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PubMed1999

New AccI polymorphism in the follicle-stimulating hormone beta-subunit gene and its prevalence in three Southeast Asian populations.

A thymine-cytosine substitution was identified in exon 3 (codon 76, TAT to TAC) of the human follicle-stimulating hormone (FSH) beta-subunit gene. The nucleotide change led to creation of an AccI digestion site. The frequencies of the A allele (with AccI site) in Chinese (n = 201), Malays (n = 168) and Indians (n = 132) were 0.358, 0.333 and 0.402, respectively. The new FSH beta-subunit marker may be useful in gene tracking and association studies.

Alleles↗
PubMed1993

A tetrapeptide within a receptor-binding region of human follicle-stimulating hormone beta-subunit, hFSH-beta-(34-37), regulates sodium-calcium exchange in Sertoli cells.

In a previous study, we showed that binding of FSH by cultured rat Sertoli cells significantly inhibited basal levels of Na+/Ca2+ exchange. Similar inhibition was observed when proteoliposomes enriched with bovine calf testis follicle-stimulating hormone (FSH) receptors were stimulated with FSH. In the present study, we screened a series of overlapping synthetic peptide amides, representing the entire primary structure of the beta-subunit of hFSH, for their effects on sodium-dependent calcium uptake (as 45Ca2+) by monolayer cultures of Sertoli cells from immature rats. hFSH-beta-(33-53), previously identified as a receptor binding region of hFSH-beta-subunit, significantly (P < 0.05) inhibited Na+/Ca2+ exchange. A tetrapeptide [TRDL, hFSH-beta-(34-37)] contained within this sequence, was observed to be equally as active as hFSH-beta-(33-53) at 200 microM, suggesting that the regulatory effect of hFSH-beta-(33-53) on sodium-dependent 45Ca2+ influx was due to residues 34-37. hFSH-beta-(81-95) also inhibited Na(+)-dependent calcium influx, although to a lesser extent than hFSH-beta-(33-53) or hFSH-beta-(34-37). Sodium-dependent 45Ca2+ entry into Sertoli cells was enhanced in a concentration-related manner when extracellular sodium was replaced by equimolar concentrations (up to 135 mM) of choline chloride. hFSH-beta-(34-37) significantly reduced basal uptake of 45Ca2+ in choline-containing buffer, but was without effect in buffer containing 135 mM NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1988

Identification of a receptor binding region on the beta subunit of human follicle-stimulating hormone.

Mouse epidermal growth factor (mEGF) and the beta subunit of follicle-stimulating hormone (hFSH) (hFSH-beta) have been shown to inhibit binding of intact hFSH to its testes membrane receptor in vitro. Both hFSH-beta and mEGF contain the tetrapeptide sequence Thr-Arg-Asp-Leu (TRDL). Previous results demonstrated that synthetic TRDL inhibited binding of intact hFSH to receptor. We therefore investigated the possibility that TRDL was located on an exposed region of FSH-beta using a polyclonal antiserum to hFSH [NHPP anti-hFSH batch 4 (AB4)] which recognized determinants on intact hFSH and its beta subunit, but not the alpha subunit. Pituitary FSH preparations from several mammalian species produced parallel inhibition curves in a heterologous [AB4 and 125I-labeled ovine FSH (125I-oFSH)] radioimmunoassay with relative potencies similar to those observed for the same preparations assayed by radioligand receptor assay. This antiserum also competitively inhibited 125I-FSH binding to receptor. Thus, AB4 appeared to recognize antigenic determinants that are highly conserved and located at or near regions involved with hormone recognition of receptor for FSH. Synthetic TRDL inhibited 50% of 125I-hFSH binding to antiserum at a concentration of 1.36 mg/tube (9 x 10(-3) M). Other tetrapeptides (Thr-Pro-Arg-Lys and Lys-Thr-Cys-Thr) had no inhibitory activity at comparable concentrations. A mixture of the free amino acids T, R, D, and L inhibited radioligand binding only at significantly higher concentrations than TRDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Pituitary tumorigenesis targeted by the ovine follicle-stimulating hormone beta-subunit gene regulatory region in transgenic mice.

Targeted tumorigenesis in transgenic mice has been a powerful tool for the study of gene expression and oncogenesis, as well as for the production of differentiated immortal cell lines from rare cell types. Follicle-stimulating hormone (FSH) is secreted by the gonadotrope cells of the anterior pituitary gland and plays a pivotal role in mammalian reproduction. Here we have used the regulatory region of the ovine FSH beta gene to direct expression of the SV40 T antigen oncogene to gonadotrope cells in the pituitary of transgenic mice. Two of five transgenic mouse lines bearing this fusion gene rapidly developed pituitary tumors, with appearance of adenomatous foci as early as 6 weeks of age, resulting in death by 12 weeks of age in both genders. Histologic examination of tumor development over time revealed that increases in cell proliferation and dysplasia were accompanied by decreases in synthesis of pituitary hormones, indicating dedifferentiation of the pituitary cells. Histological features observed in these tumors were in agreement with this rapid transformation of cell phenotype. Tumors were multifocal in origin, and the most highly transformed cell types observed consisted of giant pale basophilic cells with enormous hyperploid nuclei associated with infiltrating neuronal-like cells, which were very abundant at later stages of tumor development. Mitotic indices were much higher in transgenic than wild-type pituitaries, as expected. Morphologic analysis of the gonads of these transgenic mice showed no major developmental differences, as compared to wild-type littermates, however the length of the seminiferous tubules in transgenic males was greater than age-matched wild-type animals. Despite this phenotype difference, both genders were fertile, with normal sperm development observed in males and normal estrous cycle stages in females. Moreover, while 8 -- 10-week-old transgenic males had much lower blood levels of FSH than littermates, transgenic female FSH levels were the same as those of wild-type females. These animals offer a unique and potentially useful model of organ-specific tumorigenesis, where a multistage pathway of tumor development is evident, both histologically and temporally. Study of such models will advance our knowledge on the physiological and molecular mechanisms involved in gene expression as well as tumor formation.

Animals↗
PubMed1994

In situ hybridization analysis of anterior pituitary hormone gene expression during fetal mouse development.

We used 35S-labeled oligonucleotides and cRNAs (riboprobes) to detect the temporal order and spatial pattern of anterior pituitary hormone gene expression in (B6CBF1 x B6CBF1)F2 fetal mice from embryonic Day 9.5 (E9.5) to postnatal Day 1 (P1). Pro-opiomelanocortin (POMC) mRNA was expressed in the basal diencephalon on Day E10.5, in the ventromedial zone of the pars distalis on Day E12.5, and in the pars intermedia on Day E14.5. The common alpha-glycoprotein subunit (alpha-GSU) mRNA first appeared in the anterior wall of Rathke's pouch on Day E11.5 and extended to the pars tuberalis and ventromedial zone of the pars distalis on Day E12.5. Thyroid-stimulating hormone-beta (TSH beta) subunit mRNA was expressed initially in both the pas tuberalis and ventromedial pars distalis on Day E14.5, with an identical spatial distribution to alpha-GSU at the time. In contrast, luteinizing hormone-beta (LH beta) subunit and follicle-stimulating hormone beta (FSH beta) subunit mRNAs were detected initially only in the ventromedial pars distalis on Days E16.5 and E17.5, respectively, in an identical distribution to each other. POMC-, alpha-GSU-, TSH beta, LH beta-, and FSH beta-positive cells within the pars distalis all increased in number and autoradiographic signal with differing degrees of spatial expansion posteriorly, laterally, and dorsally up to Day P1. POMC expression was typically the most intense and extended circumferentially to include the entire lateral and dorsal surfaces of the pars distalis. The expression of both growth hormone (GH) and prolactin (PRL) started coincidentally on Day E15.5. However PRL cells localized in the ventromedial area similarly to POMC and the glycoprotein hormone subunits, whereas GH cells were found initially in a more lateral and central distribution within the lobes of the pars distalis. Somatotrophs increased dramatically in number and autoradiographic signal, extending throughout the pars distalis except for the most peripheral layer of cells on Day E17.5. Mammotrophs also increased in number but less abundantly than somatotrophs, and PRL expression remained more confined to central-medial and ventrolateral areas of the pars distalis up to Day P1. These data demonstrate distinctive patterns of expression for each of the major anterior pituitary hormone genes during development of the mouse pituitary gland and suggest that different groups of committed cells are the immediate precursors to the terminally differentiated hormone-secreting cell types.

Animals↗
PubMed1987

Molecular cloning and nucleotide sequence analysis of complementary deoxyribonucleic acid for the beta-subunit of rat follicle stimulating hormone.

To provide a hybridization probe for analysis of the regulation of rat gonadotropin subunit mRNA levels, an effort was made to isolate a cloned cDNA for the beta-subunit of rat FSH (FSH beta). Using a cloned bovine FSH beta cDNA as a hybridization probe, a rat pituitary lambda gt10 cDNA library was screened and a single, strongly hybridizing clone identified. The 874 base pair cDNA insert from this clone contains the complete sequence of rat FSH beta including an amino-terminal precursor segment. Hybridization of this cloned cDNA to rat pituitary RNA demonstrated the presence of an approximately 2.0 kilobase RNA species containing FSH beta sequences. Cloned rat cDNA was also used to demonstrate that estrogen treatment of ovariectomized female rats results in decreases in mRNA concentrations for FSH beta and the beta-subunit of LH with somewhat smaller decreases in alpha-subunit mRNA concentrations. Little or no change was detected in the mRNA for the beta-subunit of TSH.

Amino Acid Sequence↗
PubMed1995

Hormonal regulation of human follicle-stimulating hormone-beta subunit gene expression: GnRH stimulation and GnRH-independent androgen inhibition.

Previous studies from our laboratory demonstrated that chronic testosterone administration to castrated transgenic mice suppressed human follicle-stimulating hormone-beta (FSH beta) mRNA levels transcribed from a human transgene to approximately 20% of control values. In the present study we used primary pituitary cultures prepared from the transgenic mice and in vivo experiments in hypogonadal (hpg) mice carrying the human transgene to assess the role of hypothalamic gonadotropin-releasing hormone (GnRH) in this inhibitory action. The levels of human FSH beta mRNA in monolayer cultures of pituitary cells were decreased by 24-hour treatments with 10 nM testosterone propionate or 5 alpha-dihydrotestosterone to 13 and 26% of control values, respectively, in the absence of GnRH. For the in vivo experiments we introduced the 10-kb human FSH beta transgene into the hpg genetic background by selective crossbreeding. Daily injections of 1 microgram GnRH for 14 days induced expression of the human FSH beta gene in male and female mice. Maximal effects were obtained by GnRH treatment of gonadectomized, hpg transgenic mice. Human FSH beta mRNA levels rose to approximately 4- or 10-fold that of control males and females, respectively. The stimulation was blocked completely by simultaneous administration of testosterone propionate in males and partially by estradiol in females. Pituitary content of immunoreactive FSH paralleled the mRNA changes. These data suggest that testosterone feedback inhibits the human FSH beta subunit gene directly at the pituitary gland in addition to the indirect mechanism of GnRH suppression. Furthermore, the in vitro data indicate that the suppression of human FSH beta gene expression is at least partly a direct androgen effect that does not require aromatization of testosterone to estradiol.

Androgens↗
PubMed1993

Primary amenorrhoea and infertility due to a mutation in the beta-subunit of follicle-stimulating hormone.

We report a woman with primary amenorrhoea and infertility associated with an isolated deficiency of pituitary follicle-stimulating hormone (FSH), but normal luteinizing hormone (LH) secretion. Ovulation was induced by administration of exogenous FSH and resulted in a successful pregnancy. Sequence analysis of the FSH beta-subunit gene indicated that she is homozygous for a two nucleotide frameshift deletion in the coding sequence. Her mother and son are heterozygous for this mutation. This deletion results in an alteration of amino acid codons 61-86 followed by a premature termination codon. The predicted truncated beta-subunit peptide lacks regions which are important for association with the alpha subunit and for binding to and activation of the FSH receptor. Abnormalities of FSH structure or function might be an under recognised but treatable cause of infertility.

Adult↗
PubMed1990

Rapid stimulatory effect of activin-A on messenger RNA encoding the follicle-stimulating hormone beta-subunit in rat pituitary cell cultures.

Activin, a dimer of the beta-subunits of inhibin, stimulates FSH secretion by cultured rat pituitary cells. Both the cell content of FSH and total FSH (secreted plus intracellular) are increased by activin, suggesting an effect on FSH biosynthesis. To test this idea directly, we examined the effect of purified human activin-A of recombinant DNA origin (rhactivin-A) on steady state levels of mRNAs for the gonadotropin subunits in pituitary cell cultures prepared from adult male rats. A preliminary study of the time course of rhactivin-A action indicated that the first significant effect on FSH secretion was observed at 6 h, with maximal stimulation occurring at 24-72 h. A small (20-30%), but significant, increase in LH secretion was also observed by 24 h. For RNA analysis, pituitary cell-cultures were treated for 2-72 h with a maximally effective concentration (50 ng/ml) of rhactivin-A. FSH secretion in rhactivin-A-treated cultures was elevated by 2- to 2.5-fold. Intracellular FSH increased gradually from 24-72 h. Recombinant human activin-A stimulated FSH beta mRNA levels at all times examined; FSH beta mRNA levels in activin-treated cultures were already twice those in control cultures at 2 h, and the magnitude of this effect remained constant up to 72 h. Recombinant human activin-A brought about small increases in secretion and cell content of LH and free glycoprotein alpha-subunit and in LH beta and alpha mRNAs at various times. Thus, the increases in gonadotropin release and cell content stimulated by rhactivin-A can be accounted for by increases in the gonadotropin subunit mRNAs.(ABSTRACT TRUNCATED AT 250 WORDS)

Activins↗
PubMed1999

A synthetic peptide corresponding to amino acid residues 90 to 95 of human follicle-stimulating hormone beta-subunit delays the onset of puberty in female Swiss Webster mice.

We have recently reported that a synthetic peptide corresponding to amino acid residues 81-95, a receptor-binding region of the human FSH-beta-subunit, and a subdomain within this region, hFSH-beta-(90-95) (DSTDCT), prolonged vaginal estrus when administered intraperitoneally (ip) to normally cycling Swiss Webster mice. These results were similar to those we reported for a synthetic peptide corresponding to hFSH-beta-(34-37) [TRDL, a subdomain within receptor-binding region hFSH-beta-(33-53)] in the same model system. TRDL also accelerated the onset of puberty in immature mice. We now report the effects of hFSH-beta-(90-95) in prepubertal female mice. In two separate experiments, a single ip injection of 200 microg/g body weight (BW) hFSH-beta-(90-95) in phosphate buffered saline (PBS, vehicle) administered to mice on day 28 delayed first vaginal estrus by 3 days in 50% (4/8) and 62.5% (6/8) when compared to mice given vehicle alone on day 28. Vaginal opening was also delayed in mice receiving hFSH-beta-(90-95) when compared to mice injected with vehicle alone. Serum estradiol levels of vehicle-injected control mice in first vaginal estrus were three-fold higher than in mice treated with hFSH-beta-(90-95), whose vaginal smears showed no evidence of first estrus. No significant differences in ovarian or uterine weights, or serum progesterone levels, were observed between vehicle-injected control mice achieving first vaginal estrus and mice receiving hFSH-beta-(90-95) in whom first estrus was delayed. The contrasting effects on the onset of puberty of hFSH-beta-(90-95) (delay) and hFSH-beta-(34-37) (acceleration) may reflect synthetic peptide binding to different domains of the FSH receptor, resulting in variable post-binding effects. These results are consistent with our earlier study suggesting that FSH-beta-subunit-related synthetic peptides can induce significant in vivo effects on the onset of puberty in female mice.

Animals↗
PubMed2004

Sequence analysis of cDNA encoding follicle-stimulating hormone and luteinizing hormone beta-subunits in the Mongolian gerbil (Meriones unguiculatus).

To examine the molecular basis for efficient superovulation in the Mongolian gerbil, the cDNA sequences of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) beta-subunits were determined and compared with those of other mammals. FSHbeta and LHbeta cDNAs were 1637 and 507bp long, respectively, from the 5'-end to putative polyA sites. The deduced sequences of the FSHbeta and LHbeta precursor proteins were 129 and 141 amino acids in length, respectively. The amino acid sequences of both Mongolian gerbil hormone subunits showed overall similarity to those of other rodents, confirming that the combination of equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) should be effective for induction of superovulation in Mongolian gerbils, as in mice and rats. However, the use of hCG might need to be re-evaluated owing to its low homology to rodent LH.

Amino Acid Sequence↗
PubMed1989

Gonadotropin-releasing hormone regulates follicle-stimulating hormone beta-subunit gene expression in the male rat.

Since the role of GnRH in the control of FSH release and synthesis is controversial, we have examined the effect of elimination of GnRH action on gonadotropes on FSH beta gene expression, FSH release, and synthesis. GnRH stimulation of the pituitary was abolished by continuous infusion of either a GnRH antagonist or a GnRH antiserum. We also examined the effects of gonadotrope desensitization, using a continuous infusion of GnRH or GnRH agonist analog. FSH beta mRNA levels were determined by dot blot hybridization using rat FSH beta cDNA, and changes were related to pituitary and serum FSH concentrations. FSH beta mRNA levels increased after orchidectomy and correlated well with serum FSH concentrations. Overall FSH synthesis was increased after castration, as judged by elevated serum FSH and unchanged pituitary FSH content. In orchidectomized rats, continuous GnRH antagonist infusion prevented the postcastration rise in FSH beta mRNA levels and serum FSH. Pituitary FSH content was reduced at 7 days, but not at 14 days. In intact rats, GnRH antagonist infusion for 7 days had no effect on FSH beta mRNA levels, but after 14 days, there was a 33% reduction, and serum FSH was suppressed. Pituitary FSH content was decreased after GnRH antagonist treatment for 7 or 14 days. Daily injection of GnRH antiserum for 6 days abolished the increases in FSH beta mRNA levels and serum FSH in orchidectomized rats, but pituitary FSH content was unaffected. In intact rats, GnRH antiserum treatment reduced FSH beta mRNA levels by 38%, suppressed serum FSH, and decreased pituitary FSH content. When gonadotropes were desensitized by a continuous infusion of GnRH for 14 days or GnRH agonist analog for 28 days, FSH beta mRNA levels and pituitary FSH content were markedly reduced, and serum FSH was suppressed to undetectable levels. We concluded that 1) endogenous GnRH is required for the maintenance of FSH beta mRNA levels in both intact and orchidectomized rats; 2) FSH beta mRNA levels are coupled to the level of FSH biosynthesis, indicating the physiological importance of this pretranslational regulation; 3) desensitization is more effective at inhibiting FSH beta gene expression and FSH synthesis than preventing gonadotrope stimulation using the GnRH antagonist or antiserum; and 4) the actions of GnRH on FSH beta mRNA levels are paralleled by its effects on LH beta mRNA levels, suggesting that GnRH provides a common primary stimulus for the induction of both beta-subunit genes in vivo. These data provide further evidence for the crucial stimulatory role of GnRH in the control of FSH synthesis.

Animals↗
PubMed1992

Imbalanced follicle-stimulating hormone beta-subunit hormone biosynthesis in human pituitary adenomas.

Clinically nonfunctioning pituitary adenomas represent approximately 25% of all pituitary tumors. Recent studies using a number of in vitro techniques show that the majority of such tumors produce gonadotropins. Hypersecretion of uncombined gonadotropin subunits by these tumors has also been identified raising the possibility that gonadotropin biosynthetic alterations may occur in neoplastic pituitary tissue. To determine whether underlying intracellular biosynthetic alterations lead to imbalanced secretion of the gonadotropin subunits by such tumors, we investigated 1) steady state gonadotropin-subunit messenger ribonucleic acid (mRNA) levels in tumor tissue from 49 patients with clinically nonfunctioning adenomas, 2) secretion of gonadotropins in dispersed pituitary tumor cultures, and 3) serum concentrations of gonadotropins and free subunits. Northern blots of RNA extracted from surgically obtained pituitary tumor tissue were hybridized with complementary DNA probes for FSH beta, LH beta, and alpha-subunit, and quantitative analysis was done to compare alpha- and beta-subunit biosynthesis in individual tumors. Of these tumors, 47 contained sufficient RNA for Northern analysis and 77% of these tumors contained one or more of the gonadotropin-subunit mRNAs. Steady state alpha-subunit mRNA was detected in 57% of tumors, FSH beta mRNA in 49%, and LH beta in 1 (2%). We found FSH beta mRNA in excess of alpha-subunit mRNA in one-third of tumors, including 9 tumors where alpha-subunit mRNA was undetectable. In cultured cells, FSH beta was secreted in excess of alpha-subunit in 41% of tumors. For those tumors in which both mRNA and culture data were available, FSH beta mRNA and secreted subunit levels were in excess of alpha-subunit in 64% of tumors. We conclude that clinically nonfunctioning pituitary adenomas frequently synthesize excess FSH beta subunit relative to alpha-subunit. This finding is in contrast to previous data in normal pituitary or placental tissue where alpha-subunit is present in excess of beta-subunits at both the mRNA and protein levels. The free-beta-subunit hypersecretion identified in pituitary adenomas may be due to biosynthetic abnormalities intrinsic to neoplastic gonadotrophs.

Adenoma↗
PubMed1997

A synthetic peptide corresponding to amino acid residues 34 to 37 of human follicle-stimulating hormone beta-subunit accelerates the onset of puberty in male and female mice.

We have previously reported that a synthetic peptide amide corresponding to residues 34-37 (TRDL, threonine, arginine-aspartic acid-leucine) of the beta-subunit of human FSH induced prolonged vaginal estrus in normally cycling female mice (see Ref. 15). These results represented the first demonstration of an in vivo effect of a gonadotropin-related synthetic peptide on reproductive processes. We have extended these studies to examine possible effects of TRDL on the onset of puberty in female mice. In two replicated experiments, vehicle-injected control mice attained first vaginal estrus by day 39. An ip injection of 200 ug TRDL/g BW to 28-day-old prepubertal female mice, however, accelerated the onset of first vaginal estrus by 7 days in 11 of 12 (11/12) (Exp 1) and 7/9 (Exp 2) mice. Serum estradiol levels were significantly (P = 0.017) elevated in TRDL-treated mice, whereas progesterone was unchanged. Uteri of TRDL-treated mice were significantly (P = 0.003) heavier than uteri of vehicle-injected control animals of the same age and body weight. Intraluminal fluid accumulation (ballooning) at proestrus was absent in 20/21 TRDL-treated females, as were oviductal ova and ovarian corpora lutea. These phenomena are characteristic of the first estrous cycles of female mice isolated from males. To obtain further evidence for in vivo effects of TRDL, we assessed the ability of TRDL to accelerate the onset of puberty in male mice. When given as five consecutive daily ip injections of 200 ug/g BW to 28-day-old prepubertal male mice, TRDL significantly increased testis weight, when compared with vehicle-injected control mice of the same age and BW (171.3 +/- 3.8 mg vs. 151.6 +/- 4.3 mg, P = 0.001) and induced a 6.5-fold increase in serum testosterone levels. These studies confirm the previously reported in vivo activity of a synthetic peptide corresponding to human FSH-beta subunit 34-37 (TRDL) in adult female mice and extend its effects to the acceleration of the onset of puberty in immature male and female mice.

Amino Acids↗
PubMed2001

Analysis of the testicular phenotype of the follicle-stimulating hormone beta-subunit knockout and the activin type II receptor knockout mice by stereological analysis.

This study evaluated the role of FSH and activin A on testicular function using quantitative stereological analysis of testicular cell types in mice with targeted disruption of genes encoding the FSH beta-subunit and the activin type IIA receptor (ActRIIA). Using the optical dissector technique, the numbers of Sertoli cells and germ cells per testis were determined. Testis weights in homozygous males lacking the FSHbeta gene or the ActRIIA gene were decreased approximately 60% compared with wild-type or respective heterozygotes. Sertoli cell numbers decreased in both homozygous mice by 30-39%, and there was a comparable decline in germ cell numbers in both models. The degree of germ cell attrition increased in the later stages of spermatogenesis from a 46% reduction of spermatogonia to a 60% decrease in round spermatids. As the FSH levels are decreased in both models, the cellular lesion in both is most likely due to the FSH deficiency. Although the decrease in the Sertoli cell complement represents one cause of lower germ cell numbers, the ability of Sertoli cells to nurture germ cells is compromised by the lower FSH levels, as shown by a decrease in the round spermatid to Sertoli cell ratios in both homozygous models. We conclude that the defects in FSH beta-subunit gene knockout and ActRIIA knockout mice are related to diminished FSH action on both Sertoli cell proliferation and the capacity of Sertoli cells to nurture germ cells.

Activin Receptors, Type II↗