Involvement of estrogen and follicle-stimulating hormone on basal and luteinizing hormone (LH)-releasing hormone-stimulated LH secretion in RU-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 negative estrogen feedback and enhances pituitary responsiveness to LHRH. These effects of RU-486 lead to a 1-day estrous cycle shortening. Moreover, administration of RU-486 in this study increased serum estradiol-17beta and decreased FSH concentrations during diestrus (experiment 1). The aim of the study was to examine the contribution of the excess of estrogen and the deficiency of FSH during diestrus to the 1-day estrous cycle-shortening effect of RU-486 when injected on Day 1 in 4-day-cyclic rats. The aim of the second and third experiments was to evaluate 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 recombinant 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 weight and serum concentrations of LH and estradiol-17beta at 1300 h on Day 4 in rats given oil or RU-486 on Day 1 or 2. The aim of the fourth experiment was to evaluate the effect of combined LY and rhFSH treatments on uterine weight and serum levels of LH and estradiol-17beta in rats injected with RU-486 on Day 1. Administration of RU-486 on Day 1 significantly increased serum estradiol-17beta on Days 3 and 4, whereas administration on Day 2 slightly increased serum estradiol-17beta on Day 4 only. Injection of RU-486 on either Day 1 or 2 decreased FSH serum concentrations on Days 3 and 4 to a similar extent. Treatment with LY reduced both basal and LHRH-stimulated LH secretion only in rats injected with RU-486 on Day 1, while rhFSH treatment attenuated basal and stimulated LH secretion regardless of treatment. Treatment with LY and rhFSH combined completely reversed the effects of RU-486 on Day 1 on LH serum concentrations. These data suggest that both the increased estradiol-17beta and the decreased FSH serum concentrations during diestrus in rats given RU-486 on proestrus are involved in the changes of pituitary function leading to a 1-day estrous cycle shortening.