Follistatins: more than follicle-stimulating hormone suppressing proteins.
Explore the source record for details and available documents.
Amino Acid Sequence↗
Biomedical subjects
J K Findlay
Publications and source records attributed to J K Findlay.
Active immunization of Merino ewe lambs with recombinant bovine alpha inhibin advances puberty and increases ovulation rate.
Ewe lambs (n = 24-25) were immunized at 3, 7 and 15 weeks of age with recombinant bovine alpha-inhibin (rec inhibin) or with bovine monoclonal antibody purified inhibin (bMPI) obtained by immunochromatography from bovine follicular fluid or with adjuvant alone (control). Antibodies in the plasma of the lambs immunized with the inhibin preparations bound to iodinated 31 kDa bovine inhibin. Binding was minimal after the primary immunization, increased after each booster immunization and remained elevated until at least 45 weeks of age (29% for rec inhibin and 11% for bMPI). Of the group treated with rec inhibin, 10 ovulated as lambs (control 0/22; bMPI 3/21) and onset of overt oestrous activity (as hoggets) was advanced (P < 0.05) by 17 days in lambs immunized with rec inhibin. As hoggets, the ovulation rate was greater (P < 0.01) in the rec inhibin immunized lambs (4.41 +/- 0.67) than in the control animals (1.27 +/- 0.15) but not in the bMPI-treated lambs (1.40 +/- 0.16). After a further immunization at 17 months of age, however, ovulation rate increased (P < 0.01) in the bMPI-immunized group (3.40 +/- 0.47) but was unchanged in the lambs immunized with rec inhibin (2.80 +/- 0.52) and those in the control group (1.15 +/- 0.08). There were no effects of immunization on plasma concentrations of either follicle stimulating hormone (FSH) or luteinizing hormone (LH). The initial smaller response seen with the bMPI may be due to either the presence of compounds other than inhibin in such preparations or the small absolute amount of inhibin injected.(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
Binding sites for interferons on ovine and human endometrial membranes.
In the ewe, the major product of the preimplantation blastocyst is ovine trophoblast protein-1 (oTP-1), which is now classified as an omega-interferon (IFN). Receptors for IFN are present on sheep endometrium and vary cyclically, presumably modified by the actions of ovarian steroids. This study examined whether or not IFN receptors were present on human endometrium at any stage during the menstrual cycle. In addition, the steroid dependence of ovine endometrial IFN receptors was determined. Specific binding of 125I-labelled IFN (125I-IFN) to ovine endometrial membranes was substantially higher than binding to membranes derived from bovine spleen, human placenta or pooled human endometrium (relative specific binding 100:33:36:20). Human endometrial membrane preparations from proliferative-phase tissue showed very little specific binding (mean 0.8 +/- 0.3%, n = 4) in contrast to luteal-phase endometrium (2.1 +/- 0.3%, n = 8). Treatment of ovariectomized ewes with oestradiol-17 beta (E) resulted in significantly increased binding (117 +/- 7%) of 125I-IFN to endometrial tissues compared with tissue from ovariectomized (OvX, 75 +/- 7%), progesterone (P)-treated (69 +/- 7%), or (E + P)-treated (81 +/- 8%) groups (P < 0.05); all were compared with binding to pooled ovine luteal-phase tissue, 100%. There were no differences between the other three groups. Scatchard analysis showed binding affinity of the same order for the sheep and human receptors (Kd = 10(-10) mol L-1) but binding capacity was considerably lower for human (6.0 fmol mg-1) than for sheep (47-123 fmol mg-1) endometrium.(ABSTRACT TRUNCATED AT 250 WORDS)
Amnion↗
A model for follicle selection and the determination of ovulation rate in the ewe.
A model for folliculogenesis is proposed that is based as far as possible on a knowledge of physiological, rather than anatomical, changes taking place during follicle development. The model is therefore functional, rather than descriptive, and consists of five classes of follicles that have been defined by their dependency and sensitivity to gonadotrophins. These classes are: primordial, committed, gonadotrophin-responsive, gonadotrophin-dependent and ovulatory. The model is an attempt to encourage discussion and to promote the integration of morphological models of folliculogenesis with recent advances in the molecular endocrinology of the ovarian follicle. Two hypotheses for the mechanisms that determine ovulation rate are developed in light of the model. In the first, multiple ovulation results when the viability of gonadotropin-dependent follicles is enhanced. In the second, multiple ovulation is caused by increasing the number of gonadotrophin-responsive follicles available for further development; this results from the increasing rate of folliculogenesis and the throughput of follicles. The final section of this paper examines how these two hypothetical mechanisms, which are not mutually exclusive, appear to account for most of the known genetical and environmental effects on ovulation rate of sheep. In particular, the effects of nutrition, genotype, exogenous gonadotrophins, immunity to both oestrogens and androgens, and immunity to inhibin are discussed.
Animal Nutritional Physiological Phenomena↗
An update on the roles of inhibin, activin, and follistatin as local regulators of folliculogenesis.
The local actions of the inhibin-related peptides inhibin, activin, and follistatin in folliculogenesis, luteinization and atresia are reviewed. On the basis of in vitro data, it is concluded that (a) inhibin has a paracrine action positively regulating LH-induced androgen production by theca cells in addition to a peripheral role regulating FSH secretion; (b) activin has a negative paracrine action on LH-induced androgen production by theca cells; (c) activin, either alone or with FSH, has an autocrine action on granulosa cells, promoting differentiation during the preantral and early antral stages of folliculogenesis and preventing premature luteinization in the later stages of antral follicle development, leading overall to promotion and maintenance of the folliculogenic state of the follicle; and (d) follistatin modulates granulosa cell function in favor of luteinization or atresia, and its mechanism of action involves neutralizing the actions of activin by its binding properties and by a direct action of follistatin on progesterone metabolism by granulosa cells. A hypothesis for a role of activin in the acquisition of responsiveness of granulosa cells of preantral follicles to FSH is proposed.
Activins↗
Epidermal growth factor acts directly on the sheep ovary in vivo to inhibit oestradiol-17 beta and inhibin secretion and enhance progesterone secretion.
Epidermal growth factor (EGF) is a potential intra-ovarian modulator of gonadotroph action on differentiated follicular cells. Specific binding sites have been identified in the ovary and functional differentiation in cultured granulosa cells can be modulated by treatment with EGF. The aim of this study was to determine if EGF was capable of altering ovarian function in vivo during the follicular phase of the sheep oestrous cycle. Fourteen cross-bred ewes with ovarian autotransplants were treated with progestagen pessaries for 12 days. Three ewes were infused with murine EGF (mEGF) via the jugular vein (75 micrograms/kg bodyweight per 12 h) during the 12 h preceding progestagen pessary withdrawal, and received an injection of a prostaglandin analogue at 0 h to induce luteolysis. Over the same time-period, two doses of EGF were administered to other groups of ewes by infusion into the ovarian artery (low: 6 micrograms/12 h, n = 3 and high: 60 micrograms/12 h, n = 3). The remaining five ewes were not infused with EGF (controls). Jugular and ovarian venous blood samples were taken at 10-min intervals at two stages during the follicular phase (21-27 h and 38-42 h after pessary withdrawal) and every 2 h from 44 to 76 or 86 h. mEGF, LH, FSH, inhibin, androstenedione, oestradiol-17 beta and progesterone concentrations in plasma were determined using radioimmunoassays. The secretion rates of androstenedione, oestradiol, progesterone and inhibin by the ovary were calculated. EGF acted directly on the ovary in a dose-dependent manner. Oestradiol secretion was inhibited following treatment with EGF but androstenedione secretion was unaffected. EGF appears therefore to act within the granulosa cells to inhibit aromatization. Inhibin secretion was also suppressed by treatment with EGF, though it was not possible to determine if this was caused by a direct or indirect action of EGF on granulosa cells. The rate of progesterone secretion increased in ewes receiving systemic (i.e. via the jugular vein) and high-dose intra-arterial infusions of EGF, even though a preovulatory LH surge was not observed in these animals during the entire experimental period. Concomitant increases in both LH and FSH secretion were associated with these effects of EGF on ovarian function. In conclusion, EGF appears to act directly on the granulosa cells of the follicle to inhibit aromatization and also to inhibit inhibin production. The low levels of oestradiol and inhibin in the presence of high levels of gonadotrophin indicate that atresia may have been induced in medium to large antral follicles.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Radioimmunoassay of FSH-suppressing protein in the ewe: concentrations during the oestrous cycle and following ovariectomy.
A sensitive and specific heterologous radioimmunoassay for FSH-suppressing protein (FSP or follistatin) was applied to ovine plasma. Following a logit-log dose transformation, parallel dose-response lines were observed between purified bovine 35 kDa FSP used as standard and serial dilutions of ewe plasma. Activin-A, inhibin-A and a range of other proteins showed low (< 0.5%) cross-reactivity in the assay. Daily variations in the peripheral concentrations of FSP were measured across the ovine oestrous cycle. The peripheral concentrations of plasma FSP in adult ewes revealed a significant (P < 0.01) increase (33%) during the luteal phase above follicular phase levels, peaking 10 days after the LH surge. FSP concentrations were determined in arterial and venous plasma from the ovary, head, kidney and liver. A significant (P < 0.05) increase across the ovary was detected with no significant differences across the head, liver and kidney. To investigate the relationship between gonadal FSP and the pituitary, ewes underwent ovariectomy and hypophysectomy. FSP levels rose (100-110%, P < 0.01) during the period of surgery for both bilateral ovariectomy and sham ovariectomy, and then decreased significantly (37-44%) at 4-6 h after surgery. A further rise in plasma FSP (180-200% increase above pretreatment levels, P < 0.001) was observed 10-12 h after ovariectomy and sham ovariectomy. FSP levels then returned to preoperative levels during the following 26 h. Plasma FSP levels in long-term ovariectomized and hypophysectomized ewes were not significantly different from preoperative levels. To determine whether the pattern of plasma FSP seen during the ovariectomy study was due to the effect of the induction of anaesthesia, ewes were treated with sodium thiopentone and halothane or 0.9% (w/v) NaCl by procedures of similar duration to that used during surgery. Both treatments resulted in an elevation of FSP levels (33-62%) over pretreatment values only at the time of induction of anaesthesia. To examine further whether this rise in plasma FSP observed after anaesthesia was due to a stress response and therefore under the control of the pituitary-adrenal axis, ewes were treated with ACTH, dexamethasone or saline only. A further group of sheep were exposed to a barking dog for 10 min. No change in FSP levels compared with pretreatment levels or saline-treated controls were noted following any of these treatments.(ABSTRACT TRUNCATED AT 400 WORDS)
Adrenocorticotropic Hormone↗
Immunolocalization of the vasoconstrictor endothelin in human endometrium during the menstrual cycle and in umbilical cord at birth.
OBJECTIVE: Our objective was to determine the localization of immunoreactive endothelin in human cyclic endometrium and in umbilical cord during normal delivery and after cesarean section. STUDY DESIGN: Fixed dated endometrial tissue (n = 41) and umbilical cord (n = 6) were subjected to immunohistochemistry with an antiserum cross reacting with endothelin-1, -2 and -3. RESULTS: Low levels of stromal endometrial staining were seen throughout the cycle. The strongest staining was in luminal epithelium throughout the secretory phase and in glandular epithelium in the late-secretory phase. In umbilical cord the most intense immunoreactivity was present on the amnion cells on the outer cord, with some staining in intermittent cells in the Wharton's jelly and in umbilical vein cells. No differences were detected between cord from normal delivery or cesarean section. CONCLUSION: A paracrine role is suggested for endothelin in regulation of endometrial function and a role in vasoconstriction in the umbilical cord at birth.
Adult↗
Acute effect of PMSG on ovarian androgen-binding sites in the intact immature female rat.
Androgen-binding activity in ovaries containing only immature follicles is compared with that in ovaries stimulated with pregnant mare serum gonadotrophin to induce development of large preovulatory follicles. The androgen-binding sites present in cytosols prepared from unstimulated ovaries exhibited kinetics, affinity and a range of specificities for natural and synthetic androgens consistent with those exhibited by the androgen receptor isolated from androgen-sensitive tissues. Studies of sedimentation and DNA binding suggest that the receptor-like androgen-binding site present in unstimulated ovaries exists as the 'non-activated' form which is able to undergo transformation and bind to nuclear DNA. Properties of the androgen-binding sites isolated from ovaries stimulated with gonadotrophin were very different from those of the androgen receptor present in unstimulated ovaries. Specificity for androgens was reduced, capacity for dihydrotestosterone (DHT) and methyltrienolone (R1881) increased and androgen-binding activity was associated exclusively with the 4.5S form which was not able to bind to nuclear DNA. These data confirm that a shift from a receptor-like to a nonfunctional androgen-binding site is associated with the development of ovulatory follicles and suggest that shifts in androgen-binding populations will determine the response of developing ovarian follicles to androgens.
Androgens↗
Control of inhibin production by dispersed human luteal cells in vitro.
The production of inhibin in vitro by dispersed cells from early to mid (Days 16-19) and late stage (Day 23) human corpus luteum (CL) was examined, and the effects of human chorionic gonadotrophin (hCG), follicle stimulating hormone (FSH), oestradiol and testosterone on inhibin production were determined. Corpora lutea from five subjects in the early to mid luteal stage and three subjects in late luteal stage were dispersed with enzymes and the luteal cells cultured in medium supplemented with 5% calf serum and either FSH (1, 10 or 100 ng mL-1), oestradiol-17 beta (2.5, 5 or 10 micrograms mL-1) or testosterone (0.25, 1 or 5 micrograms mL-1) with or without hCG (1 I.U. mL-1). Cells were cultured for 1 to 3 days without changes of medium, and the concentrations of progesterone, oestradiol and immunoreactive inhibin in the medium were measured by radioimmunoassay. Cells from both types of CL produced inhibin in vitro under basal conditions, but only cells from early to mid CLs responded to hCG with a significant increase in inhibin production. Both progesterone and oestradiol production were stimulated by hCG in both groups of CL. Inhibin concentrations in the cell cultures declined with time in culture, particularly in the late CL group, whereas the concentration of steroids increased. Neither FSH, oestradiol nor testosterone significantly changed inhibin production in either CL group. It was concluded that inhibin production by human luteal cells in vitro is influenced by the age of the CL, and is dependent on LH (hCG) but not on FSH or sex steroids.
Adult↗
Studies in vitro of effects of steroid hormones and the blastocyst on endometrial function in the sheep.
Normal endometrial function is a result of regulation by the combination of ovarian steroids and local agents arising from within the embryo-maternal unit. We have used in vitro techniques to examine the role of steroid hormones and ovine trophoblast interferon on endometrial function in the ewe. Immunolocalization of oestrogen receptors in endometrial tissue demonstrated marked changes throughout the cycle and in early pregnancy with maximal concentrations during the follicular and very early luteal phases. Protein secretion from highly purified cultured ovine stromal and epithelial endometrial cells, and the direction of secretion from polarized epithelial cells, has been examined by incorporation of [35S]methionine and by one- and two-dimensional gel electrophoresis. Protein synthesis is greater in stromal than in epithelial cells and more protein is secreted apically than basally from epithelial cells. A number of common and some different proteins are secreted by the two cell types. One secreted protein is matrix metalloproteinase-3 (stromelysin) which degrades components of basement membranes. Ovine trophoblast interferon attenuates the production of prostaglandins from ovine endometrial cells but its action is not by an effect on localization or concentration of the enzyme prostaglandin synthase or on expression of the gene for prostaglandin synthase. Such studies in vitro contribute to our understanding of how the endometrium is prepared for implantation.
Animals↗
Effects of activin and follicle-stimulating hormone (FSH)-suppressing protein/follistatin on FSH receptors and differentiation of cultured rat granulosa cells.
The aim of this study was to investigate the actions of both activin and FSH-suppressing protein (FSP)/follistatin either alone or in combination on FSH receptor number and on the responsiveness of granulosa cells to FSH and LH. Granulosa cells were harvested from diethylstilbestrol-treated immature Sprague-Dawley rats and cultured 48 h in serum-free medium with or without treatment. Activin treatment alone (3-100 ng/ml) resulted in a 4-fold increase in FSH receptor number with no change in binding affinity. This effect of activin was inhibited 31% by FSP (100 ng/ml) treatment which alone had no effect on FSH receptor number. Treatment with activin (100 ng/ml) prevented FSH-induced down-regulation of FSH receptor number, whereas at lower concentrations (3-30 ng/ml) activin enhanced down-regulation of FSH receptor number by 20% (P less than 0.05). In contrast, FSP alone prevented FSH-induced down-regulation by increasing FSH receptor number up to 40-50%. Pretreatment of granulosa cells with activin, but not FSP, for 24 h increased the responsiveness of cells to FSH (20 ng/ml) and LH (40 ng/ml) shown by increases in aromatase activity, progesterone, and immunoreactive inhibin production over and above control in a manner which depended upon activin doses. We conclude that 1) activin enhancement of FSH action on rat granulosa cells may be mediated in part via regulation of FSH receptor number, and 2) the effects of FSP on granulosa cells are likely to be due to its activin binding properties.
Activins↗
Interaction between activin and follicle-stimulating hormone-suppressing protein/follistatin in the regulation of basal inhibin production by cultured rat granulosa cells.
There is evidence that FSH-suppressing protein (FSP) antagonizes the action of activin on the differentiation of rat granulosa cells by binding activin in vitro. We tested the interaction of activin and FSP in this in vitro system by examining the effects of FSP on activin dose-related stimulation of immunoreactive inhibin release by rat granulosa cells. Granulosa cells (2 x 10(5) viable cells/well) from diethylstilbestrol-treated immature rats were cultured for 48 h in McCoy's 5a serum-free medium with additives and increasing doses of bovine FSP (0-30 nM) and human recombinant activin (0-20 nM). Inhibin was measured in the medium by RIA. Activin caused a dose-related increase in basal inhibin production, which was maximal between 4-10 nM activin (ED50, 0.6 nM). With the addition of FSP, an apparent increase in the ED50 of the activin dose-response curves was observed, but there were no changes in the maximum response. This pattern closely resembled that of chemical antagonism of an agonist by an agent that binds with relatively high affinity to form a biologically inactive complex. Based on this premise, apparent high affinity activin binding to FSP was determined by Scatchard analysis to have a Kd of 0.13 +/- 0.07 nM (mean +/- SD) and to occur in a 2:1 or greater FSP/activin molar ratio. These data support the proposition that the antagonistic effect of FSP on activin is due to the formation of an inactive complex.
Activins↗
Expression of mRNA for follicle-stimulating hormone suppressing protein in ovarian tissues of cows.
The expression of bovine follicle-stimulating hormone (FSH)-suppressing protein (FSP) mRNA was investigated in different ovarian tissues of cows. Northern blot analysis, using a cDNA probe to bovine FSP, demonstrated that the FSP gene in the bovine ovary is highly expressed in a pool of isolated granulosa cells. Two bands (2.8 and 1.8 kb) were observed in all tissues expressing the mRNA. FSP mRNA was low in small antral follicles and increased in growing follicles to reach a maximum in preovulatory follicles. Low amounts of mRNA of steady state FSP were observed in all stages of the corpus luteum as well as in the corpus luteum of pregnant cows, in the corpus albicans and theca tissue, whereas this mRNA could not be detected in the liver. These results are consistent with the hypothesis that, in cows, FSP functions as an autocrine regulator in developing follicles to facilitate luteinization of granulosa cells.
Animals↗
Regulation of steady-state follistatin mRNA levels in rat granulosa cells in vitro.
The regulation of steady-state follistatin mRNA levels by different pituitary hormones and peptide factors was examined in granulosa cell cultures derived from diethylstilboestrol-treated immature rats. Cytosolic RNA from cell cultures was prepared by lysis and equal amounts of RNA from all samples were analysed with a solution-hybridization assay using a 32P-labelled antisense probe corresponding to a part of exon 5 together with a part of the 5' end of exon 6 of the rat follistatin gene. In addition, a specific 35S-labelled probe for cyclophilin was used as an internal standard. The results show that 5 micrograms FSH/l for 24 to 72 h stimulated steady-state follistatin mRNA levels, reaching levels 18.5-fold higher than controls. LH (0.2-100 micrograms/l) had only minor effects on follistatin mRNA levels in FSH-primed granulosa cells and prolactin, GH and IGF-I did not show any significant effects. Activin raised basal as well as FSH-stimulated steady-state follistatin mRNA levels up to ten- and twofold above controls respectively, whereas epidermal growth factor was found to inhibit FSH-stimulated follistatin mRNA levels in a dose-dependent manner. It is concluded that follistatin mRNA levels in granulosa cells are regulated by FSH rather than LH, and that the stimulation by FSH can be inhibited by epidermal growth factor but enhanced by activin. Activin alone was also capable of stimulating follistatin mRNA.
Activins↗
Modulation of differentiation of rat granulosa cells in vitro by interferon-gamma.
The effects of recombinant rat interferon-gamma (rRaIFN-gamma) and rat IFN (RaIFN, a mixture of IFN-gamma and -alpha) on basal and FSH-induced ovarian granulosa cell function were studied. Granulosa cells were harvested from diethylstilboestrol-treated immature rats and cultured (2 x 10(5) viable cells/well per 0.5 ml) in serum-free medium with or without treatment for 48 h. In the presence of FSH (20 ng/ml), rRaIFN-gamma (10-1000 U/ml) significantly inhibited FSH-stimulated aromatase activity (76.4 +/- 2.3% maximum inhibition compared with FSH treatment alone), inhibin (40.4 +/- 3.7%), progesterone (47.7 +/- 8.6%) and 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OHP) (51.8 +/- 1.7%) production in a dose-dependent manner. Furthermore, rRaIFN-gamma inhibited FSH- and forskolin (FSK; 30 mumol/l)-induced extracellular cAMP accumulation (46.0 +/- 6.6% and 29.1 +/- 7.3% respectively). The inhibitory effect of rRaIFN-gamma on FSK-induced cAMP was accompanied by decreased FSK-induced aromatase activity, inhibin, progesterone and 20 alpha-OHP production. rRaIFN-gamma had no detectable effect on aromatase activity, progesterone production and 20 alpha-OHP production in the absence of FSH, but significantly stimulated basal inhibin production by 1.5-fold. rRaIFN-gamma alone also caused a small but significant increase in basal levels of cAMP. The time-course studies showed that FSH-induced aromatase activity and inhibin production were consistently suppressed by rRaIFN-gamma, FSH-induced progesterone and 20 alpha-OHP were inhibited at 1 and 2 days and then stimulated on days 3, 4 and 5 relative to FSH alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Rat follistatin: ontogeny of steady-state mRNA levels in different tissues predicts organ-specific functions.
Follistatin (FS), a monomeric glycoprotein which specifically binds activin, is expressed in many tissues. This study investigated 1) the ontogeny of the steady-state FS mRNA levels in different extragonadal tissues and 2) whether the ratio of the differential splicing products, FS 344 or its carboxy-truncated form FS 317, is changed during postnatal development. Whereas the levels of FS mRNA 344 in the kidney showed a profound increase from the day of birth to adulthood, the levels in the muscle peaked during the infantile period and then declined. Brain cortex, heart and thymus also showed tissue specific expression in the steady-state mRNA level of FS during postnatal development. None of the tissues showed a measurable change in the ratio of the mRNA for FS 344 and FS 317. The FS mRNA 344 levels in male and female kidney were not different. It is concluded that the ontogeny of steady state FS mRNA varies in a tissue specific manner during postnatal development of the rat and may be involved in modulating the outcome of activin.
Animals↗
Interactions between activin and follicle-stimulating hormone-suppressing protein and their mechanisms of action on cultured rat granulosa cells.
Direct roles of follicle-stimulating hormone (FSH)-suppressing protein (FSP) and activin in regulation of ovarian granulosa cell differentiation have been reported recently. The present study further investigated the effects of these peptides on steroidogenesis and inhibin production as well as cAMP generation in cultured granulosa cells from immature, diethylstilbestrol (DES)-treated rats. In the presence of FSH (20 ng/ml) and activin (30 ng/ml), which enhanced FSH-induced aromatase activity, progesterone production and inhibin production, FSP (1-100 ng/ml) reversed the stimulating activities of activin in a dose-dependent manner. In addition, activin reversed the inhibitory effects of FSP on FSH-induced aromatase activity and inhibin production. In the presence of FSH, activin enhanced FSH-stimulated extracellular cAMP accumulation, and FSP caused a reduction in extracellular cAMP. Activin but not FSP also stimulated basal cAMP level. In the presence of forskolin, a potent stimulant of adenyl cyclase activity which stimulated extracellular cAMP, aromatase activity, progesterone production and inhibin production, activin augmented the effect of forskolin on all four parameters, whereas FSP significantly enhanced progesterone production without changing the other three parameters. Our findings suggest that activin action on rat granulosa cells may be mediated via regulation of cAMP generation. The action of FSP and FSH and/or activin-dependent, consistent with either an action as an activin binding protein or by a direct action of FSP on the granulosa cells.
Activins↗