus monkey the maximal protective effect of FSH is reached after a period of treatment between 7 and 16 days.

  12. Corifollitropin alfa, a long-acting follicle-stimulating hormone agonist for the treatment of infertility.

    PubMed

    Loutradis, Dimitris; Drakakis, Petros; Vlismas, Antonis; Antsaklis, Aristidis

    2009-04-01

    Corifollitropin alfa is being developed by Schering-Plough Corp as an injectable, long-acting follicle-stimulating hormone (FSH) agonist for the treatment of infertility. A single dose of corifollitropin alfa could initiate and sustain multifollicular growth in patients undergoing controlled ovarian stimulation, such as during in vitro fertilization or intracytoplasmic sperm injection. The agent comprises an alpha-subunit, which is identical to that of FSH, and a beta-subunit, which is produced by the fusion of the C-terminal peptide from the beta-subunit of chorionic gonadotropin to the beta-subunit of FSH. Corifollitropin alfa has a longer half-life compared with FSH and thus requires less frequent dosing. The drug was well tolerated and does not appear to be associated with any serious adverse events or the formation of antibodies. The initial results from a large, phase III, double-blind clinical trial indicated that the ongoing pregnancy rate achieved with corifollitropin alfa treatment was high and similar to the rate established with daily treatment of recombinant FSH. The number of oocytes retrieved following the administration of corifollitropin alfa was slightly higher compared with the number observed with daily recombinant FSH treatment. Thus, corifollitropin alfa has the potential to serve as a viable fertility agent and to gain a place in the infertility market. PMID:19337959

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

    PubMed Central

    Rinaldi, Leonardo; Selman, Helmy

    2016-01-01

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

  14. Which factors play a role in clinical decision-making in subfertility?

    PubMed

    van der Steeg, Jan W; Steures, Pieternel; Eijkemans, Marinus J C; Habbema, J Dik F; Bossuyt, Patrick M M; Hompes, Peter G A; van der Veen, Fulco; Mol, Ben W J

    2006-04-01

    Sixteen vignettes of subfertile couples were constructed by varying fertility history, post-coital test, sperm motility, FSH concentration and Chlamydia antibody titre (CAT). Thirty-five gynaecologists estimated probabilities of treatment-independent pregnancy, intrauterine insemination (IUI) and IVF. Thereafter, they chose IUI, IVF or no treatment. The relative contribution of each factor to probability estimates and to subsequent treatment decisions was calculated. Duration of subfertility and maternal age were the most important contributors for gynaecologists' estimates of treatment-independent pregnancy [relative contribution (RC) 41, 26%]. Maternal age and FSH concentration were the most important contributors in the estimates for IUI (RC: 51, 25%) and for IVF (RC: 64, 31%). The decision to start IVF was mainly determined by maternal age, duration of subfertility, FSH concentration and CAT. The relative contribution of maternal age and duration of subfertility was in concordance with existing prediction models, whereas previous pregnancy and FSH concentration were under- and overestimated respectively. In conclusion, maternal age, duration of subfertility and FSH concentration are the main factors in clinical decision-making in subfertility. Gynaecologists overestimate the importance of FSH concentration, but underestimate that of a previous pregnancy, as compared with their importance reported in prediction models and guidelines. PMID:16740221

  15. Inhibition of NF-κB promotes autophagy via JNK signaling pathway in porcine granulosa cells.

    PubMed

    Gao, Hui; Lin, Lu; Haq, Ihtesham Ul; Zeng, Shen-Ming

    2016-04-22

    The transcription factor nuclear factor-κB (NF-κB) plays an important role in diverse processes, including cell proliferation and differentiation, apoptosis and inflammation. However, the role of NF-κB in porcine follicle development is not clearly elucidated. In this study, we demonstrated that follicle stimulating hormone (FSH) increased the level of inhibitor of NF-κB (IκB) protein and promoted the cytoplasmic localization of p65, indicating that FSH inhibits the activation of NF-κB in porcine granulosa cells. Moreover, inhibition of NF-κB by FSH or another specific inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), could activate JNK signaling and enhance autophagic activity in porcine granulosa cells. Knockdown of RelA (p65) Subunit of NF-κB by RNA interference abrogated the activation of JNK signaling pathway and the increase of autophagic protein expression by FSH. Meanwhile, the functional significance of FSH or PDTC-mediated autophagy were further investigated. Our results demonstrated that the increased autophagy promoted progesterone secretion in porcine granulosa cells. Blockage of autophagy by chloroquine obviated the FSH or PDTC-induced progesterone production. Taken together, these results indicate that inhibition of NF-κB increased autophagy via JNK signaling, and promote steroidogenesis in porcine granulosa cells. Our results provide new insights into the regulation and function of autophagy in mammalian follicle development. PMID:27016483

  16. Steroidogenic and maturation-inducing potency of native gonadotropic hormones in female chub mackerel, Scomber japonicus

    PubMed Central

    2012-01-01

    Background The gonadotropins (GtHs), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are produced in the pituitary gland and regulates gametogenesis through production of gonadal steroids. However, respective roles of two GtHs in the teleosts are still incompletely characterized due to technical difficulties in the purification of native GtHs. Methods Native FSH and LH were purified from the pituitaries of adult chub mackerel, Scomber japonicus by anion-exchange chromatography and immunoblotting using specific antisera. The steroidogenic potency of the intact chub mackerel FSH (cmFSH) and LH (cmLH) were evaluated in mid- and late-vitellogenic stage follicles by measuring the level of gonadal steroids, estradiol-17beta (Ε2) and 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P). In addition, we evaluated the maturation-inducing potency of the GtHs on same stage follicles. Results Both cmFSH and cmLH significantly stimulated E2 production in mid-vitellogenic stage follicles. In contrast, only LH significantly stimulated the production of 17,20beta-P in late-vitellogenic stage follicles. Similarly, cmLH induced final oocyte maturation (FOM) in late-vitellogenic stage follicles. Conclusions Present results indicate that both FSH and LH may regulate vitellogenic processes, whereas only LH initiates FOM in chub mackerel. PMID:22950645

  17. Effects of gonadotropins on bovine oocytes matured in TCM-199.

    PubMed

    Choi, Y H; Carnevale, E M; Seidel, G E; Squire, E L

    2001-09-01

    The effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) during in vitro maturation of bovine oocytes in TCM-199 without serum were evaluated. Bovine oocytes with compact cumulus cells were collected from slaughterhouse-derived ovaries and cultured in Hepes-buffered TCM-199 supplemented with 5 mg/mL BSA, 1 microg/mL estradiol-17beta, FSH (0, 0.015, 0.05, 0.15, 1.5 or 15 ng/mL; Experiment 1), LH (0, 0.14, 1, 7 or 49 microg/mL; Experiment 2) and combinations of 1 or 10 ng/mL FSH and 1 or 10 microg/mL LH (Experiment 3) at 39 degrees C in 5% CO2 in air. After 22 h of maturation, cumulus expansion was estimated by scoring from 0 (no expansion) to 4 (full expansion of cumulus mass). In vitro fertilization was done with Percoll (45/90%) separated bull sperm at 1 x 10(6) sperm/mL in fert-TALP with 5 U/mL heparin. At 18 to 20 h post-insemination, presumptive zygotes were transferred to a chemically defined medium (CDM-1) supplemented with 0.5% BSA and nonessential amino acids for 72 h and then moved to CDM-2, additionally supplemented with essential amino acids. Zygotes were cultured at 39 degrees C in 5% CO2, 5% O2 and 90% N2 for 8 days. During Experiments 1 and 2, cumulus expansion increased in proportion to concentrations of FSH and LH. Cleavage rates and development to blastocysts were not significantly different among FSH and LH treatments. In Experiment 3, cumulus expansion of bovine oocytes was maximal when 1 ng/mL FSH and 1 microg/mL LH were added to IVM medium, but cumulus expansion again was not related to developmental ability, although cleavage rates were improved slightly (P<0.05) by the combination of LH and FSH. Blastocyst quality, estimated by the size of inner cell mass, was not different between combinations of FSH and LH, and the numbers of nuclei were not different. Although expansion of cumulus cells surrounding bovine oocytes was altered in response to FSH and/or LH in semi-defined medium, cumulus expansion was not related to

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

    PubMed

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

    2012-12-01

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

  19. Gonadotropin-releasing hormone, estradiol, and inhibin regulation of follicle-stimulating hormone and luteinizing hormone surges: implications for follicle emergence and selection in heifers.

    PubMed

    Haughian, James M; Ginther, O J; Diaz, Francisco J; Wiltbank, Milo C

    2013-06-01

    Mechanisms regulating gonadotropin surges and gonadotropin requirements for follicle emergence and selection were studied in heifers. Experiment 1 evaluated whether follicular inhibins regulate the preovulatory luteinizing hormone (LH)/follicle-stimulating hormone (FSH) surges elicited by gonadotropin-releasing hormone (GnRH) injection (Hour = 0) and the subsequent periovulatory FSH surge. Treatments included control (n = 6), steroid-depleted bovine follicular fluid (bFF) at Hour -4 (n = 6), and bFF at Hour 6 (n = 6). Gonadotropins in blood were assessed hourly from Hours -6 to 36, and follicle growth tracked by ultrasound. Consistent with inhibin independence, bFF at Hour -4 did not impact the GnRH-induced preovulatory FSH surge, whereas treatment at Hour 6 delayed onset of the periovulatory FSH surge and impeded growth of a new follicular wave. Experiment 2 examined GnRH and estradiol (E2) regulation of the periovulatory FSH surge. Treatment groups were control (n = 8), GnRH-receptor antagonist (GnRHr-ant, n = 8), and E2 + GnRHr-ant (n = 4). GnRHr-ant (acyline) did not reduce the concentrations of FSH during the periovulatory surge and early follicle development (<7.0 mm) was unaffected, although subsequent growth of a dominant follicle (>8.0 mm) was prevented by GnRHr-ant. Addition of E2 delayed both the onset of the periovulatory FSH surge and emergence of a follicular wave. Failure to select a dominant follicle in the GnRHr-ant group was associated with reduced concentrations of LH but not FSH. Maximum diameter of F1 in controls (13.3 ± 0.5 mm) was greater than in both GnRHr-ant (7.7 ± 0.3 mm) and E2 + GnRHr-ant (6.7 ± 0.8 mm) groups. Results indicated that the periovulatory FSH surge stems from removal of negative stimuli (follicular E2 and inhibin), but is independent of GnRH stimulation. Emergence and early growth of follicles (until about 8 mm) requires the periovulatory FSH surge but not LH pulses. However, follicular deviation and late-stage growth of

  20. Effect of inter-cycle interval on oocyte production in humans in the presence of the weak androgen DHEA and follicle stimulating hormone: a case-control study

    PubMed Central

    2014-01-01

    Background In various animal models androgens have been demonstrated to enhance follicle stimulating hormone (FSH) activity on granulosa cells during small growing follicle stages. To assess whether similar synergism may also exist in humans we investigated women on androgen (dehydroepiandrosterone, DHEA) supplementation with varying concomitant FSH exposure. Methods In a case controlled cohort study we determine if time interval between IVF cycles of IVF treatment with FSH had an effect on ovarian response to ovulation induction in women supplemented with DHEA. Among 85 women with known low functional ovarian reserve (LFOR), supplemented with DHEA, and undergoing at least 3 consecutive IVF cycles, 68 demonstrated short (<120 days) intervals between repeated cycles (Group 1) and were, therefore, considered to have consistent FSH exposure. In contrast 17 women (Group 2) demonstrated long (> = 120 days) intervals between repeated cycles and, therefore, were considered to demonstrate inconsistent FSH exposure. Trends in oocyte yields were compared between these groups, utilizing mixed model repeated measures ANOVA, adjusted for initial age and FSH dose. Results Only women in Group I demonstrated a linear increase in oocyte yields across their three cycles of treatments (F = 7.92; df 1, 68.6; p = 0.017). Moreover, the analysis revealed a significant interaction between the two patient groups and cycle number for retrieved oocytes (F = 6.32, df = 2, 85.9, p = 0.003). Conclusions This study offers preliminary confirmatory evidence that repeated short interval exposure to androgens in combination with FSH improves human FOR. A higher level of evidence will require prospectively randomized studies. PMID:25048047

  1. FOLLITROPIN RECEPTORS CONTAIN CRYPTIC LIGAND BINDING SITES1

    PubMed Central

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

    2007-01-01

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

  2. 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.

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

    PubMed

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

    2016-07-01

    A meta-analysis was conducted of individual patient data (n = 3292) from three randomized controlled trials of corifollitropin alfa versus rFSH: Engage (150 µg corifollitropin alfa n = 756; 200 IU rFSH n = 750), Ensure (100 µg corifollitropin alfa n = 268; 150 IU rFSH n = 128), and Pursue (150 µg corifollitropin alfa n = 694; 300 IU rFSH n = 696). Women with regular menstrual cycles aged 18-36 and body weight >60 kg (Engage) or ≤60 kg (Ensure), or women aged 35-42 years and body weight ≥50 kg (Pursue), received a single injection (100 µg or 150 µg) of corifollitropin alfa (based on body weight and age) or daily rFSH. The difference (corifollitropin alfa minus rFSH) in the number of oocytes retrieved was +1.0 (95% CI: 0.5-1.5); vital pregnancy rate: -2.2% (95% CI: -5.3%-0.9%); ongoing pregnancy rate: -1.7% (95% CI: -4.7%-1.4%); and live birth rate: -2.0% (95% CI: -5.0%-1.1%). The odds ratio for overall OHSS was 1.15 (95% CI: 0.82-1.61), and for moderate-to-severe OHSS: 1.29 (95% CI: 0.81-2.05). A single dose of corifollitropin alfa for the first 7 days of ovarian stimulation is a generally well-tolerated and similarly effective treatment compared with daily rFSH. PMID:27178762

  4. Follicle-stimulating hormone-induced rescue of cumulus cell apoptosis and enhanced development ability of buffalo oocytes.

    PubMed

    Jain, A; Jain, T; Kumar, P; Kumar, M; De, S; Gohain, M; Kumar, R; Datta, T K

    2016-04-01

    The effect of follicle-stimulating hormone (FSH) on apoptotic status of cumulus cells, expression of proapoptotic and antiapoptotic genes, and development rate of in vitro fertilization-produced buffalo embryos were investigated. FSH supplementation in in vitro maturation-medium resulted in a dose-dependent reduction in the expression of proapoptotic genes namely, BCL2-associated X protein (BAX), cytochrome c, and caspase-3 and increase in the expression of antiapoptotic genes such as B-cell lymphoma 2 (BCL2) and X-linked inhibitor of apoptosis protein (XIAP) in cumulus cells of mature oocyte. Cumulus expansion, oocyte maturation, cleavage, and blastocyst development rates were significantly higher (P < 0.05) in 5 and 10-μg/mL FSH-supplemented groups as compared with control. Significant increase in the expression of FSH receptor messenger RNA was also found with 5 and 10-μg/mL FSH (P < 0.05). Terminal deoxynucleotidyl transferase dUTP nick end labeling assay confirmed that the population of apoptotic cumulus cells of matured oocytes was reduced in the FSH-treated groups as compared with control (P < 0.05). In conclusion, our data suggest that FSH may attenuate apoptosis in cumulus cells via mitochondria-dependent apoptotic pathway by increasing XIAP expression, resulting in a more favorable ratio of BCL2/BAX expression and decreasing the cytochrome c and caspase-3 expression, eventually contributing to developmental competence of oocytes. The information generated will help in improving the in vitro embryo production program in buffalo. PMID:26774556

  5. Follicle-stimulating Hormone Activation of Hypoxia-inducible Factor-1 by the Phosphatidylinositol 3-Kinase/AKT/Ras Homolog Enriched in Brain (Rheb)/Mammalian Target of Rapamycin (mTOR) Pathway Is Necessary for Induction of Select Protein Markers of Follicular Differentiation*

    PubMed Central

    Alam, Hena; Maizels, Evelyn T.; Park, Youngkyu; Ghaey, Shail; Feiger, Zachary J.; Chandel, Navdeep S.; Hunzicker-Dunn, Mary

    2006-01-01

    We sought to elucidate the role of AKT in follicle-stimulating hormone (FSH)-mediated granulosa cell (GC) differentiation. Our results define a signaling pathway in GCs whereby the inactivating phosphorylation of tuberin downstream of phosphatidylinositol (PI) 3-kinase/AKT activity leads to Rheb (Ras homolog enriched in brain) and subsequent mTOR (mammalian target of rapamycin) activation. mTOR then stimulates translation by phosphorylating p70 S6 kinase and, consequently, the 40 S ribosomal protein S6. Activation of this pathway is required for FSH-mediated induction of several follicular differentiation markers, including luteinizing-hormone receptor (LHR), inhibin-α, microtubule-associated protein 2D, and the PKA type IIβ regulatory subunit. FSH also promotes activation of the transcription factor hypoxia-inducible factor-1 (HIF-1). FSH-stimulated HIF-1 activity is inhibited by the PI 3-kinase inhibitor LY294002, the Rheb inhibitor FTI-277 (farne-syltransferase inhibitor-277), and the mTOR inhibitor rapamycin. Finally, we find that the FSH-mediated up-regulation of reporter activities for LHR, inhibin-α, and vascular endothelial growth factor is dependent upon HIF-1 activity, because a dominant negative form of HIF-1α interferes with the up-regulation of these genes. These results show that FSH enhances HIF-1 activity downstream of the PI 3-kinase/AKT/Rheb/mTOR pathway in GCs and that HIF-1 activity is necessary for FSH to induce multiple follicular differentiation markers. PMID:14982927

  6. Neonatal exposure to xenoestrogens impairs the ovarian response to gonadotropin treatment in lambs.

    PubMed

    Rivera, Oscar E; Varayoud, Jorgelina; Rodríguez, Horacio A; Santamaría, Clarisa G; Bosquiazzo, Verónica L; Osti, Mario; Belmonte, Norberto M; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2015-06-01

    Bisphenol A (BPA) and diethylstilbestrol (DES) are xenoestrogens, which have been associated with altered effects on reproduction. We hypothesized that neonatal xenoestrogen exposure affects the ovarian functionality in lambs. Thus, we evaluated the ovarian response to exogenous ovine FSH (oFSH) administered from postnatal day 30 (PND30) to PND32 in female lambs previously exposed to low doses of DES or BPA (BPA50: 50 μg/kg per day, BPA0.5: 0.5 μg/kg per day) from PND1 to PND14. We determined: i) follicular growth, ii) circulating levels of 17β-estradiol (E2), iii) steroid receptors (estrogen receptor alpha, estrogen receptor beta, and androgen receptor (AR)) and atresia, and iv) mRNA expression levels of the ovarian bone morphogenetic protein (BMPs) system (BMP6, BMP15, BMPR1B, and GDF9) and FSH receptor (FSHR). Lambs neonatally exposed to DES or BPA showed an impaired ovarian response to oFSH with a lower number of follicles ≥2 mm in diameter together with a lower number of atretic follicles and no increase in E2 serum levels in response to oFSH treatment. In addition, AR induction by oFSH was disrupted in granulosa and theca cells of lambs exposed to DES or BPA. An increase in GDF9 mRNA expression levels was observed in oFSH-primed lambs previously treated with DES or BPA50. In contrast, a decrease in BMPR1B was observed in BPA0.5-postnatally exposed lambs. The modifications in AR, GDF9, and BMPR1B may be associated with the altered ovarian function due to neonatal xenoestrogen exposure in response to an exogenous gonadotropin stimulus. These alterations may be the pathophysiological basis of subfertility syndrome in adulthood. PMID:25778539

  7. Dopamine antagonist-induced reproductive function in anoestrous mares: gonadotrophin secretion and the effects of environmental cues.

    PubMed

    Daels, P F; Fatone, S; Hansen, B S; Concannon, P W

    2000-01-01

    The effect of the dopamine antagonist sulpiride on FSH secretion and onset of reproductive activity in anoestrous mares under different environmental conditions was investigated. In Expt 1, sulpiride (0.5 mg (-)-sulpiride kg(-1) twice a day) had no affect on FSH pulse frequency, mean FSH concentration, basal FSH concentration or FSH pulse amplitude in anoestrous mares. These data do not support the hypothesis that dopamine inhibits reproductive activity by suppressing GnRH secretion, as it does in other species. In Expt 2, the interval to first ovulation (14.8 +/- 1.9 days; range 12-22 days) in five mares treated with sulpiride (0.5 mg (-)-sulpiride kg(-1) twice a day) housed indoors under extended daylength (16 h light: 8 h dark) was significantly shorter (P < 0.02) than in six untreated mares housed indoors under extended daylength (34.3 +/- 5.5; range 16-52 days and seven untreated mares housed outside under natural photoperiod (73 +/- 10; range 37-107 days). However, if the FSH secretion parameters at the start of treatment are treated as covariants, each has a significant effect (P < 0.05) on the interval to ovulation and sulpiride treatment does not have a significant effect. In Expt 3, the interval to first ovulation was not significantly different in sulpiride-treated (200 mg (-)-sulpiride twice a day) and untreated mares maintained outside under natural photoperiod. These results indicate that sulpiride treatment combined with increased temperature (indoor housing) and stimulatory photoperiod (extended daylength) results in a shorter interval to first ovulation and that a nonstimulatory environment decreases the effect of treatment on the interval to first ovulation. The role of FSH secretion at the time of treatment remains to be determined. PMID:20681129

  8. Pregnancy-associated plasma protein-a production in rat granulosa cells: stimulation by follicle-stimulating hormone and inhibition by the oocyte-derived bone morphogenetic protein-15.

    PubMed

    Matsui, Motozumi; Sonntag, Barbara; Hwang, Seong Soo; Byerly, Tara; Hourvitz, Ariel; Adashi, Eli Y; Shimasaki, Shunichi; Erickson, Gregory F

    2004-08-01

    Pregnancy-associated plasma protein-A (PAPP-A) is the major IGF binding protein-4 (IGFBP-4) protease in follicular fluid, consistent with its proposed role in folliculogenesis. Despite growing interest, almost nothing is known about how PAPP-A expression is regulated in any tissue. Here we show that FSH and oocytes regulate PAPP-A expression in granulosa cells (GCs). By in situ hybridization, ovary PAPP-A mRNA was markedly increased by pregnant mare serum gonadotropin treatment, and the message was localized to the membrana GCs but not cumulus GCs (CGCs) of dominant follicles. To explore the mechanism, we used primary cultures of rat GCs. Control (untreated) cells produced little or no PAPP-A spontaneously. Conversely, FSH markedly stimulated PAPP-A mRNA and protein in a dose- and time-dependent fashion. Interestingly, PAPP-A expression in isolated CGCs was also strongly induced by FSH, and the induction was inhibited by added oocytes. To investigate the nature of the inhibition, we tested the effect of oocyte-derived bone morphogenetic protein-15 (BMP-15). BMP-15 alone had no effect on basal levels of PAPP-A expression by cultures of membrana GCs or CGCs. However, BMP-15 markedly inhibited the FSH stimulation of PAPP-A production in a dose-dependent manner. The cleavage of IGFBP-4 by conditioned media from FSH-treated GCs was completely inhibited by anti-PAPP-A antibody, indicating the IGFBP-4 protease secreted by GCs is PAPP-A. These results demonstrate stimulatory and inhibitory roles for FSH and BMP-15, respectively, in regulating PAPP-A production by GCs. We propose that FSH and oocyte-derived BMP-15 form a controlling network that ensures the spatiotemporal pattern of GC PAPP-A expression in the dominant follicle. PMID:15087430

  9. Synthetic peptides based upon a three-dimensional model for the receptor recognition site of follicle-stimulating hormone exhibit antagonistic or agonistic activity at low concentrations.

    PubMed Central

    Hage-van Noort, M; Puijk, W C; Plasman, H H; Kuperus, D; Schaaper, W M; Beekman, N J; Grootegoed, J A; Meloen, R H

    1992-01-01

    Follicle-stimulating hormone (follitropin, FSH) belongs to a group of closely related glycoprotein hormones that contain two noncovalently linked dissimilar subunits designated alpha and beta. By using synthetic peptides, several receptor interaction sites in these hormones have been identified; however, the peptides have a reduced potency (lowest effective concentration of 10(-4) to 10(-5) M) relative to the hormone itself (10(-8) to 10(-11) M). This suggests that the peptides represent only a portion of a larger recognition site in the intact hormone that comprises parts of both the beta and the alpha chains. To develop peptides that exhibit FSH-antagonistic activity at low concentrations, we have constructed a three-dimensional model for FSH, which is based on an alignment of both the beta and the alpha chains of glycoprotein hormones with thioredoxin, for which x-ray diffraction data are available. This model resulted in the prediction of a conformational receptor-binding site in FSH, in which (parts of) three earlier proposed binding regions on the FSH molecule [namely, the regions FSH alpha-(34-37), with the amino acid sequence SRAY; FSH beta-(40-43), with the amino acid sequence TRDL; and FSH beta-(87-94), the "determinant loop" with the amino acid sequence CDSDSTDC] are located within 10 A of one another. On the basis of this model, peptides have been synthesized in which two of these binding regions are linked by a synthetic amino acid whose length was derived from the model, Ac-TDSDS-NH-(CH2)5-CO-SRAY-NH2 and Ac-SRAY-NH-(CH2)4-CO-TRDL-NH2. Both peptides inhibited FSH-induced cAMP production in Sertoli cells at 1000-fold lower concentrations (10(-7) M) than the peptides Ac-TRDL-NH2, Ac-SRAY-NH2, or Ac-TDSDS-NH2. In another peptide, Ac-TDSDS-NH-(CH2)5-CO-SRAY-NH-(CH2)4-CO-TRDL-NH2, all three binding regions have been linked. This peptide appeared to be a strong agonist of FSH action, as measured by the ability to stimulate cAMP production, at concentrations

  10. Regulation of the phosphoinositide pathway in cultured Sertoli cells from immature rats: effects of follicle-stimulating hormone and fluoride

    SciTech Connect

    Quirk, S.M.; Reichert, L.E. Jr.

    1988-07-01

    Many hormones elicit effects on target cells by stimulating the enzyme phospholipase-C, which catalyzes the hydrolysis of phosphoinositides to the intracellular second messengers diacylglycerol and inositol phosphates. The present study examined the roles of FSH and guanine nucleotide-binding proteins (G-proteins) in regulating the hydrolysis of phosphoinositides in Sertoli cells. Sertoli cell cultures prepared from 16- to 18-day-old rats were incubated for 24 h with myo-(2-3H) inositol to label endogenous phospholipids. Treatment of cells from 0.5-20 min with preparations of ovine FSH ranging in potency from 1-60 times that of NIH FSH S1 did not affect accumulation of inositol phosphates. Levels of total (3H)inositol phosphates ((3H)inositol mono-, di-, and triphosphates (IP, IP2, and IP3)) in FSH-treated cultures was 75-120% the levels in control cultures over the various time intervals studied. Addition of testosterone and the combination of testosterone plus retinoic acid, agents that have been shown to potentiate effects of FSH in other systems, did not affect accumulation of inositol phosphates in response to FSH. In contrast to the lack of effect on accumulation of inositol phosphates, FSH stimulated 4- to 11-fold increases in estradiol secretion over 24 h of culture, indicating that Sertoli cells were viable and responsive to FSH. AIF4- has been shown to activate G-proteins involved in regulation of adenylate cyclase activity. In the present study, AIF4- induced 4- to 5-fold increases in IP, IP2, and IP3 in experiments wherein FSH had no effect. Pretreatment of Sertoli cells with pertussis toxin (100 and 1000 ng/ml) for 24 h inhibited fluoride-induced generation of IP, IP2, and IP3 by 24-51%. Similar treatment with cholera toxin had no effect on basal or fluoride-induced generation of IP2 or IP3, but increased fluoride-induced generation of IP by 20-34%.

  11. The meiotic response of cumulus cell-enclosed mouse oocytes to follicle-stimulating hormone in the presence of different macromolecules.

    PubMed

    Downs, S M; Dow, M P; Fagbohun, C F

    1991-06-01

    Experiments were carried out to determine the effect of different macromolecules on the follicle-stimulating hormone (FSH)-induced maturation of mouse oocytes in culture. Cumulus cell-enclosed oocytes (CEO) were isolated from gonadotropin-primed mice and maintained in meiotic arrest for 17-18 h with the cAMP analogue, dibutyryl cAMP (dbcAMP). Germinal vesicle breakdown (GVB) was stimulated by the addition of FSH. Medium was supplemented with either no macromolecule or with varying concentrations of polyvinylpyrrolidone (PVP), polyvinylalcohol (PVA), crystallized bovine serum albumin (BSA), or fetal bovine serum (FBS). Oocyte maturation in all FSH-free cultures occurred at a frequency of about 30% or below. High frequencies of maturation were achieved when FSH was added to macromolecule-free medium or to cultures containing PVP, PVA, or BSA. Crystallized BSA was the most effective of these in supporting stimulation of maturation (94% GVB at 3 mg/ml, compared with 72-74% with synthetic polymer-supplemented or macromolecule-free media). The BSA effect was not due to contaminating fatty acids, and a less pure fraction V BSA was not as effective in supporting FSH-induced maturation. FBS suppressed FSH stimulation of maturation in a dose-dependent fashion. Sera from pigs, goats, horses, and rats were also inhibitory, but bovine calf serum (BCS) permitted a high maturation frequency (80% GVB). When added to medium containing either FBS or BCS, crystallized BSA had no effect on FSH-stimulated maturation, but fraction V BSA suppressed maturation in both serum-supplemented media. Under no conditions did FSH stimulate maturation in cumulus cell-free oocytes. These results demonstrate that hormone-induced oocyte maturation is supported in vitro by nonprotein polymers as well as BSA and that the behavior of the oocyte-cumulus cell complex depends on the purity of the BSA sample. In addition, serum contains inhibitory factors that suppress the positive response to FSH. Thus, the

  12. Modulating Intrafollicular Hormonal Milieu in Controlled Ovarian Stimulation: Insights From PPAR Expression in Human Granulosa Cells.

    PubMed

    Tatone, Carla; Benedetti, Elisabetta; Vitti, Maurizio; Di Emidio, Giovanna; Ciriminna, Rosanna; Vento, Maria Elena; Cela, Vito; Borzì, Placido; Carta, Gaspare; Lispi, Monica; Cimini, Anna Maria; Artini, Paolo Giovanni

    2016-04-01

    Controlled ovarian stimulation (COS) leading to ovulation of multiple follicles is a crucial aspect of biomedical infertility care. Nevertheless, biomarkers useful for COS management are still lacking. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors relevant to steroid metabolism in granulosa cells (GCs). We investigated whether PPARs and their steroidogenic targets were differentially expressed in GCs differentiated under different recombinant or urinary gonadotropin preparations. GCs from women subjected to COS with r-hFSH, r-hFSH/r-hLH, or hMG-HP were processed to assess expression of PPARα, PPARβ/δ, PPARγ, and steroidogenic enzymes under PPAR modulation. As an evidence of their activation, all PPAR isotypes with their coactivators, the retinoic-X-receptors (RXRs), localized in the nucleus. When GCs from r-hFSH/r-hLH group were compared with r-hFSH, a significant reduction of PPARα protein was observed. By contrast, an increase of PPARβ/δ at both protein and mRNA levels along with that of PPARγ protein were detected. The steroidogenic enzymes 17βHSD IV, 3βHSD II, and HMG-CoA red were downregulated in the r-hFSH/r-hLH group in comparison to r-hFSH unlike CYP19A1 that remained unchanged. In GCs from urinary FSH-LH stimulation (hMG-HP), PPARα was more expressed in comparison with r-hFSH/r-hLH group. Likewise, 3βHSD II and 17βHSD IV were increased suggesting that hMG-HP partially mimicked r-hFSH/r-hLH effects. In summary, transcript analysis associated to protein investigation revealed differential effects of COS protocols on PPARs and their steroidogenic targets in relation to LH and gonadotropin source. These observations candidate PPARs as new biomarkers of follicle competence opening new hypotheses on COS effects on ovarian physiology. J. Cell. Physiol. 231: 908-914, 2016. © 2015 Wiley Periodicals, Inc. PMID:26332656

  13. The Correlations of Anti-Mullerian Hormone, Follicle-Stimulating Hormone and Antral Follicle Count in Different Age Groups of Infertile Women

    PubMed Central

    Barbakadze, Ludmila; Kristesashvili, Jenara; Khonelidze, Natalia; Tsagareishvili, Gia

    2015-01-01

    Background The objective of our study was to identify the correlations between the tests currently used in ovarian reserve assessment: anti-Mullerian hormone (AMH), follicle stimulating hormone (FSH) and antral follicle count (AFC) and to distinguish the most reliable markers for ovarian reserve in order to select an adequate strategy for the initial stages of infertility treatment. Materials and Methods In this prospective study, 112 infertile women were assessed. Subjects were divided into three age groups: group I <35 years (n=39), group II 35-40 years (n=31), and group III 41-46 years (n=42). AMH, FSH and AFC were determined on days 2-3 of the patients’ menstrual cycles. Results There was a significantly elevated negative correlation between age and AMH level (rs=-0.67, p<0.0001) and AFC (rs=-0.55, p<0.0001). We observed a significantly positive correlation between age and FSH (rs=0.38, p<0.0001). AMH negatively correlated with FSH (rs=-0.48, p<0.0001) and positively with AFC (r=-0.71, p=0.0001). There was a moderate negative relation between FSH and AFC (r=-0.41, p=0.0001) and moderate positive relation between age and FSH (rs=0.38, p<0.0001). The correlation analysis performed in separate groups showed that AMH and AFC showed a statistically significant positive correlation for group I (r=0.57, p<0.0001), group II (r=0.69, p<0.0001) and group III (r=0.47, p<0.002). A statistically significant correlation between FSH and AMH was detected only in groups I (r=-0.41, p<0.02) and II (r=-0.55, p<0.0001). A statistically significant correlation existed between FSH and AFC only in group III (r=-0.42, p<0.006), as well as between age and AFC only in group I (r=-0.35, p<0.03). Conclusion Currently, AMH should be considered as the more reliable of the ovarian reserve assessments tests compared to FSH. There is a strong positive correlation between serum AMH level and AFC. The use of AMH combined with AFC may improve ovarian reserve evaluation. PMID:25780521

  14. Systemic concentrations of hormones during the development of follicular waves in mares and women: a comparative study

    PubMed Central

    Ginther, O J; Beg, M A; Gastal, E L; Gastal, M O; Baerwald, A R; Pierson, R A

    2010-01-01

    Changes in systemic concentrations of FSH, LH, oestradiol and progesterone during the ovulatory follicular wave were compared between 30 mares and 30 women. Based on a previous study, the emergence of the future ovulatory follicle was defined as occurring at 13.0 mm in mares and 6.0 mm in women, and deviation in diameter between the two largest follicles was expected to begin at 22.7 mm in mares and 10.3 mm in women. Mean FSH concentrations were high in mares during the luteal phase, resulting from statistically identified FSH surges occurring in individuals on different days and in different numbers (mean, 1.5 ± 0.2 surges/mare); the internadir interval was 3.9 ± 0.3 days. In contrast, mean FSH in women was low during the luteal phase and increased to a prolonged elevation during the follicular phase. The prolonged elevation was apparent in each individual (internadir interval, 15.2 ± 0.4 days). Changes in LH or oestradiol concentrations encompassing deviation were not detected in mares, but both hormones increased slightly but significantly between emergence and deviation in women. The hypothesis that a greater number of growing follicles causes a greater predeviation decrease in FSH was supported for mares (r, −0.39; P < 0.04), but a similar negative correlation (r, −0.36) was not significant in women. The hypothesis that the increase in oestradiol during the luteal phase in women was at least partly attributable to luteal-phase anovulatory follicular waves was not supported. Normalization of FSH concentrations to the day of emergence showed maximum value on the day of emergence with a significant increase and decrease on each side of emergence in both species. The day of expected deviation occurred 3 days after emergence during the decline in FSH in both species. These results indicated that the previously reported striking similarities in emergence and deviation between mares and women during the ovulatory follicular wave are associated with species

  15. The global effect of follicle-stimulating hormone and tumour necrosis factor α on gene expression in cultured bovine ovarian granulosa cells

    PubMed Central

    2014-01-01

    Background Oocytes mature in ovarian follicles surrounded by granulosa cells. During follicle growth, granulosa cells replicate and secrete hormones, particularly steroids close to ovulation. However, most follicles cease growing and undergo atresia or regression instead of ovulating. To investigate the effects of stimulatory (follicle-stimulating hormone; FSH) and inhibitory (tumour necrosis factor alpha; TNFα) factors on the granulosa cell transcriptome, bovine ovaries were obtained from a local abattoir and pools of granulosa cells were cultured in vitro for six days under defined serum-free conditions with treatments present on days 3–6. Initially dose–response experiments (n = 4) were performed to determine the optimal concentrations of FSH (0.33 ng/ml) and TNFα (10 ng/ml) to be used for the microarray experiments. For array experiments cells were cultured under control conditions, with FSH, with TNFα, or with FSH plus TNFα (n = 4 per group) and RNA was harvested for microarray analyses. Results Statistical analysis showed primary clustering of the arrays into two groups, control/FSH and TNFα/TNFα plus FSH. The effect of TNFα on gene expression dominated that of FSH, with substantially more genes differentially regulated, and the pathways and genes regulated by TNFα being similar to those of FSH plus TNFα treatment. TNFα treatment reduced the endocrine activity of granulosa cells with reductions in expression of FST, INHA, INBA and AMH. The top-ranked canonical pathways and GO biological terms for the TNFα treatments included antigen presentation, inflammatory response and other pathways indicative of innate immune function and fibrosis. The two most significant networks also reflect this, containing molecules which are present in the canonical pathways of hepatic fibrosis/hepatic stellate cell activation and transforming growth factor β signalling, and these were up regulated. Upstream regulator analyses also predicted TNF, interferons γ and

  16. Suppression in the secretion of follicle-stimulating hormone and luteinizing hormone, and ovarian follicle development in heifers continuously infused with a gonadotropin-releasing hormone agonist.

    PubMed

    Gong, J G; Campbell, B K; Bramley, T A; Gutierrez, C G; Peters, A R; Webb, R

    1996-07-01

    A novel experimental model was developed in cattle to investigate the requirement for FSH and LH during ovarian follicle growth and development. On Day 5 of the estrous cycle, 7 heifers were each implanted with an osmotic minipump containing a GnRH agonist (GnRHa), Buserelin (release rate, 2.5 micrograms/h). Another 7 heifers served as controls. Each minipump was replaced 28 days later with a second pump, which was left in place for a further 20 days. Blood samples were collected daily throughout the experimental period, and frequent samples were also collected on both days of minipump insertion and at 10 days after insertion of the second pump. The ovaries of all heifers were scanned daily by real-time ultrasonography to monitor follicular dynamics. All controls displayed 2 or 3 waves of FSH and follicular development per estrous cycle during the experiment. Insertion of the first minipump produced a large LH and FSH surge and induced ovulation in all 7 animals. Within 8 days of the start of treatment, serum LH concentrations fell to basal levels; they then remained constant at this level throughout the infusion period, only beginning to recover 4-5 days after the termination of infusion. After the initial increase, FSH returned to basal levels before showing a normal wave that was coincident with the emergence, growth, and regression of a dominant follicle. However, despite the peak levels of FSH, dominant follicles from the next wave failed to grow beyond 7-9 mm; they remained at this size for 3 wk until 3-4 days after insertion of the second minipump, when FSH fell precipitously to reach low levels that were maintained throughout the remainder of the infusion. After this fall in FSH concentrations, these follicles regressed rapidly, and no antral follicles > 4 mm were detected until after the termination of treatment. Thereafter, FSH concentrations increased significantly; the increase was accompanied by the emergence of a follicular wave and development of a

  17. Profiling follicle stimulating hormone-induced gene expression changes in normal and malignant human ovarian surface epithelial cells.

    PubMed

    Ho, Shuk-Mei; Lau, Kin-Mang; Mok, Samuel Chi-Ho; Syed, Viqar

    2003-07-01

    Epidemiological data have implicated the pituitary gonadotropin follicle stimulating hormone (FSH) as both a risk factor for and a protective agent against epithelial ovarian cancer. Yet, little is known about how this hormone could play such opposing roles in ovarian carcinogenesis. Complementary DNA microarrays containing 2400 named genes were used to examine FSH-induced gene expression changes in ovarian cancer (OC) and immortalized normal human ovarian surface epithelial (HOSE) cell lines. Two-way t-statistics analyses of array data identified two distinct sets of FSH-regulated genes in HOSE and in established OC cell lines established from patients (OVCA cell lines). Among the HOSE cell lines, FSH increased expression of 57% of the 312 genes and downregulated 43%. In contrast, FSH diminished expression of 92% of the 177 genes in the OVCA cell lines. All but 18 of the genes affected by FSH in HOSE cell lines were different from those altered in OVCA cell lines. Among the 18 overlapping genes, nine genes exhibited the same direction of change following FSH challenge, while the other nine showed discordance in response between HOSE and OVCA cell lines. The FSH-induced differential expression of seven out of nine genes was confirmed by real-time RT-PCR. Gene-specific antisense oligonuleotides (ODNs) were used to inhibit the expression of genes encoding GTPase activating protein (rap1GAP), neogenin, and restin in HOSE and OVCA cells. Antisense ODNs to neogenin and restin, but not an antisense ODN to rap1GAP, were effective in inhibiting OVCA cell growth, diminishing proliferating cell nuclear antigen expression, and increasing caspase 3 activities. Furthermore, the ODN to rap1GAP was further shown to be ineffective in altering migration properties of OVCA cell lines. HOSE cell proliferation was not affected by treatment with any of the antisense ODNs. In summary, gene profiling data reveal for the first time that FSH may exert different biological actions on OVCA

  18. A human FSHB transgene encoding the double N-glycosylation mutant (Asn(7Δ) Asn(24Δ)) FSHβ subunit fails to rescue Fshb null mice.

    PubMed

    Wang, Huizhen; Butnev, Vladimir; Bousfield, George R; Kumar, T Rajendra

    2016-05-01

    Follicle-stimulating hormone (FSH) is a gonadotrope-derived heterodimeric glycoprotein. Both the common α- and hormone-specific β subunits contain Asn-linked N-glycan chains. Recently, macroheterogeneous FSH glycoforms consisting of β-subunits that differ in N-glycan number were identified in pituitaries of several species and subsequently the recombinant human FSH glycoforms biochemically characterized. Although chemical modification and in vitro site-directed mutagenesis studies defined the roles of N-glycans on gonadotropin subunits, in vivo functional analyses in a whole-animal setting are lacking. Here, we have generated transgenic mice with gonadotrope-specific expression of either an HFSHB(WT) transgene that encodes human FSHβ WT subunit or an HFSHB(dgc) transgene that encodes a human FSHβ(Asn7Δ 24Δ) double N-glycosylation site mutant subunit, and separately introduced these transgenes onto Fshb null background using a genetic rescue strategy. We demonstrate that the human FSHβ(Asn7Δ 24Δ) double N-glycosylation site mutant subunit, unlike human FSHβ WT subunit, inefficiently combines with the mouse α-subunit in pituitaries of Fshb null mice. FSH dimer containing this mutant FSHβ subunit is inefficiently secreted with very low levels detectable in serum. Fshb null male mice expressing HFSHB(dgc) transgene are fertile and exhibit testis tubule size and sperm number similar to those of Fshb null mice. Fshb null female mice expressing the mutant, but not WT human FSHβ subunit-containing FSH dimer are infertile, demonstrate no evidence of estrus cycles, and many of the FSH-responsive genes remain suppressed in their ovaries. Thus, HFSHB(dgc) unlike HFSHB(WT) transgene does not rescue Fshb null mice. Our genetic approach provides direct in vivo evidence that N-linked glycans on FSHβ subunit are essential for its efficient assembly with the α-subunit to form FSH heterodimer in pituitary. Our studies also reveal that N-glycans on FSHβ subunit are

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

    SciTech Connect

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

    1991-06-01

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

  20. Follicle-stimulating Hormone Activates Extracellular Signal-regulated Kinase but Not Extracellular Signal-regulated Kinase Kinase through a 100-kDa Phosphotyrosine Phosphatase*

    PubMed Central

    Cottom, Joshua; Salvador, Lisa M.; Maizels, Evelyn T.; Reierstad, Scott; Park, Youngkyu; Carr, Daniel W.; Davare, Monika A.; Hell, Johannes W.; Palmer, Stephen S.; Dent, Paul; Kawakatsu, Hisaaki; Ogata, Masato; Hunzicker-Dunn, Mary

    2006-01-01

    In this report we sought to elucidate the mechanism by which the follicle-stimulating hormone (FSH) receptor signals to promote activation of the p42/p44 extracellular signal-regulated protein kinases (ERKs) in granulosa cells. Results show that the ERK kinase MEK and upstream intermediates Raf-1, Ras, Src, and L-type Ca2+ channels are already partially activated in vehicle-treated cells and that FSH does not further activate them. This tonic stimulatory pathway appears to be restrained at the level of ERK by a 100-kDa phosphotyrosine phosphatase that associates with ERK in vehicle-treated cells and promotes dephosphorylation of its regulatory Tyr residue, resulting in ERK inactivation. FSH promotes the phosphorylation of this phosphotyrosine phosphatase and its dissociation from ERK, relieving ERK from inhibition and resulting in its activation by the tonic stimulatory pathway and consequent translocation to the nucleus. Consistent with this premise, FSH-stimulated ERK activation is inhibited by the cell-permeable protein kinase A-specific inhibitor peptide Myr-PKI as well as by inhibitors of MEK, Src, a Ca2+ channel blocker, and chelation of extracellular Ca2+. These results suggest that FSH stimulates ERK activity in immature granulosa cells by relieving an inhibition imposed by a 100-kDa phosphotyrosine phosphatase. PMID:12493768

  1. Role of luteinizing hormone in luteotropic complex of pregnant hamster

    SciTech Connect

    Tamura, H.; Greenwald, G.S.

    1987-04-01

    Hamsters were hypophysectomized on day 4 of pregnancy and injected subcutaneously on days 4-7 with various combinations of 200 ..mu..g prolactin (Prl), 10 ..mu..g follicle-stimulating hormone (FSH), and 20 ..mu..g luteinizing hormone (LH) in polyvinylpyrrolidone (PVP) to decrease its rate of absorption or in saline. End points for luteal function on day 8 were maintenance of pregnancy, serum progesterone (P/sub 4/), luteal weight, and luteal binding for human chorionic gonadotropin, FSH, and Prl. After hypophysectomy, a drastic decline occurred in all parameters including an 89% decrease in luteal weight. Injection of Prl did not maintain pregnancy nor serum P/sub 4/ but partially maintained luteal weight and human chorionic gonadotropin binding sites per corpus luteum. The minimal luteotropic complex of Prl and FSH was effective in maintaining pregnancy and significantly increased serum P/sub 4/ and Prl and FSH receptors but not to control levels. Thus, the luteotropic activity of LH was only demonstrable when it was injected in a long-acting form; when delivered as a bolus, LH (saline) was luteolytic. P/sub 4/ and estradiol were measured by radioimmunoassay. Radioiodinated gonadotropins were prepared. The percentage of tracer reacting with an excess of receptor were 51% of /sup 125/I-FSH and 45.9% of /sup 125/I-hCG using whole homogenates of hamster ovaries.

  2. Gankyrin facilitates follicle-stimulating hormone-driven ovarian cancer cell proliferation through the PI3K/AKT/HIF-1α/cyclin D1 pathway.

    PubMed

    Chen, J; Bai, M; Ning, C; Xie, B; Zhang, J; Liao, H; Xiong, J; Tao, X; Yan, D; Xi, X; Chen, X; Yu, Y; Bast, R C; Zhang, Z; Feng, Y; Zheng, W

    2016-05-12

    Gankyrin is a regulatory subunit of the 26kD proteasome complex. As a novel oncoprotein, gankyrin is expressed aberrantly in cancers from several different sites and has been shown to contribute to oncogenesis in endometrial and cervical carcinomas. Neither gankyrin's contribution to the development of epithelial ovarian cancer nor its interaction with follicle-stimulating hormone (FSH)-driven proliferation in ovarian cancer has been studied. Here we have found that gankyrin is overexpressed in ovarian cancers compared with benign ovarian cystadenomas and that gankyrin regulates FSH upregulation of cyclin D1. Importantly, gankyrin regulates PI3K/AKT signaling by downregulating PTEN. Prolonged AKT activation by FSH stimulation of the FSH receptor (FSHR) promotes gankyrin expression, which, in turn, enhances AKT activation by inhibiting PTEN. Overexpression of gankyrin decreases hypoxia inducible factor-1α (HIF-1α) protein levels, but has little effect on HIF-1α mRNA levels, which could be attributed to gankyrin mediating HIF-1α protein stability via the ubiquitin-proteasome pathway. Reduction in HIF-1α protein stability led to attenuation of the binding with cyclin D1 promoter, resulted in abolishment of the negative regulation of cyclin D1 by HIF-1α, which promotes proliferation of ovarian cancer cells. Our results document that gankyrin regulates HIF-1α protein stability and cyclin D1 expression, ultimately mediating FSH-driven ovarian cancer cell proliferation. PMID:26364616

  3. Laser homeostatics on delayed onset muscle soreness

    NASA Astrophysics Data System (ADS)

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

    2011-01-01

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

  4. An activating mutation of the follicle-stimulating hormone receptor autonomously sustains spermatogenesis in a hypophysectomized man

    SciTech Connect

    Gromoll, J.; Simoni, M.; Nieschlag, E.

    1996-04-01

    As both gonadotropins, LH and FSH, are required for normal spermatogenesis, patients with pituitary insufficiency need hCG plus human menopausal gonadotropin therapy to induce spermatogenesis and establish fertility. In a patient hypophysectomized because of a pituitary tumor, who, despite undetectable serum gonadotropin levels, had normal testis volume and semen parameters and fathered three children under testosterone substitution alone, we hypothesized an activating mutation of the FSH receptor. Exon 10 of the FSH receptor gene was amplified from genomic DNA by PCR, screened by single stranded conformation polymorphism gel electrophoresis, and sequenced. We identified a heterozygous A{r_arrow}G base change at nucleotide position 1700, leading to an Asp,Gly transition in codon 567 in the third intracytoplasmatic loop. COS-7 cells transiently transfected with the mutated receptor displayed a 1.5-fold increase in basal cAMP production compared to wild-type receptor, indicating that this mutation leads to ligand-independent constitutive activation of the FSH receptor. We conclude that this activating mutation of the FSH receptor, the first ever described, autonomously sustains spermatogenesis in the absence of gonadotropins. 31 refs., 5 figs., 1 tab.

  5. Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis

    SciTech Connect

    Hsueh, A.J.W.; Dahl, K.D.; Vaughan, J.; Tucker, E.; Rivier, J.; Bardin, C.W.; Vale, W.

    1987-07-01

    Inhibin, a gonadal hormone capable of preferential suppression of pituitary follicle-stimulating hormone (FSH) secretion, has recently been purified. The major form of this protein is an ..cap alpha beta.. heterodimer encoded by two separate genes. In contrast to the FSH-suppressing action of the ..cap alpha beta.. heterodimer, the ..beta beta.. homodimer stimulates FSH secretion. Luteinizing hormone (LH)-secreting pituitary cells and gonadal androgen-producing cells have long been shown to form a closed-loop feedback axis. Based on recent studies demonstrated the FSH stimulation of inhibin biosynthesis by ovarian granulosa and testis Sertoli cells, an additional closed-loop feedback axis exists between pituitary FSH- and gonadal inhibin-producing cells. Because uncharacterized Sertoli cell factors have been suggested to either stimulate or inhibit androgen production by testicular Leydig cells, the authors have tested the intragonadal paracrine actions of heterodimers and homodimers of inhibin subunits. In primary cultures of testis cells, the ..cap alpha beta.. heterodimer of inhibin enhances Leydig cell androgen biosynthesis stimulated by LH, whereas the ..beta beta.. homodimer suppresses androgen production. The data indicate that the inhibin-related gene products synthesized by Sertoli and granulosa cells may form heterodimers or homodimers to serve as intragonadal paracrine signals in the modulation of LH-stimulated androgen biosynthesis and allow cross-communication between the two feedback loops.

  6. Effects of 3, 5, 3'-triiodothyronine (t3) and follicle stimulating hormone on apoptosis and proliferation of rat ovarian granulosa cells.

    PubMed

    Zhang, Cheng; Guo, Li; Zhu, Baochang; Feng, Yun; Yu, Shangyu; An, Na; Wang, Xiaoxia

    2013-10-31

    Thyroid hormone (TH) is important for normal reproductive functions and dysregulation of TH support is associated with reproductive disorders. We have previously reported that 3,5,3'-triiodothyronine (T₃) increases follicle stimulating hormone (FSH)-induced preantral follicle growth in vitro. Interaction of hormones with apoptosis and proliferation of granulosa cells is poorly understood. The present study investigated the role and the mechanism of T₃ and/or FSH on granulosa cell apoptosis and proliferation. Granulosa cells harvested from DES-primed immature rats were exposed to T₃ (1 nM) and/or FSH (100 ng/ml) for 24-48 h. We demonstrated by TUNEL assays that the hormones prevented cells from C8-ceramide-induced apoptosis. The Src/PI3K/Akt pathway was involved in the regulation of granulosa cell survival. While ineffective alone, T₃ significantly enhanced the proliferating cell nuclear antigen (PCNA) content of FSH-induced granulosa cells, consistent with the cell number pattern after treatment. Moreover, the action of the hormones on cell proliferation was also shown to be mediated by the Src/PI3K/Akt pathway. Taken together, these results suggest that T₃ potentiates the cell survival action of FSH through inhibiting cell apoptosis and promoting cell proliferation. Moreover, the protective and survival effects of hormones are mediated by the activation of Src/PI3K/Akt pathway. PMID:24032715

  7. NONOBSTRUCTIVE AZOOSPERMIA, FOLLICLE-STIMULATING HORMONE AS A MARKER OF SUCCESSFUL SPERM RETRIEVAL.

    PubMed

    Khelaia, A; Saker, Z; Tsintsadze, O; Managadze, L

    2015-12-01

    Testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) was revolutionized treatment of infertile men with azoospermia. Predictive factors for the presence of spermatozoa in testis are still under debate. Serum FSH levels reflect the state of seminiferous epitelium. Serum FSH has been evaluated as a predictor of success sperm retrieval rate (SRR) in NOA (37 cases 46XY men), but even among men with the highest FSH (30,0 - 40,0 mU/ml) spermatozoon was found. Men with FSH serum level 10 - 15 mU/ml had the SRR 0%. TESA is as a simple, minimally invasive approach for sperm retrieval. In our study sperm retrieval rate was 46%. In our practice we advised TESA as a first step and FSH can predict the success. TESA it is not only a diagnostic procedure to define the level of spermatogenesis, but also a therapeutic technique to retrieve sperm for ICSI. Also, in cases of negative results after TESE and hypospermatogenesis by histopatology we advised re-TESA after 3-6 months. PMID:26719547

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

    PubMed

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

    2009-07-01

    The aim of this study is to evaluate whether occupational exposure to urban stressors could cause alterations in the follicle-stimulating hormone (FSH) levels in traffic policemen compared to a control group. After excluding the subjects with main confounding factors, traffic policemen and male controls were matched by age, working life, body mass index (BMI), drinking habit, cigarette smoking history, and daily consumption of Italian coffee, 166 traffic policemen and 166 controls were included into the study. FSH levels were significantly higher in traffic policemen compared to male controls (P < 0.05). The distribution of FSH values in traffic policemen and controls was significant (P < 0.05). Our results suggest that occupational exposure to low doses of chemical and psychosocial stressors may alter plasma levels of FSH in traffic policemen more than in the control group. If the results obtained are confirmed by further research, the plasma levels of FSH may be used as early biological markers, valuable for the group, used in occupational set even before the appearance of disorders of male fertility. PMID:19671632

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

    SciTech Connect

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

    1988-01-05

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

  10. Different follicle stimulating hormone/luteinizing hormone ratios for ovarian stimulation.

    PubMed

    Duijkers, I J; Vemer, H M; Hollanders, J M; Willemsen, W N; Bastiaans, L A; Hamilton, C J; Thomas, C M; Borm, G F

    1993-09-01

    The aim of the present study was to investigate whether reducing the amount of luteinizing hormone (LH) in gonadotrophic preparations impairs follicular growth in in-vitro fertilization (IVF) cycles during suppression of endogenous LH levels. A selected group of 20 IVF patients was randomly divided into two groups. One group was treated with Org 31338 [follicle stimulating hormone (FSH)/LH 3:1], the other group with Metrodin (purified FSH), both during pituitary down-regulation with buserelin. A fixed daily dose of 150 IU FSH i.m. was given. Serum concentrations of FSH, LH, oestradiol and progesterone were determined frequently and serial ultrasound examinations were performed. Multiple follicular growth with concomitant rise of oestradiol levels was observed in all cycles. The duration of the stimulation phase was shorter in the group treated with Org 31338 than in the group treated with Metrodin. The number of follicles and oocytes and the fertilization rate was larger and the mean embryo quality was higher in the Org 31338 group, but the differences did not reach statistical significance. No significant differences were found in hormonal values. In women with normal endocrine profiles, lowering of the LH activity in gonadotrophic preparations during gonadotrophin-releasing hormone agonist treatment results in adequate ovarian stimulation. However, a preparation with some LH needed a shorter stimulation than a purified FSH preparation. Whether the other beneficial effects of Org 31338 also occur in a larger population needs further investigation. PMID:8253923

  11. Does inhibin-B help us to confidently refuse diagnostic testicular biopsy in azoospermia?

    PubMed Central

    Moradi, Mahmoudreza; Alemi, Mohsen; Moradi, Asaad; Izadi, Babak; Parhodah, Farajollah; Torkaman Asadi, Fatemeh

    2012-01-01

    Background: In the recent years, the use of laboratory blood factors such as FSH and inhibin-B for the assessment of spermatogenesis in different studies has increased; of course, the conflicting results have also been achieved. Objective: To investigate if the measurement of inhibin-B can help surgeon to reduce unnecessary diagnostic testicular biopsies in males with azoospermia. Materials and Methods: This cross-sectional study was done during July 2006 to September 2007 on 41 patients with azoospermia. FSH and inhibin-B were measured and bilateral open testicular biopsy was performed for all patients. Results: Sperm was seen in 29% of biopsies that in 100% of these samples inhibin-B was more than 100 pg/mL and FSH was less than twice the normal (p=0.001). Inhibin-B had significant correlation inversely with testicular fibrosis and Sertoli cell only syndrome (p=0.043 and p=0.011, respectively) and directly with incomplete spermatocytic maturation arrest and obstructive azoospermia (p=0.027 and p=0.013, respectively). FSH was only correlated with obstructive azoospermia (p=0.001). Conclusion: We suggest that if FSH is less than twice the normal, inhibin-B should be measured and if its level is less than 100 pg/mL, we can cancel about the half of unnecessary diagnostic testicular biopsies. PMID:25243000

  12. Dibromochloropropane (DBCP): an 8-year reevaluation of testicular function and reproductive performance

    SciTech Connect

    Potashnik, G.; Yanai-Inbar, I.

    1987-02-01

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

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

    PubMed

    Sanyal, D; Chatterjee, S

    2016-06-01

    This retrospective study assessed treatment preferences and outcome with testosterone or HCG / HCG-FSH combination in Indian male idiopathic hypogonadotropic hypogonadism (IHH) subjects (n = 31) above 18 years of age. 38.7% of IHH study subjects had no fertility plans and chose 3 monthly intramuscular testosterone undecanoate. 73.7% of subjects with fertility plans chose human chorionic gonadotropin (HCG) alone due to cost considerations. Spermatogenesis occurred in 21.4% on HCG alone and 60% of subjects on HCG with follicle-stimulating hormone (FSH) combination. Treatment failure is higher than published Western rates. FSH and HCG combination regimen is costly but superior to HCG alone. However, treatment failure still persists, suggesting unknown testicular defect in IHH. PMID:26341841

  14. Influence of BMP-2 on early follicular development and mRNA expression of oocyte specific genes in bovine preantral follicles cultured in vitro.

    PubMed

    Rossi, Rodrigo O D S; da Cunha, Ellen V; Portela, Antonia M L R; Passos, José R S; Costa, José J N; Silva, Anderson W B; Saraiva, Márcia V A; Peixoto, Christina A; Donato, Mariana A M; van den Hurk, Robert; Silva, José R V

    2016-03-01

    This study evaluates the effect of different concentrations (0, 10, 50 and 100ng/mL) of bone morphogenetic protein-2 (BMP-2) on primordial and secondary follicle development. It also investigates the effects of FSH and BMP-2 on the growth, morphology, ultrastructure and expression of mRNA for GDF9, NLRP5 and NPM2 genes in secondary follicles cultured for 18 days. The presence of BMP-2 at all tested concentrations increased the development of primordial follicles in vitro, but the highest concentration of BMP-2 (100 ng/mL) reduced the percentage of normal follicles when compared with tissues cultured with 10 ng/mL BMP-2. During culture of secondary follicles, in contrast to higher concentrations (50 or 100 ng/mL), 10 ng/mL BMP-2 kept the morphology of follicles during initial stages of in vitro culture. This concentration of BMP-2 also benefits maintenance of the ultrastructure of 18-day cultured follicles. The presence of both BMP-2 and FSH in culture medium resulted in a significant (P<0.05) increase in follicular diameter after 18 days of culture. However, both FSH and BMP-2 reduced follicular mRNA expression of GDF9 and NLRP5 when compared to follicles cultured in media containing only FSH. In combination with FSH, BMP-2 reduced the mRNA levels of NPM2, when compared to follicles cultured in control medium. It is concluded from these data that 10 ng/mL BMP-2 promotes the growth of primordial in vitro and it helps to maintain the ultrastructure of secondary follicles, while FSH is more important for better expression of follicular markers like GDF9 and NLRP5. PMID:26435174

  15. Transcription of follicle-stimulating hormone subunit genes is modulated by porcine LIM homeobox transcription factors, LHX2 and LHX3

    PubMed Central

    YOSHIDA, Saishu; KATO, Takako; NISHIMURA, Naoto; KANNO, Naoko; CHEN, Mo; UEHARU, Hiroki; NISHIHARA, Hiroto; KATO, Yukio

    2016-01-01

    The LIM-homeobox transcription factors LHX2 and LHX3s (LHX3a and LHX3b) are thought to be involved in regulating the pituitary glycoprotein hormone subunit genes Cga and Fshβ. These two factors show considerable differences in their amino acid sequences for DNA binding and protein-protein interactions and in their vital function in pituitary development. Hence, we compared the DNA binding properties and transcriptional activities of Cga and Fshβ between LHX2 and LHX3s. A gel mobility shift assay for approximately 1.1 kb upstream of Cga and 2.0 kb upstream of Fshβ varied in binding profiles between LHX2 and LHX3s. DNase I footprinting revealed DNA binding sites in 8 regions of the Cga promoter for LHX2 and LHX3s with small differences in the binding range and strength. In the Fshβ promoter, 14 binding sites were identified for LHX2 and LHX3, respectively. There were alternative binding sites to either gene in addition to similar differences observed in the Cga promoter. The transcriptional activities of LHX2 and LHX3s according to a reporter assay showed cell-type dependent activity with repression in the pituitary gonadotrope lineage LβT2 cells and stimulation in Chinese hamster ovary lineage CHO cells. Reactivity of LHX2 and LHX3s was observed in all regions, and differences were observed in the 5'-upstream region of Fshβ. However, immunohistochemistry showed that LHX2 resides in a small number of gonadotropes in contrast to LHX3. Thus, LHX3 mainly controls Cga and Fshβ expression. PMID:26853788

  16. Effects of follicle-stimulating hormone and 17beta-estradiol on proliferation of chicken embryonic ovarian germ cells in culture.

    PubMed

    Xie, Meina; Zhang, Caiqiao; Zeng, Weidong; Mi, Yuling

    2004-12-01

    The effects of follicle-stimulating hormone (FSH) and 17beta-estradiol (E2) on chicken ovarian germ cell proliferation were evaluated through a germ-somatic cell coculture model. Ovarian cells from the left ovaries of 18-day-old chicken embryos were cultured in serum-free McCoy's 5A medium at 39 degrees C and challenged with FSH (0.25-1.0 IU/mL) or E2 (10(-8)-10(-5) M) alone and in combination for 48 h. The number of germ cells was counted, and the proliferating cells were immunolocalized by a specific antibody against proliferating cell nuclear antigen (PCNA). The labeling index (LI) was determined for germ cells. Results revealed that germ cells could survive and kept proliferating under support of somatic cells. Germ cells were localized by expression of a specific antibody for stem cell factor receptor c-kit. Both FSH (0.25-1.0 IU/mL) and E2 (10(-7)-10(-5) M) alone induced a marked increase in germ cell number (P<0.05), and PCNA-LI of germ cells was greater in FSH-treated groups (0.25-1.0 IU/mL) and E2-treated groups (10(-8)-10(-5) M), compared with vehicle-treated group (P<0.05). Furthermore, FSH manifested a synergistic effect with E2 (10(-6)-10(-5) M) in stimulating germ cell proliferation. These results indicate that FSH might interact with estrogen to promote ovarian germ cell proliferation in embryonic chickens near hatching. PMID:15596398

  17. Transcription of follicle-stimulating hormone subunit genes is modulated by porcine LIM homeobox transcription factors, LHX2 and LHX3.

    PubMed

    Yoshida, Saishu; Kato, Takako; Nishimura, Naoto; Kanno, Naoko; Chen, Mo; Ueharu, Hiroki; Nishihara, Hiroto; Kato, Yukio

    2016-06-17

    The LIM-homeobox transcription factors LHX2 and LHX3s (LHX3a and LHX3b) are thought to be involved in regulating the pituitary glycoprotein hormone subunit genes Cga and Fshβ. These two factors show considerable differences in their amino acid sequences for DNA binding and protein-protein interactions and in their vital function in pituitary development. Hence, we compared the DNA binding properties and transcriptional activities of Cga and Fshβ between LHX2 and LHX3s. A gel mobility shift assay for approximately 1.1 kb upstream of Cga and 2.0 kb upstream of Fshβ varied in binding profiles between LHX2 and LHX3s. DNase I footprinting revealed DNA binding sites in 8 regions of the Cga promoter for LHX2 and LHX3s with small differences in the binding range and strength. In the Fshβ promoter, 14 binding sites were identified for LHX2 and LHX3, respectively. There were alternative binding sites to either gene in addition to similar differences observed in the Cga promoter. The transcriptional activities of LHX2 and LHX3s according to a reporter assay showed cell-type dependent activity with repression in the pituitary gonadotrope lineage LβT2 cells and stimulation in Chinese hamster ovary lineage CHO cells. Reactivity of LHX2 and LHX3s was observed in all regions, and differences were observed in the 5'-upstream region of Fshβ. However, immunohistochemistry showed that LHX2 resides in a small number of gonadotropes in contrast to LHX3. Thus, LHX3 mainly controls Cga and Fshβ expression. PMID:26853788

  18. The role of corifollitropin alfa in controlled ovarian stimulation for IVF in combination with GnRH antagonist.

    PubMed

    Seyhan, Ayse; Ata, Baris

    2011-01-01

    Corifollitropin alfa is a synthetic recombinant follicle-stimulating hormone (rFSH) molecule containing a hybrid beta subunit, which provides a plasma half-life of ∼65 hours while maintaining its pharmocodynamic activity. A single injection of corifollitropin alfa can replace daily FSH injections for the first week of ovarian stimulation for in vitro fertilization. Stimulation can be continued with daily FSH injections if the need arises. To date, more than 2500 anticipated normoresponder women have participated in clinical trials with corifollitropin alfa. It is noteworthy that one-third of women did not require additional gonadotropin injections and reached human chorionic gonadotropin criterion on day 8. The optimal corifollitropin dose has been calculated to be 100 μg for women with a body weight ≤60 kg and 150 μg for women with a body weight >60 kg, respectively. Combination of corifollitropin with daily gonadotropin-releasing hormone antagonist injections starting on stimulation day 5 seems to yield similar or significantly higher numbers of oocytes and good quality embryos, as well as similar ongoing pregnancy rates compared with women stimulated with daily rFSH injections. Stimulation characteristics, embryology, and clinical outcomes seem consistent with repeated corifollitropin-stimulated assisted reproductive technologies cycles. Multiple pregnancy or ovarian hyperstimulation syndrome rates with corifollitropin were not increased over daily FSH regimen. The corifollitropin alfa molecule does not seem to be immunogenic and does not induce neutralizing antibody formation. Drug hypersensitivity and injection-site reactions are not increased. Incidence and nature of adverse events and serious adverse events are similar to daily FSH injections. Current trials do not provide information regarding use of corifollitropin alfa in anticipated hyper- and poor responders to gonadotropin stimulation. Although corifollitropin alfa is unlikely to be teratogenic

  19. Infantile 4-tert-octylphenol exposure transiently inhibits rat ovarian steroidogenesis and steroidogenic acute regulatory protein (StAR) expression

    SciTech Connect

    Myllymaeki, S.A. . E-mail: saanmy@utu.fi; Karjalainen, M.; Haavisto, T.E.; Toppari, J.; Paranko, J.

    2005-08-22

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

  20. Gonadotropin ratio affects the in vitro growth of rhesus ovarian preantral follicles.

    PubMed

    Kim, Yoon Young; Yun, Jun-Won; Kim, Jong Min; Park, Chung Gyu; Rosenwaks, Zev; Liu, Hung Ching; Kang, Byeong-Cheol; Ku, Seung-Yup

    2016-04-01

    In vitro follicle growth (IVFG) strategy is critical in the fertility preservation of cancer survivors; however, its optimal protocol needs to be developed using primate models since the availability of human samples is limited. Only a few previous studies have reported the successful IVFG of rhesus monkey ovaries using low-dose follicle-stimulating hormone (FSH) (0.3 or 3 ng/mL) and long-term culture (up to 5 weeks) and it is still uncertain in regard to the optimal culture duration and effective dose of treated gonadotropins applicable to the IVFG of rhesus preantral follicles. Recently, we have reported that the FSH to luteinizing hormone (LH) ratio affects the in vitro growth of murine ovarian follicles. We aimed to investigate whether gonadotropin ratios affect the efficiency of rhesus follicular growth in vitro Ovaries were collected from six necropsied rhesus macaques (4-9 years) and preantral follicles were retrieved and cultured for 14 days using 200 mIU/mL FSH. The characteristics of follicular growth were compared between the FSH:LH=1:1 (n=24) and FSH:LH=2:1 (n=24) groups. High concentration gonadotropin treatment shortened the duration required for in vitro maturation of rhesus preantral follicles. The FSH:LH=2:1 group showed a faster follicular growth and enabled the acquisition of mature oocytes, although the expression of growth differentiation factor (GDF)-9 and anti-Müllerian hormone (AMH) did not differ significantly between the two groups. Taken together, high dose gonadotropin treatment can shorten the duration of IVFG and the gonadotropin ratio is important in the IVFG of rhesus monkey ovaries. PMID:26980777

  1. Gonadotropin stimulation regimens for follicular aspiration and in vitro embryo production from calf oocytes.

    PubMed

    Armstrong, D T; Irvine, B J; Earl, C R; McLean, D; Seamark, R F

    1994-01-01

    Crossbred beef x dairy calves were randomly allocated at 3 wk of age to different gonadotropin treatment regimens for stimulation of follicle development and induction of oocyte maturation in vivo. Follicular responses were assessed laparoscopically, and oocytes were aspirated for assessment of maturational state or for in vitro fertilization (IVF) and culture to determine developmental capacity. Follicle-stimulating Hormone (FSH), administered in a single subcutaneous injection together with a low dosage of PMSG, was as effective as the same total dosage of FSH administered in 6 injections over a 3-d period. Without accompanying PMSG, this dose of FSH was ineffective in stimulating follicle development. The mean number of preovulatory follicles (> 5mm, with hyperemic appearance) doubled with each successive stimulation at 3-wk intervals, reaching 35 follicles per calf at 9 wk of age. Oocyte yields ranged from 55 to 81% of follicles aspirated, and did not differ significantly among age, FSH regimen and oocyte maturation stimulus. A combination of LH + FSH was more effective in stimulating cumulus cell expansion than LH by itself (73 vs 22% of recovered oocyte-cumulus cell complex (OCC) respectively; P<0.05). Of 33 unselected immature oocytes (cumulus unexpanded) subjected to in vitro maturation (IVM) and IVF, 30% developed to blastocysts during co-culture with bovine oviduct epithelial cells, which was not significantly different from 25% of 36 oocytes from adult ovaries which reached the blastocyst stage under similar conditions. The results indicate that follicle responses of calf ovaries to FSH stimulation increase progressively from 3 to 9 wk of age, and that oocytes recovered laparoscopically from these follicles produce blastocysts in culture at rates similar to oocytes from adult cattle ovaries collected at slaughter. The approach offers promise for embryo production from donor calves of superior genetic merit for embryo transfer, thereby enhancing the rate

  2. Follicle-stimulating hormone potentiates the steroidogenic activity of chorionic gonadotropin and the anti-apoptotic activity of luteinizing hormone in human granulosa-lutein cells in vitro.

    PubMed

    Casarini, Livio; Riccetti, Laura; De Pascali, Francesco; Nicoli, Alessia; Tagliavini, Simonetta; Trenti, Tommaso; La Sala, Giovanni Battista; Simoni, Manuela

    2016-02-15

    Luteinizing hormone (LH) and choriogonadotropin (hCG) are glycoprotein hormones regulating ovarian function and pregnancy, respectively. Since these molecules act on the same receptor (LHCGR), they were traditionally assumed as equivalent in assisted reproduction techniques (ART), although differences between LH and hCG were demonstrated at molecular and physiological level. In this study, we demonstrated for the first time that co-treatment with a follicle-stimulating hormone (FSH) dose in the ART therapeutic range potentiates different LH- and hCG-dependent responses in vitro, measured in terms of cAMP, phospho-CREB, -ERK1/2 and -AKT activation, gene expression, progesterone and estradiol production in human granulosa-lutein cells (hGLC). We show that in the presence of FSH, hCG biopotency is about 5-fold increased, in the presence of FSH, in terms of cAMP activation. Accordingly, CREB phosphorylation and steroid production is increased under hCG and FSH co-treatment. LH effects, evaluated as steroidogenic cAMP/PKA pathway activation, do not change in the presence of FSH, which, however, increases LH-dependent ERK1/2 and AKT, but not CREB phosphorylation, resulting in anti-apoptotic effects. The different modulatory activity of FSH on LH and hCG action in vitro corresponds to their different physiological functions, reflecting proliferative effects exerted by LH during the follicular phase and before trophoblast development, and the high steroidogenic potential of hCG requested to sustain pregnancy from the luteal phase onwards. PMID:26690776

  3. Gonadotropin ratio affects the in vitro growth of rhesus ovarian preantral follicles

    PubMed Central

    Kim, Yoon Young; Yun, Jun-Won; Kim, Jong Min; Park, Chung Gyu; Rosenwaks, Zev; Liu, Hung Ching; Kang, Byeong-Cheol; Ku, Seung-Yup

    2016-01-01

    In vitro follicle growth (IVFG) strategy is critical in the fertility preservation of cancer survivors; however, its optimal protocol needs to be developed using primate models since the availability of human samples is limited. Only a few previous studies have reported the successful IVFG of rhesus monkey ovaries using low-dose follicle-stimulating hormone (FSH) (0.3 or 3 ng/mL) and long-term culture (up to 5 weeks) and it is still uncertain in regard to the optimal culture duration and effective dose of treated gonadotropins applicable to the IVFG of rhesus preantral follicles. Recently, we have reported that the FSH to luteinizing hormone (LH) ratio affects the in vitro growth of murine ovarian follicles. We aimed to investigate whether gonadotropin ratios affect the efficiency of rhesus follicular growth in vitro. Ovaries were collected from six necropsied rhesus macaques (4–9 years) and preantral follicles were retrieved and cultured for 14 days using 200 mIU/mL FSH. The characteristics of follicular growth were compared between the FSH:LH=1:1 (n=24) and FSH:LH=2:1 (n=24) groups. High concentration gonadotropin treatment shortened the duration required for in vitro maturation of rhesus preantral follicles. The FSH:LH=2:1 group showed a faster follicular growth and enabled the acquisition of mature oocytes, although the expression of growth differentiation factor (GDF)-9 and anti-Müllerian hormone (AMH) did not differ significantly between the two groups. Taken together, high dose gonadotropin treatment can shorten the duration of IVFG and the gonadotropin ratio is important in the IVFG of rhesus monkey ovaries. PMID:26980777

  4. Mechanisms of enhanced osteoclastogenesis in girls and young women with Turner's Syndrome.

    PubMed

    Faienza, Maria Felicia; Brunetti, Giacomina; Ventura, Annamaria; Piacente, Laura; Messina, Maria Francesca; De Luca, Filippo; Ciccarelli, Maria; Oranger, Angela; Mori, Giorgio; Natale, Maria Pia; Gigante, Margherita; Ranieri, Elena; Gesualdo, Loreto; Colucci, Silvia; Cavallo, Luciano; Grano, Maria

    2015-12-01

    Subjects with hypergonadotropic hypogonadism due to Turner's syndrome show low cortical mineral density, osteoporosis and risk of fractures. It is not clear if this bone fragility derives from chromosomal abnormalities or is the result of inadequate bone formation due to estrogen deficiency. The aim of this study was to investigate the cellular mechanisms underlying bone fragility in subjects with Turner's syndrome before induction of puberty and after hormonal replacement therapy (HRT). For this purpose, we have evaluated the osteoclastogenic potential of non-fractioned and T-cell depleted cultures of peripheral blood mononuclear cells (PBMCs) belonging to girls with Turner's syndrome who had not been treated with HRT yet, girls and young women who were on HRT and age-matched controls. Untreated subjects showed high FSH serum levels, whereas the other subjects displayed normal FSH serum levels. T-cell immunophenotype was analyzed through flow cytometry. Biochemical and DXA analyses were performed. Spontaneous osteoclastogenesis in non-fractioned and T-cell depleted cultures of PBMC belonging to girls with high FSH levels was more evident than in cultures of subjects with normal FSH levels. In the former, osteoclastogenesis was sustained by monocytes expressing high levels of c-fms, TNF-α and RANK, and T-cells producing high RANKL and TNF-α; in the latter it was supported by T-cells expressing high RANKL levels. CD4(+)CD25(high) T-cells were reduced in all subjects, whereas CD3(+)/CD16(+)/CD56(+) NKT-cells were increased in those with high FSH levels. High RANKL and CTX levels were detected in the sera. Bone impairment was already detectable by DXA in subjects aged under 10, although it became more evident with aging. In conclusion, our results demonstrated that bone fragility in subjects with Turner's syndrome is associated to enhanced osteoclastogenesis. This process seems to be due to high FSH serum levels before HRT, whereas it is caused by high RANKL during

  5. Follicle-stimulating hormone/cAMP regulation of aromatase gene expression requires β-catenin

    PubMed Central

    Parakh, Tehnaz N.; Hernandez, Jennifer A.; Grammer, Jean C.; Weck, Jennifer; Hunzicker-Dunn, Mary; Zeleznik, Anthony J.; Nilson, John H.

    2006-01-01

    Estrogens profoundly influence the physiology and pathology of reproductive and other tissues. Consequently, emphasis has been placed on delineating the mechanisms underlying regulation of estrogen levels. Circulating levels of estradiol in women are controlled by follicle-stimulating hormone (FSH), which regulates transcription of the aromatase gene (CYP19A1) in ovarian granulosa cells. Previous studies have focused on two downstream effectors of the FSH signal, cAMP and the orphan nuclear receptor steroidogenic factor-1 (NR5A1). In this report, we present evidence for β-catenin (CTNNB1) as an essential transcriptional regulator of CYP19A1. FSH induction of select steroidogenic enzyme mRNAs, including Cyp19a1, is enhanced by β-catenin. Additionally, β-catenin is present in transcription complexes assembled on the endogenous gonad-specific CYP19A1 promoter, as evidenced by chromatin immunoprecipitation assays. Transient expression and RNAi studies demonstrate that FSH- and cAMP-dependent regulation of this promoter is sensitive to alterations in the level of β-catenin. The stimulatory effect of β-catenin is mediated through functional interactions with steroidogenic factor-1 that involve four acidic residues within its ligand-binding domain, mutation of which attenuates FSH/cAMP-induced Cyp19a1 mRNA accumulation. Together, these data demonstrate that β-catenin is essential for FSH/cAMP-regulated gene expression in the ovary, identifying a central and previously unappreciated role for β-catenin in estrogen biosynthesis, and a potential broader role in other aspects of follicular maturation. PMID:16895991

  6. Protein synthesis inhibitors prevent both spontaneous and hormone-dependent maturation of isolated mouse oocytes

    SciTech Connect

    Downs, S.M. )

    1990-11-01

    The present study was carried out to examine the role of protein synthesis in mouse oocyte maturation in vitro. In the first part of this study, the effects of cycloheximide (CX) were tested on spontaneous meiotic maturation when oocytes were cultured in inhibitor-free medium. CX reversibly suppressed maturation of oocytes as long as maturation was either initially prevented by the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (IBMX), or delayed by follicle-stimulating hormone (FSH). In the second part of this study, the actions of protein synthesis inhibitors were tested on hormone-induced maturation. CEO were maintained in meiotic arrest for 21-22 h with hypoxanthine, and germinal vesicle breakdown (GVB) was induced with follicle-stimulating hormone (FSH). Three different protein synthesis inhibitors (CX, emetine (EM), and puromycin (PUR)) each prevented the stimulatory action of FSH on GVB in a dose-dependent fashion. This was accompanied by a dose-dependent suppression of 3H-leucine incorporation by oocyte-cumulus cell complexes. The action of these inhibitors on FSH- and epidermal growth factor (EGF)-induced GVB was next compared. All three drugs lowered the frequency of GVB in the FSH-treated groups, below even that of the controls (drug + hypoxanthine); the drugs maintained meiotic arrest at the control frequencies in the EGF-treated groups. Puromycin aminonucleoside, an analog of PUR with no inhibitory action on protein synthesis, had no effect. The three inhibitors also suppressed the stimulatory action of FSH on oocyte maturation when meiotic arrest was maintained with the cAMP analog, dbcAMP.

  7. Evaluation of two treatments in superovulation of mares.

    PubMed

    Rosas, C A; Alberio, R H; Barañao, J L; Agüero, A; Chaves, M G

    1998-05-01

    The efficiency of superovulating mares with an enriched fraction of equine follicle-stimulating hormone (feFSH) and an equine pituitary extract (EPE) with similar FSH content but differing in the LH amount was compared. Mares were randomly assigned to an feFSH (n = 5) or EPE (n = 5) treatment. The experimental period was of 2 successive estrous cycles, with the first cycle as the control. At Days 6 and 7 of the estrous cycle, the mares received 250 micrograms i.m. cloprostenol. The treatments consisted of daily injections of 25 mg feFSH or EPE beginning on Day 6 post ovulation. Mares were inseminated every other day until the last ovulation was detected. When the mares in the control and treatment cycles developed at least 1 or 2 > or = 35-mm follicle, respectively, the treatment was interrupted, and a single injection of EPE (25 mg, i.v.) was administered to induce ovulation(s). Nonsurgical embryo recovery was performed 6 or 7 d after ovulation in both control and treatment cycles. The number of ovulations per mare was not significantly different (P > 0.05) between feFSH and EPE groups, but both were higher (P < 0.05) than that of the control cycle. The number of recovered embryos per ovulation was similar (P > 0.05) for control, feFSH and EPE groups. The high amount of LH presented in EPE did not affect the superovulatory response of the mares. Superovulatory treatments increased the ovulation rate of mares but did not affect the embryo recovery rate per ovulation. PMID:10732063

  8. Developmental Programming: Exogenous Gonadotropin Treatment Rescues Ovulatory Function But Does Not Completely Normalize Ovarian Function in Sheep Treated Prenatally with Testosterone1

    PubMed Central

    Steckler, Teresa L.; Lee, James S.; Ye, Wen; Inskeep, E. Keith; Padmanabhan, Vasantha

    2008-01-01

    Prenatal testosterone treatment leads to LH excess as well as ovarian follicular and ovulatory defects in the adult. These disruptions may stem from LH excess, abnormal FSH input, compromised ovarian sensitivity to gonadotropins, or intrinsic ovarian defects. To determine if exogenous gonadotropins rescue ovarian and ovulatory function of testosterone-treated sheep, the release of endogenous LH and biopotent FSH in control and prenatal testosterone-treated sheep was blocked with a GnRH antagonist during the first two breeding seasons and with LH/FSH coadministered in a manner approximating natural follicular phase. An acidic mix of FSH was administered the first 36 h at 2-h intervals and a less acidic mix for the next 12 h at 1-h intervals (different FSH preparations were used each year), and ovulation was induced with hCG. Circulating FSH and estradiol responses to gonadotropins measured in 2-h samples differed between treatment groups in Year 1 but not in Year 2. Ovarian follicular distribution and number of corpora lutea (in ewes that ovulated) tracked by ultrasonography and luteal progesterone responses were similar between control and prenatal testosterone-treated females but differed between years. Furthermore, hCG administration induced large cystic and luteinized follicles in both groups of females in Year 2, although the growth rate differed between control and prenatal testosterone-treated females. Our findings provide evidence that 1) ovulatory response in prenatal testosterone-treated females can be rescued with exogenous gonadotropins, 2) resultant follicular response is dependent on the nature of gonadotropic input, and 3) an abnormal follicular milieu may underlie differences in developmental trajectory of cystic follicles in prenatal testosterone-treated females. PMID:18524978

  9. Characterization of Functionally Typical and Atypical Types of Polycystic Ovary Syndrome

    PubMed Central

    Hirshfeld-Cytron, Jennifer; Barnes, Randall B.; Ehrmann, David A.; Caruso, Anthony; Mortensen, Monica M.; Rosenfield, Robert L.

    2009-01-01

    Context: The typical polycystic ovary syndrome (PCOS) phenotype includes 17-hydroxyprogesterone (17OHP) hyperresponsiveness to GnRH agonist (GnRHag) testing. Functionally atypical PCOS lacks this feature. Objective: The hypothesis was tested that the typical PCOS ovarian dysfunction results from intrinsically increased sensitivity to LH/human chorionic gonadotropin (hCG) due to a flaw in FSH action. Participants/Design/Interventions/Main Outcome Measures: After phenotyping a cohort of 60 women, steroid and inhibin-B responses to gonadotropins were evaluated in representative typical (n = 7) and atypical (n = 5) PCOS and healthy controls (n = 8). Submaximal hCG testing before and after an FSH test dose was performed in random order before and after prolonged ovarian suppression by depot GnRHag. Setting: The study was performed at a Clinical Research Center. Results: Of our PCOS cohort, 68% were the typical type. Typical PCOS had 17OHP hyperresponsiveness and, unlike controls, significant androgen and estradiol responses to hCG. FSH increased inhibin-B and did not inhibit free testosterone or enhance estradiol responsiveness to hCG, all unlike controls. After ovarian suppression, 17OHP, androstenedione, and inhibin-B responsiveness to gonadotropin testing persisted. Atypical PCOS had significantly higher body mass index but lower ovarian volume and plasma free testosterone than typical PCOS. Steroid responses to hCG were insignificant and similar to controls. FSH suppressed free testosterone but stimulated inhibin-B. The estradiol level after combined hCG-FSH was subnormal. Free testosterone was less GnRHag suppressible than in typical PCOS. Conclusions: Typical PCOS is characterized by intrinsic ovarian hypersensitivity to hCG to which excessive paracrine FSH signaling via inhibin-B may contribute. Atypical PCOS is due to a unique type of ovarian dysfunction that is relatively gonadotropin hyposensitive. PMID:19240152

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

    PubMed Central

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

    2009-01-01

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

  11. Control of gonadotrophin secretion by steroid hormones in castrated male transsexuals. I. Effects of oestradiol infusion on plasma levels of follicle-stimulating hormone and luteinizing hormone.

    PubMed

    Goh, H H; Chew, P C; Karim, S M; Ratnam, S S

    1980-02-01

    Twenty-four infusions of oestradiol (E2) in graded doses ranging from 0--200 micrograms administered over a period of 7 hours were carried out in eleven healthy male transsexuals who had undergone sex reassignment at least 3 months previously. Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and E2 were analysed by radioimmunoassay, while sex hormone binding globulin (SHBG) was measured using 3H-testosterone as the saturating ligand. Infusion of 5--200 micrograms of E2 raised plasma E2 to levels ranging from 38.4--367.8 pg/ml which present 83%--800% of levels found in a control group of sixty-three normal males. SHBG capacity remained unchanged at all doses of E2 studied. No change in plasma levels of FSH and LH was observed in control infusions and infusion of 5 micrograms of E2. From 10 micrograms-200 micrograms, suppression of plasma levels of FSH was noted at the 5--7 hour period. The suppression increased up to 20 micrograms and thereafter the levels of FSH remained constant. On the other hand, the suppression of LH increased up to the highest E2 dose (200 micrograms) studied. Further, significant suppression of LH occurred earlier than the 5--7 hours as the dose of E2 increased. These observations are consistent with the conclusions that: (1) E2 plays a part in the regulation of secretion of FSH and LH in men; and (2) at doses higher than physiological, E2 exerts a differential effect on the secretion of FSH and LH. PMID:6772356

  12. Abnormal gonadotropin release and carbohydrate metabolism in morbid obese women.

    PubMed

    Sheu, W H; Lee, W J

    1997-12-31

    Obese women are associated with clinical symptoms suggestive of abnormal reproductive functions including irregular menses and infertility. Previous studies of gonadotropin release in obese women, basal or after luteal hormone releasing hormone (LHRH) stimulation, are controversial. Obese women are also often characterized by glucose intolerance and hyperinsulinemia which might relate to their excessive body fat. To understand the link between abnormal gonadotropin release, carbohydrate metabolism and percent body fat, we examined 17 premenopausal morbid obese women with body mass index (BMI) 38.7 +/- 1.6 Kg/m2 (mean +/- SEM) and 16 age-matched lean controls with BMI 19.7 +/- 0.6 Kg/m2. Plasma glucose, insulin and C-peptide values were measured before and 30, 60, 90 and 120 min after a 75 gm oral glucose tolerant test (OGTT). Each individual also received LHRH test which involved determinations of serum LH and FSH values at basal, 15, 30 and 60 min after injection of LHRH for 0.1 mg intravenously. Women with morbid obesity had significantly greater responses of glucose, insulin and C-peptide values as compared with lean women (all p < 0.001, two-way ANOVA). Despite that basal concentrations were not different, serum LH, FSH and ratio of LH to FSH values in response to LHRH test showed significantly lesser increase in obese women than lean controls. Percent body fat, determined by bioelectrical impedance analysis, correlated positively with plasma glucose, insulin and C-peptide responses to OGTT while negatively with ratio of LH to FSH responses (r = -0.418, p < 0.01) to LHRH test. Body mass index also correlated inversely with ratio of LH to FSH responses (r = -0.472, p < 0.01). In conclusion, morbid obese women had glucose intolerance, hyperinsulinemia and lower responses of serum LH and FSH values as compared with lean women. Excessive body fat play an important role in mediating these carbohydrate and gonadotropin abnormalities. PMID:9551249

  13. LH supplementation in mild stimulations cycles without pituitary suppression: a retrospective analysis.

    PubMed

    Paragona, Mizar; Rossini, Matteo; Dattilo, Maurizio; Stamm, Juerg

    2013-02-01

    A cohort of patients addressed to a mild stimulation protocol was retrospectively analysed aiming at evaluating the effect of a luteinizing hormone (LH) activity containing stimulation compared to a pure follicle-stimulating hormone (FSH) drive in absence of any pituitary suppression. Due to a referral bias, the two groups (human FSH (hFSH) n = 210; hMG n = 105) were imbalanced for age with the hFSH group (mean age 38.4) being significantly older than the hMG group (mean age 36.8). But the clinical pregnancy rates (20%) did not differ between the groups. Secondary outcome variables showed a higher number of oocytes retrieved (3.02 vs. 2.31) and higher estradiol levels (1148 vs. 820) in the hMG/younger group whereas the fertilization rate (FR) was higher (54.8 vs. 63.8) in the FSH older/group. In spite of the LH content in the hMG product (~10 IU per vial), the LH concentration on the day of human chorionic gonadotropin (hCG) was higher, although non-significantly, in the hFSH group. We suppose hCG contained in hMG inhibited to some extent the natural release of LH from the non-suppressed pituitary. Concluding, the mild stimulation clinical pregnancy rates are satisfactory independently of the treatment choice. The hMG group showed a trend for a lower efficacy. This phenomenon might be limited to non suppressed cycles, but should be taken in due account also when designing full dose controlled ovarian hyperstimulation (COH) treatments. PMID:23256611

  14. Association between serum 25-hydroxyvitamin D and ovarian reserve in pre-menopausal women

    PubMed Central

    Jukic, Anne Marie Z.; Steiner, Anne Z.; Baird, Donna D.

    2014-01-01

    Objective Vitamin D has been linked to anti-Müllerian hormone levels, suggesting a possible association with greater ovarian reserve, but large population-based studies are lacking. Our objective was to explore the association between vitamin D and FSH in premenopausal women. Methods The Uterine Fibroid Study (1996 – 1999) enrolled randomly-selected 30 – 49 year-old members of a Washington D. C. health plan (N=1430). Women provided a blood and urine sample in addition to questionnaire data. The vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) was measured in stored plasma samples. Urinary FSH (mIU/mg creatinine) was measured with an immunofluorometric assay. To obtain baseline measures, this investigation was limited to urine samples collected in the first 5 days of the menstrual cycle or 5 days prior to menses onset. Additionally, post-menopausal women and women using oral contraceptives were excluded, leaving 527 women in our analysis. FSH was creatinine-adjusted, normalized by log-transformation, and then modeled with multivariable linear regression. Results The median 25(OH)D level was 12 ng/mL, with approximately 75% of participants below the recommended level of 20 ng/mL. FSH and 25(OH)D were inversely related. For an increase of 10 ng/mL in 25(OH)D, urinary FSH decreased 14% (95% Confidence Interval: −23%, −5%), p=0.003. Conclusions Vitamin D is inversely related to FSH. This is consistent with literature relating low vitamin D with lower anti-Müllerian hormone. Prospective studies should investigate whether low levels of vitamin D contribute to decreased ovarian reserve. PMID:25093721

  15. Testosterone and Male Infertility.

    PubMed

    Ohlander, Samuel J; Lindgren, Mark C; Lipshultz, Larry I

    2016-05-01

    Hypogonadism and its therapies have a significant impact on male fertility potential. It is necessary to determine the etiology to treat and counsel the patient appropriately on therapeutic options. For the hypogonadal male on exogenous testosterone, management should begin with cessation of the exogenous testosterone and supplemental subcutaneous human chorionic gonadotropin and an oral follicle-stimulating hormone (FSH)-inducing agent to allow reestablishment of the hypothalamic-pituitary-gonadal axis and spermatogenesis. Further supplemental therapy with recombinant FSH in some patients may be necessary to achieve optimal semen parameters. PMID:27132576

  16. When is treatment with clomiphene or gonadotropin IUI futile? Results of FASTT and FORT-T, two prospective randomized controlled trials

    PubMed Central

    Kaser, Daniel J.; Goldman, Marlene B.; Fung, June L.; Alper, Michael M.; Reindollar, Richard H.

    2014-01-01

    Study objective To determine if day 3 FSH and E2 levels at the upper limits of normal affect live birth rates and treatment trajectory in a conventional vs. ‘fast track’ treatment program for IVF. Design Secondary analysis of two randomized controlled trials, FASTT and FORT-T. Setting Multicenter study in a state with mandated insurance coverage. Patients Infertile women ages 21 to 42 years randomized to conventional or accelerated treatment with controlled ovarian hyperstimulation (COH)-IUI and/or IVF (n=603 patients contributing 2,717 total cycles). Interventions Patients were stratified according to basal FSH and E2: FSH <10mIU/mL and E2 <40pg/mL (Group 1A), FSH <10mIU/mL and E2 ≥40 pg/mL (Group 1B), FSH 10–15 mIU/mL and E2 <40pg/mL (Group 2A) and FSH 10–15 mIU/mL and E2 ≥40 pg/mL (Group 2B). Main outcome measures Number of cancelled cycles, disenrollment for poor response and cumulative live birth rates per couple. Results Women in Groups 2A and 2B were more likely to have cancelled cycles and be disenrolled for poor response. While no live births occurred in Group 2B during COH-IUI (0/19 couples, 0/58 cycles), IVF still afforded these patients a reasonable chance of success (6/18 couples, 6/40 cycles, 33.3% live birth rate per couple). The specificity and positive predictive value of basal FSH 10–15 mIU/mL and E2 ≥40 pg/mL for no live birth during COH-IUI treatment were both 100%. Conclusions Women who initiated infertility treatment with FSH 10–15 mIU/mL and E2 ≥ 40 pg/mL on day 3 testing were unlikely to achieve live birth after COH-IUI treatment. PMID:25226857

  17. EFFECT OF SULFAMETHAZINE AND PHOTOSTIMULATION ON GENE EXPRESSION OF VASOACTIVE INTESTINAL POLYPEPTIDE (VIP) AND PHOSPHODIESTERASE IN THE LATERAL SEPTAL ORGAN (LSO) AND PITUITARY GONADOTROPIN CONTENT IN THE CHICK.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most birds living in the temperate zone use seasonal changes in day length as predictive environmental cues to initiate and terminate breeding. Long day illumination induces rapid gonadal developmen tand stimulates gonadotropin-releasng hormone (GnRH), follicle stimulating hormone (FSH), luteinizin...

  18. MULTIPLE STABLE PERIODIC SOLUTIONS IN A MODEL FOR THE HORMONAL REGULATION OF THE MENSTRUAL CYCLE

    EPA Science Inventory

    ABSTRACT

    The pituitary hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the ovarian hormones, estradiol (E2), progesterone (P4), and inhibin (Ih), are five hormones important for the regulation and maintenance of the human menstrual cycle. The...

  19. 78 FR 13316 - National Forest System Land Management Planning Directives

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-27

    ...The Forest Service has issued proposed directives to Forest Service Handbook (FSH 1909.12) and Manual (FSM 1920) establishing procedures and responsibilities for implementing the National Forest System (NFS) land management planning regulation. Issuance of these proposed directives will provide consistent overall guidance to Forest Service Line Officers and Agency employees in developing,......

  20. 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

  1. 36 CFR 215.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... implementing land and resource management plans. Projects and activities implementing a land and resource... a land and resource management plan on National Forest System lands and is subject to the notice and... statement (EIS) nor an environmental assessment (EA) is required (40 CFR 1508.4; FSH 1909.15, Chapter...

  2. 36 CFR 215.17 - Informal disposition.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... distances, alternative types of meetings (such as telephone conferences or video conferences) may be... and reconsideration of decisions to take action guidance in FSH 1909.15, Chapter 10, section 18, and... and disposition of the unresolved portion of the appeal shall continue (§ 215.18)....

  3. Krohne Flow Indicator and High Flow Alarm Local Indicator and High Flow Alarm of Helium Flow from the SCHe Purge Lines C and D to the Process Vent

    SciTech Connect

    MISKA, C.R.

    2000-09-03

    Flow Indicators/alarms FI/FSH-5*52 and -5*72 are located in the process vent lines connected to the 2 psig SCHe purge lines C and D. They monitor the flow from the 2 psig SCHe purge going to the process vent. The switch/alarm is non-safety class GS.

  4. 21 CFR 862.1300 - Follicle-stimulating hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Follicle-stimulating hormone test system. 862.1300... Systems § 862.1300 Follicle-stimulating hormone test system. (a) Identification. A follicle-stimulating hormone test system is a device intended to measure follicle-stimulating hormone (FSH) in plasma,...

  5. Downregulation of the expression of inhibin α subunit and betaglycan in porcine cystic follicles

    PubMed Central

    WANG, Chunqiang; LI, Chunjing; LI, Hongjiao; MA, Wei; CHEN, Shuxiong; ZHAO, Yun; RAO, Jiahui; ZHOU, Xu

    2015-01-01

    Inhibins, as members of the transforming growth factor beta (TGF-β) superfamily, downregulate the synthesis and secretion of follicle-stimulating hormone (FSH) in an endocrine manner. The role of inhibin/betaglycan in the ovary regulation recently gained attention. To date, no data exist on the function of inhibin α subunit and betaglycan in cystic follicles. In this study, the expressions of inhibin α subunit and betaglycan in cystic follicles were investigated using immunohistochemistry, real-time PCR and Western blot analysis. Both inhibin α subunit and betaglycan immunoreactivities were mainly localized in the granulosa cells of follicles. Expression of inhibin α subunit and betaglycan was inferior in cystic follicles compared with that in normal large follicles. However, the result of enzyme-linked immunosorbent assay showed no significant difference in the decreasing in concentration of inhibin α subunit in cystic follicular fluid compared with the control (P>0.05). In this study, we explored the effects of FSH on betaglycan expression in granulosa cells in vitro. As expected, a significant increase in the expressions of betaglycan mRNA and protein in granulosa cells was observed in response to exogenous FSH (30 ng/ml) (P<0.05) compared with the control. Consequently, this study provides evidence that the expressions of inhibin α subunit and betaglycan are inferior in cystic follicles, and this may be caused by the decrease in FSH in the presence of a cystic follicle. PMID:26097017

  6. Prepubertal endocrine follow-up in subjects with Wilms' tumor

    SciTech Connect

    Perrone, L.; Sinisi, A.A.; Sicuranza, R.; Di Tullio, M.T.; Indolfi, P.; Giuliano, M.G.; Bellastella, A.; Faggiano, M.

    1988-01-01

    Twenty-three prepubertal subjects treated for Wilms' tumor (10 males and 13 females) were endocrinologically evaluated off therapy from 0.5 to 4.08 years. They were divided into two groups: 11 subjects (6M, 5F) who had received chemotherapy only (group 1) and 12 (4M, 8F) who had in addition received abdominal radiation (1,500-3,000 rads) (group 2). Follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid-stimulating hormone (TSH), free thyroxine (FT4), free tri-iodo thyronine (FT3), testosterone (T), estradiol-17 beta (E2), and cortisol (F) were measured by radioimmunoassay (RIA). Plasma levels of TSH, PRL, FT4, FT3, and F were normal in both groups, as were FSH, LH, T, and E2 in group 1. In group 2, female subjects showed FSH levels significantly higher than controls, while LH and E2 were normal; male subjects showed significantly higher LH levels, while FSH and T levels were normal. These results indicate that in the treatment protocol used by us for Wilms' tumor (WT), chemotherapy does not affect endocrine function, whereas abdominal radiation seems to damage gonadal function directly. The present findings indicate that gonadal damage may be revealed in WT before puberty not only in females, as has been previously reported, but also in male subjects.

  7. Metabolism of testosterone by human granulosa cells in culture: influence of follicle-stimulating hormone and luteinizing hormone

    SciTech Connect

    Moon, Y.S.; Duleba, A.; Leung, P.C.; Gomel, V.

    1982-03-15

    Human granulosa cells were isolated from follicles (8 to 15 mm) and cultivated for 24 hours in the presence or absence of follicle-stimulating hormone (NIH-FSH-HS-1, 1 microgram/ml) and luteinizing hormone (NIAMDD-hLH-1, 1 microgram/ml). Testosterone -4-14C was added subsequently to all cultures for 4-, 6-, and 24-hour periods. Of the seven metabolites of testosterone studied, 17 beta-estradiol (E2) and estrone (E1) were the major products. In all patients, levels of E2 were three to ten times higher than those of E1. Production of E2, but not E1, was stimulated by either follicle-stimulating hormone (FSH) or luteinizing hormone (LH). The cells of the largest follicle (15 mm) showed greater response to LH than to FSH. Production of the other C19 and C18 metabolites was very low or negligible. These results further suggest that FSH regulates the aromatization of testosterone in human granulosa cells, and that LH may have the same effect on the matured follicle during the preovulatory period.

  8. Testicular failure

    MedlinePlus

    ... the scrotum Other tests may show low bone mineral density and fractures. Blood tests may show a low level of testosterone and high levels of prolactin, FSH , and LH . Your doctor may also order a semen analysis to examine the number of healthy sperm you ...

  9. Anorchia

    MedlinePlus

    ... of the voice, and increase in muscle mass) Tests include: Anti-Mullerian hormone levels Bone density FSH and LH levels Surgery to look for male reproductive tissue Testosterone levels (low) Ultrasound or MRI to look for testes in the abdomen X,Y karyotype

  10. Possible role of IGF2 receptors in regulating selection of 2 dominant follicles in cattle selected for twin ovulations and births

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Abundance of IGF-2 receptor (IGF2R), FSH receptor (FSHR), and LH receptor (LHCGR) mRNA in granulosa cells (GCs) or theca cells (TCs) or both cells as well as estradiol (E2), progesterone (P4), and androstenedione concentrations in follicular fluid were compared in cows genetically selected (Twinner)...

  11. Cumulus cell gene expression associated with pre-ovulatory acquisition of developmental competence in bovine oocytes.

    PubMed

    Bunel, A; Nivet, A L; Blondin, P; Vigneault, C; Richard, F J; Sirard, M A

    2014-01-01

    The final days before ovulation impact significantly on follicular function and oocyte quality. This study investigated the cumulus cell (CC) transcriptomic changes during the oocyte developmental competence acquisition period. Six dairy cows were used for 24 oocyte collections and received FSH twice daily over 3 days, followed by FSH withdrawal for 20, 44, 68 and 92 h in four different oestrous cycles for each of the six cows. Half of the cumulus-oocyte complexes were subjected to in vitro maturation, fertilisation and culture to assess blastocyst rate. The other half of the CC underwent microarray analysis (n=3 cows, 12 oocyte collections) and qRT-PCR (n=3 other cows, 12 oocyte collections). According to blastocyst rates, 20 h of FSH withdrawal led to under-differentiated follicles (49%), 44 and 68 h to the most competent follicles (71% and 61%) and 92 h to over-differentiated ones (51%). Ten genes, from the gene lists corresponding to the three different follicular states, were subjected to qRT-PCR. Interestingly, CYP11A1 and NSDHL gene expression profiles reflected the blastocyst rate. However most genes were associated with the over-differentiated status: GATM, MAN1A1, VNN1 and NRP1. The early period of FSH withdrawal has a minimal effect on cumulus gene expression, whereas the longest period has a very significant one and indicates the beginning of the atresia process. PMID:23827322

  12. Comparative gene expression profiling in human cumulus cells according to ovarian gonadotropin treatments.

    PubMed

    Assou, Said; Haouzi, Delphine; Dechaud, Hervé; Gala, Anna; Ferrières, Alice; Hamamah, Samir

    2013-01-01

    In in vitro fertilization cycles, both HP-hMG and rFSH gonadotropin treatments are widely used to control human follicle development. The objectives of this study are (i) to characterize and compare gene expression profiles in cumulus cells (CCs) of periovulatory follicles obtained from patients stimulated with HP-hMG or rFSH in a GnRH antagonist cycle and (ii) to examine their relationship with in vitro embryo development, using Human Genome U133 Plus 2.0 microarrays. Genes that were upregulated in HP-hMG-treated CCs are involved in lipid metabolism (GM2A) and cell-to-cell interactions (GJA5). Conversely, genes upregulated in rFSH-treated CCs are implicated in cell assembly and organization (COL1A1 and COL3A1). Interestingly, some genes specific to each gonadotropin treatment (NPY1R and GM2A for HP-hMG; GREM1 and OSBPL6 for rFSH) were associated with day 3 embryo quality and blastocyst grade at day 5, while others (STC2 and PTX3) were related to in vitro embryo quality in both gonadotropin treatments. These genes may prove valuable as biomarkers of in vitro embryo quality. PMID:24151596

  13. Effects of postoperative adjuvant chemotherapy and radiotherapy on testicular function in men undergoing treatment for soft tissue sarcoma

    SciTech Connect

    Shamberger, R.C.; Sherins, R.J.; Rosenberg, S.A.

    1981-05-15

    Testicular function was studied in 26 men with sarcoma who received adjuvant treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate (with or without radiotherapy). Testicular size, sperm output, and serum FSH, LH and testosterone levels were assessed after treatment. Five of 17 men who received chemotherapy or chemotherapy with radiotherapy to the neck, arm, chest or leg, had normal testicular function. Eight of the remaining 12 men who provided ejaculates were oligospermic or azoospermic and serum FSH was increased threefold and LH twofold; testosterone levels were normal. In men less than 40 years old, the mean FSH level was less than that of men over 40 years of age (P = 0.05), suggesting that recovery from the injury was age-related. By contrast, all nine men who received chemotherapy plus radiotherapy to the abdomen or thigh had decreased testicular size, azoospermia, fourfold increase in FSH, and twofold increase in LH levels; but testosterone concentration was normal. These data indicate that reversible testicular injury occurs after treatment with doxorubicin, cyclophosphamide, and high-dose methotrexate; recovery is age-related. However, these agents in combination with use of adjuvant radiotherapy to the thigh or abdomen may produce permanent testicular injury even in young patients.

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

    PubMed Central

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

    2014-01-01

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

  15. 78 FR 73820 - Publicly Managed Recreation Opportunities, Recreation Fees

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-09

    ... Forest Service RIN 0596-AD09 Publicly Managed Recreation Opportunities, Recreation Fees AGENCY: Forest... final directive providing direction on recreation fees in chapter 30 of new Forest Service Handbook (FSH) 2309.13. This chapter enumerates the requirements for recreation fees charged by the Forest...

  16. Early effects of cranial irradiation on hypothalamic-pituitary function

    SciTech Connect

    Lam, K.S.; Tse, V.K.; Wang, C.; Yeung, R.T.; Ma, J.T.; Ho, J.H.

    1987-03-01

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

  17. Downregulation of the expression of inhibin α subunit and betaglycan in porcine cystic follicles.

    PubMed

    Wang, Chunqiang; Li, Chunjing; Li, Hongjiao; Ma, Wei; Chen, Shuxiong; Zhao, Yun; Rao, Jiahui; Zhou, Xu

    2015-11-01

    Inhibins, as members of the transforming growth factor beta (TGF-β) superfamily, downregulate the synthesis and secretion of follicle-stimulating hormone (FSH) in an endocrine manner. The role of inhibin/betaglycan in the ovary regulation recently gained attention. To date, no data exist on the function of inhibin α subunit and betaglycan in cystic follicles. In this study, the expressions of inhibin α subunit and betaglycan in cystic follicles were investigated using immunohistochemistry, real-time PCR and Western blot analysis. Both inhibin α subunit and betaglycan immunoreactivities were mainly localized in the granulosa cells of follicles. Expression of inhibin α subunit and betaglycan was inferior in cystic follicles compared with that in normal large follicles. However, the result of enzyme-linked immunosorbent assay showed no significant difference in the decreasing in concentration of inhibin α subunit in cystic follicular fluid compared with the control (P>0.05). In this study, we explored the effects of FSH on betaglycan expression in granulosa cells in vitro. As expected, a significant increase in the expressions of betaglycan mRNA and protein in granulosa cells was observed in response to exogenous FSH (30 ng/ml) (P<0.05) compared with the control. Consequently, this study provides evidence that the expressions of inhibin α subunit and betaglycan are inferior in cystic follicles, and this may be caused by the decrease in FSH in the presence of a cystic follicle. PMID:26097017

  18. The effect of dietary protein on reproduction in the mare. V. Endocrine changes and conception during the early post partum period.

    PubMed

    van Niekerk, F E; van Niekerk, C H

    1998-09-01

    Pregnant Anglo-Arab and Thoroughbred mares (n = 24) were divided randomly according to age and breed into 4 groups of 6 mares each from approximately 6 weeks before their expected foaling date. Diets received by the 4 groups varied in essential amino-acid and total protein contents. Serum progestagen, FSH and LH concentrations were determined from the day of parturition until foal heat and during the 1st oestrous cycle following foal heat. Serum progestagen, FSH and LH concentrations did not differ between the treatment groups. Progestagen concentrations were high (mean = 7.0: 5.2-16.4 ng/ml) at parturition but decreased rapidly within 48 h. As progestagen concentrations decreased LH concentrations increased from Days 3-6 post partum to reach maximum values at, or the day after ovulation. FSH concentrations declined 3-4 d after parturition and increased 2-3 d before ovulation at foal heat. The duration of elevated progestagen concentrations during the luteal phase of the subsequent oestrous cycle affected the interovulatory period. A 12-14 d FSH cyclical releasing pattern occurred. Season/photoperiod affected the resumption of normal oestrous cyclicity during the post partum period. The duration of the 1st oestrous cycle after foal heat in mares fed a low-quality protein diet showed a greater range (13-30 d) compared to mares fed a high-quality protein diet (18-26 d). PMID:9850510

  19. Measurement of the free alpha subunit of human glycoprotein hormones by a monoclonal antibody-based immunoradiometric assay, and further exploration of antigenic sites on the choriogonadotropin molecule

    SciTech Connect

    Norman, R.J.; Haneef, R.; Buck, R.H.; Joubert, S.M.

    1987-07-01

    Three monoclonal antibodies were raised against the free alpha subunit of choriogonadotropin (hCG); each recognized a different antigenic site on the molecule. One (antibody 42) preferentially bound to the alpha subunit when it was coupled to the beta subunit as dimeric choriogonadotropin (hCG), thyrotropin (TSH), lutropin (LH), or follitropin (FSH). Antibody 71 showed some cross-reaction with intact FSH; antibody 75 was more specific for the alpha subunit. All were of low affinity (10(-7) to 10(-8) mol/L), but when combined in immunoradiometric assays (IRMAS) they proved to be as sensitive as current radioimmunoassays involving polyclonal antibodies. Advantages of the combination of antibody 75 bound to the solid phase and antibody 71 as the radiolabeled antibody were: detection limit of at least 0.1 micrograms/L; linear dilution of serum and urine; insignificant cross-reaction with intact hCG, allowing direct assay in pregnancy fluids; and a coefficient of variation less than 3% over the reference interval for nonpregnant women. There was 4% cross-reaction with intact FSH, suggesting that the epitopes recognized by nos. 71 and 75 are more exposed in FSH and that perhaps there is less folding in this molecule than in intact hCG.

  20. The Effect of Camphor on Sex Hormones Levels in Rats

    PubMed Central

    Shahabi, Sima; Jorsaraei, Seyed Gholam Ali; Akbar Moghadamnia, Ali; Barghi, Effat; Zabihi, Ebrahim; Golsorkhtabar Amiri, Masoumeh; Maliji, Ghorban; Sohan Faraji, Alieh; Abdi Boora, Maryam; Ghazinejad, Neda; Shamsai, Hajar

    2014-01-01

    In some traditional therapies, it has been claimed that camphor (a crystalline ketone obtained from cinnamomum camphora) would be a suppressor of sexual behaviors and sex hormones. This study evaluated the effects of camphor on sex hormones, like luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone. In this experimental study, 56 male rats were divided into 5 groups, including control (n=12), sham (n=11) and three treatment groups (n=11) in three different doses. The sham groups received daily intra peritoneal (IP) injections of the vehicle (ethanol 10%) for 30 days. Three treatment groups received different daily IP injections of the camphor (1, 2 and 5 mg/Kg) for 30 days and the control groups didn’t received anything. Serums were used for assaying LH, FSH and testosterone. The level of LH significantly increased in all doses of camphor among the treatment groups as compared to the control (p<0.05), but camphor in doses 2 and 5 mg/Kg significantly reduced the FSH level as compared to control group (p<0.05). No significant changes were seen in testosterone levels. Camphor increased level of LH, decreased level of FSH, whereas it failed to change level of testosterone. The claim of inhibitory effect of camphor on sexual activity could not be confirmed by this study. More investigations in this field are suggested. PMID:24567939

  1. The effect of camphor on sex hormones levels in rats.

    PubMed

    Shahabi, Sima; Jorsaraei, Seyed Gholam Ali; Akbar Moghadamnia, Ali; Barghi, Effat; Zabihi, Ebrahim; Golsorkhtabar Amiri, Masoumeh; Maliji, Ghorban; Sohan Faraji, Alieh; Abdi Boora, Maryam; Ghazinejad, Neda; Shamsai, Hajar

    2014-01-01

    In some traditional therapies, it has been claimed that camphor (a crystalline ketone obtained from cinnamomum camphora) would be a suppressor of sexual behaviors and sex hormones. This study evaluated the effects of camphor on sex hormones, like luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone. In this experimental study, 56 male rats were divided into 5 groups, including control (n=12), sham (n=11) and three treatment groups (n=11) in three different doses. The sham groups received daily intra peritoneal (IP) injections of the vehicle (ethanol 10%) for 30 days. Three treatment groups received different daily IP injections of the camphor (1, 2 and 5 mg/Kg) for 30 days and the control groups didn't received anything. Serums were used for assaying LH, FSH and testosterone. The level of LH significantly increased in all doses of camphor among the treatment groups as compared to the control (p<0.05), but camphor in doses 2 and 5 mg/Kg significantly reduced the FSH level as compared to control group (p<0.05). No significant changes were seen in testosterone levels. Camphor increased level of LH, decreased level of FSH, whereas it failed to change level of testosterone. The claim of inhibitory effect of camphor on sexual activity could not be confirmed by this study. More investigations in this field are suggested. PMID:24567939

  2. Electroacupuncture Modulates Reproductive Hormone Levels in Patients with Primary Ovarian Insufficiency: Results from a Prospective Observational Study

    PubMed Central

    Zhou, Kehua; Jiang, Jingxi; Wu, Jiani; Liu, Zhishun

    2013-01-01

    To investigate the effects of electroacupuncture (EA) on serum FSH, E2, and LH levels, women with primary ovarian insufficiency (POI) were treated with EA once a day, five times a week for the first four weeks and once every other day, three times a week, for the following two months, and then were followed up for three months. Serum E2, FSH, and LH levels were measured at baseline, at the end of treatment, and during followup. A total of 11 women with POI were included in this prospective consecutive case series study. Compared with baseline, patients' serum E2 increased, FSH decreased, and LH decreased (P = 0.002, 0.001, and 0.002, resp.) after EA treatment, and these effects persisted during followup. With treatment, 10 patients resumed menstruation (10/11, 90.91%), whereas one patient remained amenorrhea. During followup, two patients, including the one with amenorrhea during treatment, reported absence of menstruation. Temporary pain occurred occasionally, and no other adverse events were found during treatment. The results suggest that EA could decrease serum FSH and LH levels and increase serum E2 level in women with POI with little or no side effects; however, further randomized control trials are needed. PMID:23533511

  3. Effects of estrogens, clomiphene and castration in a male transsexual with as compared to those without hypersecretion of gonadotropins.

    PubMed

    Goh, H H; Ratnam, S S

    1990-06-01

    A 24-year-old male-to-female transsexual with hypersecretion of gonadotropins was studied with regard to his recovery from sex steroid hormone treatment before his sex change operation and the effects of castration, clomiphene tests and estrogens on the hypersecretion of gonadotropins. Computer-assisted tomography and X-ray results indicated that the possibility that the hypersecretion of gonadotropins was not associated with a pituitary adenoma could not be ruled out. After a period of recovery from previous sex steroid hormone therapy, inappropriately high FSH and LH levels in the presence of normal male levels of testosterone and estradiol were found. The latter normal levels failed to suppress both the FSH and LH levels. From the clomiphene challenge tests carried out before and after the sex reassignment operation, the estradiol infusion studies and treatment with ethinyl estradiol after the sex reassignment operation, it appears that the hypersecretion of gonadotropins was responsive to the negative feedback effect of estrogens. However, the sensitivity, especially that of FSH, was very attenuated. Even after 23 weeks of ethinyl estradiol treatment FSH remained well above the upper limit for normal men. The results showed that before his sex change operation the hypersecretion of gonadotropins in the patient was probably under autonomous control. Testicular factors at normal male concentrations appear to have a minimal negative feedback effect on the hypersecretion of gonadotropins. However, hypersecretion of gonadotropins can be suppressed by prolonged exposure to estrogens. PMID:2118708

  4. Eight-cell parthenotes originated from in vitro grown sheep preantral follicles.

    PubMed

    Luz, V B; Araújo, V R; Duarte, A B G; Celestino, J J H; Silva, T F P; Magalhães-Padilha, D M; Chaves, R N; Brito, I R; Almeida, A P; Campello, C C; Feltrin, C; Bertolini, M; Santos, R R; Figueiredo, J R

    2012-11-01

    We investigated the effect of the leukemia inhibitory factor (LIF) alone or in association with follicle-stimulating hormone (FSH) on the in vitro growth and antrum formation of sheep preantral follicles. To evaluate oocyte quality, parthenogenetic activation of the oocytes recovered from in vitro grown preantral follicles was performed. Preantral follicles >110 μm in diameter were isolated and cultured for 18 days in basic medium either alone (control) or supplemented with LIF (10 or 50 ng/mL) in the absence or presence of FSH. Every 6 days the follicular survival, growth, and antrum formation were evaluated. When compared to control (P < .05), antrum formation was increased in follicles cultured in the presence of LIF10 and FSH. At the end of the culture, the oocytes underwent in vitro maturation (IVM); their viability and chromatin configuration were assessed. Although IVM was not affect by the treatments (P > .05), the numerically highest maturation rates (29.63%) were obtained when follicles were cultured in 50 ng/mL LIF (LIF50). Therefore, their oocytes were submitted to parthenogenetic activation; from which 58.3% of the mature oocytes resulted in 8-cell stage parthenotes. In conclusion, although LIF10 + FSH increases antrum formation when compared to a nonsupplemented medium (minimum essential medium), oocytes from sheep preantral follicles are capable of growing and maturing in vitro independent of LIF addition to the medium, which resulted in the formation of 8-cell parthenotes. PMID:22562971

  5. Inherent capacity of the pituitary gland to produce gonadotropins is not influenced by the number of ovarian follicles > or = 3 mm in diameter in cattle.

    PubMed

    Mossa, F; Jimenez-Krassel, F; Walsh, S; Berry, D P; Butler, S T; Folger, J; Smith, G W; Ireland, J L H; Lonergan, P; Ireland, J J; Evans, A C O

    2010-01-01

    We hypothesised that higher serum FSH concentrations in cattle with low v. high follicle numbers during follicular waves are caused by a different capacity of the pituitary gland to produce gonadotropins. Dairy cows with high (> or = 30; n = 5) and low (< or = 15; n = 5) follicle numbers were selected and serum concentrations of oestradiol and FSH during an oestrous cycle were measured. Cows were ovariectomised at oestrus and bled frequently up to 8 days after ovariectomy. After 33 days, cows were injected with gonadotropin-releasing hormone (GnRH) and bled intensively up to 8 h after GnRH injection. One day later, animals were injected with follicular fluid (FF) from bovine follicles and were bled intensively up to 2 days after the first injection. Serum concentrations of FSH and LH were measured. After 2 days, cows were killed and their pituitary glands collected. Prior to ovariectomy, serum oestradiol concentrations were similar between groups, whereas FSH concentrations were higher in cattle with low v. high numbers of follicles. No differences were detected in serum gonadotropin concentrations after ovariectomy, GnRH injection or FF challenge between groups. The results indicate that the inherent capacity of the pituitary gland to secrete gonadotropins does not differ between cattle with high v. low numbers of follicles during follicular waves. PMID:20188028

  6. Pathophysiology of polycystic ovary syndrome: the role of hyperandrogenism.

    PubMed

    Catteau-Jonard, Sophie; Dewailly, Didier

    2013-01-01

    The cardinal features of polycystic ovary syndrome (PCOS) are hyperandrogenism and oligoanovulation. The increase in ovarian androgen production is a fundamental characteristic of PCOS and, although enigmatic, it is at the heart of one of the major issues about the pathophysiology of PCOS, i.e. whether it has developmental origins or not. Intraovarian androgens are designated as primarily responsible for the follicle excess. The defective selection of a dominant follicle in anovulatory patients results from both an insufficient secretion of FSH and a local inhibition of FSH action. Anti-müllerian hormone (AMH) seems to be involved in the latter by repressing the FSH-dependent aromatase activity. AMH level is increased in PCOS because of the follicle excess and increased production per follicle. Therefore, in anovulatory patients, serum FSH, although at low to normal plasma concentrations, would not be able to induce a decrease in AMH sufficient to allow the expression of aromatase. In conclusion, the fundamental anomaly of PCOS is still unknown, but it can be hypothesized that any genetic, epigenetic or environmental factor leading to intraovarian hyperandrogenism can result in PCOS. PMID:24002402

  7. Evidence for possible involvement of IGF type II receptors (IGF2R) in regulating growth of two concomitant dominant follicles in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Regulation of multiple ovulations in monotocous species such as cattle is not well understood. Gene expression of the FSH receptor (FSHR) in granulosa (GC), and LH receptor (LHR) and IGF2R in GC and theca (TC) cells, as well as estradiol (E2) and progesterone (P4) levels in follicular fluid (FF) wer...

  8. Reduction of dehydroepiandrosterone sulfate synthesis in women with polycystic ovary syndrome by human menopausal gonadotropin but not purified urinary follicle stimulating hormone: a comparative pilot study.

    PubMed

    Turkmen, S; Backstrom, T; Idil, M

    2004-08-01

    We aimed to compare the effects of two different gonadotropins on steroid production in patients with polycystic ovary syndrome (PCOS). The study group comprised 20 infertile patients diagnosed with PCOS who were accepted into in vitro fertilization-embryo transfer and gamete intra-Fallopian transfer programs. Ten patients were consecutively allocated to a purified urinary follicle stimulating hormone (FSH) administration group while the other ten received human menopausal gonadotropin (hMG). All patients were pretreated with a gonadotropin releasing hormone-agonist. The patients were followed by daily vaginal ultrasonography until at least two follicles reached a diameter of 17 mm or an estradiol value of at least 100 pg/ml per follicle. To induce ovulation, human chorionic gonadotropin was given. On the 3rd day of menstruation, serum estradiol, luteinizing hormone (LH), FSH, total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), insulin-like growth factor-I and insulin were measured. These same parameters were measured again on the day of follicle aspiration in both serum and follicular fluid. In both groups, the serum levels of estradiol and androstenedione were raised significantly, and on aspiration day the serum level of DHEAS was significantly raised in the FSH group but not in the hMG group. Our findings suggest that in PCOS patients exogenous hMG induces a different steroid synthesis pattern compared to pure FSH, hypothetically by reduction of the delta-5 steroid synthesis pathway in the adrenals and/or in the ovary. PMID:15624268

  9. Pituitary self-priming actions of gonadotropin-releasing hormone. Kinetics of estradiol's potentiating effects on gonadotropin-releasing hormone-facilitated luteinizing hormone and follicle-stimulating hormone release in healthy postmenopausal women.

    PubMed

    Veldhuis, J D; Evans, W S; Rogol, A D; Kolp, L; Thorner, M O; Stumpf, P

    1986-06-01

    We examined the kinetically distinct characteristics of estradiol's effects upon pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in response to pulses of exogenous gonadotropin-releasing hormone (GnRH) in healthy postmenopausal individuals. The putative self-priming actions of GnRH on LH and FSH release were tested by intravenous injections of equal paired doses of GnRH (10 micrograms) before and after 1, 5, 10, and 30 d of pure estradiol-17 beta delivery via an intravaginal silastic ring. Self-priming actions of GnRH, as defined by heightened gonadotropin release in response to the second pulse of GnRH compared with the first, were completely absent in the hypoestrogenemic state. However, estradiol administration unmasked GnRH self-priming in a time-dependent fashion, with maximal expression after 5 and 10 d of steroid replacement, followed by attenuation by 30 d. Since estradiol's modulation of GnRH action was expressed differentially on LH and FSH release, we suggest that such facilitation of GnRH-stimulated pituitary LH and FSH release may provide an additional mechanism for dissociated secretion of gonadotropic hormones in health or disease. PMID:3086382

  10. 36 CFR 219.62 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... necessary (40 CFR 1508.9; FSH 1909.15, Chapter 40). Environmental impact statement (EIS). A detailed written statement as required by section 102(2)(C) of the National Environmental Policy Act (NEPA) of 1969 (40 CFR 1508.11; 36 CFR 220). Formal comments. See substantive formal comments. Lead objector. For an...

  11. 36 CFR 219.62 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... necessary (40 CFR 1508.9; FSH 1909.15, Chapter 40). Environmental impact statement (EIS). A detailed written statement as required by section 102(2)(C) of the National Environmental Policy Act (NEPA) of 1969 (40 CFR 1508.11; 36 CFR 220). Formal comments. See substantive formal comments. Lead objector. For an...

  12. 36 CFR 219.62 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... necessary (40 CFR 1508.9; FSH 1909.15, Chapter 40). Environmental impact statement (EIS). A detailed written statement as required by section 102(2)(C) of the National Environmental Policy Act (NEPA) of 1969 (40 CFR 1508.11; 36 CFR 220). Formal comments. See substantive formal comments. Lead objector. For an...

  13. Increased serum inhibin B levels in postmenopausal women with altered thyroid function.

    PubMed

    Viceconti, N; Luisi, S; Nardo, S; Gargano, L; Franchi, A; Sibilla, R; Canettieri, G; Petraglia, F; Centanni, M

    2003-08-01

    Hyper- and hypothyroidism have significant effects on the female reproductive system. However, little in the way of data is available on the relationship between ovarian paracrine control and thyroid function. This study was aimed at characterising the serum levels of inhibin B in relation to altered thyroid function. Serum inhibin B and FSH levels were measured in 91 women (51 regularly cycling and 40 postmenopausal). The mean serum concentration of inhibin B in euthyroid cycling women (0.025 +/- 0.018 microg/l) was similar to that observed in hyper- and hypothyroid patients (0.022 +/- 0.015 and 0.018 +/- 0.014 microg/l, respectively, p=ns). Inhibin B levels were obviously reduced (-72%) in euthyroid postmenopausal women. In contrast, in hyper- and hypothyroid postmenopausal women, inhibin B levels remained substantially at the premenopausal level. So far, serum inhibin B appeared to be significantly increased in both hyperthyroid patients (0.025 +/- 0.014 microg/l; p<0.0001) and in hypothyroid patients (0.016 +/- 0.006 microg/l; p=0.0006). Altered thyroid function did not affect FSH levels at fertile age. However, a significant decrease of FSH levels was observed in hyper- and hypothyroid (-52% and -43%, respectively) postmenopausal women. Nevertheless, these FSH levels remained in the postmenopausal range. These results indicate that an altered thyroid function affects serum inhibin B levels in postmenopausal women. PMID:12953168

  14. Diethylstilbestrol increases the density of prolactin cells in male mouse pituitary by inducing proliferation of prolactin cells and transdifferentiation of gonadotropic cells.

    PubMed

    Shukuwa, Keiko; Izumi, Shin-Ichi; Hishikawa, Yoshitaka; Ejima, Kuniaki; Inoue, Satoshi; Muramatsu, Masami; Ouchi, Yasuyoshi; Kitaoka, Takashi; Koji, Takehiko

    2006-07-01

    Diethylstilbestrol (DES) has been implicated in mammalian abnormalities. We examined the effects of DES on follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) cells in the pituitaries of male mice treated with various doses of DES for 20 days. DES reduced the density of FSH and LH cells in a dose-dependent manner, but increased that of PRL cells. When the expression of estrogen receptor (ER) alpha and beta was assessed, an induction of ERbeta by DES was found predominantly in PRL cells. However, since these effects were abolished in ERalpha knockout mice, DES appears to act primarily through ERalpha. When the expression of Ki-67 and Pit-1 in PRL cells was examined at various time-points after DES treatment, some PRL cells became Ki-67 positive at 10-15 days, and Pit-1-positive cells were increased at 5-15 days. Furthermore, some FSH and LH cells became Pit-1 positive, and co-localized with PRL at 5-10 days. Our results indicate that DES increases PRL cells by inducing proliferation of PRL cells and transdifferentiation of FSH/LH cells to PRL cells. PMID:16468032

  15. LH (Luteinizing Hormone) Test

    MedlinePlus

    ... LH and FSH may be ordered when a boy or girl does not appear to be entering puberty at ... pubic hair Growth of testicles and penis in boys Beginning of menstruation in girls ^ Back to top What does the test result ...

  16. 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

  17. Gonadotrophins modulate hormone secretion and steady-state mRNA levels for activin receptors (type I, IIA, IIB) and inhibin co-receptor (betaglycan) in granulosa and theca cells from chicken prehierarchical and preovulatory follicles.

    PubMed

    Lovell, Tristan M; Al-Musawi, Sara L; Gladwell, Richard T; Knight, Philip G

    2007-06-01

    Ovarian follicle development is regulated through endocrine and local mechanisms. Increasing evidence indicates roles for transforming growth factor beta superfamily members, including inhibins and activins. We recently identified divergent expression of mRNAs encoding activin receptors (ActR) and inhibin co-receptor betaglycan in chicken follicles at different stages of maturation. Here, we compare the actions of LH and FSH (0, 1, 10, 100 ng/ml) on levels of mRNA for ActRI, ActRIIA, ActRIIB and betaglycan in chicken granulosa and theca cells (GC and TC) from preovulatory (F1) and prehierarchical (6-8 mm) follicles. The expression of mRNAs for LH-R and FSH-R and production of inhibin A, oestradiol and progesterone were also quantified. FSH decreased ActRIIB and ActRI mRNA levels in 6-8 mm GC, whereas LH increased the mRNA levels. Both LH and FSH enhanced ActRIIA (5- and 8.5-fold) and betaglycan mRNA expression (2- and 3.5-fold) in 6-8 mm GC. In 6-8 mm TC, LH and FSH both increased the betaglycan mRNA level (7- and 3.5-fold respectively) but did not affect ActRI, ActRIIA and ActRIIB transcript levels. In F1 GC, both LH and FSH stimulated ActRI (2- and 2.4-fold), ActRIIB (3.2- and 2.7-fold) and betaglycan (7- and 4-fold) mRNA levels, while ActRIIA mRNA was unaffected. In F1 TC, LH and FSH reduced ActRIIA (35-50%) and increased (4.5- and 7.6-fold) betaglycan mRNA, but had no effect on ActRI and ActRIIB transcript levels. Results support the hypothesis that expression of ActR and betaglycan are differentially regulated by gonadotrophins during follicle maturation in the hen. This may represent an important mechanism for fine-tuning follicle responsiveness to local and systemic activins and inhibins. PMID:17636170

  18. Pre-Selection Test to Identify High Responder Donor Goats.

    PubMed

    Balaro, Mfa; Brandão, F Z; Maia, Alrs; Souza-Fabjan, Jmg; Cueto, M I; Gibbons, A E; Fonseca, J F

    2016-06-01

    The aim of the study was to evaluate the feasibility of pre-selection of high or low responder does prior to the superovulatory protocols. Twenty Saanen does received 800 IU of equine chorionic gonadotropin (eCG) at the end of long-term progestogen treatment. Fourteen days later, a second progestogen protocol associated with a multiple-dose follicle stimulation hormone (FSH) treatment (5 IU/kg of FSH, in six decreasing doses between days 4 to 6 of the protocol) was administered. Transrectal ultrasound was used to assess the follicular status at the beginning of superovulatory treatments, at the oestrous onset and on the seventh day of the oestrous cycle for counting corpora lutea (CL). A significant lower number of CL was obtained in eCG-treated in comparision with FSH-treated does (p < 0.05). A quartic regression was able to explain the relationship between the number of CL in response to both treatments (r(2) =0.50; p < 0.05). Seventy per cent (14 of 20) of does maintained the same ovulatory response (high or low) after treatments. The Kappa (κ = 0.40; p < 0.05) and Spearman (rs = 0.39; p = 0.08) coefficients were able to show a relationship between treatments. Regarding the follicular status, there is a significant relationship between the number of small follicles (r = 0.71; r(2) =0.47; p < 0.01) and total follicles (r = 0.60; p < 0.01) at eCG and first FSH dose with the number of CL. Moreover, it was found a negative relationship between the presence of large follicles and the number of CL in response to eCG treatment (r = -0.44; p < 0.05), but not from FSH (p > 0.05). In conclusion, the screening test with eCG has the potential to identify Saanen does that will better respond to the superovulatory protocol with FSH. In addition, it highlighted the importance of an ultrasound evaluation prior to the beginning of superovulatory treatments with FSH to characterize the follicular status and identify the potential donors of high

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

  20. Maintenance of oestradiol production and expression of cytochrome P450 aromatase enzyme mRNA in long-term serum-free cultures of pig granulosa cells.

    PubMed

    Picton, H M; Campbell, B K; Hunter, M G

    1999-01-01

    Studies were carried out to investigate the conditions required for maintenance of aromatase activity and expression in long-term cultures of pig granulosa cells. Cells from large (> 2 mm) and small (< or = 2 mm) follicles were cultured at 37 degrees C with 5% CO2 in McCoys 5a medium supplemented with 0.1% (w/v) BSA, testosterone (100 micrograms l-1), insulin (10 micrograms l-1) and long R3 insulin-like growth factor I (IGF-I) (100 micrograms l-1). Cells were cultured with five concentrations of USDA pFSH-I-2 (0-100 micrograms l-1) for 48, 96 or 144 h with or without fetal calf serum (FCS). The number of cells and oestradiol, progesterone and inhibin production were measured. In marked contrast to oestradiol production from cells cultured in plates precoated with FCS, 1 microgram FSH l-1 was optimal for the maintenance of high oestradiol production by granulosa cells from large follicles after 144 h of serum-free culture. Culture with FCS promoted cell proliferation, reduced oestradiol production, and supported FSH-dependent (P < 0.01) increased progesterone and inhibin production indicating cellular luteinization. Northern blot analysis of total RNA from cells cultured with 1 microgram FSH l-1 detected 2.5 and 1.8 kb transcripts encoding aromatase cytochrome P450 (P450arom) and cholesterol side-chain cleavage cytochrome P450 (P450scc), respectively. Transcript expression was hormone sensitive, irrespective of the presence of FCS. High concentrations of FSH (100 micrograms l-1) stimulated expression of P450scc, but inhibited P450arom expression as the cells luteinized after 144 h of culture. This serum-free system, which maintains the aromatase enzyme complex, is fundamental if physiologically relevant observations are to be made of the mechanisms regulating follicle hierarchy development from long-term cultures of pig cells. PMID:10341724

  1. Disruption of Bidirectional Oocyte-Cumulus Paracrine Signaling During In Vitro Maturation Reduces Subsequent Mouse Oocyte Developmental Competence1

    PubMed Central

    Yeo, Christine X.; Gilchrist, Robert B.; Lane, Michelle

    2009-01-01

    Oocyte-cumulus cell bidirectional communication is essential for normal development of the oocyte and cumulus cells (CCs) within the follicle. We showed recently that addition of recombinant growth differentiation factor 9 (GDF9), which signals through the SMAD2/3 pathway, during mouse oocyte in vitro maturation (IVM) increased fetal viability. This study thus aimed to observe the effects of disrupting oocyte-CC bidirectional communication during IVM on oocyte developmental competence and fetal outcomes. Cumulus-oocyte complexes (COCs) from equine chorionic gonadotropin-primed prepubertal (CBA/C57BL6) mice were cultured with or without 50 mIU/ml follicle-stimulating hormone (FSH) and 10 ng/ml epidermal growth factor (EGF) or 4 μM SMAD2/3 inhibitor SB-431542. Cumulus expansion and first polar body extrusion were then assessed, or COCs were fertilized and stained to evaluate sperm entry or cultured to the blastocyst stage. Embryo development and blastocyst quality were assessed, and Day 4.5 blastocysts were transferred to pseudopregnant recipients to analyze fetal outcomes. SMAD2/3 inhibition or FSH/EGF absence during IVM resulted in decreased cumulus expansion. First polar body extrusion and sperm entry were decreased in the absence of FSH/EGF, whereas only sperm entry was affected in SB-431542-matured COCs. Embryo development and blastocyst rates were unaffected; however, blastocyst quality was significantly altered, with reduced inner cell mass cell numbers in embryos derived from COCs matured in both treatments. When COCs were matured with SB-431542 in the absence of FSH/EGF, cumulus expansion was reduced, but fertilization, embryo development, and embryo quality were not. Inhibition of SMAD2/3 signaling in the presence of FSH/EGF significantly reduced fetal survival but had no effect on implantation or fetal and placental dimensions and morphology. PMID:19144958

  2. Male gonadal function in coeliac disease: III. Pituitary regulation.

    PubMed

    Farthing, M J; Rees, L H; Dawson, A M

    1983-12-01

    Pituitary regulation of gonadal function was investigated in 39 consecutive men with treated and untreated coeliac disease and in an intestinal disease control group of 19 men with Crohn's disease of similar age and general nutritional status. Basal serum FSH concentration was increased in 10 of the coeliacs (26%) compared to only two of 19 men with Crohn's disease (11%). This abnormality was observed with equal frequency in both treated and untreated coeliacs, and was not associated with oligospermia. Serum LH concentration was increased in eight of 15 untreated coeliacs (53%) with sub-total villous atrophy, an abnormality which unlike the elevation of serum FSH, appears to return towards normal after gluten withdrawal. Serum LH was high in coeliacs despite marked elevation of the free testosterone index. Exaggerated responses of FSH and LH to LHRH were found in 89% and 45% respectively, of coeliacs with sub-total villous atrophy. However, exaggerated responses of LH alone were found more frequently in coeliacs than in men with Crohn's disease (P less than 0.02) and unlike the exaggerated FSH responses, LH responses were closely related to jejunal morphology. Exaggerated responses of FSH and LH in coeliacs were commonly found when basal gonadotrophin concentrations were normal. The occurrence of exaggerated gonadotrophin responses could not be related to plasma concentration of testosterone, dihydrotestosterone, oestradiol or the free testosterone index. Serum prolactin was modestly raised in 25% of untreated and partially treated coeliacs and in the same proportion of men with Crohn's disease. Elevated serum prolactin concentrations never exceeded 809 mU/l and were not associated with impotence or infertility. This study provides further evidence that in men with coeliac disease there is a derangement of pituitary regulation of gonadal function. This would seem to be part of a wider disturbance of central regulatory mechanisms of endocrine function in coeliac

  3. Insulin Receptor Substrate 1, the Hub Linking Follicle-stimulating Hormone to Phosphatidylinositol 3-Kinase Activation.

    PubMed

    Law, Nathan C; Hunzicker-Dunn, Mary E

    2016-02-26

    The ubiquitous phosphatidylinositol 3-kinase (PI3K) signaling pathway regulates many cellular functions. However, the mechanism by which G protein-coupled receptors (GPCRs) signal to activate PI3K is poorly understood. We have used ovarian granulosa cells as a model to investigate this pathway, based on evidence that the GPCR agonist follicle-stimulating hormone (FSH) promotes the protein kinase A (PKA)-dependent phosphorylation of insulin receptor substrate 1 (IRS1) on tyrosine residues that activate PI3K. We report that in the absence of FSH, granulosa cells secrete a subthreshold concentration of insulin-like growth factor-1 (IGF-1) that primes the IGF-1 receptor (IGF-1R) but fails to promote tyrosine phosphorylation of IRS1. FSH via PKA acts to sensitize IRS1 to the tyrosine kinase activity of the IGF-1R by activating protein phosphatase 1 (PP1) to promote dephosphorylation of inhibitory Ser/Thr residues on IRS1, including Ser(789). Knockdown of PP1β blocks the ability of FSH to activate PI3K in the presence of endogenous IGF-1. Activation of PI3K thus requires both PKA-mediated relief of IRS1 inhibition and IGF-1R-dependent tyrosine phosphorylation of IRS1. Treatment with FSH and increasing concentrations of exogenous IGF-1 triggers synergistic IRS1 tyrosine phosphorylation at PI3K-activating residues that persists downstream through protein kinase B (AKT) and FOXO1 (forkhead box protein O1) to drive synergistic expression of genes that underlies follicle maturation. Based on the ability of GPCR agonists to synergize with IGFs to enhance gene expression in other cell types, PP1 activation to relieve IRS1 inhibition may be a more general mechanism by which GPCRs act with the IGF-1R to activate PI3K/AKT. PMID:26702053

  4. Effects of clinical, laboratuary and pathological features on successful sperm retrieval in non-obstructive azoospermia

    PubMed Central

    Güneri, Çağrı; Alkibay, Turgut; Tunç, Lütfi

    2016-01-01

    Objective The study aims to evaluate the correlation of testicular sperm extraction (TESE) and histopathology with various features of non-obstructive azoospermia (NOA) cases who consulted to our university-based infertility clinic, and the probability of prompting couples about TESE success and to investigate the cost reduction chance through cost-beneficial aspects. Material and methods One hundred and twenty-five patients were enrolled in this study. Age, unprotected intercourse period, age of puberty, and concomittant diseases were noted. Testicular volumes were measured. The correlations between genetic test results and serum levels of Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), free testosterone, prolactine were investigated. Results The incidence of NOA among infertile men was found to be 15.1%. Median age of the cases was 33.1 years. Decrease in TESE success rate was seen in the group aged >30, and those who practiced unprotected intercourse for more than 10 years. TESE success rate was 40 percent. The required negative correlation between FSH levels, and testicular volume was not observed when the patient had additional diseases and/or genitourinary surgery. FSH and LH levels were significantly different between TESE- positive and negative groups (p=0.006, and p=0.001 respectively). Success rate in bilateral TESE group was 14.2%, and 96% of TESE- negative patients had bilateral TESE. Fifteen of 118 patients had Y chromosome microdeletions. These results were similar in both TESE- positive and negative group. Conclusion None of the parameters investigated herein predicted succesful TESE outcomes. However, in cases with increased FSH and AZFa/AZFb deletion before application of bilateral TESE, in cases of increased FSH and AZFa/AZFb deletion, detailed information should be given to these patients about low success rates and risk of disease inheritance which may reduce procedural costs. Knowing groups with poor prognosis, may help

  5. Long-term follow-up of testicular function following radiation therapy for early-stage Hodgkin's disease

    SciTech Connect

    Kinsella, T.J.; Trivette, G.; Rowland, J.; Sorace, R.; Miller, R.; Fraass, B.; Steinberg, S.M.; Glatstein, E.; Sherins, R.J.

    1989-06-01

    Seventeen male patients with pathological staged I-IIIA1 Hodgkin's disease were followed prospectively for radiation damage to the testes from low-dose scattered irradiation. During conventionally fractionated radiation therapy, the testicular dose ranged from 6 to 70 cGy. Testicular function was measured in a prospective fashion by repeated analyses (every 6 to 12 months) of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Patients were also followed by serial semen analyses and by a questionnaire on fertility. The follow-up period ranged from 3 to 7 years after completion of radiation therapy. In patients receiving greater than or equal to 20 cGy, there was a dose-dependent increase in serum FSH values following irradiation, with the maximum difference at 6 months compared with pretreatment levels. All patients showed a return to normal FSH values within 12 to 24 months following irradiation. No significant changes in LH and testosterone were observed in this patient group. Eight patients with a normal pretreatment semen analysis provided serial semen samples and two patients showed transient oligospermia with complete recovery by 18 months following treatment. Four patients have fathered normal offspring following radiation therapy. We conclude that low doses (greater than 20 cGy) of scatter irradiation during treatment for Hodgkin's disease can result in transient injury to the seminiferous tubule as manifested by elevations of FSH for 6 to 24 months following treatment. Below 20 cGy, FSH values remained in the normal range. No evidence of Leydig cell injury (using LH and testosterone) was seen in this dose range (up to 70 cGy). Thus, patients with early-stage Hodgkin's disease can be treated with radiation therapy with little to no risk of irreversible testicular injury. Radiation treatment techniques to shield the testes are discussed.

  6. Anti-Mullerian hormone as a predictive endocrine marker for embryo production in the goat.

    PubMed

    Monniaux, Danielle; Baril, Gérard; Laine, Anne-Lyse; Jarrier, Peggy; Poulin, Natividad; Cognié, Juliette; Fabre, Stéphane

    2011-12-01

    Recently, we demonstrated the relationship between anti-Müllerian hormone (AMH) circulating concentrations, ovarian follicles, and embryo production in cattle. However, they have not yet been established in a species with a seasonal breeding activity. Thus, goats were subjected to repeated in vivo embryo production during the breeding season, at the end of the breeding season, and at the end of the anestrus season. Embryo production after FSH treatment was highly repeatable for each goat. Plasma AMH concentrations, measured before the first FSH treatment, were highly correlated with the number of collected, transferable, and freezable embryos, resulting from the three sessions of embryo production. Plasma AMH concentrations transiently decreased after each exogenous FSH treatment, but they showed little change with season, and no relationship was observed between AMH and endogenous FSH concentrations during seasonal transitions. Follicles of 1-5 mm in diameter were the main target of the FSH treatment and were major contributors to circulating AMH concentrations. Granulosa cell AMH expression decreased as the follicle approached terminal development, while the expression of maturation markers (CYP19A1 and FSHR) increased. In conclusion, circulating AMH concentrations can be predictive of the capacity of a donor goat to produce high or low numbers of high-quality embryos. This prediction could be accurately made from a single blood measurement of AMH during either breeding or anestrus seasons. Variability in the number of gonadotropin-responsive follicles of 1-5 mm in diameter between individuals resulted in the differences in circulating AMH concentrations measured between individuals. PMID:21930684

  7. [Hypogonadotropic hypogonadism and delayed puberty: differential diagnosis using the LH-RH-infusion test].

    PubMed

    Vierhapper, H

    1983-08-26

    Serum concentrations of LH and FSH were determined during an intravenous infusion of LH-RH (200 micrograms, t = 4 hours) in 8 patients (age: 15 to 20 years) with delayed sexual maturation and retarded bone age. Four patients who by clinical criteria were later recognized as suffering from hypogonadotropic hypogonadism (HH) presented during the infusion of LH-RH with only a small response of LH (and, in three cases, of FSH). In 3 patients with HH a deficiency of endogenous LH-RH due to a hypothalamic defect was suggested by an enhanced secretion of LH and FSH during a second LH-RH infusion test performed after priming of the pituitary by pulsatile, subcutaneous infusions of LH-RH (50 micrograms/night for 9 consecutive nights). The fourth patient with HH, who suffered from a pituitary adenoma, failed to display this enhanced secretion of gonadotropins following pituitary priming by intermittent administration of LH-RH. As compared with the patients with HH, 4 patients in whom puberty, although delayed, later occurred spontaneously (pubertas tarda, PT), presented with a considerably more pronounced secretion of LH and FSH during the infusion of LH-RH, and priming by intermittent subcutaneous LH-RH failed to achieve further enhancement of the secretion of LH and FSH during a second infusion test in these patients. The intravenous infusion of LH-RH in combination with a protocol of pituitary priming offers a possibility of distinguishing patients with delayed puberty from those with various forms of hypogonadotropic hypogonadism. PMID:6417915

  8. The effect of temporary meiotic attenuation on the in vitro maturation outcome of bovine oocytes.

    PubMed

    Farghaly, T; Khalifa, E; Mostafa, S; Hussein, M; Bedaiwy, M; Ahmady, A

    2015-08-01

    The aim of this study was to investigate the effect of delaying maturation by extended culture of immature bovine oocytes in prematuration medium (PMC) containing single maturation inhibitor on their meiotic resumption and embryonic development. Bovine immature oocytes were cultured in M199 containing 10 μM of either inhibitor (roscovitine, cilostamide, or forskolin) for either 72 or 120 h followed by up to 48 h in maturation media supplemented with 7.5 IU follicle-stimulating hormone (FSH)/luteinizing hormone (LH). Two control groups were used. In untreated control, immature oocytes were cultured in the same medium as the experimental group without any inhibitors. In the FSH/LH control group, oocytes were cultured directly in the maturation medium supplemented with FSH/LH up to 48 h. In vitro matured oocytes were then inseminated with frozen-thawed bull sperm. Fertilization, defined as two-cell division 48 h post-insemination, and blastocyst formation were recorded. Total maturation rate for the 72-h group was 73%, 70%, 66%, and 69% for roscovitine, forskolin, cilostamide, and FSH/LH control, respectively, with no significant difference indicating that inhibitors have no negative effect on the oocyte maturation rate. The total fertilization rate for the 72-h group revealed that cilostamide (47%) and roscovitine (35%) were significantly higher than FSH/LH control (20%). The total blastocyst formation rates per inseminated oocytes revealed that among treatment groups, roscovitine (20%) had significantly higher rate than forskolin (9%). Overall, 72-h exposure period had better outcomes than 120 h in all the treated groups. In conclusion, prematuration culture of the bovine oocytes in the presence of maturation inhibitor for 72-h period at 10 μM concentration is sufficient in improving the bovine oocyte developmental competence. PMID:25784604

  9. Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis.

    PubMed Central

    Hsueh, A J; Dahl, K D; Vaughan, J; Tucker, E; Rivier, J; Bardin, C W; Vale, W

    1987-01-01

    Inhibin, a gonadal hormone capable of preferential suppression of pituitary follicle-stimulating hormone (FSH) secretion, has recently been purified. The major form of this protein is an alpha beta heterodimer encoded by two separate genes. In contrast to the FSH-suppressing action of the alpha beta heterodimer, the beta beta homodimer stimulates FSH secretion. Luteinizing hormone (LH)-secreting pituitary cells and gonadal androgen-producing cells have long been shown to form a closed-loop feedback axis. Based on recent studies demonstrating the FSH stimulation of inhibin biosynthesis by ovarian granulosa and testis Sertoli cells, an additional closed-loop feedback axis exists between pituitary FSH- and gonadal inhibin-producing cells. Because uncharacterized Sertoli cell factors have been suggested to either stimulate or inhibit androgen production by testicular Leydig cells, we have tested the intragonadal paracrine actions of heterodimers and homodimers of inhibin subunits. In primary cultures of testis cells, the alpha beta heterodimer of inhibin enhances Leydig cell androgen biosynthesis stimulated by LH, whereas the beta beta homodimer suppresses androgen production. Furthermore, similar modulatory actions of inhibin-related proteins were found in cultured ovarian theca-interstitial cells and theca explants treated with LH. In contrast, treatment with the inhibin-related proteins alone did not affect gonadal steroidogenesis. Our data indicate that the inhibin-related gene products synthesized by Sertoli and granulosa cells may form heterodimers or homodimers to serve as intragonadal paracrine signals in the modulation of LH-stimulated androgen biosynthesis and allow cross-communication between the two feedback loops. PMID:3474640

  10. Events surrounding the initiation of puberty with long term subcutaneous pulsatile gonadotropin-releasing hormone in a female patient with Kallman's syndrome.

    PubMed

    Seibel, M M; Claman, P; Oskowitz, S P; McArdle, C; Weinstein, F G

    1985-09-01

    An 18-yr-old woman with primary amenorrhea, anosmia, and total lack of secondary sexual development was treated for 230 days using sc pulsatile GnRH. GnRH testing with 100 micrograms, sc, initially revealed a peak FSH to LH ratio greater than 1. After 28 days of treatment, this ratio had reversed. A dosage of 20 micrograms/2 h for 200 days resulted in a LH to FSH ratio greater than 2. Widening the interval to 20 micrograms/3 h significantly lowered LH, but not FSH, levels. Increasing the frequency to 20 micrograms/90 min again increased the LH to FSH ratio. Twenty-four-hour testing revealed a sleep-entrained PRL rise both during and after GnRH therapy, but no sleep-entrained rise in LH. Ultrasound monitoring revealed cyclic changes in ovarian diameter at 30- to 60-day intervals that coincided with cyclic increases in LH and estradiol. The uterine fundus doubled in length between days 50 and 110 of treatment. The patient progressed from Tanner pubic hair and breast stage I to stage II during treatment, which was terminated due to an allergic reaction to GnRH. This study provides the first report of hormonal and ultrasound events surrounding puberty induction with GnRH in the female. We conclude widening the interval of GnRH administration can reduce LH levels while maintaining FSH levels, cyclic changes in ovarian diameter, LH, and estradiol occur before menarche, and although pulsatile GnRH provides a fascinating model for the study of puberty in the female, the chronicity of therapy needed and its potential for allergic reaction make this method of inducing puberty suboptimal. PMID:3926811

  11. The effects of a long-term psychosocial stress on reproductive indicators in the baboon.

    PubMed

    O'Connor, Kathleen A; Brindle, Eleanor; Shofer, Jane; Trumble, Benjamin C; Aranda, Jennifer D; Rice, Karen; Tatar, Marc

    2011-08-01

    Psychosocial stress is thought to negatively impact fecundity, but human studies are confounded by variation in nutrition and lifestyle. Baboons offer a useful model to test the effect of prolonged mild stress on reproductive indicators in a controlled setting. Following relocation from social groups to solitary housing, a previously documented stressful event for nonhuman primates, daily urine samples, tumescence, and menstrual bleeding were monitored in twenty baboons (Papio sp.) for 120-150 days. Specimens were assayed for estrone conjugates (E1C), pregnanediol-3-glucuronide (PDG), follicle-stimulating hormone (FSH), and cortisol. Linear mixed effects models examined (1) the effects of stress on frequency of anovulation, hormone levels, tumescence and cycle length, and (2) the relationship of cortisol with reproductive indicators. Despite cortisol levels indicative of stress, anovulation was negligible (1% in 102 cycles). PDG, FSH, cycle length, and tumescence declined during the first four cycles, but began recovery by the fifth. Cortisol was negatively associated with FSH but not associated with PDG, E1C or tumescence. Ovulation, E1C, and luteal phase length were not affected. Tumescence tracked changes in FSH and PDG, and thus may be a useful indicator of stress on the reproductive axis. Elevated cortisol was associated with reduced FSH, supporting a model of cortisol action at the hypothalamus rather than the gonad. After four to five menstrual cycles the reproductive indicators began recovery, suggesting adjustment to new housing conditions. In conclusion, individual housing is stressful for captive baboons, as reflected by cortisol and reproductive indicators, although ovulation, a relatively direct proxy for fecundity, is unaffected. PMID:21702002

  12. Effects of intracerebroventricular infusion of genistein on gonadotrophin subunit mRNA and immunoreactivity of gonadotrophins and oestrogen receptor-alpha in the pituitary cells of the anoestrous ewe.

    PubMed

    Polkowska, Jolanta; Ridderstråle, Yvonne; Wańkowska, Marta; Romanowicz, Katarzyna; Misztal, Tomasz; Madej, Andrzej

    2004-12-01

    The present study was designed to demonstrate whether genistein, a synthetic phytoestrogen, infused into the third ventricle of the brain could affect the gonadotrophic cells regarding the presence of oestrogen receptor-alpha immunoreactivity and gonadotrophin subunit mRNA hybridising reaction in the ewe. Ewes (n=7), aged 2 years, in early anoestrous season were infused with Ringer-Locke solution (control, n=3) or 10 microg/100 microl/h of genistein (n=4) into the third ventricle over a 5 h period and slaughtered the following morning. Immunoreactivity of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and oestrogen receptor-alpha (ERalpha) was determined in the adenohypophysis by immunohistochemistry using antibodies raised against LHbeta, FSHbeta, and ERalpha. Messenger RNA analyses were performed by non-isotope in situ hybridisation using sense and antisense riboprobes produced from beta subunits of LH and FSH cDNA clones. Computer image analysis was used to determine the percent of cells exhibiting immunohistochemical and/or hybridising reaction. It was found that in ewes infused with genistein, the percentage of LH-positive cells and the density of immunoreactive-LHbeta material decreased significantly (PFSH cells or on the expression of mRNA for FSHbeta. The percentage of ERalpha-positive cells increased significantly after genistein infusions (PFSH cells (PFSH-cells and change the endocrine activity of LH-producing cells of anoestral ewes. PMID:15531133

  13. Correlation analysis for follicle-stimulating hormone and C-terminal cross-linked telopetides of type i collagen in menopausal transition women with osteoporosis

    PubMed Central

    Wang, Bing; Song, Yang; Chen, Yan; Wang, En-Sheng; Zheng, Dan; Qu, Fan; Zhou, Jian-Hong

    2015-01-01

    The sudden drop in estrogen in post-menopausal women can lead to osteoporosis. About one in three women aged more than 50 years experienced an osteoporotic fracture. The aim of this study is to explore function of follicle-stimulating hormone (FSH) in bone metabolism and osteoporosis in menopausal transition women. 164 cases of women in menopausal transition were included, and which were divided into three groups, including < 40 years group, 40-50 years group and > 50 years group. All of patients must with empty stomach, and 5 ml blood was collected from median cubital vein between second day to ninth day in menstruation period. Examination of FSH and C-terminal cross-linked telopetides of type I collagen (CTx) was performed by using ECLIA assay. The results indicated that CTx levels were distinguished among the different aged group, with the increasing level following with the increased age. FSH level in both of < 40 years and 40-50 years old women were positively correlated with CTx level (P < 0.05). The spearman rank correlation analysis results also showed that there were no significant correlation between CTx level and FSH level in > 50 years old women. There were significant differences for the CTx level between 0-40 mIU/ml group and > 40 40 mIU/ml group in all of the three ages group (P < 0.05). In conclusion, it’s clinically significant for the combining examination of FSH and CTx in menopausal transition women, which could observe the bone metabolize changes quickly and sensitively, and prevent or therapy the osteoporosis in a further step. PMID:25932182

  14. Ovotoxic Effects of Galactose Involve Attenuation of Follicle-Stimulating Hormone Bioactivity and Up-Regulation of Granulosa Cell p53 Expression

    PubMed Central

    Banerjee, Sayani; Chakraborty, Pratip; Saha, Piyali; Bandyopadhyay, Soma Aditya; Banerjee, Sutapa; Kabir, Syed N.

    2012-01-01

    Clinical evidence suggests an association between galactosaemia and premature ovarian insufficiency (POI); however, the mechanism still remains unresolved. Experimental galactose toxicity in rats produces an array of ovarian dysfunction including ovarian development with deficient follicular reserve and follicular resistance to gonadotrophins that characterize the basic tenets of human POI. The present investigation explores if galactose toxicity in rats attenuates the bioactivity of gonadotrophins or interferes with their receptor competency, and accelerates the rate of follicular atresia. Pregnant rats were fed isocaloric food-pellets supplemented with or without 35% D-galactose from day-3 of gestation and continuing through weaning of the litters. The 35-day old female litters were autopsied. Serum galactose-binding capacity, galactosyltransferase (GalTase) activity, and bioactivity of FSH and LH together with their receptor competency were assessed. Ovarian follicular atresia was evaluated in situ by TUNEL. The in vitro effects of galactose were studied in isolated whole follicles in respect of generation of reactive oxygen species (ROS) and expression of caspase 3, and in isolated granulosa cells in respect of mitochondrial membrane potential, expression of p53, and apoptosis. The rats prenatally exposed to galactose exhibited significantly decreased serum GalTase activity and greater degree of galactose-incorporation capacity of sera proteins. LH biopotency and LH-FSH receptor competency were comparable between the control and study population, but the latter group showed significantly attenuated FSH bioactivity and increased rate of follicular atresia. In culture, galactose increased follicular generation of ROS and expression of caspase 3. In isolated granulosa cells, galactose disrupted mitochondrial membrane potential, stimulated p53 expression, and induced apoptosis in vitro; however co-treatment with either FSH or estradiol significantly prevented

  15. Leptin concentrations in the follicular phase of spontaneous cycles and cycles superovulated with follicle stimulating hormone.

    PubMed

    Messinis, I E; Milingos, S; Zikopoulos, K; Kollios, G; Seferiadis, K; Lolis, D

    1998-05-01

    It has been reported that oestradiol may play a role in the production of leptin from adipocytes. To investigate this relationship further, nine normally ovulating women were studied during two menstrual cycles, i.e. an untreated spontaneous cycle and a cycle treated with follicle stimulating hormone (FSH) from cycle day 2 until the day of human chorionic gonadotrophin (HCG) injection. Serum leptin values on cycle day 2 did not differ significantly between the spontaneous and the FSH cycles. In the spontaneous cycles, leptin values declined gradually and significantly up to day 7 and then increased progressively up to the day of luteinizing hormone (LH) surge onset, at which point they achieved the highest values. In the FSH cycles, serum leptin values increased gradually and significantly up to day 6, remaining stable thereafter, and were in the midfollicular phase significantly higher than in the spontaneous cycles. Significant positive correlations were found between mean values of leptin and mean values of oestradiol during the second half of the follicular phase in the spontaneous cycles and during the first half in the FSH cycles. A significant negative correlation was found between these two parameters in the spontaneous cycles during the first half of the follicular phase. Serum leptin levels were significantly higher in the midluteal than in the follicular phase in both cycles. These results demonstrate for the first time significant changes in leptin values during the follicular phase of the human menstrual cycle and a significant increase during superovulation induction with FSH. It is suggested that oestradiol may be involved in the regulation of leptin production in women. PMID:9647537

  16. Plasma levels of follicle-stimulating and luteinizing hormones during the reproductive cycle of wild and cultured Senegalese sole (Solea senegalensis).

    PubMed

    Chauvigné, François; Fatsini, Elvira; Duncan, Neil; Ollé, Judith; Zanuy, Silvia; Gómez, Ana; Cerdà, Joan

    2016-01-01

    The intensive culture of the Senegalese sole (Solea senegalensis) is hampered by the low or null fertilization rates exhibited by the first generation (F1) of reared males. To investigate the regulation of the reproductive processes in this species by the pituitary gonadotropins follicle-stimulating and luteinizing hormones (Fsh and Lh, respectively), we developed a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) for Lh measurements. Quantification of the Fsh and Lh plasma levels in cultured sole using the Lh ELISA developed here, and a previously developed ELISA for Fsh, indicated that in both males and females circulating Fsh steadily increased during autumn and winter and prior to the major spawning in spring, whereas an Lh surge occurred specifically during spawning. The increase in Fsh was associated with a rise of plasma levels of the steroid hormones testosterone (T), 11-ketotestosterone (11-KT) and estradiol-17β (E2), but that of Lh was concomitant with a strong decline of the levels of E2 in females and of 11-KT in males, possibly reflecting a rapid steroidogenic shift promoting the final maturation of gametes. Comparison of the plasma levels of gonadotropins and steroids between wild and F1 fish during autumn and spring revealed that F1 males showed significantly lower plasma Lh titres compared to wild males, whereas the levels of T and 11-KT were similar or more elevated in the F1 fish. These data suggest that an impaired Lh secretion during spawning, and perhaps altered Lh-mediated mechanisms in the testis, may be underlying causes for the low reproductive performance of Senegalese sole F1 males. PMID:26419696

  17. The frequency of follicle stimulating hormone receptor gene polymorphisms in Iranian infertile men with azoospermia

    PubMed Central

    Gharesi-Fard, Behrouz; Ghasemi, Zahra; Shakeri, Saeed; Behdin, Shabnam; Aghaei, Fatemeh; Malek-Hosseini, Zahra

    2015-01-01

    Background: Azoospermia is the medical condition of a man not having any measurable level of sperm in his semen. Follicle stimulating hormone (FSH) is a member of the glycoprotein hormone family that plays an important role in human reproduction because of its essential role in normal spermatogenesis. Various Single Nucleotide Polymorphisms (SNPs) have been reported within FSH receptor (FSHR) gene that may affect the receptor function. Objective: The present study aimed to investigate the correlation between two FSHR SNPs at positions A919G, A2039G, and susceptibility to azoospermia in a group of Iranian azoospermic men. The association between FSH levels within the sera and A919G and A2039G alleles and genotypes were also investigated. Materials and Methods: This case control study was performed on 212 men with azoospermia (126 non-obstructive and 86 obstructive) and 200 healthy Iranian men. Two FSHR gene SNPs were genotyped using PCR-RFLP method. The relationship between FSH levels within the sera and A919G and A2039G alleles and genotypes were also investigated. Results: Statistical analysis indicated that at A919G position, AA genotype and A allele were more frequent in obstructive azoospermia cases compared to non-obstructive or normal men (p=0.001). Regarding A2039G polymorphisms, no significant difference was observed between both azoospermia groups and the controls. The mean level of serum FSH was higher in the non-obstructive men compared to the obstructive patients (23.8 versus 13.8, respectively, p= 0.04). Conclusion: The results of the present study indicated that the genetic polymorphisms in the FSHR gene might increase the susceptibility to azoospermia in Iranian men. PMID:26730241

  18. Nomogram to predict the number of oocytes retrieved in controlled ovarian stimulation

    PubMed Central

    Moon, Kyoung Yong; Kim, Hoon; Lee, Joong Yeup; Lee, Jung Ryeol; Jee, Byung Chul; Suh, Chang Suk; Kim, Ki Chul; Lee, Won Don; Lim, Jin Ho

    2016-01-01

    Objective Ovarian reserve tests are commonly used to predict ovarian response in infertile patients undergoing ovarian stimulation. Although serum markers such as basal follicle-stimulating hormone (FSH) or random anti-Müllerian hormone (AMH) level and ultrasonographic markers (antral follicle count, AFC) are good predictors, no single test has proven to be the best predictor. In this study, we developed appropriate equations and novel nomograms to predict the number of oocytes that will be retrieved using patients' age, serum levels of basal FSH and AMH, and AFC. Methods We analyzed a database containing clinical and laboratory information of 141 stimulated in vitro fertilization (IVF) cycles performed at a university-based hospital between September 2009 and December 2013. We used generalized linear models for prediction of the number of oocytes. Results Age, basal serum FSH level, serum AMH level, and AFC were significantly related to the number of oocytes retrieved according to the univariate and multivariate analyses. The equations that predicted the number of oocytes retrieved (log scale) were as follows: model (1) 3.21–0.036×(age)+0.089×(AMH), model (2) 3.422–0.03×(age)–0.049×(FSH)+0.08×(AMH), model (3) 2.32–0.017×(age)+0.039×(AMH)+0. 03×(AFC), model (4) 2.584–0.015×(age)–0.035×(FSH)+0.038×(AMH)+0.026×(AFC). model 4 showed the best performance. On the basis of these variables, we developed nomograms to predict the number of oocytes that can be retrieved. Conclusion Our nomograms helped predict the number of oocytes retrieved in stimulated IVF cycles. PMID:27358830

  19. Effects of differential pulse frequencies of chicken gonadotrophin-releasing hormone-I (cGnRH-I) on laying hen gonadotrope responses in vitro.

    PubMed

    Soñez, M C; Soñez, C A; Mugnaini, M T; Haedo, M; Romera, S A; Lombardo, D M; Delhon, G A

    2010-12-01

    The aim of this work was to determine the effects of cGnRH I pulse frequencies on FSH and LH release and the changes in features and number of cultured laying hen FSH-cells and LH-cells in vitro. Primary adenohypophyseal cell cultures taken from laying hens were stimulated by four 5 min pulses using 1 or 10 nM cGnRH, administered with interpulses between pulses at 15, 30 or 60 min. Pulse frequencies and dose dependent effects were examined in six separate experiments including two controls. After the last interpulse time, the supernatants were collected and stored at -70° C until the performance of an indirect enzyme-linked immunosorbent assay (ELISA) using chicken LH and chicken FSH antisera at 1:1000 and 1:2000 dilutions, respectively. Supernatants were coated in duplicate on the inner surface of Immulon 2 plates and later blocked with the optimal solutions. They were incubated with each antiserum and subsequently with isotype-specific peroxidase-labeled anti-rabbit antibodies. Hydrogen peroxide/o-phenylenediamine was added as substrate/chromogen and the optical density (OD) was determined at 492 nm. The ABC immunocytochemical method was performed to characterize and re-count the gonadotropes employing anti-chicken FSH and anti-chicken LH as primary antibodies. The number of FSH-LH cells was obtained using stereological analysis and the data were statistically processed. The ODs obtained for each anti-hormone were compared with the control groups and with each other. Significant differences were found in number of aggregated-positive LH cells, which decreased with 1 nM cGnRH-I, 15 vs. 30 min pulses, increased with 30 vs. 60 min pulses, and also with 10 nM cGnRH-I, 30 vs. 60 min pulses. Aggregated positive FSH cells, however, did not show significant differences in percentage at any GnRH dose or pulse frequencies, but did show activity at low pulse frequencies of 15 and 30 min. The results suggest that LH cells varied in percentage in a dose dependent manner at

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

    SciTech Connect

    Johnson, G.P.

    1987-01-01

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

  1. Comparison of pharmacokinetic and safety profiles between Bemfola(®) and Gonal-f(®) after subcutaneous application.

    PubMed

    Wolzt, Michael; Gouya, Ghazeleh; Sator, Michael; Hemetsberger, Thomas; Irps, Charlotte; Rettenbacher, Manfred; Vcelar, Brigitta

    2016-06-01

    Recombinant human follicle stimulating hormone (r-hFSH) is effective and safe for controlled ovarian stimulation. Bemfola(®) (Finox AG, Burgdorf, Switzerland), a new biosimilar r-hFSH, has proven comparable non-clinical pharmacological profiles to those of the widely used Gonal-f(®) (Serono Pharma S.p.A., Bari, Italy). The objective of this study was to show that Bemfola(®) yields comparable clinical pharmacokinetic (PK) and safety profiles to Gonal-f(®) in healthy female subjects. In this randomized, Phase I trial conducted in healthy female volunteers (N = 32), a 2-period, balanced 2-treatment crossover design was used. A single subcutaneous dose of 225 IU Bemfola(®) or Gonal-f(®) was administered in each treatment period per sequence. Blood was collected for pharmacokinetic analysis until 10 days after each r-hFSH treatment. For down-regulation of endogenous FSH subjects were given a depot injection with leuprolide acetate prior to the study drug in either sequence. Pharmacokinetic data was available for 23 subjects. No appreciable differences in key PK parameters were detected between the r-hFSH products as per non-compartmental PK analysis [i.e. for Bemfola(®) and Gonal-f(®) respectively AUC0-192 424.90 and 432.75 IU h/L, C max 0.98 and 0.95 IU/L, T max 24.0 h (range 6.0-24.0) and 24.0 h (range 9.0-24.0), t 1/2 43.58 h [standard deviation (SD 14.17)] and 42.58 h (SD 16.47), and K e 0.0075 1/h (SD 0.003) and 0.0077 1/h (SD 0.002)]. Subgroup analysis for estradiol (E2) response was similar for Bemfola(®) and Gonal f(®) (AUC(0--120) p = 0.21 and C max p = 0.82). No major safety issues were identified and no immunogenic reaction to r-hFSH was observed. The results of this study indicate that a single dose of Bemfola(®) exhibits pharmacokinetic and safety profiles comparable to Gonal-f(®) in healthy young women. PMID:25633239

  2. Testicular volume in relation to hormonal indices of gonadal function in community-dwelling elderly men.

    PubMed

    Mahmoud, A M; Goemaere, S; El-Garem, Y; Van Pottelbergh, I; Comhaire, F H; Kaufman, J M

    2003-01-01

    Aging is accompanied by involutional changes in testicular function; limited data suggest a decrease in bilateral testicular volume (BTV). We studied BTV by ultrasonography in relation to serum gonadal hormones in 115 healthy elderly men (median age, 78 yr) and 42 young men (median age, 26.5 yr). Elderly men had a clearly smaller BTV (mean, 20.6 vs. 29.7 ml; P < 0.001), whereas serum inhibin B was slightly but significantly decreased (mean, 176.8 vs. 212.8 ng/liter; P = 0.04); lower values in the elderly were observed for bioavailable (Bio) testosterone (T), Bio 17 beta-estradiol, inhibin B/FSH (mean, 18 vs. 58 ng/mU; P < 0.001), and T/LH ratios. In the elderly and the young, respectively, BTV was associated with inhibin B (r = 0.53, P < 0.001; r = 0.41, P < 0.01), FSH (r = -0.53, P < 0.001; r = -0.48, P < 0.01), and inhibin B/FSH ratio. Only in the old men was BTV significantly associated with LH (r = -0.32; P < 0.001), Bio T (r = 0.26; P < 0.01), and T/LH (r = 0.48; P < 0.001). In a multivariate analysis, FSH, inhibin B, and Bio T were independently associated with BTV in the elderly (R(2) = 0.34). Receiver operating characteristics curve analysis indicated that BTV at a criterion value of 14.3 ml had a sensitivity of 46% and a specificity of 79% to predict low serum Bio T levels in the elderly. In conclusion, the moderately decreased BTV observed in elderly men, strongly associated with a decrease of the inhibin B/FSH ratio, is consistent with a reduced Sertoli cell mass, compensated by increased FSH stimulation resulting in only limited decrease of Sertoli cell function. Finding of a low testicular volume in elderly men can contribute to the diagnosis of hypogonadism, but this criterion has low sensitivity to detect decreased T production. PMID:12519849

  3. Diminished Ovarian Reserve, Clomid, and Traditional Chinese Medicine: A Case Study

    PubMed Central

    Marx, Benjamin L.

    2012-01-01

    Abstract Background Infertility caused by diminished ovarian reserve (DOR) can result from an endocrinological imbalance. A rise in follicle stimulating hormone (FSH) and decrease in antral follicle count (AFC) for women age ≤35 can lower pregnancy rates to <5%, and increase miscarriage rates to >75%. Chinese medicine may improve FSH and AFC levels in patients with DOR. It is common for women to seek adjunctive Traditional Chinese Medicine (TCM) treatment with biomedical clomid treatment. Objective This article reports the case of a female with DOR who had completed three multiple, serial clomid cycles from September to December 2005, and for whom clomid failed. Design, Setting, and Patient This is a case study of a 34-year-old patient with a 5-year history of infertility caused by DOR. She was treated in a private practice in Bellevue, WA. Intervention TCM treatment—including acupuncture and herbal therapy—lasted from from January 2007 to April 2007. Main Outcome Measures The main outcomes sought were improvements in this patient's reproductive hormone panel, including tests for FSH, estradiol, and AFC levels; in addition a pregnancy outcome was desired. Results After 4 months of TCM treatment, the patient returned to biomedical care. Pregnancy was not achieved during three more clomid cycles, although she had improvements her levels of FSH (from 14.5 mIU/mL to 8.7 mIU/mL) and AFC (from 10–12 to 16–18 total). After 3 more cycles with clomid, her FSH level increased to 16.8 mIU/mL and her AFC level was <10. Conclusions After three failed clomid cycles, a patient with DOR had improved FSH and AFC levels when she received TCM treatment. However, this patient was still unable to conceive although three more clomid cycles were attempted. More research is needed to discern demographically which patients benefit best from multiple, serial clomid interventions. In addition, it is important to investigate more-integrative treatments for patients with DOR

  4. Radioimmunoassay of inhibin: serum responses to unilateral and bilateral orchidectomy.

    PubMed

    Schanbacher, B

    1988-11-01

    An overnight double antibody RIA using a rabbit antiserum to porcine inhibin alpha-chain [Tyr30] (1-30) NH2 [pI alpha(1-30)], radioiodinated pI alpha(1-30), and a preprecipitated second antibody complex has been developed to measure inhibin concentrations in sera and other biological fluids. The assay is accurate, precise (intraassay coefficient of variation, 4.8%), sensitive (25 pM; 2.5 fmol/tube), and specific for inhibin. The synthetic reference standard pI alpha(1-30) produced a displacement curve that paralleled intact male ovine and bovine sera, crude bovine follicular fluid, and a partially purified porcine follicular fluid reference preparation (WHO/NIH 86/690). Bilateral castration of prepubertal and postpubertal ram lambs resulted in a rapid decrease in serum inhibin concentrations and a subsequent increase in serum FSH. Inhibin levels were high in prepubertal lambs (approximately 375 pM), but these levels were not sustained near the time of puberty (approximately 180 pM). Intensive sampling by jugular venipuncture after castration indicated a 50% drop in circulating inhibin levels within 2 h of testes removal with chronic castrate levels (approximately 75 pM) achieved by 6 h postcastration. A rapid fall in circulating levels of inhibin was also observed after unilateral castration, but these values stabilized within hours to levels intermediate (i.e. approximately 200 pM) to those of intact and bilateral castrate rams. Hemicastrates exhibited a more subtle rise in serum FSH after testis removal, with FSH and inhibin levels of prepubertal hemicastrates returning to mature intact ram values by 15 weeks of age. Serum inhibin levels remained low and FSH levels high at 14 days in unilateral castrate postpubertal rams. Inhibin immunoreactivity increased abruptly in castrate ewes and rams injected iv with 5 ml bovine follicular fluid. Serum inhibin reached 300 pM immediately after bovine follicular fluid injection, and castrate FSH levels decreased 30% to a

  5. Contemporary pharmacological manipulation in assisted reproduction.

    PubMed

    Huirne, Judith A F; Lambalk, Cornelis B; van Loenen, Andre C D; Schats, Roel; Hompes, Peter G A; Fauser, Bart C J M; Macklon, Nick S

    2004-01-01

    Follicle-stimulating hormone (FSH) treatment to induce follicular development in anovulating women and multiple follicular development for assisted conception has been incorporated in almost all reproductive treatment cycles in the form of either urinary, purified urinary or recombinant preparations. Besides improved tolerance and theoretically lower chances of infection by prions, the latter may be more effective in terms of clinical pregnancy rates, FSH requirement and cost effectiveness. The low-dose, step-up protocol to induce monofollicular development, which is applied worldwide, has to compete with the equally effective but health economically beneficial step-down protocol. The long protocol using recombinant FSH 150 IU/day is advocated when using gonadotropin-releasing hormone (GnRH) agonists in in vitro fertilisation (IVF) or intracytoplasmatic sperm injection treatment. However, the current paradigmatic hyperstimulation came under scrutiny after the introduction of the GnRH antagonists, which allow milder and more convenient approaches with acceptable cancellation and pregnancy rates but lower requirements for FSH. Risk of ovarian hyperstimulation syndrome (OHSS) can be further eliminated if recombinant luteinising hormone (rLH) or GnRH agonists are used to trigger oocyte maturation and ovulation; the latter require pituitary responsiveness and are therefore excluded in agonist protocols. FSH and LH are both required for appropriate folliculo- and steroidogenesis. In hypogonadotropic women, the addition of LH (human menopausal gonadotropin, human chorionic gonadotropin or rLH) is therefore obligate to achieve appropriate follicular growth and pregnancy. The role of LH in ovulation induction is still a matter of debate, although in GnRH agonistic protocols there seems to be a 'therapeutic window'; levels that are too high or too low have detrimental effects on IVF outcome. To broaden the pharmaceutical armoury, recent efforts have been directed towards the

  6. Comparing two different superovulation protocols on ovarian activity and fecal glucocorticoid levels in the brown brocket deer (Mazama gouazoubira)

    PubMed Central

    2014-01-01

    Background Stress is a limiting factor in assisted reproduction in wild animals maintained in captivity. However, the knowledge of assisted reproduction techniques for wild animals is useful for future in situ and ex situ conservation programs. Thus, this study evaluated the ovulation rate, presence of functional corpora lutea and fecal glucocorticoid levels following treatments promoting superovulation in captive brown brocket deer. Methods The crossover design used six hinds, allocated to two groups (n = 6): eCG Treatment, CIDR for 8 days, followed by 0.25 mg of EB on day 0, 700 IU of eCG on day 4 following device insertion and 265 mug of PGF2alfa on day 8; and FSH Treatment, CIDR for 7.5 days, followed by 0.25 mg of EB on day 0, 130 mg of FSH in 8 equal doses and 265 mug of PGF2alfa on day 7.5. Induced adrenal activity and treatment efficacy were evaluated by corpora lutea (CL) counts and fecal glucocorticoid and progestin concentration (ng/g feces) analyses for five different phases: Pre, two days before treatment; Early, first four days of treatment; Late, last four days of treatment; Total, entire treatment period; and Post, five days posttreatment. Results eCG Treatment resulted in the highest number of CL (P lower than 0.05). There was no significant difference for fecal glucocorticoid concentrations in five different time periods between the treatments; however Pre fecal glucocorticoid concentrations (90.06+/−19.64) were significantly different from Late (200.76+/−26.39) within FSH Treatment. The mean fecal progestin concentration and mean ovulation rate were higher in eCG Treatment (4293.69+/−769.47, 7.0+/−1.8) than in FSH Treatment (1571.26+/−240.28, 2.6+/−0.8) (P lower than or equal to 0.05). Conclusions Although the eCG Treatment induced a good superovulatory response, with the formation of functional corpora lutea, we cannot yet affirm that we have established a suitable protocol for induction of SOV in the species M

  7. Efficacy and Safety of Pergoveris in Assisted Reproductive Technology—ESPART: rationale and design of a randomised controlled trial in poor ovarian responders undergoing IVF/ICSI treatment

    PubMed Central

    Humaidan, P; Schertz, J; Fischer, R

    2015-01-01

    Introduction The results of a recent meta-analysis showed that adding recombinant human luteinising hormone (r-hLH) to recombinant human follicle-stimulating hormone (r-hFSH) for ovarian stimulation was beneficial in poor responders, resulting in a 30% relative increase in the clinical pregnancy rate compared with r-hFSH monotherapy. However, a limitation of the meta-analysis was that the included studies used heterogeneous definitions of poor ovarian response (POR). Furthermore, the use of r-hLH supplementation during ovarian stimulation is a topic of ongoing debate, and well-designed, adequately powered, multicentre, randomised controlled trials in this setting are warranted. Therefore, the objective of the ESPART trial is to explore the possible superiority of a fixed-dose combination of r-hFSH plus r-hLH over r-hFSH monotherapy in patients with POR, as per a definition aligned with the European Society of Human Reproduction and Embryology (ESHRE) Bologna criteria. Methods and analysis Phase III, randomised, single-blind, parallel-group trial in women undergoing in vitro fertilisation and/or intracytoplasmic sperm injection. Approximately 946 women aged 18–<41 years from 18 countries will be randomised (1:1) to receive a fixed-dose combination of r-hFSH plus r-hLH in a 2:1 ratio (Pergoveris) or r-hFSH monotherapy (GONAL-f). The primary end point is the total number of retrieved oocytes per participant. Secondary end points include: ongoing pregnancy rate, live birth rate, implantation rate, biochemical pregnancy rate and clinical pregnancy rate. Safety end points include: incidence and severity of ovarian hyperstimulation syndrome, and of adverse events and serious adverse events. Ethics and dissemination The study will be performed in accordance with ethical principles that have their origin in the Declaration of Helsinki, with the International Conference on Harmonisation–Good Clinical Practice guidelines and all applicable regulatory requirements. All

  8. Serum inhibin B levels reflect Sertoli cell function in normal men and men with testicular dysfunction.

    PubMed

    Anawalt, B D; Bebb, R A; Matsumoto, A M; Groome, N P; Illingworth, P J; McNeilly, A S; Bremner, W J

    1996-09-01

    We used a recently developed ELISA format to test the hypothesis that inhibin B is the physiologically active form of inhibin in men. We measured and compared inhibin A, inhibin B, and pro-alpha-C-related immunoreactive peptides (pro-alpha-C-RI) in normal men before and after perturbations of their gonadotropin levels and baseline values in normal men and men with various disturbances of the hypothalamic-pituitary-testicular axis including men with idiopathic hypogonadotropic hypogonadism, infertile men with elevated FSH, men with Klinefelter's syndrome, and orchidectomized men. Mean serum inhibin concentrations were significantly higher in normal men than untreated men with idiopathic hypogonadotropic hypogonadism, infertile men with elevated FSH, untreated men with Klinefelter's syndrome, and orchidectomized men (187 +/- 28 vs 45 +/- 11, 37 +/- 6, 11 +/- 3, and < or = 10 pg/mL, respectively; P < 0.05). Inhibin B levels were below the limit of detection in all of the orchidectomized men. Pro-alpha-C-RI levels were detectable in all men studied including the orchidectomized men, and no significant differences in the pro-alpha-C-RI levels were noted between the normal men and men with various testicular diseases were noted except that orchidectomized men had significantly lower pro-alpha-C-RI levels than all other groups (P < 0.05). Inhibin A was undetectable in all men tested in this study. Six normal men who were administered exogenous levonorgestrel and testosterone had significantly lower serum gonadotropin, inhibin B, and pro-alpha-C-RI levels during the treatment period than the control and recovery periods (P < 0.05). Ten normal men who were administered human recombinant FSH had significantly higher peak serum FSH (21.85 +/- 3.23 IU/L vs. 3.01 +/- 0.51 IU/L), inhibin B (311 +/- 88 pg/mL vs. 151 +/- 23 pg/mL) and pro-alpha-C-RI (646 +/- 69 vs. 402 +/- 38 pg/mL) levels during the treatment period than the baseline values (P < 0.05). We conclude that inhibin B

  9. EEAP boiler and chiller study at Fort Sam Houston, Texas. Final report

    SciTech Connect

    1995-09-18

    This energy conservation study was performed by Huitt-Zollars Inc, for the U.S. Army Engineer District (USAED), Fort Worth, under contract number DACAC63-94-D-0015. The study was conducted at Fort Sam Houston (FSH) in San Antonio, Texas, between November 28, 1994 and June 15, 1995. The site survey, data collection and analysis was performed by John Carter, E.I.T, Tom Holthaus, P.E., Walter H. Williams III, P.E., and C.A. Pieper, P.E.. The purpose of the study was to perform a limited site survey of specific buildings at the facility, identify specific Energy Conservation Opportunities (ECOs) that exist, and then evaluate these ECOs for technical and economic feasibility. These ECOs were limited to central boiler and chiller plant systems serving specific building groups at FSH.

  10. Effects of Space Flight on Ovarian-Hypophyseal Function in Postpartum Rats

    NASA Technical Reports Server (NTRS)

    Burden, H. W.; Zary, J.; Lawrence, I. E.; Jonnalagadda, P.; Davis, M.; Hodson, C. A.

    1997-01-01

    The effect of space flight in a National Aeronautics and Space Administration (NASA) shuttle was studied in pregnant rats. Rats were launched on day 9 of gestation and recovered on day 20 of gestation. On day 20 of gestation, rats were unilaterally hysterectomized and subsequently allowed to go to term and deliver vaginally. There was no effect of space flight on pituitary and ovary mass postpartum. In addition, space flight did not alter healthy and atretic ovarian antral follicle populations, fetal wastage in utero, plasma concentrations of progesterone and luteinizing hormone (LH) or pituitary content of follicle stimulating hormone (FSH). Space flight significantly increased plasma concentrations of FSH and decreased pituitary content of LH at the postpartum sampling time. Collectively, these data show that space flight, initiated during the postimplantation period of pregnancy, and concluded before parturition, is compatible with maintenance of pregnancy and has minimal effects on postpartum hypophyseal parameters; however, none of the ovarian parameters examined was altered by space flight.

  11. [Preservation of gonadotrophic function and pregnancy in Sheehan's syndrome: a case report and review of the literature].

    PubMed

    Vieira, H B; Knoepfelmacher, M; Salgado, L R; Wajchenberg, B L; Liberman, B

    1995-01-01

    Pregnancy occurring in patient with Sheehan's syndrome is seldom described. It depends on the preservation of LH and FSH secretion after the pituitary apoplexy event. PURPOSE--To report a patient with Sheehan's syndrome who became pregnant twice after the pituitary apoplexy episode and to discuss the maintenance of gonadotrophic function. METHOD--Clinical aspects are described and the pituitary reserve evaluation was performed as well as a computerized tomography and a magnetic resonance imaging of the brain. RESULTS--Gonadotrophic and thyrotrophic function were preserved and the neuroradiologic evaluation disclosed an empty sella turcica preservation of the posterior lobe of the hypophysis. CONCLUSION--A patient with Sheehan's syndrome is reported in whom the LH and FSH pituitary secretion was preserved allowing normal pregnancy twice after the pituitary apoplexy. PMID:8520595

  12. Effect of timing of oestradiol benzoate injection relative to gonadotropin treatment on superovulatory response, and on embryo yield and quality in beef heifers.

    PubMed

    Yaakub, H; Duffy, P; O'Callaghan, D; Boland, M P

    1998-09-11

    Variation in superovulatory responses in cattle may be related to the stage of follicular growth at the time of gonadotropin treatment. Waves of follicle growth are regulated by both follicle-stimulating hormone (FSH) and oestradiol. The objective of experiment 1 was to determine the dynamics of follicle wave emergence and the relationship with FSH and oestradiol concentrations, after treatment of heifers with oestradiol benzoate (ODB) in the presence of an intravaginal progesterone-releasing device (CIDR-B). Experiment 2 examined the superovulatory response, embryo yield and quality following treatment with porcine follicle-stimulating hormone (pFSH) at different times relative to ODB injection. In experiment 1, 28 beef heifers were treated with a CIDR for 9 days and allocated at random to one of four groups to receive either: (I) CIDR only, or 5 mg ODB given as a single intramuscular injection at (II) day 0 (d0); (III) day 1.5 (d1.5); or (IV) day 3 (d3) post CIDR insertion. Ovaries were examined using daily ultrasound and blood samples were collected twice daily for 11 days. In experiment 2, 96 heifers were treated with a CIDR and 5 mg ODB as in experiment 1, and were allocated using a 4 x 3 factorial design plan to a superovulation programme using three doses (400 IU; 600 IU; 800 IU) of pFSH. FSH was given for 4 days at 12-h intervals beginning 6.5 days after CIDR insertion. Heifers received prostaglandin analogue 12 h before CIDR removal and were inseminated (AI) at 48 and 60 h post CIDR withdrawal and embryos were recovered 7 days after AI. In experiment 1, the interval from CIDR insertion to follicle wave emergence (FWE) was longer (P < 0.05) in heifers treated with ODB at d1.5 (5.4 +/- 0.4 days) and d3 (5.1 +/- 0.6 days) compared to heifers treated with CIDR only (2.4 +/- 0.4 days). On the basis of time to proposed injection of pFSH heifers would have had follicle emergence 4.4, 2.3, 1.5 and 1.4 days prior to pFSH for groups I, II, III and IV, respectively

  13. Variable X-linked recessive hypopituitarism with evidence of gonadotropin deficiency in two pre-pubertal males.

    PubMed

    Zipf, W B; Kelch, R P; Bacon, G E

    1977-04-01

    Two half-brothers with short stature secondary to growth hormone deficiency and a family history implicating X-linked transmission were studied extensively for other endocrine abnormalities. The proband had a normal physical examination, except for small stature and small external genitalia. ACTH and TSH release were normal. LH and FSH responses during an i.v. GnRH test were severely blunted. His half-brother also had a normal physical examination, except for severe short stature and very small external genitalia. Deficiencies of ACTH, and TSH as well as GH were documented. An i.v. GnRH test showed no LH or FSH response. These studies support the existence of an X-linked recessive form of hypopituitarism and portend the clinical usefulness of the i.v. GnRH test in evaluating gonadotropin reserve. PMID:192503

  14. Small testicles with impaired production of sperm in adult male survivors of childhood malignancies

    SciTech Connect

    Siimes, M.A.; Rautonen, J. )

    1990-03-15

    Testicular size has been studied in 66 adult men who survived leukemia (n = 14) or cancer (n = 52) in childhood. Mean follow-up time was 14.5 years. The testicular size was measured as the length and breadth in mm; testicular volume index was calculated. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and prolactin were measured. A sperm sample was obtained from 46 men. The patients had smaller testicles than healthy medical students; 51 had small testicles. The size was the smallest in patients who survived leukemia. Multivariate analysis showed that the variables with independent effects on testicular size were cranial and testicular irradiation and therapy with cyclophosphamide. Sperm production was dependent on testicular size. We conclude that determination of serum FSH combined with testicular size may offer a practical approach for predicting the subsequent testicular damage in boys with malignancies.

  15. Testosterone and disinhibited personality in healthy males.

    PubMed

    Aluja, Anton; García, Luis F; García, Óscar; Blanco, Eduardo

    2016-10-01

    The relationship among testosterone (T), free testosterone (FT), bioavailable testosterone (BT) and personality were studied in a sample of 105 healthy males (26.71±9.68years old). The possible effects of age and other hormones, such as luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), and albumin (ALB) were controlled. Personality was assessed by the novelty seeking scale of Cloninger's Temperament-Character Inventory (TCI), and a reduced version of the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). Main results show that there is a weak association among three measures of testosterone with novelty seeking, sociability and, to a lesser extent, with impulsive sensation seeking. Our data, as expected, confirmed previous results and also suggest that these relationships are strongly affected by the age variable. LH, FSH and SHBG hormones play no role in the reported relationships. PMID:27291990

  16. Clinical use of GnRH agonists in canine and feline species.

    PubMed

    Fontaine, E; Fontbonne, A

    2011-04-01

    GnRH (gonadotrophin releasing hormone) is a key hormone of reproductive function in mammals; agonist forms have been largely developed, and data concerning their use in small animal reproduction are now abundant. GnRH agonists act by a two-step mechanism. First, their agonist properties on the pituitary will cause marked LH (luteinizing hormone) and FSH (follicle-stimulating hormone) secretion into the bloodstream, accompanied by an increase in the concentrations of sex steroid hormones. Then, in case of constant administration, GnRH agonists will lead to pituitary desensitization, and FSH and LH levels will collapse. These two effects have been widely documented, and these compounds have many potential benefits in a clinical context, capitalizing both on their stimulating and sterilizing effects. PMID:20964727

  17. Hormones in Synergy: Regulation of the Pituitary Gonadotropin Genes

    PubMed Central

    Thackray, Varykina G.; Mellon, Pamela L.; Coss, Djurdjica

    2009-01-01

    The precise interplay of hormonal influences that governs gonadotropin hormone production by the pituitary includes endocrine, paracrine and autocrine actions of hypothalamic gonadotropin-releasing hormone (GnRH), activin and steroids. However, most studies of hormonal regulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the pituitary gonadotrope have been limited to analyses of the isolated actions of individual hormones. LHβ and FSHβ subunits have distinct patterns of expression during the menstrual/estrous cycle as a result of the integration of activin, GnRH, and steroid hormone action. In this review, we focus on studies that delineate the interplay among these hormones in the regulation of LHβ and FSHβ gene expression in gonadotrope cells and discuss how signaling cross-talk contributes to differential expression. We also discuss how recent technological advances will help identify additional factors involved in the differential hormonal regulation of LH and FSH. PMID:19747958

  18. Fox Tales: Regulation of Gonadotropin Gene Expression by Forkhead Transcription Factors

    PubMed Central

    Thackray, Varykina G.

    2013-01-01

    Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are produced by pituitary gonadotrope cells and are required for steroidogenesis, the maturation of ovarian follicles, ovulation, and spermatogenesis. Synthesis of LH and FSH is tightly regulated by a complex network of signaling pathways activated by hormones including gonadotropin-releasing hormone, activin and sex steroids. Members of the forkhead box (FOX) transcription factor family have been shown to act as important regulators of development, homeostasis and reproduction. In this review, we focus on the role of four specific FOX factors (FOXD1, FOXL2, FOXO1 and FOXP3) in gonadotropin hormone production and discuss our current understanding of the molecular function of these factors derived from studies in mouse genetic and cell culture models. PMID:24099863

  19. Influence of solid-liquid separation strategy on biogas yield from a stratified swine production system.

    PubMed

    Cestonaro do Amaral, André; Kunz, Airton; Radis Steinmetz, Ricardo Luis; Scussiato, Lucas Antunes; Tápparo, Deisi Cristina; Gaspareto, Taís Carla

    2016-03-01

    As the fourth largest swine producer and exporter, Brazil has increased its participation in the global swine production market. Generally, these units concentrate a large number of animals and generate effluents that must be correctly managed to prevent environmental impacts, being anaerobic digestion is an interesting alternative for treating these effluents. The low-volatile solid concentration in the manure suggests the need for solid-liquid separation as a tool to improve the biogas generation capacity. This study aimed to determine the influence of simplified and inexpensive solid-liquid separation strategies (screening and settling) and the different manures produced during each swine production phase (gestating and farrowing sow houses, nursery houses and finishing houses) on biogas and methane yield. We collected samples in two gestating sow houses (GSH-a and GSH-b), two farrowing sow houses (FSH-a and FSH-b), a nursery house (NH) and a finishing house (FH). Biochemical methane potential (BMP) tests were performed according to international standard procedures. The settled sludge fraction comprised 20-30% of the raw manure volume, which comprises 40-60% of the total methane yield. The methane potential of the settled sludge fraction was approximately two times higher than the methane potential of the supernatant fraction. The biogas yield differed among the raw manures from different swine production phases (GSH-a 326.4 and GSH-b 577.1; FSH-a 860.1 and FSH-b 479.2; NH -970.2; FH 474.5 NmLbiogas.gVS(-1)). The differences were relative to the production phase (feed type and feeding techniques) and the management of the effluent inside the facilities (water management). Brazilian swine production has increased his participation in the global market, been the fourth producer and the fourth exporter. The segregation of swine production in multiple sites has increased its importance, due to the possibilities to have more specialized units. Generally, these units

  20. Clinical characteristics in Taiwanese women with polycystic ovary syndrome

    PubMed Central

    2015-01-01

    Polycystic ovary syndrome (PCOS) is one of the most common hormonal endocrine disorders in women of reproductive age. It consists of a heterogeneous collection of signs and symptoms that together form a disorder spectrum. The diagnosis of PCOS is principally based on clinical and physical findings. The extent of metabolic abnormalities in women with PCOS varies with phenotype, body weight, age, and ethnicity. For general population, the prevalence of hyperandrogenism and oligomenorrhea decreases with age, while complications such as insulin resistance and other metabolic disturbances increase with age. Obese women with PCOS have a higher risk of developing oligomenorrhea, amenorrhea, hyperandrogenemia, insulin resistance, and lower luteinizing hormone (LH) to follicle stimulation hormone (FSH) ratios than non-obese women with PCOS. The LH to FSH ratio is a valuable diagnostic tool in evaluating Taiwanese women with PCOS, especially in the diagnosis of oligomenorrhea. Overweight/obesity is the major determinant of cardiovascular and metabolic disturbances in women of reproductive age. PMID:26473107

  1. Features of diagnostics and treatment of partial androgen deficiency of aging men

    PubMed Central

    2014-01-01

    Introduction Decreasing of testosterone level is an important part of a male elderly. Material and methods To describe this phenomenon a PubMed and national databases were searched for 17β–dehydrotestosterone, common testosterone, free testosterone, 17β–estradiol, luteinizing hormone, partial androgen deficiency of aging men. Results The reduction in intensity of the processes of tissue renewal of the testicles results in a partial androgen deficiency of aging men. A decrease in the levels of total and free testosterone and an increase in the levels of 5α–dihydrotestosterone, 17β–estradiol, sex hormone binding globulin, LH and FSH, along with a decrease in the amplitude of the rhythm of incretion of LH, FSH and total testosterone will testify to a deficiency of testosterone. Conclusions It is very important to make an individualized selection of the dose of testosterone preparation which enters the blood plasma. PMID:25667762

  2. Sperm counts and serum follicle-stimulating hormone levels before and after radiotherapy and chemotherapy in men with testicular germ cell cancer

    SciTech Connect

    Berthelsen, J.G.

    1984-02-01

    Sperm counts were low (median, 15 X 10(6) per ejaculate) and serum follicle-stimulating hormone (FSH) levels were moderately elevated (median, 31 IU/l) after unilateral orchiectomy and immediately before radiotherapy and chemotherapy in 34 patients with seminomas and 20 patients with nonseminomatous germ cell tumors. The scattered radiation (0.2 to 1.3 Gray (Gy)) reaching the remaining testicle during radiotherapy caused azoospermia in more than two thirds of the patients. A median of 540 days elapsed after the end of treatment before spermatozoa were again found in semen samples, while a median of 1250 days passed before the pretreatment sperm count was reached. One to 5 years after treatment, sperm counts were still low (median, 6 X 10(6) per ejaculate) and serum FSH was elevated (median, 61 IU/l). The adjuvant chemotherapy given to the 20 patients with nonseminomatous tumors did not appear to affect restitution appreciably.

  3. Effect of tulsi (Ocimum Sanctum Linn.) on sperm count and reproductive hormones in male albino rabbits.

    PubMed

    Sethi, Jyoti; Yadav, Mridul; Sood, Sushma; Dahiya, Kiran; Singh, Veena

    2010-10-01

    Fresh leaves of Ocimum Sanctum (OS) were used to study its effect on male reproductive function (sperm count and reproductive hormones) in male albino rabbits. Animals in the test group received supplementation of 2 g of fresh leaves of OS per rabbit for 30 days, while the control group was maintained on normal diet for the same duration. Sperm count and hormonal estimation [testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH)] were done in serum samples of both groups and compared. A significant decrease was noted in the sperm count in test group rabbits. Serum testosterone levels showed marked increase while FSH and LH levels were significantly reduced in OS-treated rabbits. The results suggest the potential use of OS as an effective male contraceptive agent. PMID:21455446

  4. The role of sex and sex-related hormones in cognition, mood and well-being in older men and women.

    PubMed

    Castanho, Teresa Costa; Moreira, Pedro Silva; Portugal-Nunes, Carlos; Novais, Ashley; Costa, Patrício Soares; Palha, Joana Almeida; Sousa, Nuno; Santos, Nadine Correia

    2014-12-01

    Alterations in hormone levels during aging impact on cognition and mood. Serum concentration levels of testosterone (TT), estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS) and prolactin (PRL) were assessed in 120 community-dwellers (51+ years of age, males and females), in a cross-sectional approach. Performance clusters based on executive functioning (GENEXEC), memory (MEM), mood and well-being were obtained. In males, higher PRL levels associated with worse cognitive performance, lower well-being, and higher scores in depression scales, and lower E2 with poorer cognition and higher depressive mood. DHEAS positively associated with GENEXEC and MEM. Nutritional status significantly associated with PRL (positively) and with DHEAS (negatively). Findings indicate that besides the more exhaustively studied E2 and TT, variations in the levels of sex-related hormones such as PRL, FSH, LH and DHEAS are of interest for the mental health aging profile particularly in men. PMID:25196100

  5. Plasma mineral profiles and hormonal activities of normal cycling and repeat breeding crossbred cows: A comparative study

    PubMed Central

    Barui, Abhijit; Batabyal, Subhasis; Ghosh, Sarbaswarup; Saha, Debjani; Chattopadhyay, Saibal

    2015-01-01

    Aim: The present study was carried out to compare the associated role of micro minerals and hormones in repeat breeding animals with the normal crossbred cows. Materials and Methods: Blood samples were collected from 10 normal cycling and 10 repeat breeding crossbred cows of Ramakrishna Mission Ashram, Narendrapur to study the plasma mineral profile and hormonal activities. Results: Zn was found to be highly significant (p<0.01) between the two groups. Follicle stimulating hormone (FSH) and progesterone showed significant (p<0.05) difference in repeat breeding animal from the normal cyclic animal, whereas no significant differences were observed in Ca, P, Cu, Se, Co, luteinizing hormone and estradiol level. Conclusion: It may conclude that repeat breeding condition of crossbred cows in farm condition is mainly due to the low level of progesterone, FSH and zinc. PMID:27046994

  6. Effects of cyclic increase in gonadotropins on the in vitro development of primordial follicles to antral stage.

    PubMed

    Fabbri, Raffaella; Pasquinelli, Gianandrea; Parazza, Isabella; Macciocca, Maria; Magnani, Valentina; Battaglia, Cesare; Paradisi, Roberto; Venturoli, Stefano

    2012-10-01

    The aim of this study was to evaluate the effects of FSH and LH on follicle development during a long-term culture of cryopreserved human ovarian tissue, using morphological and ultrastructural examinations. Thawed ovarian tissue slices from a 4-year-old child with Wilms tumor were cultured for 32 weeks in two different culture conditions, without (medium A) and with (medium B) a monthly peaked increase in FSH and LH. At week 32, in the medium B cultured tissue, a cluster of preantral follicles associated with two oocytes prematurely ovulated was observed, suggesting that the cyclic increase of gonadotropins promoted thawed follicles to grow up to the antral stage. However, the integrity and coordinated follicle development were not maintained. Indeed, ultrastructural analysis showed a well-preserved "naked" oocyte with concomitant features of immaturity and maturity, as if this culture condition had led to an asynchronous maturation of oocyte cytoplasmic components. PMID:23025653

  7. Prolactin and gonadotrophin changes following generalised and partial seizures.

    PubMed Central

    Dana-Haeri, J; Trimble, M r; Oxley, J

    1983-01-01

    Postictal values of prolactin, LH and FSH have been recorded in patients with both generalised tonic-clonic and partial seizures. Elevations of prolactin and LH were seen immediately and at 20 minutes in males and females with generalised attacks. At sixty minutes values for prolactin had fallen to baseline levels, but LH remained elevated. FSH values were increased in females only, at twenty and sixty minutes. Following partial seizures prolactin was elevated, especially with complex partial seizures, at twenty minutes. These results are discussed in the light of known electrophysiological mechanisms relating to partial seizures, and clinical guidelines for the use of neurohormonal tests in the evaluation of seizures are suggested. PMID:6405014

  8. Factors influencing the outcome of intrauterine insemination (IUI): age, clinical variables and significant thresholds.

    PubMed

    Speyer, B E; Abramov, B; Saab, W; Doshi, A; Sarna, U; Harper, J C; Serhal, P

    2013-10-01

    The aim was to investigate the influence of various biological factors upon the outcome of intrauterine insemination (IUI). The total IUI history (856 cycles) of 352 couples was studied. Live-birth showed a strong negative correlation with female age but no correlation with male age. Antimüllerian hormone (AMH) and antral follicle count (AFC) correlated negatively with female age, and follicle stimulating hormone (FSH) correlated positively. Significant thresholds were found for all three variables, and also for total motile count (TMC) in the prepared sperm. Calculating pregnancy losses per positive pregnancy showed a strong correlation with increasing female age. This was highly significant for biochemical losses but not for fetal heart miscarriages. Male age had no effect on rate of pregnancy loss. In conclusion, female age, FSH, AMH and TMC are good predictive factors for live-birth and therefore relate to essential in vivo steps in the reproductive process. PMID:24127958

  9. Thyroidectomy prevents the development of photorefractoriness and the associated rise in plasma prolactin in starlings

    SciTech Connect

    Goldsmith, A.R.; Nicholls, T.J.

    1984-05-01

    Intact and radiothyroidectomized male starlings were transferred from short (8-hr) to long (16-hr) day lengths and measurements made of testicular development and of plasma prolactin concentrations. In intact birds the testes reached full maturity within 3 weeks and regressed after 6 weeks of photostimulation, indicative of the development of photorefractoriness . Prolactin levels increased gradually, reaching maximal values at the time of testicular regression. Testicular growth was normal in the thyroidectomized birds. Removal of the testes from thyroidectomized birds after 1 year on long days resulted in a marked rise in plasma FSH, indicating that these birds were indeed not photorefractory ; FSH levels in the refractory-intact starlings remained low after castration. These results confirm that the presence of an intact thyroid gland is essential for the development of photorefractoriness and for the release of prolactin which normally follows photostimulation.

  10. 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.

  11. Anterior pituitary gland assessment in sickle cell anaemia patients with delayed menarche.

    PubMed

    Abbiyesuku, F M; Osotimehin, B O

    1999-01-01

    Pituitary gland dysfunction and its contribution to menarcheal delay in sickle cell anaemia patients was investigated. Ten SS patients mean age 17.5 years who had not achieved menarche were recruited and 10 each of AS and AA controls, mean ages 17.4 and 17.7 years were used as controls to study the effect of the heterozygous state. Dynamic studies with LHRH and TRH were performed for 60 minutes and LH, FSH, PRL and TSH assays were done. Median basal values were significantly lower in the SS patients compared with the AS and AA controls for LH, FSH and PRL. LH: 3.0; 7.1; 7.7 U/L, FSH: 2.1: 4.3: 5.1 U/L. PRL: 94.5; 590; 390 U/L, respectively. The median basal TSH values did not show any significant difference between the SS subjects (7.3 U/L) and the AS and AA controls (5.4 U/L) and 5.6 U/L, respectively. The readily releasable pool also showed the same pattern for LH, FSH and PRL as the basal values while the SS subjects had higher median TSH releasable pool values that were significantly different from those of the AA controls. From the prolactin responses three subjects demonstrated maturational delay in menarcheal achievement while seven demonstrated isolated gonadotrophin deficiency. It is concluded that SS patients with delayed menarche have a hypothalamopituitary axis dysfunction that gives rise to delay in menarcheal achievement and metabolic adaptations to stress of illness. The heterozygous state did not delay menarcheal onset. PMID:12953990

  12. Luteinizing hormone-releasing hormone (LH-RH) as a diagnostic and research tool in gynecologic endocrinology.

    PubMed

    Taymor, M L; Thompson, I E; Berger, M J; Patton, W

    1974-11-15

    A study is reported on the effects of 150 mcg. of luteinizing hormone-releasing hormone (LH-RH), administered iv to 48 women with 5 types of secondary oligoamenorrhea, on the serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Levels. At Time 0, patients with pituitary disease showed a markedly diminished LH response and patients with polycystic ovarian disease with enlarged ovaries showed a brisk, elevated LH response. FSH levels in patients with pituitary disease and polycystic ovarian disease showed a negligible rise at Time 0. 9 of 10 patients with pituitary disease and 5 of 9 patients with dietary amenorrhea had a low LH response 30 minutes after LH-RH administration. FSH response 60 minutes after injection in patients with pituitary disease and polycystic ovarian disease seemed to be lowered though too much overlap prevented a complete diagnosis. The conclusion of this initial study is that through baseline determinations of FSH and LH, along with a LH-RH stimulation test, useful data are provided for determining whether amenorrhea is due to ovarian or pituitary failure. A 2nd study evaluated the effects of 150 mcg of LH-RH administered iv before and after the im administration of various dosages of estrogen and progesterone to anovulatory women. A vigorous response in pituitary gonadotropin, particularly LH, was observed with LH-RH administered only. The effect with estrogen and progesterone was diminished pituitary response in terms of LH production. It is concluded that estrogen and progesterone exert a negative feedback effect on gonadotropin secretion at the hypothalamic and pituitary levels. PMID:4611213

  13. Architecture of GnRH-Gonadotrope-Vasculature Reveals a Dual Mode of Gonadotropin Regulation in Fish.

    PubMed

    Golan, Matan; Zelinger, Einat; Zohar, Yonathan; Levavi-Sivan, Berta

    2015-11-01

    The function and components of the hypothalamic-pituitary axis are conserved among vertebrates; however, in fish, a neuroglandular mode of delivery (direct contact between axons and endocrine cells) was considered dominant, whereas in tetrapods hypothalamic signals are relayed to their targets via the hypophysial portal blood system (neurovascular delivery mode). By using a transgenic zebrafish model we studied the functional and anatomical aspects of gonadotrope regulation thus revisiting the existing model. FSH cells were found to be situated close to the vasculature whereas the compact organization of LH cells prevented direct contact of all cells with the circulation. GnRH3 fibers formed multiple boutons upon reaching the pituitary, but most of these structures were located in the neurohypophysis rather than adjacent to gonadotropes. A close association was observed between FSH cells and GnRH3 boutons, but only a fifth of the LH cells were in direct contact with GnRH3 axons, suggesting that FSH cells are more directly regulated than LH cells. GnRH3 fibers closely followed the vasculature in the neurohypophysis and formed numerous boutons along these tracts. These vessels were found to be permeable to relatively large molecules, suggesting the uptake of GnRH3 peptides. Our findings have important implications regarding the differential regulation of LH and FSH and contradict the accepted notion that fish pituitary cells are mostly regulated directly by hypothalamic fibers. Instead, we provide evidence that zebrafish apply a dual mode of gonadotrope regulation by GnRH3 that combines both neuroglandular and neurovascular components. PMID:26261873

  14. Early prenatal androgenization results in diminished ovarian reserve in adult female rhesus monkeys

    PubMed Central

    Dumesic, D.A.; Patankar, M.S.; Barnett, D.K.; Lesnick, T.G.; Hutcherson, B.A.; Abbott, D.H.

    2009-01-01

    BACKGROUND Early prenatal androgenization (PA) accelerates follicle differentiation and impairs embryogenesis in adult female rhesus monkeys (Macaca mulatta) undergoing FSH therapy for IVF. To determine whether androgen excess in utero affects follicle development over time, this study examines whether PA exposure, beginning at gestational days 40–44 (early treated) or 100–115 (late treated), alters the decline in serum anti-Mullerian hormone (AMH) levels with age in adult female rhesus monkeys and perturbs their ovarian response to recombinant human FSH (rhFSH) therapy for IVF. METHODS Thirteen normal (control), 11 early-treated and 6 late-treated PA adult female monkeys had serum AMH levels measured at random times of the menstrual cycle or anovulatory period. Using some of the same animals, basal serum AMH, gonadotrophins and steroids were also measured in six normal, five early-treated and three late-treated PA female monkeys undergoing FSH therapy for IVF during late-reproductive life (>17 years); serum AMH also was measured on day of HCG administration and at oocyte retrieval. RESULTS Serum AMH levels in early-treated PA females declined with age to levels that were significantly lower than those of normal (P ≤ 0.05) and late-treated PA females (P ≤ 0.025) by late-reproductive life. Serum AMH levels positively predicted numbers of total/mature oocytes retrieved, with early-treated PA females having the lowest serum AMH levels, fewest oocytes retrieved and lowest percentage of females with fertilized oocytes that cleaved. CONCLUSIONS Based on these animals, early PA appears to program an exaggerated decline in ovarian reserve with age, suggesting that epigenetically induced hormonal factors during fetal development may influence the cohort size of ovarian follicles after birth. PMID:19740899

  15. Radioimmunoassay of inhibin: serum responses to unilateral and bilateral orchidectomy

    SciTech Connect

    Schanbacher, B.

    1988-11-01

    An overnight double antibody RIA using a rabbit antiserum to porcine inhibin alpha-chain (Tyr30) (1-30) NH2 (pI alpha(1-30)), radioiodinated pI alpha(1-30), and a preprecipitated second antibody complex has been developed to measure inhibin concentrations in sera and other biological fluids. The assay is accurate, precise (intraassay coefficient of variation, 4.8%), sensitive (25 pM; 2.5 fmol/tube), and specific for inhibin. The synthetic reference standard pI alpha(1-30) produced a displacement curve that paralleled intact male ovine and bovine sera, crude bovine follicular fluid, and a partially purified porcine follicular fluid reference preparation (WHO/NIH 86/690). Bilateral castration of prepubertal and postpubertal ram lambs resulted in a rapid decrease in serum inhibin concentrations and a subsequent increase in serum FSH. Inhibin levels were high in prepubertal lambs (approximately 375 pM), but these levels were not sustained near the time of puberty (approximately 180 pM). Intensive sampling by jugular venipuncture after castration indicated a 50% drop in circulating inhibin levels within 2 h of testes removal with chronic castrate levels (approximately 75 pM) achieved by 6 h postcastration. A rapid fall in circulating levels of inhibin was also observed after unilateral castration, but these values stabilized within hours to levels intermediate (i.e. approximately 200 pM) to those of intact and bilateral castrate rams. Hemicastrates exhibited a more subtle rise in serum FSH after testis removal, with FSH and inhibin levels of prepubertal hemicastrates returning to mature intact ram values by 15 weeks of age. Serum inhibin levels remained low and FSH levels high at 14 days in unilateral castrate postpubertal rams. Inhibin immunoreactivity increased abruptly in castrate ewes and rams injected iv with 5 ml bovine follicular fluid.

  16. Normal gonadotropin production and fertility in gonadotrope-specific Bmpr1a knockout mice.

    PubMed

    Zhou, Xiang; Wang, Ying; Ongaro, Luisina; Boehm, Ulrich; Kaartinen, Vesa; Mishina, Yuji; Bernard, Daniel J

    2016-06-01

    Pituitary follicle-stimulating hormone (FSH) synthesis is regulated by transforming growth factorβsuperfamily ligands, most notably the activins and inhibins. Bone morphogenetic proteins (BMPs) also regulate FSHβ subunit (Fshb) expression in immortalized murine gonadotrope-like LβT2 cells and in primary murine or ovine primary pituitary cultures. BMP2 signals preferentially via the BMP type I receptor, BMPR1A, to stimulate murine Fshb transcription in vitro Here, we used a Cre-lox approach to assess BMPR1A's role in FSH synthesis in mice in vivo Gonadotrope-specific Bmpr1a knockout animals developed normally and had reproductive organ weights comparable with those of controls. Knockouts were fertile, with normal serum gonadotropins and pituitary gonadotropin subunit mRNA expression. Cre-mediated recombination of the floxed Bmpr1a allele was efficient and specific, as indicated by PCR analysis of diverse tissues and isolated gonadotrope cells. Furthermore, BMP2 stimulation of inhibitor of DNA binding 3 expression was impaired in gonadotropes isolated from Bmpr1a knockout mice, confirming the loss of functional receptor protein in these cells. Treatment of purified gonadotropes with small-molecule inhibitors of BMPR1A (and the related receptors BMPR1B and ACVR1) suppressed Fshb mRNA expression, suggesting that an autocrine BMP-like molecule might regulate FSH synthesis. However, deletion of Bmpr1a and Acvr1 in cultured pituitary cells did not alter Fshb expression, indicating that the inhibitors had off-target effects. In sum, BMPs or related ligands acting via BMPR1A or ACVR1 are unlikely to play direct physiological roles in FSH synthesis by murine gonadotrope cells. PMID:27029473

  17. Kinetic study of internalization and degradation of sup 131 I-labeled follicle-stimulating hormone in mouse Sertoli cells and its relevance to other systems

    SciTech Connect

    Shimizu, A.; Kawashima, S. )

    1989-08-15

    The behavior of 131I-labeled follicle-stimulating hormone (FSH) after binding to cell-surface receptors in cultured Sertoli cells of C57BL/6NCrj mice was investigated. Sertoli cells cultured in F12/DME were pulse-labeled with 131I-FSH for 10 min at 4 degrees C, followed by cold chase for various periods of time. After the cold chase Sertoli cells were treated with 0.2 M acetate (pH 2.5) to dissociate membrane-bound 131I-FSH (surface radioactivity). The medium containing radioactivity after cold chase was mixed with 20% trichloroacetic acid, centrifuged, and the radioactivity of the supernatant was measured (degraded hormone). The radiolabeled materials associated with each process (surface binding, internalization, and degradation) were concentrated with ultrafiltration and characterized with gel filtration and/or thin layer chromatography. The effects of lysosomotropic agents, NH4Cl and chloroquine, were studied. The cold chase study at 32 degrees C showed that the surface radioactivity was the largest among the three kinds of radioactivities associated with each process immediately after pulse labeling, but the surface radioactivity rapidly decreased, while the internalized radioactivity increased. The cold chase study at 4 degrees C did not show such time-related changes in radioactivities, and a high level of surface radioactivity constantly persisted. The surface and internalized radioactivities were due to 131I-FSH, and the degraded radioactivity was mainly due to (131I)monoiodotyrosine. When Sertoli cells were cultured with lysosomotropic agents, the internalized radioactivity increased, while the degraded radioactivity decreased. Based on these observations, a kinetic model was proposed and the relationships among the surface, internalized, and degraded radioactivities and cold chase time were calculated algebraically.

  18. Expression Levels of PPARγ and CYP-19 in Polycystic Ovarian Syndrome Primary Granulosa Cells: Influence of ω-3 Fatty Acid

    PubMed Central

    Zaree, Mina; Shahnazi, Vahideh; Fayezi, Shabnam; Darabi, Maryam; Mehrzad-Sadaghiani, Mahzad; Darabi, Masoud; Khani, Sajjad; Nouri, Mohammad

    2015-01-01

    Background The omega-3 fatty acid (ω-3 fatty acid) such as eicosapentaenoic acid (EPA) is currently used in the clinic as a nutritional supplement in the treatment of poly- cystic ovarian syndrome (PCOS). The present study was designed to investigate the ef- fect of EPA on the expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and cytochrome P450 aromatase (encoded by the CYP-19) in primary cultured granulosa cells (GC) from patients undergoing in vitro fertilization (IVF), and also to compare these effects with those in GC of PCOS patients. Materials and Methods In this experimental study, human GC were isolated, pri- mary cultured in vitro, exposed to a range of concentrations of the EPA and in- vestigated with respect to gene expression levels of PPARγ and CYP-19 using real time-polymerase chain reaction (PCR). The participants (n=30) were the patients admitted to the IVF Center in February-March 2013 at Alzahra Hospital, Tabriz, Iran, who were divided into two groups as PCOS (n=15) and non-PCOS (n=15) women (controls). Results All doses of the EPA significantly induced PPARγ mRNA gene expression level as compared to the control recombinant follicle stimulating hormone (rFSH) alone condi- tion. High doses of EPA in the presence of rFSH produced a stimulatory effect on expres- sion level of PPARγ (2.15-fold, P=0.001) and a suppressive effect (0.56-fold, P=0.01) on the expression level of CYP-19, only in the PCOS GC. Conclusion EPA and FSH signaling pathway affect differentially on the gene ex- pression levels of PPARγ and CYP-19 in PCOS GC. Altered FSH-induced PPARγ activity in PCOS GC may modulate the CYP-19 gene expression in response to EPA, and possibly modulates the subsequent steroidogenesis of these cells. PMID:26246878

  19. Superovulation in wood bison (Bison bison athabascae): Effects of progesterone, treatment protocol and gonadotropin preparations for the induction of ovulation.

    PubMed

    Palomino, J Manuel; Cervantes, Miriam P; McCorkell, Robert B; Mapletoft, Reuben J; Adams, Gregg P

    2016-04-01

    Experiments were done to determine the ovarian response and embryo production following superstimulation of wood bison. In Experiment 1 (Anovulatory season), the efficacy of pLH vs. hCG for inducing ovulation was compared in wood bison superstimulated with a single dose of pFSH in 0.5% hyaluronan and the effect of exogenous progesterone (PRID) on superovulatory response and embryo quality was examined. In Experiment 2 (Ovulatory season), the efficacy of pLH vs. hCG for the induction of ovulation was compared in wood bison superstimulated with pFSH in a single intramuscular dose vs. a two-dose regimen 48 h apart (split dose) in 0.5% hyaluronan. In Experiment 1, the number of CL was greater (P < 0.05) in bison treated with hCG than pLH (6.6 ± 1.8 vs. 2.8 ± 0.8) and in those that were not given PRID (6.0 ± 1.5 vs. 2.7 ± 1.0). There was no effect of progesterone treatment on embryo quality. In Experiment 2, the number of CL was greater (P < 0.05) in bison treated with hCG than with pLH (6.3 ± 0.8 vs. 3.8 ± 1.2) and in bison superstimulated with split dose vs. single dose of FSH (7.1 ± 0.9 vs. 3.0 ± 0.8). The number of ova/embryos and freezable embryos did not differ among groups in either experiment. In conclusion, hCG induced a greater ovulatory response than pLH in both seasons. Two doses of FSH induced the greatest superovulatory response during the ovulatory season. Exogenous progesterone did not improve embryo quality during the anovulatory season. PMID:26898393

  20. Alterations in Hormone Levels After Adjuvant Chemoradiation in Male Rectal Cancer Patients

    SciTech Connect

    Yoon, Frederick H.; Perera, Francisco Fisher, Barbara; Stitt, Larry

    2009-07-15

    Purpose: To evaluate follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels after postoperative chemoradiation in men with rectal cancer. Methods and Materials: Forty-three men with rectal cancer had baseline and postchemoradiation FSH, LH, and testosterone measured. Adjuvant chemoradiation consisted of two 5-day cycles of bolus 5-fluorouracil (5-FU) every 4 weeks at a dose of 500 mg/m{sup 2}/d followed by concurrent chemoradiation followed by two additional 5-day cycles of 5-FU at a dose of 450 mg/m{sup 2}/d. Continuous-infusion 5-FU at 225 mg/m{sup 2}/d was given during radiation. Pelvic radiation consisted of a three- or four-field technique with a median dose of 54.0 Gy in 30 fractions. Results: Median follow-up was 6.1 years. Mean baseline FSH levels increased from 5.3 to a peak of 23.9 IU/L (p < 0.001) 13-24 months after chemoradiation. Mean baseline LH levels increased from 4.3 to a peak of 8.5 IU/L (p < 0.001) within 6 months after chemoradiation. Mean testosterone levels decreased from 15.4 nmol/L at baseline to 8.0 nmol/L more than 4 years after chemoradiation. Mean testosterone to mean LH ratio decreased from 4.4 at baseline to 1.1 after 48 months posttreatment, suggesting a continued decrease in Leydig cell function with time. Testicular dose was measured in 5 patients. Median dose was 4 Gy (range, 1.5-8.9 Gy). Conclusions: Chemoradiation in men with rectal cancer causes persistent increases in FSH and LH levels and decreases in testosterone levels.

  1. Changes in plasma gonadotrophin and prolactin concentrations following castration of the pony stallion.

    PubMed

    Collingsworth, M G; Fuller, Z; Cox, J E; Argo, C M

    2001-03-15

    Concentrations of gonadotrophins and prolactin were recorded in pony stallions castrated during the early breeding season, to examine the regulatory role of the gonad at a time when testosterone has been postulated to exert positive feedback on LH secretion. Further, gonadotrophin concentrations in geldings are reported to return to values within the normal range of the entire stallion. In an attempt to characterize this species-specific reversal, the gonadotrophin concentrations of 6 male ponies castrated on 25 March were monitored for 4 months, and 4 stallions were used to generate control data. Blood samples were collected daily, from 3 d before to 10 d after castration (Day 0), and weekly thereafter until Day 122. The pituitary response to castration was immediate. Castration resulted in a previously unreported, dramatic (13-fold) but transient (3 d) surge in circulating concentrations of LH. Concentrations of LH and FSH increased in a logarithmically scaled (LH, R2 = 0.77; FSH, R2 = 0.93) manner over the subsequent 5 wk, during which temporal changes in concentrations of both hormones were strongly correlated (R2 = 0.97). The ratio of plasma gonadotrophin concentrations was consistent throughout (LH:FSH, 1.43 +/- 0.04). Maximal concentrations of LH (20.58 +/- 1.97 ng/mL, Day 34.8 +/- 3.2) were attained approximately 2 wk before the peak in FSH (16.99 +/- 1.97 ng/mL, Day 49.7 +/- 3.0). Plasma gonadotrophin concentrations exceeded those of entire stallions throughout the study. The equine testes inhibited LH secretion during the early breeding season, and no chronic decrease in plasma gonadotrophin concentrations was recorded. However, the LH surge evident for 3 d immediately afer castration, may be related to the dynamic seasonal interaction between gonadal steroids and the regulation of pituitary gonadotrophin release. PMID:11322243

  2. Pituitary-gonadal hormones during prolonged residency in Antarctica

    NASA Astrophysics Data System (ADS)

    Sawhney, R. C.; Malhotra, A. S.; Prasad, Rajendra; Pal, Karan; Kumar, Rajesh; Bajaj, A. C.

    Plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL) and testosterone levels were measured in nine eugonadal men in New Delhi and during the 1st week of different months of their stay at Dakshin Gangotri in Antarctica. During their 12-month stay in Antarctica, they were exposed to a severely cold climate, long polar nights and polar days, high wind velocity, increased amounts of solar and ultraviolet radiation and geomagnetism, as well as physical and social isolation. Plasma testosterone tended to increase in March, but a significant increase (P<0.05) was not seen until April. The mean testosterone levels in May, June, September and November were also significantly higher than the March or New Delhi values. The absolute values of LH, FSH and PRL did not show any month-to-month changes in Antarctica. However, when the hormone levels were expressed as a percentage of the individual annual Antarctic mean, significant differences as a percentage of the individual annual Antarctic mean, significant differences were observed. The testosterone peak in April, May and June was associated with an increase in LH. The nadirs of testosterone, LH, FSH and PRL were seen in either July or August. FSH showed the highest values in March, whereas the highest PRL values were seen in November. These observations suggest the presence of circannual variations in gonadotropin, PRL and LH in Antarctica which are independent of polar days and polar nights. It appears that factors other than the duration of daylight might be involved in regulating these changes. The significance of maintenance of testosterone levels in the supra-physiological range in Antarctica remains unknown but may be important in acclimatization/habituation to the extreme polar cold by increasing basal metabolic rate, protein synthesis and erythropoiesis.

  3. The aryl hydrocarbon receptor is required for normal gonadotropin responsiveness in the mouse ovary

    SciTech Connect

    Barnett, Kimberly R.; Tomic, Dragana; Gupta, Rupesh K.; Babus, Janice K.; Roby, Katherine F.; Terranova, Paul F.; Flaws, Jodi A.

    2007-08-15

    The aryl hydrocarbon receptor (AHR) mediates the toxicity of a variety of environmental chemicals. Although little is known about the physiological role of the AHR, studies suggest that it plays an important role in regulating ovulation because Ahr deficient (AhRKO) mice have a reduced number of ovulations compared to wild-type (WT) mice. The reasons for the reduced ability of AhRKO mice to ovulate are unknown. Normal ovulation, however, requires estrous cyclicity, appropriate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and LH and FSH responsiveness. Thus, the purpose of this study was to test the hypothesis that Ahr deletion regulates ovulation by altering cyclicity, FSH and LH levels, follicle-stimulating hormone receptor (Fshr) and luteinizing hormone receptor (Lhcgr) levels and/or gonadotropin responsiveness. The data indicate that AhRKO and WT mice have similar levels of FSH and LH, but AhRKO mice have reduced Fshr and Lhcgr mRNA levels compared to WT mice. Furthermore, AhRKO ovaries contain fewer corpora lutea compared to WT ovaries after 5 IU equine chorionic gonadotropin (eCG) treatment. Lastly, both AhRKO and WT mice ovulate a similar number of eggs in response to 5 IU human chorionic gonadotropin (hCG), but AhRKO mice ovulate fewer eggs than WT mice in response to 2.5 IU and 1.25 IU hCG. Collectively, these data indicate that AhRKO follicles have a reduced capacity to ovulate compared to WT follicles and that this is due to reduced responsiveness to gonadotropins. Thus, in addition to mediating toxicity of environmental chemicals, the Ahr is required for normal ovulation.

  4. Bone Morphogenetic Protein 15 in the Pro-Mature Complex Form Enhances Bovine Oocyte Developmental Competence

    PubMed Central

    Sudiman, Jaqueline; Sutton-McDowall, Melanie L.; Ritter, Lesley J.; White, Melissa A.; Mottershead, David G.; Thompson, Jeremy G.; Gilchrist, Robert B.

    2014-01-01

    Developmental competence of in vitro matured (IVM) oocytes needs to be improved and this can potentially be achieved by adding recombinant bone morphogenetic protein 15 (BMP15) or growth differentiation factor (GDF9) to IVM. The aim of this study was to determine the effect of a purified pro-mature complex form of recombinant human BMP15 versus the commercially available bioactive forms of BMP15 and GDF9 (both isolated mature regions) during IVM on bovine embryo development and metabolic activity. Bovine cumulus oocyte complexes (COCs) were matured in vitro in control medium or treated with 100 ng/ml pro-mature BMP15, mature BMP15 or mature GDF9 +/− FSH. Metabolic measures of glucose uptake and lactate production from COCs and autofluorescence of NAD(P)H, FAD and GSH were measured in oocytes after IVM. Following in vitro fertilisation and embryo culture, day 8 blastocysts were stained for cell numbers. COCs matured in medium +/− FSH containing pro-mature BMP15 displayed significantly improved blastocyst development (57.7±3.9%, 43.5±4.2%) compared to controls (43.3±2.4%, 28.9±3.7%) and to mature GDF9+FSH (36.1±3.0%). The mature form of BMP15 produced intermediate levels of blastocyst development; not significantly different to control or pro-mature BMP15 levels. Pro-mature BMP15 increased intra-oocyte NAD(P)H, and reduced glutathione (GSH) levels were increased by both forms of BMP15 in the absence of FSH. Exogenous BMP15 in its pro-mature form during IVM provides a functional source of oocyte-secreted factors to improve bovine blastocyst development. This form of BMP15 may prove useful for improving cattle and human artificial reproductive technologies. PMID:25058588

  5. Influence of stress on gonadotrophin induced testicular recrudescence in the lizard Mabuya Carinata.

    PubMed

    Yajurvedi, H N; Menon, Sneha

    2005-07-01

    Administration (ip) of FSH (10 IU/0.1 ml distilled water (dw)/lizard/alternate days/30 days) to adult male lizards, Mabuya carinata, during the early recrudescence phase of the reproductive cycle caused activation of spermatogenic and steroidogenic activity of the testis, as shown by a significant increase in mean number of spermatogonia, primary spermatocytes and spermatids, and serum levels of testosterone, as compared to initial controls. In addition, there were abundant spermatozoa in the lumen of the seminiferous tubules. Interestingly, administration of a similar dosage of FSH to lizards exposed to stressors (handling, chasing, and noise randomly applied, five times a day for 30 days) resulted in a significant increase in mean number of spermatogonia and primary spermatocytes over initial control values, whereas the number of secondary spermatocytes and spermatids and serum levels of testosterone did not significantly differ from those of initial controls, and were significantly lower than FSH treated normal lizards. Further, spermatozoa were infrequently found in the seminiferous tubules of these lizards. Treatment controls (receiving 0.1 ml dw/lizard/alternate days for 30 days) did not show significant variation in mean number of spermatogonia, spermatocytes and spermatids, and serum levels of testosterone from initial controls. Another group of lizards was exposed to stressors and did not receive FSH. These lizards showed a significant decrease in mean number of secondary spermatocytes compared to treatment controls and all other parameters did not significantly differ from those of both control groups. The results reveal that gonadotrophin-induced spermatogonial proliferation occurs under stressful conditions, whereas progress of spermatogenesis beyond primary spermatocyte stage is impaired due to inhibition (under stress) of gonadotrophin induced steroidogenic activity in M. carinata. PMID:15945072

  6. Opioidergic control of gonadotrophin secretion in the prepubertal gilt during restricted feeding and realimentation.

    PubMed

    Cosgrove, J R; Booth, P J; Foxcroft, G R

    1991-01-01

    Prepubertal gilts, having undergone a 7-day period of feed restriction to a maintenance ration, were allocated to one of 4 treatments; restricted feeding at 09:00 and 17:00 h for an 8th day both with (Group RN) and without (Group R) administration of the opioid antagonist naloxone hydrochloride (1 mg.kg-1 at 09:30 h followed by 0.5 mg.kg-1 at hourly intervals for 7 h), or feed to appetite with (Group ALN) and without (Group AL) naloxone administration. Gilts were bled at 10-min intervals on Day 8 from morning to evening feed and plasma LH, FSH and prolactin concentrations were measured by radioimmunoassay. Compared with Group R gilts, Group AL gilts exhibited significantly (P less than or equal to 0.05) higher mean and maximum LH concentrations and pulsatility, lower prolactin concentrations (P less than 0.05) but no significant difference in FSH secretion. Naloxone significantly depressed the increase in LH after re-feeding (Group ALN) (P less than 0.05). Once again there were no significant effects on FSH secretion. Naloxone also significantly depressed prolactin secretion in feed-restricted gilts (P less than 0.05). These results confirm that re-feeding of feed-restricted prepubertal gilts stimulates an immediate increase in LH secretion and that this elevation is not mediated via a suppression of inhibitory endogenous opioidergic tone. Rather, naloxone treatment appeared to expose a latent inhibition of LH secretion. The control of LH secretion is distinct from that of FSH in this model. PMID:1899888

  7. Induction of ovarian function by using short-term human menopausal gonadotrophin in patients with ovarian failure following cytotoxic chemotherapy for haematological malignancy.

    PubMed

    Chatterjee, R; Mills, W; Katz, M; McGarrigle, H H; Goldstone, A H

    1993-07-01

    Currently no treatment has proved successful in inducing ovarian steroidogenic and/or gametogenic recovery in patients with haematological malignancies treated by cytotoxic chemotherapy once biochemical failure becomes manifest i.e., when FSH levels exceed 40 IU/L. This paper reports two such cases with classical biochemical ovarian failure in which ovarian function was induced by brief stimulation with Human Menopausal Gonadotrophin (HMG). PMID:7693105

  8. Proteomic and functional profiles of a follicle-stimulating hormone positive human nonfunctional pituitary adenoma.

    PubMed

    Wang, Xiaowei; Guo, Tianyao; Peng, Fang; Long, Ying; Mu, Yun; Yang, Haiyan; Ye, Ningrong; Li, Xuejun; Zhan, Xianquan

    2015-06-01

    Nonfunctional pituitary adenoma (NFPA) is highly heterogeneous with different hormone-expressed subtypes in NFPA tissues including follicle-stimulating hormone (FSH) positive, luteinizing hormone-positive, FSH/luteinizing hormone-positive, and negative types. To analyze in-depth the variations in the proteomes among different NFPA subtypes for our long-term goal to clarify molecular mechanisms of NFPA and to detect tumor biomarker for personalized medicine practice, a reference map of proteome of a human FSH-expressed NFPA tissue was described here. 2DE and PDQuest image analysis were used to array each protein. MALDI-TOF PMF and human Swiss-Prot databases with MASCOT search were used to identify each protein. A good 2DE pattern with high level of between-gel reproducibility was attained with an average positional deviation 1.98 ± 0.75 mm in the IEF direction and 1.62 ± 0.68 mm in the SDS-PAGE direction. Approximately 1200 protein spots were 2DE-detected and 192 redundant proteins that were contained in 141 protein spots were PMF-identified, representing 107 nonredundant proteins. Those proteins were located in cytoplasm, nucleus, plasma membrane, extracellular space, and so on, and those functioned in transmembrane receptor, ion channel, transcription/translation regulator, transporter, enzyme, phosphatase, kinase, and so on. Several important pathway networks were characterized from those identified proteins with DAVID and Ingenuity Pathway Analysis systems, including gluconeogenesis and glycolysis, mitochondrial dysfunction, oxidative stress, cell-cycle alteration, MAPKsignaling system, immune response, TP53-signaling, VEGF-signaling, and inflammation signaling pathways. Those resulting data contribute to a functional profile of the proteome of a human FSH-positive NFPA tissue, and will serve as a reference for the heterogeneity analysis of NFPA proteomes. PMID:25809007

  9. Pituitary-gonadal hormones during prolonged residency in Antarctica.

    PubMed

    Sawhney, R C; Malhotra, A S; Prasad, R; Pal, K; Kumar, R; Bajaj, A C

    1998-08-01

    Plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL) and testosterone levels were measured in nine eugonadal men in New Delhi and during the 1st week of different months of their stay at Dakshin Gangotri in Antarctica. During their 12-month stay in Antarctica, they were exposed to a severely cold climate, long polar nights and polar days, high wind velocity, increased amounts of solar and ultraviolet radiation and geomagnetism, as well as physical and social isolation. Plasma testosterone tended to increase in March, but a significant increase (P < 0.05) was not seen until April. The mean testosterone levels in May, June, September and November were also significantly higher than the March or New Delhi values. The absolute values of LH, FSH and PRL did not show any month-to-month changes in Antarctica. However, when the hormone levels were expressed as a percentage of the individual annual Antarctic mean, significant differences as a percentage of the individual annual Antarctic mean, significant differences were observed. The testosterone peak in April, May and June was associated with an increase in LH. The nadirs of testosterone, LH, FSH and PRL were seen in either July or August. FSH showed the highest values in March, whereas the highest PRL values were seen in November. These observations suggest the presence of circannual variations in gonadotropin, PRL and LH in Antarctica which are independent of polar days and polar nights. It appears that factors other than the duration of daylight might be involved in regulating these changes. The significance of maintenance of testosterone levels in the supra-physiological range in Antarctica remains unknown but may be important in acclimatization/habituation to the extreme polar cold by increasing basal metabolic rate, protein synthesis and erythropoiesis. PMID:9780846

  10. Endogenous Sex Hormones Impact the Progression of Subclinical Atherosclerosis in Women during the Menopausal Transition

    PubMed Central

    El Khoudary, Samar R.; Wildman, Rachel P.; Matthews, Karen; Thurston, Rebecca C.; Bromberger, Joyce T.; Sutton-Tyrrell, Kim

    2012-01-01

    Objective To determine whether endogenous sex hormones (estradiol (E2), testosterone (T), sex hormone binding globulin (SHBG), and follicle-stimulating hormone (FSH)) are longitudinally associated with progression of atherosclerosis among women at midlife. Methods 249 Pre- or early peri-menopausal women (42–57 years) from the Study of Women’s Health Across the Nation (SWAN) were followed for up to 9 years (median=3.7 years) and had up to 5 repeated measures of common carotid intima-media thickness (IMT) and adventitial diameter (AD). Linear mixed models were used for statistical analysis. Final models included age at baseline, time since baseline, cycle day of blood draw, race, income, SBP, BMI, insulin resistance index, lipids, C-reactive protein and co-morbidity. Results In final models for IMT, each one log unit decrease in SHBG was associated with a 0.005 mm/year increase in IMT progression (P=0.003). E2, T, and FSH were not associated with level or progression of IMT. For AD, each one log unit decrease in E2 was associated with a 0.012 mm/year increase in AD progression (P=0.04) and each one log unit increase in FSH was associated with a 0.016 mm/year increase in AD progression (P=0.003). T and SHBG were not associated with progression or level of AD. Conclusions Independent of SBP, BMI, lipids and other covariates, lower E2 and SHBG, and higher FSH were associated with increased subclinical atherosclerosis progression in women at midlife. PMID:22981430

  11. Honey and metformin ameliorated diabetes-induced damages in testes of rat; correlation with hormonal changes

    PubMed Central

    Nasrolahi, Ozra; Khaneshi, Fereshteh; Rahmani, Fatemeh; Razi, Mazdak

    2013-01-01

    Background: The global prevalence of diabetes mellitus is on rise. Diabetes-induced oxidative stress has been known to affect liver, pancreas, kidney and reproductive organs pathologically. Honey is a natural product of bee with antioxidant properties. Objective: Current study aimed to analyze the protective effects of Metformin (MF) alone and MF+ natural honey co-administration on diabetes-induced histological derangements in testis of rats. Materials and Methods: Thirty six, mature male Wistar rats were randomly divided into six groups including; control, honey-dosed non-diabetic, diabetes-induced (65 mg/kg, single dose), honey-administrated diabetic (1.0 g/kg/day), Metformin-received diabetic (100 mg/kg/day), Metformin and honey-co-treated diabetic which were followed 40 days. The animals were anesthetized by diethyl ether and the blood samples were collected. The serum levels of testosterone, Insulin, LH and FSH analyzed using antibody enzyme immunoassay method. The testicular tissues were dissected out and underwent to histological analyses. Results: The biochemical analyses revealed that the diabetes resulted in significantly reduced testosterone (p<0.01), LH and FSH (P<0.01, 0.001) levels in serum. Light microscopic analyses showed remarkable (p<0.01) reduction in seminiferous tubules diameter (STD), spermiogenesis index (SPI) and thickness of the epithelium in the diabetic group versus control and co-treated groups. Simultaneous administration of the honey with MF could fairly up-regulate testosterone, LH and FSH levels. The animals in metformin and honey-treated group exhibited with improved tubules atrophy, elevated spermiogenesis index and germinal epithelium thickness. Conclusion: Our data indicated that co-administration of Metformin and honey could inhibit the diabetes-induced damages in testicular tissue. Moreover, the simultaneous administration of metformin and honey up-regulated the diabetes-reduced insulin, LH, FSH and testosterone levels. This

  12. Estrogen positive feedback on LH secretion in transsexuality.

    PubMed

    Gooren, L J; Rao, B R; van Kessel, H; Harmsen-Louman, W

    1984-01-01

    In order to test the hypothesis whether there is variation in hormonal levels or response to hormonal manipulation that could permit a distinction between heterosexuals and transsexuals, we designed the following protocol: Six male-to-female (m-to-f) transsexuals, six heterosexual control females and six female-to-male (f-to-m) transsexuals were given estradiol benzoate (E2B) (4.5 micrograms/kg/12 hr) for five days. In the female population, E2B treatment was initiated on day 5 of the menstrual cycle. In all the subjects blood luteinizing hormone (LH) and follicle stimulating hormone (FSH), estradiol-17 beta (E2) and testosterone (T) levels were measured twice daily. Additionally, LH and FSH responses to LHRH (100 micrograms iv) stimulation prior to and on day 5 of the E2B treatment were evaluated. In the m-to-f transsexuals, T levels decreased sharply and progressively during estrogen treatment, along with a fall in LH and FSH levels. The magnitude of the LH and FSH responses to LHRH stimulation also decreased following estrogen administration. In the heterosexual female controls and in the f-to-m transsexuals, estrogen administration increased LH levels to a minimum of 100% above initial values from day 3 onwards. Interestingly, the magnitude of the LH increase in the f-to-m transsexuals was greater than that of the heterosexual female controls. In both groups, LHRH stimulation resulted in a greater LH response compared to that prior to estrogen treatment. Our present observations, based on blood hormonal levels and responses to hormonal manipulations do not permit a distinction between heterosexual females and f-to-m transsexuals. There was no convincing evidence for the existence of a positive estrogen feedback on LH secretion in m-to-f transsexuals. These results contradict some of the reported hypotheses concerning hormonal alterations in these individuals. PMID:6436856

  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. The Anti-Epileptic Drug Valproic Acid (VPA) Inhibits Steroidogenesis in Bovine Theca and Granulosa Cells In Vitro

    PubMed Central

    Glister, Claire; Satchell, Leanne; Michael, Anthony E.; Bicknell, Andrew B.; Knight, Philip G.

    2012-01-01

    Valproic acid (VPA) is used widely to treat epilepsy and bipolar disorder. Women undergoing VPA treatment reportedly have an increased incidence of polycystic ovarian syndrome (PCOS)-like symptoms including hyperandrogenism and oligo- or amenorrhoea. To investigate potential direct effects of VPA on ovarian steroidogenesis we used primary bovine theca (TC) and granulosa (GC) cells maintained under conditions that preserve their ‘follicular’ phenotype. Effects of VPA (7.8–500 µg/ml) on TC were tested with/without LH. Effects of VPA on GC were tested with/without FSH or IGF analogue. VPA reduced (P<0.0001) both basal (70% suppression; IC50 67±10 µg/ml) and LH-induced (93% suppression; IC50 58±10 µg/ml) androstenedione secretion by TC. VPA reduced CYP17A1 mRNA abundance (>99% decrease; P<0.0001) with lesser effects on LHR, STAR, CYP11A1 and HSD3B1 mRNA (<90% decrease; P<0.05). VPA only reduced TC progesterone secretion induced by the highest (luteinizing) LH dose tested; TC number was unaffected by VPA. At higher concentrations (125–500 µg/ml) VPA inhibited basal, FSH- and IGF-stimulated estradiol secretion (P<0.0001) by GC without affecting progesterone secretion or cell number. VPA reversed FSH-induced upregulation of CYP19A1 and HSD17B1 mRNA abundance (P<0.001). The potent histone deacetylase (HDAC) inhibitors trichostatin A and scriptaid also suppressed TC androstenedione secretion and granulosal cell oestrogen secretion suggesting that the action of VPA reflects its HDAC inhibitory properties. In conclusion, these findings refute the hypothesis that VPA has a direct stimulatory action on TC androgen output. On the contrary, VPA inhibits both LH-dependent androgen production and FSH/IGF-dependent estradiol production in this in vitro bovine model, likely by inhibition of HDAC. PMID:23152920

  15. Effects of selected endocrine disruptors on meiotic maturation, cumulus expansion, synthesis of hyaluronan and progesterone by porcine oocyte-cumulus complexes.

    PubMed

    Mlynarcíková, Alzbeta; Nagyová, Eva; Ficková, Mária; Scsuková, Sona

    2009-04-01

    In most mammals, before ovulation, cumulus cells synthesize a large amount of hyaluronan (HA) that is organized into an extracellular matrix (ECM), which provides an essential microenvironment for in vivo oocyte fertilization. This process is called cumulus expansion. The present study assessed effects of selected endocrine disruptors (bisphenol A, BPA; 4-chloro-3-methyl phenol, CMP; di(2-ethylhexyl) phthalate, DEHP; and benzyl butyl phthalate, BBP) in a range of 100pM-100microM, on follicle-stimulating hormone (FSH)-induced meiotic maturation and cumulus expansion of porcine oocyte-cumulus complexes (OCC) cultured in vitro. Moreover, FSH-stimulated production of hyaluronic acid (HA) and progesterone by cumulus cells was measured. Both phenols, BPA and CMP (100microM), significantly affected meiotic maturation of oocytes. The number of oocytes that underwent germinal vesicle breakdown (GVBD) (78.7% and 72.4%, respectively) as well as the rate of oocytes that reached metaphase II stage (MII) (50% and 53.6%, respectively) after 44h culture were decreased compared to control (89.6% for GVBD and 81.5% for MII). FSH-stimulated expansion of cumulus was altered by the highest concentration of BPA and CMP (70% and 64%, respectively vs. 80.3% in control). Although BPA did not alter FSH-stimulated HA synthesis by cumulus cells, its incorporation within the complex was reduced to a half of control value. Progesterone production by OCC was significantly changed in the presence of BPA or DEHP. Finally, our results provide valuable information that oocyte meiotic progression was adversely affected during in vitro culture with endocrine disruptors. PMID:19162163

  16. Luteinizing hormone induces mouse vas deferens protein expression in the murine ovary.

    PubMed

    Brockstedt, E; Peters-Kottig, M; Badock, V; Hegele-Hartung, C; Lessl, M

    2000-07-01

    The aim of our study was to isolate and identify novel proteins that are involved in the process of ovulation. To achieve this goal we used the technique of proteome analysis. Comparison of ovary protein patterns, obtained by high resolution two-dimensional gel electrophoresis from recombinant FSH (rFSH)- and rFSH + human CG (hCG)-treated mice, showed significant differences in protein spot positions and intensities. Subsequent analysis of one of these proteins was performed by mass spectrometry, resulting in the identification of the mouse vas deferens protein (MVDP). MVDP, which was absent in the two-dimensional gel electrophoresis protein pattern of rFSH-primed mice and appeared 3 h after the hCG surge, is a member of the aldo-keto reductase superfamily and was originally identified in the mouse vas deferens. This is the first study describing MVDP expression and regulation by LH in the ovary. Northern blot analysis of female mice tissues showed that mvdp messenger RNA (mRNA) was only present in adrenal glands and in hCG-treated ovaries. In situ hybridization studies localized the mvdp mRNA unequivocally to ovarian thecal and interstitial cells with an expression profile starting already 1.5 h, and decreasing 24 h, after LH treatment. In the adrenal glands, mvdp mRNA was not regulated by LH and localized in the cells of the zona fasciculata. In murine adrenocortical cells, a recent study proposed a detoxifying role of MVDP. MVDP might fulfill the same function in the ovary; however, because of its strong and early transcriptional induction by LH, it is also possible that MVDP catalyses another important step during the cascade of events occurring at the time of ovulation. PMID:10875260

  17. Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: a systematic review and meta-analysis

    PubMed Central

    Hooper, L.; Ryder, J.J.; Kurzer, M.S.; Lampe, J.W.; Messina, M.J.; Phipps, W.R.; Cassidy, A.

    2009-01-01

    BACKGROUND Hormonal effects of soy and isoflavones have been investigated in numerous trials with equivocal findings. We aimed to systematically assess the effects of soy and isoflavones on circulating estrogen and other hormones in pre- and post-menopausal women. METHODS The Cochrane Library, MEDLINE and EMBASE (plus reviews and experts) were searched to December 2007. Inclusion of randomized or residential crossover trials of soy or isoflavones for 4 or more weeks on estrogens, SHBG, FSH, LH, progesterone and thyroid hormones in women was assessed independently in duplicate. Six percent of papers assessed were included. Data concerning participants, interventions, outcomes, potential effect modifiers and trial quality characteristics were extracted independently in duplicate. RESULTS Forty-seven studies (11 of pre-, 35 of post- and 1 of perimenopausal women) were included. In premenopausal women, meta-analysis suggested that soy or isoflavone consumption did not affect primary outcomes estradiol, estrone or SHBG concentrations, but significantly reduced secondary outcomes FSH and LH [by ∼20% using standardized mean difference (SMD), P = 0.01 and 0.05, respectively]. Menstrual cycle length was increased by 1.05 days (95% CI 0.13, 1.97, 10 studies). In post-menopausal women, there were no statistically significant effects on estradiol, estrone, SHBG, FSH or LH, although there was a small statistically non-significant increase in total estradiol with soy or isoflavones (∼14%, SMD, P = 0.07, 21 studies). CONCLUSIONS Isoflavone-rich soy products decrease FSH and LH in premenopausal women and may increase estradiol in post-menopausal women. The clinical implications of these modest hormonal changes remain to be determined. PMID:19299447

  18. Follicle-stimulating Hormone Regulates Pro-apoptotic Protein Bcl-2-interacting Mediator of Cell Death-Extra Long (BimEL)-induced Porcine Granulosa Cell Apoptosis*

    PubMed Central

    Wang, Xian-Long; Wu, Yi; Tan, Lu-Bin; Tian, Zhen; Liu, Jing-Hao; Zhu, De-Sheng; Zeng, Shen-Ming

    2012-01-01

    The pro-apoptotic protein Bim (B-cell lymphoma-2 (Bcl-2)-interacting modulator of cell death) has recently been identified and shown to promote cell death in response to several stimuli. In this report, we investigated the role of Bim in porcine follicular atresia. Initially, Bim cDNA was cloned and characterized from porcine ovarian tissue. Porcine Bim had three alternative splicing variants (Bim-extra long, Bim-long, and Bim-short), all containing the consensus Bcl-2 homology 3 domain. We then found the Bim-extra long (BimEL) protein, the most abundant isoform of Bim, was strongly expressed and co-localized with apoptotic (TUNEL-positive) granulosa cells from porcine atretic follicles. Furthermore, overexpression of BimEL triggered apoptosis in granulosa cells. In primary granulosa cell cultures under basal conditions, we observed that BimEL expression was dampened by treatment with follicle-stimulating hormone (FSH). The role of the PI3K/Akt pathway in the regulation of repression was clarified by the use of the PI3K inhibitor, LY294002, and by transfection with Akt siRNA. Forkhead Box Protein O3a (FoxO3a), a well defined transcriptional activator of Bim, was phosphorylated at Ser-253 and inactivated after FSH stimulation. Also, FSH abolished FoxO3a nuclear accumulation in response to LY294002. Finally, chromatin immunoprecipitation assays demonstrated that FoxO3a directly bound and activated the bim promoter. Taken together, we conclude that BimEL induces porcine granulosa cell apoptosis during follicular atresia, and its expression is regulated by FSH via the PI3K/Akt/FoxO3a pathway. PMID:22235114

  19. Chemotherapy-Related Amenorrhea and Menopause in Young Chinese Breast Cancer Patients: Analysis on Incidence, Risk Factors and Serum Hormone Profiles

    PubMed Central

    Liem, Giok S.; Mo, Frankie K. F.; Pang, Elizabeth; Suen, Joyce J. S.; Tang, Nelson L. S.; Lee, Kun M.; Yip, Claudia H. W.; Tam, Wing H.; Ng, Rita; Koh, Jane; Yip, Christopher C. H.; Kong, Grace W. S.; Yeo, Winnie

    2015-01-01

    Purpose In this prospective cross-sectional study on young premenopausal breast cancer patients, the objectives were to: determine the incidences of chemotherapy-related amenorrhea (CRA) and menopause (CRM); identify associated factors; and assess plasma levels of estradiol (E2) and follicular stimulating hormone (FSH) among patients who developed menopause. Methods Eligibility criteria include Chinese stage I-III breast cancer patients, premenopausal, age ≤45 at breast cancer diagnosis, having received adjuvant chemotherapy, within 3–10 years after breast cancer diagnosis. Detailed menstrual history prior to and after adjuvant treatment was taken at study entry. Patients’ background demographics, tumor characteristics and anti-cancer treatments were collected. The rates of CRA and CRM were determined. Analysis was conducted to identify factors associated with CRM. For postmenopausal patients, levels of E2 and FSH were analyzed. Results 286 patients were recruited; the median time from breast cancer diagnosis to study entry was 5.0 years. 255 patients (91.1%) developed CRA. Of these, 66.7% regained menstruation. At the time of study entry, 137 (48.9%) had developed CRM, amongst whom 84 were age ≤45. On multivariate analysis, age was the only associated factor. Among patients with CRM, the median FSH was 41.0 IU/L; this was significantly lower in those who were taking tamoxifen compared to those who were not (20.1 vs. 59.7 IU/L, p<0.0001). The E2 level was <40 pmol/L; there was no difference between those who were still on tamoxifen or not. Conclusion After adjuvant chemotherapy, the majority of young Chinese breast cancer patients developed CRA; ~50% developed CRM, with 61% at age ≤45. Age at diagnosis is the only factor associated with CRM. FSH level may be affected by tamoxifen intake. PMID:26485568

  20. Intracerebroventricular infusion of neuropeptide Y up-regulates synthesis and accumulation of luteinizing hormone but not follicle stimulating hormone in the pituitary cells of prepubertal female lambs.

    PubMed

    Wańkowska, Marta; Lerrant, Yannick; Wójcik-Gładysz, Anna; Starzec, Anna; Counis, Raymond; Polkowska, Jolanta

    2002-02-01

    Neuropeptide Y (NPY) is a putative neuroregulator of the reproductive axis in the central nervous system. In this study we evaluated the effects of central infusion of exogenous NPY on the secretory activity of pituitary gonadotrophic cells in prepubertal lambs. Immature female Merino sheep (n=12) were infused of Ringer solution (control) or 50 microg of NPY to the third ventricle for 5 min and then slaughtered 3 h later. Immunoreactive luteinizing hormone (LH) and follicle stimulating hormone (FSH) cells were localised by immunohistochemistry using antibody raised against LHbeta and FSHbeta. Messenger RNA analyses were performed by in situ hybridisation using sense and antisense riboprobes produced from beta subunits of LH and FSH cDNA clones. The results were generated by computer image analysis to determine the area fraction occupied by immunoreactive and/or hybridising cells and optical density for immunostaining and hybridisation signal. LH in the blood plasma was determined by radioimmunoassay. It was found, that in the lambs infused with NPY the area fraction and optical density for immunoreactive LH cells and mRNA LHbeta-expressing cells increased significantly (P<0.001), compared to the vehicle-infused animals. The concentration of LH in the blood plasma did not differ between control and treated groups. The NPY infusions had no effect on the immunoreactivity of FSH cells or on expression of mRNA for FSHbeta. In conclusion we suggest that NPY may be an important component of mechanisms stimulating the synthesis and storage but not the release of LH in the pituitary gonadotrophs from prepubertal female sheep. In addition, this effect is specific for LH, no such effect was apparent on FSH. PMID:11841917

  1. Thiofluorographene-hydrophilic graphene derivative with semiconducting and genosensing properties.

    PubMed

    Urbanová, Veronika; Holá, Kateřina; Bourlinos, Athanasios B; Čépe, Klára; Ambrosi, Adriano; Loo, Adeline Huiling; Pumera, Martin; Karlický, František; Otyepka, Michal; Zbořil, Radek

    2015-04-01

    We present the first example of covalent chemistry on fluorographene, enabling the attachment of -SH groups through nucleophilic substitution of fluorine in a polar solvent. The resulting thiographene-like, 2D derivative is hydrophilic with semiconducting properties and bandgap between 1 and 2 eV depending on F/SH ratio. Thiofluorographene is applied in DNA biosensing by electrochemical impedance spectroscopy. PMID:25692678

  2. Predicting pregnancy in women undergoing in-vitro fertilization with basal serum follicle stimulating hormone levels between 10.0 and 11.9 IU/L

    PubMed Central

    Levin, Dan; Jun, Sunny H.; Dahan, Michael H.

    2015-01-01

    Objective To evaluate the results of the in vitro fertilization (IVF) cycle outcomes in women whose borderline basal follicle stimulating hormone (FSH) levels were between 10.0 and 11.9 IU/L and to analyze the predictors of pregnancy in this population. Material and Methods A prospective cohort study was performed at an academic teaching hospital; participants were infertile couples in which the women were undergoing IVF treatment and had borderline basal highest FSH levels between 10.0 and 11.9 IU/L. Statistical modeling was performed to determine risk factors for pregnancy and clinical pregnancy. Results A clinical pregnancy rate of 26.5% per cycle and 35% per patient was found in the study population. Among all subjects and non-intracytoplasmic sperm injection (ICSI) subjects, younger age, higher gravidity, higher number of mature follicles on day of Human Chorionic gonadotrophin (hCG) triggering, higher number of oocytes retrieved, and number of embryos produced were significant discriminators between individuals who conceived and those who did not. However, only the number of embryos predicted those who had a clinical pregnancy when compared with those who did not. Higher gravidity, and basal estradiol (E2) levels, and lower maximum basal FSH levels predicted clinical pregnancy in non-ICSI patients. Among ICSI patients, the only predictor of pregnancy was a thicker endometrium. A trend towards higher pregnancy rates was noted in ICSI patients. Conclusion We showed that pregnancy rates per cycle and per patient in this population were not significantly different than those in patients with a basal FSH level below 10.0 IU/L. Preliminary evidence suggests that ICSI is the fertilization method of choice in these patients. PMID:25788842

  3. Tissue localization of GM-CSF receptor in bovine ovarian follicles and its role on glucose uptake by mural granulosa cells.

    PubMed

    Peralta, O A; Bucher, D; Angulo, C; Castro, M A; Ratto, M H; Concha, Il

    2016-07-01

    The granulocyte-macrophage colony stimulating factor (GM-CSF) is a multifunctional cytokine implicated in proliferation, differentiation, and activation of several cell types including those involved in hematopoiesis and reproduction. In the present study, the expression of the α- and β-subunit genes of GM-CSF receptor during follicular development in cattle was assessed. The spatial association of α- and β-subunits of GM-CSF with follicle stimulating hormone receptor (FSHR) and 3β-hydroxysteroid dehydrogenase (3β-HSD), and the temporal associations with gene expression of hexose transporters (GLUTs) in granulosa cells of cattle were also evaluated. The effect of GM-CSF on the functionality of hexose transporters was also determined in an in vitro primary culture of granulosa cells. The spatial association of subunits of the GM-CSF receptor with 3β-HSD and FSHR suggests a potential steroidogenic regulation of GM-CSF in granulosa cells. Immunodetection of GLUTs and uptake kinetic assays confirmed expression and functionality of these genes for hexose transporters in granulosa cells of cattle. Treatment of granulosa cells with GM-CSF, FSH or insulin- like growth factor-I (IGF-I) alone increased 2-deoxyglucose (DOG) or 3-0-methylglucose (OMG) uptake; however, when cells were treated with various combination of these factors there were no additive effect. Unexpectedly, the combination of GM-CSF and FSH decreased DOG uptake compared to FSH treatment alone. Thus, the expression pattern of GM-CSF receptor subunit genes during follicle development in cattle and promotion of DOG and OMG uptake in granulosa cells indicate a role for GM-CSF, FSH and/or IGF-I alone in regulating granulosa cell metabolic activity, specifically by promoting glucose uptake. PMID:27236376

  4. A Carboxyl-terminal Sequence in the Lutropin β Subunit Contributes to the Sorting of Lutropin to the Regulated Pathway*

    PubMed Central

    Jablonka-Shariff, Albina; Pearl, Christopher A.; Comstock, Anna; Boime, Irving

    2008-01-01

    Although synthesized in the same pituitary gonadotropes, the secretion profiles of lutropin (LH) and follitropin (FSH) differ. LH is secreted through a regulated pathway and associated with a bolus release at mid-estrous cycle. In contrast, the majority of FSH is secreted constitutively with an incremental increase until ovulation. Both share an identicalα subunit, and thus theβ subunit contains determinants for sorting into the regulated pathway. Previously, we demonstrated that a hydrophobic carboxyl-terminal heptapeptide of the LHβ subunit (Leu-Ser-Gly-Leu-Leu-Phe-Leu), not found in the FSHβ subunit, influences the intracellular behavior of the LH dimer. To test the hypothesis that the peptide contributes to differential sorting, we monitored the fates of LH and LHΔT (LHβ subunit lacking the carboxyl-terminal seven amino acids) dimers in the rat somatotrope-derived GH3 cell line in which both the regulated and constitutive secretory pathways operate. Pulse-chase labeling demonstrated that the LHΔT dimer was diverted to the constitutive pathway, resulting in a significant decrease in the corresponding intracellular pool. Forskolin stimulated LH dimer release 3-fold, which was accompanied by a parallel decrease of intracellular LH; only marginal forskolin stimulation of LHΔT was seen. Immunofluorescence after cycloheximide treatment demonstrated decreased retention of LHΔT compared with LH, consistent with increased constitutive secretion of LHΔT. We also demonstrated that fusing the heptapeptide to the carboxyl terminus of the FSHβ subunit resulted in an increased regulated secretion of this FSH analog compared with wild-type FSH. These data are the first to identify a novel structural determinant responsible for the sorting of a member of the glycoprotein hormone family into the regulated secretory pathway. PMID:18292086

  5. Effects of Exendin-4 on Male Reproductive Parameters of D-Galactose Induced Aging Mouse Model

    PubMed Central

    Ahangarpour, Akram; Heidari, Hamid

    2014-01-01

    Purpose The purpose of this study was to evaluate the role of exendin-4 on reproductive alteration in a D-galactose-induced aging mouse model. Materials and Methods In this experimental study, 72 male Naval Medical Research Institute mice (20~25 g) were randomly divided into six groups: control, exendin-4 (1 nmol/kg), exendin-4 (10 nmol/kg), D-galactose (500 mg/kg), D-galactose+exendin-4 (1 nmol/kg), and D-galactose+exendin-4 (10 nmol/kg). The aging model animals were gavaged with D-galactose for six weeks, and exendin-4 was injected intraperitoneally in the last 10 days. At the end of treatment serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels were evaluated and the cauda epididymis and testis were removed to analyze the sperm count and testis morphology. Results The testis weight and volume decreased in the D-galactose group (p<0.01 and p<0.05) respectively. Exendin-4 (1, 10 nmol/kg) increased these parameters in the normal and aging mouse models. Serum LH and FSH levels increased and the sperm count decreased in the D-galactose group (p<0.05). Further, exendin-4 (1 nmol/kg) decreased LH and FSH levels and increased the serum testosterone level and sperm count in both normal and aging animals. Conclusions D-galactose can induce aging alternations in the male reproductive system such as decreased sperm count and increased serum LH and FSH levels through reactive oxygen species over production and reduced antioxidant enzyme activity. Further, co-administration of exendin-4 reduced reproductive complications of D-galactose in an aging mouse model. PMID:25606567

  6. Chromosome banding studies in two patients with XXXXY syndrome.

    PubMed Central

    Levy, C L; Sparkes, R S; Carlson, H E

    1978-01-01

    In 2 adult male patients with 49 chromosomes, an XXXXY sex chromosome constitution was confirmed by trypsin-Giemsa banding sites. Clinical findings as well as fingerprint ridge counts were typical of the syndrome. Primary hypogonadism was documented by finding low serum testosterone and raised serum LH and FSH levels. Several radiological abnormalities, not previously described in this syndrome, were seen in 1 patient. Images PMID:568665

  7. Sheehan's Syndrome A Case Report and Literature Review

    PubMed Central

    Errarhay, S; Kamaoui, I; Bouchikhi, C; Châara, H; Bouguern, H; Tizniti, S; Melhouf, A; Banani, A

    2009-01-01

    Post-partum pituitary necrosis (Sheehan's syndrome) is a rare complication of post-partum hemorrhage. The diagnosis can be erratic and often delayed. In this case report of Sheehan's syndrome in the post-partum period, the signs were characterized by agalactia, severe hypoglycemia, and low serum levels of thyroid hormones, cortico-adrenal hormones, and gonadotrophin (FSH, LH). The hypophyseal magnetic resonance imaging confirmed the diagnosis of hypopituitarism secondary to pituitary necrosis. PMID:21483515

  8. Sheehan's Syndrome A Case Report and Literature Review.

    PubMed

    Errarhay, S; Kamaoui, I; Bouchikhi, C; Châara, H; Bouguern, H; Tizniti, S; Melhouf, A; Banani, A

    2009-01-01

    Post-partum pituitary necrosis (Sheehan's syndrome) is a rare complication of post-partum hemorrhage. The diagnosis can be erratic and often delayed. In this case report of Sheehan's syndrome in the post-partum period, the signs were characterized by agalactia, severe hypoglycemia, and low serum levels of thyroid hormones, cortico-adrenal hormones, and gonadotrophin (FSH, LH). The hypophyseal magnetic resonance imaging confirmed the diagnosis of hypopituitarism secondary to pituitary necrosis. PMID:21483515

  9. Pubertal development in the male pig: effects of treatment with a long-acting gonadotropin-releasing hormone agonist on plasma luteinizing hormone, follicle stimulating hormone and testosterone.

    PubMed Central

    Trudeau, V L; Meijer, J C; Erkens, J H; van de Wiel, D F; Wensing, C J

    1992-01-01

    The effects of a long-acting gonadotropin-releasing hormone (GnRH) agonist, [D-Trp6]-GnRH (GnRH-A) on developmental profiles of plasma luteinizing hormone (LH), follicle stimulation hormone (FSH) and testosterone (T), and pituitary responsiveness to exogenous GnRH were studied in male Dutch Landrace x Large White crossbred pigs from 1 to 30 wk of age. Group 1 control animals (control; n = 12) were injected subcutaneously in the neck with vehicle at 1 and 16 wk of age. Group 2 animals (early treatment; n = 10) were injected with 600 micrograms [D-Trp6]-GnRH at 1 wk and with vehicle at 16 wk. Group 3 animals (late treatment; n = 8) were injected with vehicle and 3 mg GnRH-A at 1 and 16 wk, respectively. Group 4 animals (early plus late treatment; n = 9) were injected at both 1 and 16 wk with GnRH-A. Blood was collected by brachiocephalic puncture at weekly or biweekly intervals, and through brachiocephalic cannulae, to determine longitudinal profiles of LH, FSH and T, and plasma gonadotropin responses to intravenous injection of GnRH (0.1 microgram/kg), respectively. In control animals, LH and FSH declined over the first 5 wk of postnatal life and peaked again at 10-14 wk. Levels of both hormones were basal from 18 to 30 wk. Plasma T was high in the first week, declined progressively over the next few weeks and remained low until 24 wk when a transient increment was noted. The LH and FSH responses to acute GnRH stimulation were similar at 7 and 14 wk and declined significantly at 23 wk of age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1534270

  10. Time course of endocrine changes in the hypophysis-gonad axis induced by hypobaric hypoxia in male rats.

    PubMed

    Farias, Jorge Gonzalo; Bustos-Obregón, Eduardo; Tapia, Pablo Jose; Gutierrez, Eduardo; Zepeda, Andrea; Juantok, Camila; Cruz, Gonzalo; Soto, Gustavo; Benites, Julio; Reyes, Juan Guillermo

    2008-02-01

    Chronic hypobaric hypoxia (CHH) induces a decrease in sperm output and spermatogenesis in male rats. The mechanisms that underlie these changes in testicular function are unknown and could involve changes in the hypophysis-gonad axis. We have tested the hypothesis that changes take place in the endocrine status (FSH, follicle stimulating hormone; LH, luteinizing hormone; testosterone) of rats subjected to CHH. Male Wistar rats were maintained under normobaric or hypobaric conditions (428 torr, 4,600 m). On days 0, 5, 15 and 30 post-exposure, 12 rats were anesthetized, their body weights were measured and blood samples were collected. The testicles were fixed in 4% formaldehyde and processed for histological analysis. In this time course, the FSH levels rose by day 5 post-exposure. On subsequent days, the FSH levels decreased in rats subjected to CHH with a tendency to remain higher than the normoxic group. The LH plasma levels decreased in rats exposed to CHH. Consistent with the decrease in LH levels, the plasma testosterone level decreased significantly after 30 days of CHH exposure. Integrated analysis of hormonal changes in rats subjected to CHH and the body dehydration that occurs in HH allows us to conclude that the effects of CHH on spermatogenesis may be partially related to changes in the hypophysis-gonad hormonal axis. PMID:17984574

  11. Effects of Prenatal Dexamethasone on the Rat Pituitary Gland and Gonadotropic Cells in Female Offspring.

    PubMed

    Ristić, Nataša; Severs, Walter; Nestorović, Nataša; Jarić, Ivana; Manojlović-Stojanoski, Milica; Trifunović, Svetlana; Pendovski, Lazo; Milosević, Verica

    2016-01-01

    Glucocorticoids have a strong influence on growth and maturation of fetal organ systems, but overexposure to exogenous glucocorticoids may retard fetal growth and alter developmental processes in sensitive tissues. The aim of this study was to specifically determine whether prenatal exposure to dexamethasone (Dx) altered normal development and function of pituitary gonadotropic cells in neonatal, infant and peripubertal female offspring. On day 16 of pregnancy, rat dams received 1.0 mg Dx/kg body weight (BW) s.c., followed by 0.5 mg Dx/kg BW on days 17 and 18 of gestation. Control gravid females received the same volume of saline. Female offspring were sacrificed on days 5, 16 and 38 after delivery. The volume of the pituitary gland estimated using Cavalieri's principle was significantly reduced (p < 0.05). Using a fractionator-physical disector method, we found reduced total numbers of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) cells (p < 0.05), accompanied by a decrease (p < 0.05) in serum concentrations of FSH and LH, while the relative intensity of FSH and LH immunofluorescence remained unchanged in neonatal, infant and peripubertal female offspring prenatally exposed to Dx. The data document that overexposure to Dx during fetal development evokes developmental programming of the female reproductive system at the pituitary cellular level, which may be associated with impaired reproductive function. PMID:26950885

  12. Effectiveness of Acupuncture for Primary Ovarian Insufficiency: A Systematic Review and Meta-Analysis

    PubMed Central

    Lee, Hyangsook

    2015-01-01

    Objective. This systematic review aimed to assess current evidence from randomized controlled trials (RCTs) on the effects of acupuncture for patients with primary ovarian insufficiency (POI). Methods. We searched twelve databases to identify relevant studies published before July 2014. The outcomes were serum follicle-stimulating hormone (FSH) levels and resumption of menstruation. Two reviewers independently assessed the risk of bias using the Cochrane's tool, extracted the results, and evaluated the overall level of the evidence using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Results. Eight RCTs were selected. Acupuncture significantly lowered serum FSH levels and more women receiving acupuncture reported resumption of menses. However, the results should be interpreted with caution due to a small number of participants, high risk of bias for blinding, and likely publication bias. The level of evidence for FSH level and resumption of menses were assessed as “low” using GRADE. Conclusion. The current evidence on acupuncture for POI is insufficient to draw a firm conclusion due to scarcity of studies with a low risk of bias and likely publication bias. Further rigorously designed and conducted studies are needed to confirm the effectiveness and safety of acupuncture in patients with POI. PMID:26089949

  13. The significance of antral follicle size prior to stimulation in predicting ovarian response in a multiple dose GnRH antagonist protocol.

    PubMed

    Lai, Qiaohong; Chen, Cai; Zhang, Zhijun; Zhang, Shu; Yu, Qilin; Yang, Ping; Hu, Jun; Wang, Cong-Yi

    2013-01-01

    Prediction of ovarian responses prior to stimulation is not only useful for patient counseling, but also important in tailoring the optimal dosage of gonadotrophin for individual patients. By prospectively study of 214 women undergoing in vitro fertilization and embryo transfer (IVF-ET) treatment, we obtained data supporting that antral follicle size could be an additional valuable predictive marker other than the antral follicle count (AFC) in predicting ovarian response. Our studies revealed that AFC achieved the best predictive value in relation to the number of oocyte obtained, followed by antral follicle size, basal follicle stimulating hormone (FSH) and body mass index (BMI). Unlike AFC, antral follicle size was noted to be negatively correlated with the dosage (R = -0.493) and duration (R = -0.465) of rFSH stimulation. Antral follicle size was also found with higher negative regression coefficient (B = -0.661) as compared with that of basal FSH concentration (B = -0.326) and BMI (b = -0.281). More importantly, women with antral follicle size 6-7 mm showed significantly higher AFC, oocytes retrieved, fertilized oocytes and grade I/II embryos along with much lower transfer cycle cancellation rate (7.5% vs. 16-17%). Together, our data suggest that basal antral follicle size could be a valued predictive marker in women with IVF-ET treatment, in which women with antral follicle size 6-7 mm are likely predisposed to better IVF-ET outcomes. PMID:23330011

  14. A Novel Model for Development, Organization, and Function of Gonadotropes in Fish Pituitary

    PubMed Central

    Golan, Matan; Biran, Jakob; Levavi-Sivan, Berta

    2014-01-01

    The gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are key regulators of the reproductive axis in vertebrates. Despite the high popularity of zebrafish as a model organism for studying reproductive functions, to date no transgenic zebrafish with labeled gonadotropes have been introduced. Using gonadotropin regulatory elements from tilapia, we generated two transgenic zebrafish lines with labeled gonadotropes. The tilapia and zebrafish regulatory sequences were highly divergent but several conserved elements allowed the tilapia promoters to correctly drive the transgenes in zebrafish pituitaries. FSH cells reacted to stimulation with gonadotropin releasing hormone by proliferating and showing increased transgene fluorescence, whereas estrogen exposure caused a decrease in cell number and transgene fluorescence. Transgene fluorescence reflected the expression pattern of the endogenous fshb gene. Ontogenetic expression of the transgenes followed typical patterns, with FSH cells appearing early in development, and LH cells appearing later and increasing dramatically in number with the onset of puberty. Our transgenic lines provide a powerful tool for investigating the development, anatomy, and function of the reproductive axis in lower vertebrates. PMID:25379037

  15. Effect of Rat Medicated Serum Containing You Gui Wan on Mouse Oocyte In Vitro Maturation and Subsequent Fertilization Competence

    PubMed Central

    Jiang, Xiao-Hui; Deng, Yan-li; Lu, Hua; Duan, Heng; Zhen, Xia; Hu, Xiang; Liang, Xin

    2014-01-01

    You Gui Wan (YGW) is a classic herbal formula in traditional Chinese medicine (TCM) used for the clinical treatment of infertility. This study was to explore whether YGW has an impact on mouse oocyte maturation in vitro and subsequent fertilization competence. Rat medicated serum containing YGW was prepared by orally administrating YGW. Mouse immature oocytes were cultured with YGW medicated serum and compared to those cultured with or without normal rat serum or follicle-stimulating hormone (FSH). YGW medicated serum significantly increased the percentages of matured oocytes when compared to the groups with or without normal rat serum (P < 0.01). Furthermore, YGW medicated serum increased the rate of in vitro fertilization (IVF) when compared to the groups treated with FSH and with or without normal rat serum (P < 0.001). YGW medicated serum also had significant effects on the mRNA expressions of PKA, CREB, MAPK, PKC, PKG, and MPF and the concentrations of cAMP, cGMP, and NO in matured oocytes. These results indicate that YGW can promote mouse oocyte maturation and IVF in vitro. Signaling pathways, such as the cAMP/PKA/MAPK, the PKC-MAPK, and the NO-cGMP-PKG pathway, which are similar to those induced by FSH, may be responsible for this action. PMID:25530775

  16. Acetylshikonin from Zicao exerts antifertility effects at high dose in rats by suppressing the secretion of GTH.

    PubMed

    He, Yu; Li, Qisen; Su, Meiling; Huang, Wendong; Zhu, Banghao

    2016-08-01

    Zicao is being highlighted as a promising Chinese medicine due to all the beneficial effects that have been associated with its use. Unfortunately, studies on the toxicity of Zicao in different species are still missing and should be carried out. In this study, we investigated whether Acetylshikonin (AS) from Zicao has an anti-fertility effect through mating experiments and explored its underling mechanism. Sprague-Dawley rats received no treatment or were treated with 120, 360 or 1080 mg/kg AS extract by intragastric administration for 2 weeks. The rat pregnancy rate of the 1080 mg/kg dose group was significantly decreased relative to control group, while it recovered after a month of drug withdrawal, which indicated that the effect of antifertility is reversible. Serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in rat were significantly decreased by AS. The secretion of FSH in rat anterior pituitary cells was decreased but the synthesis was not affected. AS reduced the number of developing follicle and mature follicle in rat ovarian cortical. Maybe all of these resulted from AS decreased the expression of synaptotagmin-1 and SNAP-25 which were the critical proteins of exocytosis. Our data suggested that AS at high dose can suppress the ability of pregnancy of the rats through decreasing serum FSH and LH levels by affecting exocytosis process of gonadotropic hormone (GTH). PMID:27264949

  17. The management of infertility associated with polycystic ovary syndrome

    PubMed Central

    Homburg, Roy

    2003-01-01

    Polycystic ovary syndrome [PCOS] is the commonest cause of anovulatory infertility. Treatment modes available are numerous mainly relying on ovarian stimulation with FSH, a reduction in insulin concentrations and a decrease in LH levels as the basis of the therapeutic principles. Clomiphene citrate is still the first line treatment and if unsuccessful is usually followed by direct FSH stimulation. This should be given in a low dose protocol, essential to avoid the otherwise prevalent complications of ovarian hyperstimulation syndrome and multiple pregnancies. The addition of a GnRH agonists, while very useful during IVF/ET, adds little to ovulation induction success whereas the position of GnRH antagonists is not yet clear. Hyperinsulinemia is the commonest contributor to the state of anovulation and its reduction, by weight loss or insulin sensitizing agents such as metformin, will alone often restore ovulation or will improve results when used in combination with other agents. Laparoscopic ovarian drilling is proving equally as successful as FSH for the induction of ovulation, particularly in thin patients with high LH concentrations. Aromatase inhibitors are presently being examined and may replace clomiphene in the future. When all else has failed, IVF/ET produces excellent results. In conclusion, there are very few women suffering from anovulatory infertility associated with PCOS who cannot be successfully treated today. PMID:14617367

  18. Gonadotropins regulate ovarian germ cell mitosis/meiosis decision in the embryonic chicken.

    PubMed

    He, Bin; Mi, Yuling; Zhang, Caiqiao

    2013-05-01

    Gonadotropins are required for gametogenesis but in embryonic gonads this mechanism is not well understood. Here we use chicken embryos to investigate the mechanism that gonadotropins regulate the ovarian germ cell mitosis/meiosis decision. Treatment with follicle-stimulating hormone (FSH) delayed germ cell meiosis entry and promoted their proliferation. This action was blocked by an aromatase inhibitor. Treatment with luteinizing hormone (LH) accelerated germ cell meiosis entry and promoted transcription of 3βHSDII to increase progesterone (P4) production. In the cultured ovaries, P4 triggered meiotic initiation in germ cells. MiR181a, which acts to downregulate the NR6A1 transcript to inhibit the meiotic initiation, was upregulated by FSH and downregulated by LH. Collectively, gonadotropins regulate germ cells mitosis and meiotic initiation through steroid hormones and a miR181a-mediated pathway. In particularly, FSH delays germ cell meiosis entry and promotes cell proliferation via estrogen while LH accelerates the meiotic initiation via elevated P4 production. PMID:23422072

  19. Highly heterologous region in the N-terminal extracellular domain of reptilian follitropin receptors.