RECOMBINANT FSH-INDUCED FOLLICLE DEVELOPMENT IN IMMATURE RATS TREATEDWITH AN LHRH ANTAGONIST - A DIRECT EFFECT OF RU486 ON FOLLICULAR ATRESIA

To investigate whether the progesterone antagonist RU486 has a direct effect on ovarian function, it was administered to immature female rat s rendered hypogonadotrophic by administration of an LHRH antagonist a nd in which follicle development was stimulated by recombinant human F SH (recFSH). In the first experiments the effects of LHRH antagonist a nd recFSH on follicle growth were evaluated. Female rats of 22 days of age were injected with an LHRH antagonist (Org 30276; 500 mu g/100 g body weight) every other day. This treatment resulted in a tenfold dec rease in serum LH concentrations and a twofold decrease in serum FSH c oncentrations at day 30 and caused a reduction in the number and size of antral follicles. Treatment with recFSH (Org 32489) twice daily fro m day 26 for 4 days in a total dose ranging h-om 5 to 20 IU/animal inc reased the number and size of antral follicles in a dose-related manne r and resulted after 20 IU recFSH in a tenfold increase in the concent ration of inhibin in serum and ovaries at day 30. Once it was establis hed that LHRH antagonist treatment in immature rats could be used to s tudy the effects of gonadotrophins or steroids on follicle function, t his animal model was used to study the effects of RU486 on the ovary. RU486 was administered (twice daily for 4 days, 1 mg/injection) to LHR H antagonist-treated rats in which follicular growth and differentatio n were stimulated by 10 IU recFSH or by 10 IU recFSH plus 0.5 IU human chorionic gonadotrophin (hCG). RU486 had no effect on circulating lev els of LH and FSH, but stimulated follicular atresia both in rats trea ted with recFSH alone and in rats treated with recFSH and hCG. Inhibin concentrations both in serum and ovaries were significantly increased after hCG treatment. RU486, however, did not increase inhibin in the rats treated with recFSH and in those treated with recFSH and hCG. In summary, the present study has demonstrated that (1) immature rats tre ated with an LHRH antagonist can be used to study the effects of gonad otrophins and steroids on follicular function and (2) RU486 has a dire ct stimulatory effect on follicular atresia.