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PubMed2006

Leptin effect on nitric oxide and GnRH-induced FSH secretion from ovine pituitary cells in vitro.

The secretion of gonadotrophins from anterior pituitary cells can be modulated by leptin and signals originating from the immune system, among others, by nitric oxide (NO). There are some studies that have demonstrated a role for leptin and NO in the regulation of FSH in rodents, however, no similar data are available in regards to ewes. Therefore, the objective of the present study was to analyse the leptin effect on GnRH-induced FSH secretion from the ovine anterior pituitary cells in vitro. Additionally, the influence of leptin on NO release and its role in the GnRH and leptin-modulated secretion of FSH from pituitary gland of ewes was investigated. The obtained results show that the influence of leptin on FSH secretion is biphasic. Leptin in concentration 10(-8) and 10(-7) M/l significantly enhances, whereas 10(-6) and 10(-5) M/l of leptin suppresses FSH secretion from the pituitary cells in comparison to the control. The secretion of FSH and NO release under the influence of leptin are in very high positive correlation (r=0.77). The inhibition of NO synthesis with L-NAME., instead, disables leptin from the stimulation of FSH secretion.

Animals↗
PubMed1989

Effect of various doses of FSH upon luteal cell function in tissue culture.

Luteal cells were collected from porcine ovaries in early or midluteal phase of the cycle. The cells were cultured as monolayers for 2 days. The culture medium except that of a control one was supplemented with either 1, 10, 100 or 500 ng of FSH (NIH-FSH-S-8 OVINE) or 1, 10, 100 or 500 ng of FSH pretreated with antiserum anti-LH. Progesterone secretion by the cultures of luteal cells collected from early corpora lutea. However was stimulated by FSH in a dose-response manner when FSH was pretreated with anti-LH serum such progesterone secretion was stimulated to a lesser, although significant (P less than 0.05) extent. In contrast, FSH suppressed the secretion of estradiol by the cultures of the cells of early luteal phase, while the cells collected from the corpora lutea of midluteal phase did not respond to FSH stimulation.

Animals↗
PubMed1988

[Ovarian response and induction of ovulation with human menopausal gonadotropin of different ratio of FSH to LH content in women with ovarian insufficiency].

Human menopausal gonadotropin (hMG) with different ratios of FSH to LH content (FSH: LH = 1.2:1 (GNR 1.2), FSH:LH = 1.6:1 (GNR 1.6), FSH:LH = 3:1 (GNR 3) in biological activity, respectively) was used in this study to examine the effects of these hMGs on ovary, and subsequent follicular maturation and ovulation. In 5 women, 300 IU of hMG (GNR 1.2, GNR 1.6 and GNR 3) was injected in turns during different midfollicular phases of the cycle (day 5-day 9) and serum estradiol (E2) was measured at 0, 24 hrs, 48 hrs, 72 hrs after injection to assess ovarian response to different hMG. Serum E2 response at 24 hrs, 48 hrs, 72 hrs after injection of hMG compared to the preinjected E2 level were 2.2, 1.8, and 1.5 fold with GNR 1.2; 2.6, 2.4 and 1.9 fold with GNR 1.6; and 2.2, 2.4 and 2.3 fold with GNR 3, respectively. These hMGs were administered in turns to women who were suffering from amenorrhea (6 cases), anovulatory (8 cases) and luteal phase dysfunction (10 cases) for treatment of ovarian dysfunction. The mean doses of hMG per cycle required to induce ovulation were 1,125 IU with GNR 1.2, 1,050 IU with GNR 1.6 and 925 IU with GNR 3 in these 24 women. The success rates for ovulation with GNR 1.2, GNR 1.6 and GNR 3 were 70.8, 79.2 and 87.5%. The appearance rates for ovarian hyperstimulation syndrome (OHSS) with GNR 1.2, GNR 1.6, and GNR 3 were 4.2, 8.3 and 8.3%, respectively. These results infer that a different ratio of FSH to LH in hMG has an effect on follicular maturation and ovulation, and that the increase in the rate of ovulation and prevention of OHSS may accompany the regulating of this ratio, and that hMG with a higher FSH content (ratio of FSH to LH is more than three) should be studied further as a promising agent to use in inducing ovulation in women.

Estradiol↗
PubMed1988

The control of FSH secretion.

The secretion of FSH appears to be dominated by factors controlling the inhibition of synthesis and release acting directly at the level of the gonadotrope in the pituitary. Only minimal amounts of GnRH are necessary to stimulate and maintain the secretion of FSH, and, in contrast to LH, the release of FSH is closely linked to the rate of synthesis. Estradiol is a potent inhibitor of FSH release acting directly at the gonadotrope to inhibit mRNA transcription. In vivo, estradiol alone in physiological concentrations cannot maintain plasma concentrations within the normal levels seen during the estrus or menstrual cycle. It is probable that estradiol acts synergistically with inhibin both of which are secreted by the developing follicle. Inhibin secretion in the follicle is dependent on FSH. During the follicular phase in sheep and women peripheral plasma concentrations of inhibin remain unchanged or decline in parallel with those of FSH, and inversely to estradiol. In the luteal phase, the human corpus luteum secretes inhibin under the influence of LH. Thus inhibin together with both estradiol and progesterone secreted by the corpus luteum, accounts for the suppression of FSH and thus follicular development in the luteal phase of the human menstrual cycle.

Animals↗
PubMed1988

[Control mechanism of FSH secretion from the pituitary].

FSH secretion from the pituitary is now generally believed to be controlled only by LH-RH. However, since 1971 I have been publishing lines of evidence suggesting that FSH is controlled by both LH-RH and FSH-RH distinct from LH-RH. Recent accumulated reports suggest that lots of data cannot be explained by the one-RH theory. The one-RH theory means that both LH and FSH are regulated by a sole releasing factor, LH-RH. In 1985 we succeeded in purification of porcine and bovine follicular inhibin for the first time in the world. Its molecular weight was 32,000, which consisted of alpha-subunit (mw 20,000) and beta-subunit (mw 13,000). The site of production of inhibin was confirmed to be granulosa cell by immuno-histochemical technique and to be corpus luteum by RIA. Secretion of inhibin was stimulated by FSH, insulin, platelet extract, dibutyryl c-AMP, cholera toxin, forskolin, and inhibited by cortisol. Testosterone augmented FSH action. In the pituitary cells, inhibin inhibited synthesis of FSH, so cycloheximide could mimicked inhibin action in vitro. Inhibin did not inhibit LH release from the pituitary, but LH release stimulated by LH-RH was also inhibited by inhibin in vitro. Using anti-porcine inhibin antibody and anti bovine inhibin antibody prepared by us, we could measure blood inhibin levels during rat, pig, cow and goat sexual cycles, human menstrual cycle, human pregnancy, and clomiphene-HMG stimulated menstrual cycle. We found maximum blood inhibin levels in the luteal phase and during pregnancy. These high levels of inhibin were demonstrated to be derived from the corpus luteum, pregnant corpus luteum and placenta.(ABSTRACT TRUNCATED AT 250 WORDS)

Activins↗
PubMed1979

Gonadotrophin determination in 24-h-urine by sensitive LH and FSH radioimmunoassays.

Urinary Lutropin (LH) and Follitropin (FSH) were precipitated with acetone and measured by specific radioimmunoassays. Recovery experiments with special regard to urinary pH values were done by adding 125I-labelled LH and FSH to unprocessed urine. At pH 4.5 68.6% of LH and 66.1% of FSH were recovered. Increasing pH values up to 6.0 resulted in a significant recovery loss of 125-I-LH, but not of 125I-FSH. Immunoreactive FSH concentrations decreased significantly 6 and 48 hours after storage began at room temperature. In healthy males and females we found mean LH and FSH concentrations in 24-h-urine which were similar to those reported by others: LH: males: 22.6 IU/24-h; cycling females: 17.8 IU/24-h; postmenopausal females: 49.1 IU/24-h; FSH: males 6.0 IU/24-h: cycling females: 15.0 IU/24-h; postmenopausal females: 48.5 IU/24-h. Because of their high sensitivity and practicability, we believe that these radioimmunoassays are clinically useful approaches in assessment of pituitary and gonadal disorders in human subjects.

Drug Stability↗
PubMed1980

Effects of GnRH and ionic environment on the secretion of LH, FSH and prolactin by dispersed sheep pituitary cells.

Dispersed sheep adenohypophysial cells were used to study the effects of GnRH and ionic environment on LH, FSH and PRL release. The cells were used immediately after they were dissociated from the glands by a combination of gentle mechanical agitation and enzymatic digestion. GnRH caused a log-dose related release of LH and FSH with minimal and maximal effective doses of 10 pg ml-1 and 100 pg ml-1, respectively. Elevated level of K+ stimulated LH, FSH and PRL release. Maximal response was observed with the doses of 30--60 mmol l-1 K+ for LH and FSH, while a dose of 120 mmol l-1 was required for PRL release. The removal of Ca2+ by the addition of EDTA did not affect basal LH and FSH release but resulted in an increase of PRL release. It also abolished the release of LH and FSH induced by GnRH or by a high level of K+ but did not prevent a small and significant additive effect of K+ and GnRH. The release of PRL induced by a high level of K+ was inhibited by Ca2+ removal, but was not completely prevented at the highest K+ concentration used. The results demonstrated that the cells retained their responsiveness to secretagogues for LH, FSH and PRL immediately after dispersion.

Animals↗
PubMed1994

The use of recombinant FSH for ovulation induction.

Recombinant human FSH (recFSH) was tested in a phase II study in 50 couples superovulated for IVF. Rec FSH alone was used in 10 women (Group 1). Intranasal buserelin spray (150 micrograms x 4 daily) was used in a flare-up protocol (10 women; Group 2) or in a desensitization protocol (10 women; Group 3) in combination with rec FSH. Desensitization using Triptorelin depot (3.75 mgIM) followed by rec FSH was given to 10 women (Group 4), while the same agonist was used subcutaneously (200 micrograms/daily) in Group 5 (10 women). In the five groups rec FSH induced multiple follicular growth. Significantly more ampoules rec FSH were required when a GnRH agonist was used. I all groups 9 to 11 mature oocytes were retrieved per cycle. In 6 couples there was an absence of fertilization due to severe sperm anomalies (5 couples); one couple suffered from idiopathic infertility. Fertilization and cleavage was normal in 44 couples. Forty-three transfers of 2.3 to 2.8 embryos yielded 10 pregnancies. Nine healthy babies were born. Superovulation for IVF was successful and safe by using rec FSH alone or in combination with various GnRHa dosages and protocols.

Buserelin↗
PubMed1995

Clinical assessment of recombinant human follicle-stimulating hormone in stimulating ovarian follicular development before in vitro fertilization. Recombinant Human FSH Study Group.

OBJECTIVE: To compare the efficacy and the safety of recombinant human FSH (hFSH) with urinary hFSH for stimulating follicular development in women undergoing IVF-ET. DESIGN: Multicenter, prospective, randomized, open, parallel group, clinical study. SETTING: Eight European academic IVF units and one private IVF unit. PATIENTS: Infertile female patients aged 18 to 38 years suffering from tubal disease, mild endometriosis, or unexplained infertility. INTERVENTIONS: Pretreatment with buserelin acetate was followed by recombinant or urinary hFSH treatment started at an initial dose of 225 IU FSH/d. Dose adjustment was allowed after 5 days of FSH. After administration of hCG, a standard IVF-ET procedure was performed. MAIN OUTCOME MEASURES: Follicular development, oocyte retrieval, fertilized oocytes, duration and dose of FSH, and pregnancy. The hypothesis formulated before the study was that no difference was expected between the two FSH preparations. RESULTS: Sixty patients were treated with recombinant hFSH and 63 with urinary hFSH. The mean number (+/- SD) of growing follicles (mean diameter > 10 mm) was 10.3 +/- 4.9 and 11.2 +/- 5.2, of follicles (mean diameter > 14 mm) was 7.8 +/- 3.6 and 9.2 +/- 4.5, of retrieved oocytes was 9.3 +/- 5.0 and 10.7 +/- 5.3, and of fertilized oocytes was 5.6 +/- 3.8 and 6.5 +/- 4.3, for recombinant and urinary hFSH, respectively. The duration of FSH treatment was 9.9 +/- 2.3 and 9.4 +/- 1.8 days and the average total dose was 2270 +/- 714 and 2095 +/- 591 IU of FSH, for recombinant and urinary hFSH, respectively. Thirteen pregnancies were recorded in the recombinant hFSH group and 11 in the urinary hFSH group. Nine patients delivered 13 live infants in the recombinant hFSH group and eight delivered 13 live infants in the urinary hFSH group. In terms of safety, no difference was recorded between the groups and no anti-FSH antibodies were found in any of the patients. CONCLUSIONS: This clinical study shows that recombinant hFSH is as safe and effective as urinary hFSH in stimulating ovarian follicular development.

Adolescent↗
PubMedDate not supplied

Follicular fluid hormone concentrations after ovarian stimulation using gonadotropin preparations with different FSH/LH ratios. II. Comparison of hMG and recombinant FSH.

OBJECTIVE: A small amount of LH is necessary for 17 beta-estradiol production in the ovarian follicle. Human menopausal gonadotropin (hMG) contains equal amounts of FSH and LH activity, whereas recombinant FSH is a gonadotropin preparation without LH. The aim of the present randomized study was to investigate whether ovarian stimulation treatment with recombinant FSH or hMG resulted in different steroidal composition of follicular fluid. METHODS: Antral fluid from mature follicles was collected in in vitro fertilization cycles and concentrations of testosterone, androstenedione, estrone, estradiol, progesterone, FSH, and LH were determined. Seven patients (27 samples) were treated with hMG, 6 patients (22 samples) with recombinant FSH. RESULTS: Androgen, estrogen, progesterone, and FSH concentrations in follicular fluid tended to be lower in the group treated with recombinant FSH, but the variation was large and differences were statistically not significant. CONCLUSION: Treatment with a gonadotropin preparation containing no LH resulted in adequate androgen and estrogen levels in antral fluid of the ovarian follicle in women with normal endocrine profiles, even during pituitary suppression by a GnRH agonist. Apparently, the amount of endogenous LH was sufficient for steroid production within the follicle.

Adult↗
PubMed2003

Optimization of superovulation induction by human menopausal gonadotropin in guinea pigs based on follicular waves and FSH-receptor homologies.

The guinea pig represents an excellent animal model for the study of reproduction in humans and most domestic animals because unlike the mouse and rat, it undergoes a complete estrous cycle. In this study, we investigated the availability of ovarian oocytes during the estrous cycle, and the follicle stimulating hormone (FSH) receptor (FSH-R) homologies between guinea pigs and other species, in order to identify an effective gonadotropin and optimal time-of-application for the induction of superovulation in the guinea pig. The number of collectable ovarian oocytes showed biphasic changes with peaks at the midluteal and pre-ovulatory stages. On the other hand, the number of oocytes that matured in vitro remained constant ( approximately 10 oocytes) until day 14 post-ovulation and increased thereafter. The deduced amino acid sequence of the guinea pig FSH-R showed greater similarity to the primate FSH-R than to the rodent FSH-R, which suggests that commercially available human menopausal gonadotropin (hMG) may be a better inducer of superovulation in guinea pigs. Indeed, significantly more oocytes (5.4 +/- 1.6, range 0-17, n = 10) were obtained from hMG-treated guinea pigs at the pre-ovulatory stage than during spontaneous ovulation (3.6 +/- 0.1, n = 96; P < 0.05), whereas guinea pigs that received hMG at the midluteal stage (n = 3) did not ovulate. These results indicate that hMG is an effective, albeit stage-dependent, inducer of superovulation in the guinea pig, and that FSH-R homologies should be taken into account when choosing hormones for superovulation.

Amino Acid Sequence↗
PubMed1983

On the mechanism of action of lead in the testis: in vitro suppression of FSH receptors, cyclic AMP and steroidogenesis.

Previous evidence has shown that prenatal and neonatal exposure to low levels of Pb result in decreased FSH binding and steroidogenesis in the testes at the onset of puberty. The purpose of the present study was to determine by in vitro methods, if Pb acts by interfering directly with hormone binding, cyclic AMP production and steroidogenic enzyme activity. Sertoli cells were isolated from testes of prepubertal rats and cultured in the presence of 2.64 x 10(-4)M of either NaAc (control) or PbAc for 1, 4, 24, 48, 96 or 144 hr. There was no reduction in FSH binding and in FSH-induced cyclic AMP after a 1-4 hr exposure to Pb. After a 24-hr exposure to Pb, the cells exhibited a 10-20% decrease in FSH binding and cyclic AMP production and after 96 hr there was a 75% decrease in these 2 parameters. The inhibition was greater in cells from 16 day old than from 20 day old rats, so that in the former, after a 144 hr exposure the FSH-induced cyclic AMP of the Pb exposed cells was only 3% of the amount produced by the NaAc exposed cells (i.e. a 97% inhibition). After in vitro exposure to Pb for 48 hr, the steroidogenic activity (progesterone conversion to steroid metabolites) of Sertoli cells was significantly reduced and their steroidogenesis was no longer stimulated by FSH. A crude testicular enzyme preparation containing 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) exhibited approximately 25% reduction in activity if the assay buffer contained PbCl2 instead of the equivalent in NaCl. Prolonged in vivo exposure to Pb resulted in approximately 50% reduction in 3 beta-HSD activity. This is the first indication that in the testis Pb may act directly (immediate effect) by suppressing enzyme activities, and indirectly (long term effect) by reducing gonadotropin-receptor binding and the resultant cyclic AMP production.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Expression of extracellular domain peptides of the FSH receptor and their effect on receptor-ligand interactions in vitro.

Follicle-stimulating hormone receptor (FSH-R) displays considerable homology to luteinizing hormone receptor (LH-R) in structure and amino acid sequence. Comparison of the sequences of the extracellular domains (ECD) of the receptors reveals two regions (amino acids 4-56 and 265-319 in FSH-R) that share relatively little amino acid sequence similarity. This suggests that these variable regions may be important in providing specificity of ligand binding. We have expressed overlapping ECD peptides containing one or both of these regions (RFI, amino acids 5-125; RF2, amino acids 201-319; and RF3, amino acids 5-319) as fusion proteins in E. coli using pRSET vector. The presence of polyhistidine at the N-terminal end allowed substantial purification of the expressed proteins by a single step of affinity chromatography. The purified peptides were characterized for direct binding of hormone and their ability to block the binding of FSH and LH to the receptors. None of the peptides bound labelled hormone, while all peptides inhibited the binding of FSH to its receptor in a dose-dependent manner. However, only RF2 peptide inhibited ligand binding in a hormone-specific manner. These data suggest there is a site between amino acids 201-319 of the FSH-R ECD that is involved in FSH binding.

Amino Acid Sequence↗
PubMed2006

Developmental changes of FSH-R, LH-R, ER-beta and GnRH-I expression in the ovary of prepubertal ducks (Anas platyrhynchos).

Normal ovarian development is dependent on stimulation of the gonadotropic hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), as well as some regulatory factors locally produced in ovary, e.g. 17beta-estradiol (E2) and gonadotropin-releasing hormone (GnRH), mediated by their respective receptors. In order to elucidate the potential roles of LH, FSH, E2 and GnRH-I during early follicular development in prepubertal ducks, mRNA expression of LH-R, FSH-R, ER-beta and GnRH-I in ovaries of 1-day-old (D1), 30-day-old (D30), 60-day-old (D60) and 90-day-old (D90) ducks was measured with semi-quantitative RT-PCR using beta-actin as an internal standard. The ovary index (the ratio of ovary weight/body mass) did not change from D30 to D90, while the ovary weight and serum E2 levels rose progressively, indicating the prepubertal development of the ovary. Ovarian expression of FSH-R, LH-R, ER-beta and GnRH-I mRNA changed greatly during this period. Abundance of FSH-R and ER-beta mRNA went up gradually from D1 to D60, followed by a decline on D90. LH-R and GnRH-I mRNA expression increased from D1 to D90, reaching a peak at D90. These results indicate that the developing ovary is highly responsive to the regulation of FSH during the early stage, while close to the onset of sexual maturation, the ovary is likely more responsive to LH. In addition, the expression of GnRH-I and ER-beta mRNA in the ovary suggest that GnRH-I and E2 are involved in the regulation of prepubertal follicular development in the ovary of ducks.

Animals↗
PubMed2005

First QSAR report on FSH receptor antagonistic activity: quantitative investigations on physico-chemical and structural features among 6-amino-4-phenyltetrahydroquinoline derivatives.

A quantitative attempt has been made to correlate the structure-activity relationship (SAR) among the recently reported 6-amino-4-phenyltetrahydroquinoline derivatives as antagonists for the Gs-protein-coupled human follicle-stimulating hormone (FSH) receptor. The compounds used for the present study have been reported to show high antagonistic efficacy in vitro using a CHO-hFSHR(luc) assay. Our QSAR investigations revealed a hydrophobic type of interactions between these ligands and the FSH receptor, hence confirming the presence of a lipophilic pocket on the active site of the target structure. The positive coefficient of ClogP variable in our derived QSAR model suggests that more hydrophobic ligands are crucial for their FSH receptor antagonistic efficacy. In exploring the structural requirements among these congeners, we found an amide linkage as conducive to their FSH receptor antagonistic activity. Also, an unsubstituted 4-phenyl ring of the tetrahydroquinoline scaffold is favorable for their FSH receptor antagonistic activity. The results discussed herein could be useful in understanding the nature of interactions of these newly identified ligands as FSH receptor antagonists and in designing more potent ligands based on this novel 6-amino-4-phenyltetrahydroquinoline scaffold.

Models, Chemical↗
PubMed2006

FSH directly regulates bone mass.

Postmenopausal osteoporosis, a global public health problem, has for decades been attributed solely to declining estrogen levels. Although FSH levels rise sharply in parallel, a direct effect of FSH on the skeleton has never been explored. We show that FSH is required for hypogonadal bone loss. Neither FSHbeta nor FSH receptor (FSHR) null mice have bone loss despite severe hypogonadism. Bone mass is increased and osteoclastic resorption is decreased in haploinsufficient FSHbeta+/- mice with normal ovarian function, suggesting that the skeletal action of FSH is estrogen independent. Osteoclasts and their precursors possess G(i2alpha)-coupled FSHRs that activate MEK/Erk, NF-kappaB, and Akt to result in enhanced osteoclast formation and function. We suggest that high circulating FSH causes hypogonadal bone loss.

Animals↗
PubMed2005

Genetic complexity of FSH receptor function.

The interaction between follicle-stimulating hormone (FSH) and the FSH receptor (FSHR) is essential for normal oogenesis and spermatogenesis. Recently, single-nucleotide polymorphisms (SNPs) have been assigned to the FSHR gene. These give rise to different FSHR haplotypes that modify the action of FSH. In women, FSH sensitivities during the menstrual cycle and different cycle lengths are observed, depending on the FSHR haplotype. Thus, SNPs of the FSHR determine the ovarian response and should, therefore, be considered in controlled ovarian hyperstimulation during assisted-reproduction techniques in women with normal ovarian function. In men, the impact of the FSHR SNPs is unclear. The genetic complexity of FSHR should be considered when studying FSH action. These SNPs are one of the first examples in which genetic changes contribute to fine-tuning the endocrine regulation of reproduction. A rational pharmacogenetic approach that combines FSH dose according to the FSHR haplotype is envisaged.

Animals↗
PubMed1996

Functional and clinical consequences of mutations in the FSH receptor.

The follicle-stimulating hormone (FSH) is essential for normal gametogenesis. In females FSH is required for ovarian development and follicle maturation whereas in males FSH determines Sertoli cell number and quantitatively and qualitatively normal spermatogenesis. FSH action is mediated by a G-protein coupled receptor expressed solely in granulosa and Sertoli cells. The FSH-receptor (FSHR) gene is localized on chromosome 2 p21 and spans a region of 54 kb. It consists of ten exons; exon one to nine encode the large extracellular domain and the transmembrane domain is comprised of exon ten. Mutations in the FSHR gene could severely affect gametogenesis and result in infertility. Therefore screening programs have been initiated, in which patients with disturbed fertility were searched for mutations in the FSHR gene. Several Finnish families were identified displaying an inherited pattern of ovarian dysgenesis, a disease leading to streaky underdeveloped ovaries and primary amenorrhea. By genetic linkage the locus of the genetic defect was confined to chromosome 2 p21. Analysis of the FSHR gene resulted in the identification of a mutation (Ala189Val) homozygous in all affected females. Functional studies revealed that the mutation affects the proper protein folding and thereby inactivates the receptor. In a male patient hypophysectomized because of a pituitary tumor, who despite undetectable serum gonadotropins had normal semen parameters, we hypothesized an activating mutation of the FSHR. Screening of exon ten of the FSHR gene resulted in the identification of a Asp567Gly transition in the third intracytoplasmatic loop. Functional studies resulted in a 1.5-fold increase in basal cAMP production compared to wild type FSHR, indicating that the heterozygous mutation leads to a ligand-independent constitutive activation of the FSHR. This patient provides an exceptional model of nature defining the role of FSH in human spermatogenesis. Mutations of the FSHR might have differential effects in each gender. For example activating mutations have not been described in women, therefore it is not clear whether the constitutive activity of the receptor could disturb normal follicular development resulting in certain infertility.

Amino Acid Sequence↗