EVIDENCE THAT ANDROGENS ARE INVOLVED IN ATRESIA AND ANOVULATION INDUCED BY ANTIPROGESTERONE RU486 IN RATS

Administration of antiprogesterone RU486 to female cyclic rats results in blockade of ovulation associated with both a decreased ovulatory r elease of LH and an increased rate of follicular atresia. These rats a lso exhibit increased LH:FSH and testosterone:oestradiol ratios in ser um during the period of follicular development as well as an increase in serum concentrations of prolactin that can be suppressed by a dopam ine agonist. The increase in either prolactin or testosterone concentr ations as well as the relative deficiency in FSH might be responsible for the increase in follicular atresia. The present work evaluated the involvement of LH, FSH, prolactin and testosterone in follicular atre sia and in blockade of ovulation induced by RU486 in the cyclic rat. A lthough bromocriptine treatment did not modify the blockade of ovulati on induced by RU486, unilateral ovariectomy at metoestrus and anti-and rogen flutamide treatment reversed, in part, the effects of RU486 on b oth follicular development and ovulation. The combined increase in FSH serum concentration during dioestrus induced by unilateral ovariectom y and the treatment with flutamide had no additive effects. Furthermor e, treatment with a superovulatory amount of hFSH did not reverse the effects of RU486. Moreover, unilateral ovariectomy halved testosterone serum concentrations and flutamide treatment had no effect on LH and FSH concentrations in RU486-treated rats. It was therefore concluded t hat androgens play a role, at least in part, in the process of follicu lar atresia induced by RU486.