ACTIVIN-A AS AN INTRAOVARIAN MODULATOR - ACTIONS, LOCALIZATION, AND REGULATION OF THE INTACT DIMER IN HUMAN OVARIAN-CELLS

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.