title: Activin-A as an intraovarian modulator: actions, localization, and regulation of the intact dimer in human ovarian cells.
abstract: The actions, localization, and regulation of activin in the human ovary are unknown. Therefore, the aims of this study were (a) to define the effects of recombinant activin-A and its structural homologue, inhibin-A, on mitogenesis and steroidogenesis (progesterone secretion and aromatase activity) in human preovulatory follicular cells; (b) to localize the activin-A dimer in the human ovary by immunohistochemistry; and (c) to examine regulation of intracellular activin-A production in cultured human follicular cells. In addition to stimulating mitogenic activity, activin-A causes a dose- and time-dependent inhibition of basal and gonadotropin-stimulated progesterone secretion and aromatase activity in human luteinizing follicular cells on day 2 and day 4 of culture. Inhibin-A exerts no effects on mitogenesis, basal or gonadotropin-stimulated progesterone secretion and aromatase activity, and does not alter effects observed with activin-A alone. Immunostaining for dimeric activin-A occurs in granulosa and cumulus cells of human ovarian follicles and in granulosa-lutein cells of the human corpus luteum. cAMP, and to a lesser degree human chorionic gonadotropin and follicle-stimulating hormone, but not inhibin-A, activin-A, or phorbol 12-myristate 13-acetate, increased the immunostaining for activin-A in cultured granulosa cells. These results indicate that activin-A may function as an autocrine or paracrine regulator of follicular function in the human ovary.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143.
authors.forename: J
authors.initials: J
authors.lastname: Rabinovici
authors.forename: S J
authors.initials: SJ
authors.lastname: Spencer
authors.forename: N
authors.initials: N
authors.lastname: Doldi
authors.forename: P C
authors.initials: PC
authors.lastname: Goldsmith
authors.forename: R
authors.initials: R
authors.lastname: Schwall
authors.forename: R B
authors.initials: RB
authors.lastname: Jaffe
mesh_terms: D028341:Activins; D047072:Aromatase Inhibitors; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D007265:Inhibins / Q000502:physiology*; D010053:Ovary / Q000502:physiology*; D011374:Progesterone / Q000096:biosynthesis
chemical_list: D047072:Aromatase Inhibitors; D006063:Chorionic Gonadotropin; D028341:Activins; D011374:Progesterone; D007265:Inhibins; D005640:Follicle Stimulating Hormone