REGULATORY ROLE OF ANGIOTENSIN-II ON PROGESTERONE PRODUCTION BY CULTURED HUMAN GRANULOSA-CELLS - EXPRESSION OF ANGIOTENSIN-II TYPE-2 RECEPTOR

The role of angiotensin II (AngII) in ovarian steroidogenesis is not c learly understood. In order to study its action on progesterone synthe sis and to determine which receptor subtype is involved, granulosa cel ls obtained from women undergoing in-vitro fertilization were cultured for 2 or 4 days and then incubated in the presence of AngII (10(-7) M ) with or without human chorionic gonadotrophin (HCG, 10 IU/ml) for 3 or 18 h. In cells cultured for 2 days, incubation with AngII decreased progesterone secretion by 36%, and inhibited activity of 3 beta-hydro xysteroid dehydrogenase (3 beta-HSD) by 87% (P < 0.05), although its e xpression was not significantly reduced. However, in cells cultured fo r 4 days, progesterone production was enhanced by incubation with AngI I (38%), and no change was observed in 3 beta-HSD expression. Both inh ibitory and stimulatory effects were dose-dependent. Progesterone secr etion was increased (93%) by incubation with HCG of cells cultured for 4, but not for 2 days, and no potentiation was observed with AngII. T reatment with PD123177 completely blocked the action of AngII and decr eased the HCG-stimulated secretion of progesterone by 27%. Angiotensin type-2 (AT(2)) receptor mRNA was expressed in cells cultured for 4 da ys. In conclusion, AngII showed a regulatory role in in-vitro progeste rone production by human granulosa luteinized cells, modulating the ac tivity of 3 beta-HSD. It is likely that these actions may be mediated via membrane receptors, possibly of the AT(2) receptor family.