INVOLVEMENT OF ESTROGEN AND FOLLICLE-STIMULATING-HORMONE ON BASAL ANDLUTEINIZING-HORMONE (LH)-RELEASING HORMONE-STIMULATED LH-SECRETION INRU-486-INDUCED 3-DAY ESTROUS-CYCLE IN THE RAT

Administration of 4 mg of the antiprogestogen RU-486 on proestrus (Day 1) to 4-day-cyclic rats advances the pituitary desensitization to neg ative estrogen feedback and enhances pituitary responsiveness to LHRH. These effects of RU-486 lead to a 1-day estrous cycle shortening. Mor eover, administration of RU-486 in this study increased serum estradio l-17 beta and decreased FSH concentrations during diestrus (experiment 1). The aim of the study was to examine the contribution of the exces s of estrogen and the deficiency of FSH during diestrus to the 1-day e strous cycle-shortening effect of RU-486 when injected on Day 1 in 4-d ay-cyclic rats. The aim of the second and third experiments was to eva luate the effects of 3 mg/0.2 ml oil of the antiestrogen LY117018-HCl (LY) at 1800 h on Days 2 and 3, or 10 IU/0.2 ml saline of a recombinan t human FSH (rhFSH) at 1700 h on Day 3 and at 0900 h on Day 4, with or without 100 ng/0.5 ml saline of LHRH at 1200 h on Day 4, on uterine w eight and serum concentrations of LH and estradiol-17 beta at 1300 h o n Day 4 in rats given oil or RU-486 on Day 1 or 2. The aim of the four th experiment was to evaluate the effect of combined LY and rhFSH trea tments on uterine weight and serum levels of LH and estradiol-17 beta in rats injected with RU-486 on Day 1. Administration of RU-486 on Day 1 significantly increased serum estradiol-17 beta on Days 3 and 4, wh ereas administration on Day 2 slightly increased serum estradiol-17 be ta on Day 4 only. Injection of RU-486 on either Day 1 or 2 decreased F SH serum concentrations on Days 3 and 4 to a similar extent. Treatment with LY reduced both basal and LHRH-stimulated LH secretion only in r ats injected with RU-486 on Day 1, while rhFSH treatment attenuated ba sal and stimulated LH secretion regardless of treatment. Treatment wit h LY and rhFSH combined completely reversed the effects of RU-486 on D ay 1 on LH serum concentrations. These data suggest that both the incr eased estradiol-17 beta and the decreased FSH serum concentrations dur ing diestrus in rats given RU-486 on proestrus are involved in the cha nges of pituitary function leading to a 1-day estrous cycle shortening .