Progesterone receptor-mediated inhibition of apoptosis in granulosa cells isolated from rats treated with human chorionic gonadotropin. Biol Reprod 2000

Almost all ovarian follicles undergo atresia during follicular development. However, the number of corpora lutea roughly equals the number of preovulatory follicles in the ovary. Because apoptosis is the cellular mechanism behind follicle and luteal cell demise, this suggests a change in apoptosis susceptibility during the periovulatory period. Sex steroids are important reg-ulators of follicular cell survival and apoptosis. The aim of the present work was to study the role of progesterone receptor-mediated effects in the regulation of granulosa cell apoptosis. The levels of internucleosomal DNA fragmentation were evalu-ated in rat granulosa cells before and after induction of the nu-clear progesterone receptor, using hCG treatment to eCG-primed rats to mimic the naturally occurring LH surge. Granu-losa cells isolated from hCG-treated rats showed a several-fold increase in the expression of progesterone receptor mRNA and a 47 % decrease (P, 0.01) in DNA fragmentation after 24 h incubation in serum-free medium compared to granulosa cells isolated from rats treated with eCG only. The effect of hCG treatment in vivo was dose-dependently reversed in vitro by ad-dition of antiprogestins (Org 31710 or RU 486) to the culture medium, demonstrated by increased DNA fragmentation as well as increased caspase-3 activity. Addition of antiprogestins to granulosa cells isolated from immature or eCG-treated rats did not result in increased DNA fragmentation. The results suggest that progesterone receptor-mediated effects are involved in reg-ulating the susceptibility to apoptosis in LH receptor-stimulated preovulatory rat granulosa cells. apoptosis, granulosa cells, hCG, hormone action, LH, ovary, pro-gesterone, progesterone recepto