RU486 blocks the effects of inhibin antiserum or luteinizing hormone on the secondary follicle-stimulating hormone surge.

Abstract

Previous work in this laboratory has shown that when the antiprogesterone RU486 is administered at 1230 h on proestrus, the primary surges of LH and FSH are significantly attenuated, and the secondary FSH surge is abolished. This suppression of the secondary FSH surge occurs in RU486-treated rats despite a drop in serum inhibin, which is presumably due to the partial primary LH surge. The experiments described investigated the interrelationships among the primary LH surge, the rising proestrous levels of progesterone, and the falling levels of inhibin on proestrus on the selective secretion of FSH during the night of proestrus and the morning of estrus. Exogenous LH given to rats treated first with RU486 cannot restore the secondary surge of FSH, as it does in GnRH antagonist-blocked rats, and progesterone alone cannot restore the secondary FSH surge in an animal in which the surges are blocked with GnRH antagonist. Antiserum to inhibin superimposed on GnRH antagonist causes an enhancement of FSH levels beyond that of the secondary FSH surge, but antiserum to inhibin superimposed on RU486 does not induce a similar elevation of FSH secretion. The failure of antiserum to inhibin to increase FSH in the face of RU486 suggests that either a small amount of progesterone, or perhaps another hormone blocked by RU486, is needed to facilitate FSH secretion in response to the drop in inhibin or RU486 is acting through nonprogesterone-mediated effects to block pituitary FSH secretion.