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At least 19 recordsLinked to original sources
PubMed1995

Serum follistatin levels in women: evidence against an endocrine function of ovarian follistatin.

Follistatin is a monomeric protein first identified in and isolated from ovarian follicular fluid. Evidence that follistatin might be an ovarian endocrine hormone functioning in a negative feedback fashion to modulate pituitary FSH production is based primarily on in vitro experiments. To examine the possible role of follistatin as an endocrine agent in vivo, we sought to relate circulating levels of follistatin to ovarian activity in women. Therefore, we developed a specific and sensitive homologous RIA using antiserum generated against recombinant human follistatin for the measurement of total follistatin in the presence or absence of activin. Follistatin was measured quantitatively (106 +/- 6% recovery) using calibration standards ranging from 0.4-25 ng/tube and up to 400 microL/tube serum. Furthermore, all of the endogenous follistatin measured in human serum could be removed by adsorption to activin-coated plates. Using this homologous RIA, human follicular fluid (100-600 ng/mL; n = 75) contained 3-150 times more follistatin than serum (4-35 ng/mL), an observation consistent with the notion that serum follistatin originates from the gonad. However, further studies of follistatin levels across the normal menstrual cycle (mean +/- SE, 8.09 +/- 0.73; n = 72 daily samples from 4 women), in pregnant women (17.49 +/- 1.34; n = 8), in daily samples from 20 women undergoing ovarian stimulation by exogenous FSH (9.90 +/- 0.62; n = 119), in postmenopausal women including two ovariectomized individuals (9.57 +/- 0.43; n = 8), and in GnRH-deficient women (9.85 +/- 0.50; n = 6) failed to support the hypothesis that serum levels of follistatin reflect ovarian activity in women. Levels of follistatin measured in serum collected across normal menstrual cycles did not fluctuate. However, the roughly nanomolar concentrations of follistatin measured suggest a physiological role for this protein. Follistatin at nanomolar concentrations may be capable of binding and inactivating circulating activin and perhaps in this way limiting the biological activity of activin to local autocrine or paracrine mechanisms. Measurement of peripheral levels of follistatin apparently represents only a first, albeit crucial, step in the study of the physiological significance of this protein in human reproduction.

Endocrine Glands↗
PubMed2001

Human follistatin-related protein: a structural homologue of follistatin with nuclear localization.

Follistatin-related protein is a recently discovered glycoprotein that is highly homologous in both primary sequence and exon/intron domain structure to the activin-binding protein, follistatin. We explored their potential for functional redundancy by investigating the relative affinities and kinetics of their interactions with activin, bone morphogenic protein-6, and bone morphogenic protein-7 and by exploring their expression and distribution in human tissues and cells. Follistatin and follistatin-related protein mRNA were ubiquitous by Northern analyses, although their sites of peak distribution differed, with follistatin-related protein and follistatin predominating in the placenta and ovary, respectively. Follistatin-related protein, like follistatin, preferentially bound activin with high affinity and in an essentially irreversible fashion. Although follistatin-related protein, like follistatin, possesses a signal sequence and no known nuclear localization signals, its secretion was undetectable in most cell lines by RIA. Intriguingly, follistatin-related protein was identified as a nuclear protein in human granulosa cells and all human cell lines tested. Furthermore, Western analyses of CHO cells transfected with human follistatin-related protein revealed this protein to reside within the insoluble nuclear protein fraction. We conclude that despite its remarkably high level of similarity to follistatin with regard to structure and activin binding kinetics, follistatin-related protein is a nuclear as well as a secretory protein that may perform distinct intracellular actions.

Activins↗
PubMed1996

Pituitary activin receptor subtypes and follistatin gene expression in female rats: differential regulation by activin and follistatin.

The activins, hormones produced in the gonads and extragonadal tissues (including the pituitary), rapidly increase FSH beta messenger RNA (mRNA) and FSH secretion. In the rat, activin acts via a family of activin receptor (ActR) subunits that includes at least one type I (ActRI or ALK-2) and two homologous type II (IIA and IIB) subunits. We have previously reported that ActRIIA mRNA rises after ovariectomy (OVX). Potentially, the OVX-induced increases in ActR mRNAs could result from altered activin or the activin-binding protein follistatin. It was the purpose of the current studies to determine whether activin and/or follistatin regulated activin receptor subunit mRNAs. Adult female rat pituitaries were dissociated and plated for 48 h, transferred to wells containing follistatin or activin for 2 or 24 h, then RNA extracted for measurement of ActRI, IIA, and IIB and follistatin mRNAs. All three ActR mRNAs were easily detectable in pituitary RNA, with the relative abundance of ActRI > IIA >> IIB (18:9:1). Between 2-24 h, levels of all three ActR mRNAs increased 2- to 3-fold in wells containing medium alone, whereas levels of follistatin mRNA were unchanged. Follistatin significantly reduced FSH secretion and follistatin mRNA, but not the ActR mRNAs. Activin increased ActRI (4-fold, at 2 h), ActRIIB (2-fold, at 24 h), and follistatin (2-fold, at 24 h) mRNAs and FSH release (2-fold, at 24 h), but did not alter ActRIIA mRNA levels. We conclude that 1) pituitary ActR mRNA expression is under inhibitory tone in vivo, as suggested by the effect of pituitary removal and cell dispersion and an earlier report after OVX. 2) Pituitary-derived activin stimulates follistatin (but not ActR) mRNA production, and additional increases in follistatin mRNA can be induced by exogenous activin. 3) Higher concentrations of activin differentially regulate pituitary ActR mRNA expression, suggesting that activin exerts a positive feedback effect on its own receptor.

Activin Receptors↗
PubMed1996

Immunoradiometric assay for follistatin: serum immunoreactive follistatin levels in normal adults and pregnant women.

A sensitive and specific immunoradiometric assay for follistatin was developed using antifollistatin mouse monoclonal and rabbit polyclonal antibodies. The sensitivity of the assay was 0.5 micrograms/L, and cross-reactivities with recombinant human activin A and bovine inhibin were less than 0.1%. The intra- and interassay coefficients of variation were less than 10%, and the recovery rate was about 90% in human serum. The addition of activin A to the same sample resulted in a minimal influence on follistatin recovery, indicating that this assay system can measure the total level of activin-bound and unbound follistatin. Gel filtration analysis of human serum showed that the majority of immunoreactivity was eluted in a larger molecular size position than that of free follistatin, suggesting that the large part of follistatin is bound to other proteins, presumably activins, in serum. Using this assay, immunoreactive follistatin levels in various biological fluids and human sera were examined. The dose-response curves of porcine follicular and amniotic fluids were parallel to the standard curve, and porcine follicular fluid contained extremely high follistatin immunoreactivity (5.6 mg/L). The serum follistatin level in normal human volunteers was 13.3 +/- 4.7 micrograms/L (mean +/- SD; n = 60), with a tendency to increase gradually with age. On the other hand, the serum follistatin level was remarkably elevated in pregnant women (62.7 +/- 35.3 micrograms/L; n = 57), with a positive correlation with weeks of pregnancy. These data indicated that circulating immunoreactive follistatin is detectable in human serum, and the levels vary with physiological conditions such as aging and pregnancy.

Activins↗
PubMed1998

Regulation of pituitary follistatin and inhibin/activin subunit messenger ribonucleic acids (mRNAs) in male and female rats: evidence for inhibin regulation of follistatin mRNA in females.

The regulation of FSHbeta messenger RNA (mRNA) expression is complex and involves signals from the hypothalamus and gonads. Additionally, the local (pituitary) production of activin and follistatin appears to serve as an important modulator of endocrine signals for FSHbeta regulation. The purpose of these studies was to identify factors controlling pituitary activin/inhibin subunit and follistatin mRNA production in male and female rats. Both males and females expressed the follistatin, inhibin alpha, and betaB mRNAs, whereas the betaA mRNA was not detected. In males, levels of FSHbeta and follistatin were higher than those in females. After gonadectomy, levels of FSHbeta and follistatin increased in both sexes, whereas betaB rose only in females. In males, blockade of GnRH action from the time of castration prevented the increase in FSHbeta and follistatin, suggesting that GnRH is the primary stimulus for these gene products. In females, treatment with a GnRH antagonist only partially prevented the rise in FSHbeta, follistatin, and betaB expression, suggesting that other factors were also important. Passive immunoneutralization of circulating inhibin increased FSHbeta and follistatin (but not betaB), providing evidence that inhibin is a physiological regulator of follistatin. Replacement of estradiol at the time of ovariectomy prevented the increase in betaB mRNA, suggesting that gonadal steroids may also act via local factors to regulate FSHbeta. In summary, these studies provide evidence that GnRH, gonadal steroids, and gonadal peptides probably regulate FSHbeta expression at least in part via the intrapituitary activin/follistatin system.

Activins↗
PubMed1996

The expression and regulation of follistatin and a follistatin-like gene during avian somite compartmentalization and myogenesis.

We report on the normal and experimentally altered expression of two structurally related genes, Follistatin and Follistatin-like (Flik), in the somites of avian embryos. In normal chick embryos, Follistatin expression can first be seen in the cells of the dorsolateral somite quarter. During somite maturation, the cells of the dorsomedial quarter also express this gene. Within the dermomyotome it seems that only the muscle precursors are Follistatin-positive. The migrating precursors of limb and tongue muscle as well as the myotome cells show Follistatin expression. The manipulation experiments reveal that the expression of Follistatin in the somites can be inhibited by notochord signals. This effect can be mimicked by sonic hedgehog protein. Flik is expressed in the dorsomedial compartment of the somite and later on in the myotome. Unlike Follistatin, Flik expression requires signals emanating from the neural tube. Notochordal influences do not alter Flik expression. The expression of both genes does not depend on signals of intermediate or lateral mesoderm. Since the products of both genes are proposed to antagonize TGF-beta superfamily proteins during gastrulation and neuralization, we postulate that during myogenesis follistatin and flik counteract inhibiting effects of related molecules on muscle differentiation.

Animals↗
PubMed2005

A novel role for fibronectin type I domain in the regulation of human hematopoietic cell adhesiveness through binding to follistatin domains of FLRG and follistatin.

FLRG and follistatin belong to the family of follistatin proteins involved in the regulation of various biological effects, such as hematopoiesis, mediated by their binding to activin and BMP, both members of the TGFbeta family. To further characterize the function of FLRG, we searched for other possible functional partners using a yeast two-hybrid screen. We identified human fibronectin as a new partner for both FLRG and follistatin. We also demonstrated that their physical interaction is mediated by type I motifs of fibronectin and follistatin domains. We then analyzed the biological consequences of these protein interactions on the regulation of hematopoiesis. For the first time, we associated a biological effect with the regulation of human hematopoietic cell adhesiveness of both the type I motifs of fibronectin and the follistatin domains of FLRG and follistatin. Indeed, we observed a significant and specific dose-dependent increase of cell adhesion to fibronectin in the presence of FLRG or follistatin, using either a human hematopoietic cell line or primary cells. In particular, we observed a significantly increased adhesion of immature hematopoietic precursors (CFC, LTC-IC). Altogether these results highlight a new mechanism by which FLRG and follistatin regulate human hematopoiesis.

Binding Sites↗
PubMed2004

Follistatin-related gene expression, but not follistatin expression, is decreased in human endometrial adenocarcinoma.

OBJECTIVE: Activin A is a multifunctional growth and cell differentiation factor produced by normal endometrium, and secreted in high amounts by endometrial adenocarcinoma. In the present study we evaluated the expression of two inhibitory activin A ligands, follistatin and follistatin-related gene (FLRG), in endometrial adenocarcinoma and in age-matched healthy human endometrium. DESIGN AND METHODS: Atropic menopausal (n=13) and tumoral (n=9 adenocarcinoma) tissues were processed to evaluate mRNA expression levels (by semiquantitative RT-PCR) and peptide localization (by immunohistochemistry). Differences were evaluated by the unpaired t-test and assumed to be statistically significant when P<0.05. RESULTS: Both control and tumoral endometrial samples express and localize follistatin and FLRG. However, whereas follistatin mRNA expression did not differ significantly, FLRG was significantly lower in endometrial adenocarcinoma than in healthy endometrial specimens (P<0.0001). With respect to the localization of proteins, follistatin was immunolocalized in endometrial epithelial and vascular cells both in tumoral and healthy endometrium without any significant difference in intensity. Nuclear and cytoplasmic FLRG immunolocalization was seen in glands, and only nuclear immunolocalization was found in stroma and vessels of healthy endometrium. FLRG was weakly immunostained in endometrial adenocarcinoma. CONCLUSIONS: Whilst follistatin expression is unchanged, FLRG is down-regulated in endometrial carcinoma. As activin A is a differentiation factor of human endometrium, the present findings support an imbalance between increased activin A and decreased FLRG expression in endometrial cancer, so that the failure of the activin A pathway through FLRG may be pivotal in endometrial tumorigenesis.

Adenocarcinoma↗
PubMed2001

The activin binding proteins follistatin and follistatin-related protein are differentially regulated in vitro and during cutaneous wound repair.

Follistatin is a secreted protein that binds activin in vitro and in vivo and thereby inhibits its biological functions. Recently, related human and murine genes, designated follistatin-related gene (FLRG), were identified, and their products were shown to bind activin with high affinity. In this study we further characterized the murine FLRG protein, and we analyzed its tissue-specific expression and regulation in comparison with those of follistatin. Transient expression of the mouse FLRG protein in COS-1 cells revealed that the FLRG cDNA encodes a secreted glycoprotein. FLRG mRNA was expressed at high levels in the lung, the testis, the uterus and, particularly, the skin. Immunohistochemistry revealed the presence of FLRG in the basement membrane between the dermis and the epidermis and around blood vessels. FLRG mRNA expression was induced in keratinocytes by keratinocyte growth factor, epidermal growth factor and transforming growth factor-beta 1, and in fibroblasts by platelet-derived growth factor and epidermal growth factor. The induction was more rapid, but weaker, than that of follistatin. Most interestingly, both follistatin and FLRG were expressed during the wound healing process, but their distribution within the wound was different. The different expression pattern of FLRG and follistatin and their differential regulation suggest different functions of these activin-binding proteins in vivo.

Activins↗
PubMed1994

The tissue distribution of activin beta A- and beta B-subunit and follistatin messenger ribonucleic acids suggests multiple sites of action for the activin-follistatin system during human development.

Activins have potent effects on early morphogenetic events during amphibian embryogenesis but no evidence for their role during human development other than their expression in steroidogenic tissues has been reported. We previously showed the expression of the activin type II and IIB receptor mRNAs in several tissues of the mid-gestational human fetus with highest expression levels in developing neural, muscular and exocrine glandular organs. We now report that the mRNA transcripts for activin beta A- and beta B-subunits and for the activin-binding protein follistatin are found co-expressed in several of these extragonadal tissues. Their mRNAs were detected by Northern analyses using specific single-stranded 32P-labeled cDNA probes. In the nervous system, both activin beta A- and beta B-subunit transcripts were expressed in the cerebrum and spinal cord. Follistatin was abundantly expressed in the spinal cord whereas weaker signals where observed in the cerebrum and cerebellum. In the muscular system, beta A-subunit was abundantly expressed in the heart but to a lesser extent in the skeletal muscle while the opposite was observed for follistatin. Follistatin, and activin beta A- and beta B-subunit mRNAs were also detected in developing kidney, salivary gland, liver, and adrenal. The predominance of beta A-subunit mRNAs in the bone marrow and beta B-subunit mRNAs in the salivary gland suggests specific roles for activin A and B, respectively, in these tissues. No hybridization signal was detected for the inhibin alpha-subunit in non-steroidogenic tissues indicating that, in contrast to activins and follistatin, the effects of inhibins may be restricted to the gonads and adrenals which are known to express high levels of the alpha-subunit transcript. Taken together, our results suggest that the activin-follistatin system regulates the development of several organ systems in the mid-gestational human fetus.

Abortion, Legal↗
PubMed1994

Expression of inhibin subunits and follistatin during postimplantation mouse development: decidual expression of activin and expression of follistatin in primitive streak, somites and hindbrain.

Members of the activin family are believed to act as mesoderm-inducing factors during early amphibian development. Little is known, however, about mesoderm formation in the mammalian embryo, and as one approach to investigating this we have studied activin and follistatin expression during early mouse development. Activins are homo- or heterodimers of the beta A or beta B subunits of inhibin, itself a heterodimer consisting of one of the beta subunits together with an alpha subunit. Follistatin is a single-chain polypeptide which inhibits activin function. Expression of the inhibin alpha chain could not be detected in embryonic or extraembryonic tissues at any of the stages studied (5.5 to 8.5 days) and expression of the beta A and beta B subunits could only be observed in the deciduum in cells surrounding the embryo. Expression of follistatin could also be detected in the deciduum, but in a pattern complementary to that of the beta subunits. Embryonic expression of follistatin first occurred in the primitive streak, and at later stages transcripts were detectable in the somites and in rhombomeres 2, 4 and 6 of the hindbrain. These results are consistent with a role for activin in mesoderm formation in the mouse embryo, and suggest functions for follistatin in addition to its role as an inhibitor of activin.

Activins↗
PubMed2002

Follistatin-related protein and follistatin differentially neutralize endogenous vs. exogenous activin.

Follistatin-related protein (FSRP) is a new addition to the expanding follistatin (FS)-related gene family whose members contain at least one conserved 10-cysteine follistatin domain. In contrast to other members of this family, FSRP and follistatin also share a common exon/intron domain structure, substantial primary sequence homology, and an ability to irreversibly bind activin. In this study, we further explored the hypothesis that FSRP is a functional as well as structural homologue of FS. N-terminal sequencing of recombinant FSRP revealed that signal peptide cleavage occurs within exon 1, a significant structural difference from FS, in which cleavage occurs at the exon/intron boundary. Solid-phase radioligand competition assays revealed both FS and FSRP to preferentially bind activin with the next closest TGF-beta superfamily member, bone-morphogenic protein-7, being at least 500-fold less potent. Consistent with their similar activin-binding affinities, FSRP and FS both prevented exogenous (endocrine or paracrine) activin from accessing its receptor and inducing gene transcription in bioassays. However, FS was at least 100-fold more potent than FSRP in inhibiting gene transcription and FSH release mediated by endogenously produced (autocrine) activin-A or activin-B in multiple cell systems. Finally, FSRP lacks the heparin-binding sequence found in FS, and we found that it was also unable to bind cell surface heparin sulfated proteoglycans. These findings suggest that structural differences between FSRP and FS may underlie their different neutralizating capabilities with respect to exogenous vs. endogenous activin. Taken together with our previous studies showing that activin binding is essential for FS's biological activity, the differential activities of FSRP and FS further indicate that activin binding is necessary but not sufficient to account for all of FS's actions.

Activin Receptors↗
PubMed2000

Expression patterns of follistatin and two follistatin-related proteins during mouse development.

We compared the expression patterns of follistatin and two follistatin-related proteins (FRP and m7365) during early mouse development. m7365 is expressed continuously during preimplantation development, in contrast to FRP and follistatin. At early postimplantation stages, follistatin and 7365 are expressed from E6.0, while FRP is detected from E7.5 onwards. Although there is some overlap between the expression of these genes in the primitive streak and somites, their overall expression patterns are distinct.

Animals↗
PubMed2006

Purification of recombinant activin A using the second follistatin domain of follistatin-related gene (FLRG).

Activins are multifunctional growth factors belonging to the transforming growth factor-beta superfamily. Isolation of activins from natural sources requires many steps and only produces limited quantities. Even though recombinant preparations have been used in recent studies, purification of recombinant activins still requires multiple steps. To purify recombinant activin A, we have developed a simple method using the second follistatin domain of an activin-binding protein follistatin-related gene (FLRG). An affinity column was prepared with a partial FLRG fusion protein. The partial FLRG protein contained the second follistatin domain and the C-terminus acidic domain, and was tagged with six histidine residues at its N-terminus. The fusion protein was expressed in Escherichia coli and purified with nickel affinity column. Thereafter, the purified fusion protein was coupled to NHS-activated column. Recombinant activin A was produced in Chinese hamster ovary (CHO) cells, which were stably transfected with rat inhibin/activin betaA-subunit cDNA. After 48-h suspension culture of the cells in a serum free medium, the culture media was recovered and passed through the FLRG-coupled column. After washing with phosphate-buffered saline, bound protein was eluted out with an acidic buffer. Any significant contaminations were not detected when the purified protein was analyzed by SDS-PAGE. Apparent sizes of the protein were 14 and 28 kDa under the reduced and non-reduced conditions, respectively. Western blot analysis confirmed that the purified protein was activin A. The purified recombinant activin stimulated p3TP-lux reporter activity in CHO cells and follicle-stimulating hormone secretion from rat pituitary cells.

Activins↗
PubMed1991

Recombinant expression of human follistatin with 315 and 288 amino acids: chemical and biological comparison with native porcine follistatin.

Follistatin is a glycosylated monomeric protein originally isolated from ovarian follicular fluid based on its ability to specifically inhibit pituitary FSH release. To further explore the physiological role of follistatin, we have expressed recombinant human follistatins with 315 (rhFS-315) and 288 (rhFS-288) amino acids in Chinese hamster ovary cells under the control of the simian virus-40 promoter. The two types of FS originated from alternatively spliced mRNAs and rhFS-315 differed from rhFS-288 by having an extra 27-amino acid sequence at the carboxyl-terminal. The yield of the purified rhFS-315 and rhFS-288 after a single step of affinity chromatography on an activin-coupled Affi-Gel column was 3-5 mg/liter conditioned medium. Using the rhFS-315 and rhFS-288 as molecular mass markers, Western blotting with FS carboxyl-terminal-specific antibodies demonstrated that the majority of native FS isolated from porcine ovarian follicular fluid was neither FS-315 nor FS-288, but was composed of 300 amino acids in various forms of glycosylation. This finding is consistent with our earlier results obtained from tryptic peptide fragment analysis of native FS. Only a very small percentage (less than 1%) of native porcine FS was FS-288. In cultures of rat anterior pituitary cells, rhFS-315 (ED50, 115.2 +/- 16.2 pM) is equipotent to native porcine FS (ED50, 86.7 +/- 14.1 pM) on the suppression of FSH release, but, surprisingly, rhFS-288 (ED50, 9.6 +/- 2.2 pM) is 8-10 times more potent than the native protein, similar to the potency of inhibin-A (ED50, 8.6 +/- 0.9 pM). Interestingly, when the in vivo FSH-suppressing activity of rhFS-288 was compared to that of inhibin-A in 1-week ovariectomized adult rats, it was found that rhFS-288 was more potent and longer acting than inhibin-A. Hence, these results indicate that FS-288 is probably one of the most potent natural FSH suppressors.

Amino Acid Sequence↗
PubMed2004

Differential actions of follistatin and follistatin-like 3.

Follistatin (FS) is an important physiological regulator of activin and other TGFbeta superfamily members. The recently discovered follistatin-like 3 (FSTL3; a.k.a. FLRG; FSRP) shares significant structural and functional homology with FS, but also has some interesting differences, including a prominent nuclear localization. The existence of these two related proteins allows detailed molecular and biochemical comparisons of the biologic roles of their individual structural elements. Current studies indicate that the heparin binding sequence is essential for the ability of FS to inhibit autocrine activin but is not sufficient to confer this activity on FSTL3. Preliminary analysis of FSTL3 transgenic mice suggests that FSTL3 regulates gonadal development and function through inhibition of the paracrine activity of activin and/or other related factors. These studies have identified important structural elements necessary for biological activity of FS and FSTL3 and potential roles for FSTL3 in vivo.

Animals↗
PubMed2001

Follistatin-related protein (FSRP): a new member of the follistatin gene family.

The identification and characterization of follistatin related protein (FSRP) suggests that the follistatin (FS) gene family may actually contain two sub-families. The first includes FS and FSRP by virtue of their high degree of structural homology and comparable activin-binding activity, while the second sub-family contains extracellular matrix proteins that possess one or more 10-cysteine FS domains, but do not bind activin or related TGF-beta family members. Characterization of FSRP indicates that it binds activin with similar affinity and selectivity as FS, but does not bind heparin. Furthermore, although FSRP inhibits activin-mediated gene transcription in heterologous assays, FSRP is much less active than FS in the rat pituitary bioassay. When overexpressed in transgenic mice, FSRP may lead to interruption of follicular development and fertility in females but appears to have only a modest effect on males. These results suggest that FSRP is a structural, but not necessarily a functional homologue of FS.

Activins↗
PubMed2003

Differential binding and neutralization of activins A and B by follistatin and follistatin like-3 (FSTL-3/FSRP/FLRG).

Modulation of activin and other TGF beta superfamily signaling is the primary mechanism of action for both follistatin (FS) and FS-like 3 (FSTL-3). However, most studies of these ligands use activin A due to its wide availability. We have now tested the ability of FS288 and FSTL-3 to bind and neutralize activin B relative to activin A. Activin B bound to both FS and FSTL-3 at a potency approximately 10-fold lower than that of activin A. Moreover, whereas both activins had similar biological activity in 293 cell reporter assays, FS and FSTL-3 were approximately 3-fold more effective in neutralizing activin A relative to activin B. These results suggest that neutralization of activins A and B by FS and FSTL-3 are not identical, so that the relative activity of each activin in tissues where both are produced, such as in the ovary, could be quite different. In addition, biological systems that use primarily activin B, but which have been examined in vitro using activin A, may need to be reevaluated to determine the actual physiologic roles of FS or FSTL-3.

Activins↗