Activin-A as an intraovarian modulator: actions, localization, and regulation of the intact dimer in human ovarian cells.

Rabinovici, Jaron; Spencer, Susan J.; Doldi, Nicola; Goldsmith, Paul C.; Schwall, Ralph; Jaffe, Robert B.

doi:10.1172/jci115745

Cited by 88 publications

(45 citation statements)

References 36 publications

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“…During folliculogenesis, the differentiation status of granulosa cells determines the response to activins (Findlay 1993). Activin is produced by granulosa cells of primary to tertiary follicles of the ovary (Rabinovici et al 1992, Zhao et al 2001. It has been found to promote the release of FSH from the anterior pituitary (Katamaya et al 1990).…”

Section: Introductionmentioning

confidence: 99%

The effects of FSH and activin A on follicle development in vitro

Cossigny¹,

Findlay

Drummond

2012

Reproduction

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Numerous studies have reported on the roles of activins in gonadal regulation; however, little is known about their specific roles in early folliculogenesis. Ovarian follicular growth was investigated in 10-day cultures of day 4 postnatal whole ovaries treated with activin A (ActA; 50 ng/ml), with or without FSH (100 ng/ml) in vitro. We hypothesized that treatment with ActAGFSH would affect rates of growth and atresia in follicles. None of the treatments affected primordial follicle activation, and antral follicles were not observed after 10 days in culture. Primordial follicle numbers from all treatment groups were w20% of those in day 4 fresh ovaries, indicating that activation had occurred. In the presence of ActA, preantral follicle numbers increased significantly (P!0.0001). ActA alone decreased the proportion of atretic follicles in the primary and preantral classes, whereas the combined treatment of ActACFSH increased the proportion of atretic preantral oocytes. Real-time PCR analysis revealed that follistatin, FSH receptor, and activin bA and bB subunits were all expressed at significantly higher levels in the ActA-only treated group but not in the ActACFSH group. Here, we report novel findings supporting the role of FSH in primordial follicle survival through an action on apoptosis and a stimulatory role of ActA in the primordial to primary and preantral stages of follicle development, suggesting an inhibitory action of activin on oocyte apoptosis.

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Section: Introductionmentioning

confidence: 99%

The effects of FSH and activin A on follicle development in vitro

Cossigny¹,

Findlay

Drummond

2012

Reproduction

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“…Activin A is the most abundant isoform of activins and the most extensively studied member of the TGFβ family. Activin is produced by granulosa cells of the ovary and it has been localised in granulosa cells from primary to tertiary follicles [14]. Similar to other TGFβ family members, Activin A influences many facets of cell activities such as proliferation, differentiation, motility and apoptosis through the transmembrane receptor mediated Smad pathway.…”

Section: Introductionmentioning

confidence: 99%

Activin A inhibits activation of human primordial follicles in vitro

Ding

Thong

Krishna

et al. 2010

J Assist Reprod Genet

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Purpose To determine whether Activin A affects the activation and survival of human primordial follicles in vitro. Methods Ovarian cortical biopsies from eight women undergoing elective caesarean sections or benign gynaecological procedures were taken and cut into small pieces (1-3 mm 3 ), cultured in serum-free medium for 7 days with/without human recombinant Activin A at a concentration of either 50 or 100 ng/ml. Ovarian tissue were analysed by histology for follicle viability, development and density. Result(s) Significant activation of primordial follicles within cultured cortical tissue was observed after 7 days in control medium. However, medium supplemented with Activin A at 50 ng/ml resulted in significant inhibition of follicular activation. Increasing the concentration of Activin A to 100 ng/ml reversed the inhibitory effect. The effect of Activin A appeared to be specific to activation of non-growing (primordial) follicles into the growing population since no significant differences in follicle viability was observed between treatment groups. Conclusion(s) Activin A at a concentration of 50 ng/ml can inhibit the spontaneous activation of human primordial follicles in vitro indicating that this may be a component of the signalling mechanisms that maintain follicular quiescence.

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“…In addition to their endocrine effects on pituitary FSH secretion, inhibin and activin peptides have important autocrine and paracrine functions in the organs in which they are produced (Mather et al 1992, Findlay 1993, Woodruff 1998. Inhibins and activins regulate ovarian steroidogenesis in both rodents and primates (Hsueh et al 1987, Miró & Hillier 1992, Rabinovici et al 1992. Inhibins may also have a role in gonadal tumorigenesis (Matzuk et al 1992(Matzuk et al , 1996.…”

Section: Introductionmentioning

confidence: 99%

Regulation of immunoreactive inhibin A and B secretion in cultured human granulosa-luteal cells by gonadotropins, activin A and insulin-like growth factor type-1 receptor

Vänttinen¹,

Liu²,

Hydén-Granskog³

et al. 2000

Journal of Endocrinology

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Inhibins are gonadal glycoproteins with endocrine effects on pituitary FSH secretion and para/autocrine effects on ovarian and testicular function. The purpose of this study was to investigate the endocrine and para/autocrine regulation of inhibin A and inhibin B secretion in human ovarian granulosa-luteal cells. The cells were obtained from women undergoing in vitro fertilization, and the primary cultures were treated with FSH, LH, human chorionic gonadotropin (hCG), activin A, 8-bromo cyclic AMP (8-BrcAMP), staurosporine (a protein kinase C inhibitor) and an antagonist of IGF action (type-1 IGF receptor antibody IR3). The secretion of inhibins was measured by ELISA assays capable of reliably distinguishing between inhibin A and B.FSH, LH, hCG and 8-BrcAMP increased inhibin A secretion on average up to 180% (P<0·01), 192% (P<0·05), 210% (P<0·01) and 243% (P<0·01) respectively of the control level, while their stimulatory effect on inhibin B secretion was less pronounced (up to 167%, P<0·01; 139%, P<0·05; 127%, P>0·05; 133%, P>0·05 of the controls respectively). IR3 decreased inhibin A and B secretion down to 70% (P<0·01) and 50% (P<0·01) respectively of the control. Staurosporine decreased inhibin B secretion down to 49% (P<0·01) of the control; its effect on inhibin A secretion was not significant. Activin A increased inhibin B secretion up to fourfold of the control (P<0·05) while its effect on inhibin A secretion was insignificant.We conclude that gonadotropins via the protein kinase A signal transduction pathway are the main positive regulators of inhibin A and B secretion in human granulosa-luteal cells. The protein kinase C signal transduction pathway seems to be important especially for inhibin B secretion. Locally produced IGFs are probably important inducers of the production of both forms of inhibin in human ovaries while activins seem to upregulate inhibin B secretion.

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Activin-A as an intraovarian modulator: actions, localization, and regulation of the intact dimer in human ovarian cells.

Cited by 88 publications

References 36 publications

The effects of FSH and activin A on follicle development in vitro

The effects of FSH and activin A on follicle development in vitro

Activin A inhibits activation of human primordial follicles in vitro

Regulation of immunoreactive inhibin A and B secretion in cultured human granulosa-luteal cells by gonadotropins, activin A and insulin-like growth factor type-1 receptor

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