RU486 ON AN ESTROGEN BACKGROUND BLOCKS THE RISE IN SERUM FOLLICLE-STIMULATING-HORMONE INDUCED BY ANTISERUM TO INHIBIN OR OVARIECTOMY

We used passive immunization with an antiserum to the alpha-subunit of inhibin (anti-I) or acute ovariectomy to investigate the relationship between serum inhibin levels and FSH secretion in the presence of the progesterone/glucocorticoid antagonist RU486. We demonstrated previou sly that 1) anti-I administered at 1700 h causes serum FSH to rise on the morning of estrus, even in the presence of a GnRH antagonist, when the two treatments are delivered on proestrus; and that 2) RU486 give n on proestrus (1230 h), a time when serum estradiol levels are high, not only blocks the natural secondary FSH surge, but also suppresses t he anti-I-induced rise in serum FSH on the morning of estrus. We have now extended our studies of the relationship between inhibin and RU486 to investigate treatment with RU486 and anti-I on a different day of the cycle, estrus, when serum estradiol levels are low. When both RU48 6 and anti-I were given on estrus (1230 and 1700 h, respectively), RU4 86 failed to block the anti-I-induced rise in serum FSH on the next mo rning of metestrus, in contrast to the blockade seen with RU486 treatm ent on the day of proestrus. However, pretreatment with estradiol benz oate (50 mu g) on the evening of proestrus, before the RU486 and anti- I treatment on estrus, caused RU486 to suppress the effects of anti-I on serum FSH, as it does when given on proestrus. We then repeated the study, using ovariectomy on proestrus or estrus (1700 h) to raise ser um FSH, and assessed the effects of RU486 treatment at proestrus and e strus and estradiol benzoate treatment on proestrus. Our results indic ate that treatment with RU486 can block the postovariectomy rise in se rum FSH only in the presence of high circulating estradiol levels. We conclude that the inhibitory action of RU486 on FSH secretion after a fall in serum inhibin depends on a precedent estradiol background, pro bably due to induction of progesterone receptors by estradiol.