EFFECTS OF RU486 ON THE OVARIAN RESPONSE OF IMMATURE RATS TO PREGNANTMARES SERUM GONADOTROPIN OR DIETHYLSTILBESTROL

The purpose of this study was to further investigate the role of proge sterone in follicular development induced by pregnant mare serum gonad otrophin (PMSG) or diethylstilbestrol (DES), in pre-pubertal rats, usi ng RU486 to prevent the receptor-mediated actions of progesterone. Int act or hypophysectomized 26-day-old rats received either a single inje ction of 10 IU PMSG i.p., or 2 mg DES s.c. daily for 3 days, with or w ithout 0.8 mg RU486 s.c. daily for 3 days. Groups of rats were killed 51-96 h after the first injection. RU486 significantly increased the o varian weight gain, the ovarian and circulating concentrations of prog esterone, the concentrations of immunoreactive and bioactive LH and th e number of ovulated oocytes in intact rats. RU486 did not affect the ovarian weight increase induced by PMSG or the ovulatory response foll owing PMSG plus human chorionic gonadotrophin (HCG) in rats hypophysec tomized 24 h before initiating treatment or in intact rats where ovula tion was blocked with chlorpromazine. The ovarian weight gain, the dev elopment of antral follicles and the increments in tissue and plasma p rogesterone concentrations and luteinizing hormone (LH) plasma concent rations elicited by DES in intact rats, were further increased by conc omitant treatment with RU486, whereas the ovarian weight increase and antral follicle development induced by DES were completely inhibited b y RU486 in hypophysectomized rats. Follicles stimulated to grow by DES plus RU486, but not by DES alone, were capable of ovulating in respon se to HCG. These results show that ovarian growth and follicular devel opment induced by exogenous gonadotrophin or oestrogen in the immature rat are enhanced by RU486 and that this synergistic effect of the pro gesterone receptor blocker is either pituitary-mediated or requires th e permissive action of a pituitary factor. Overall they support a nega tive effect of progesterone on follicular development in the rat.