Progestins inhibit FSH-induced functional LH receptors in cultured rat granulosa cells.

The role of intraovarian progesterone in the control of follicular growth and development remains unclear. The presence of a rat ovary granulosa cell progesterone receptor suggests that progesterone has a direct effect on the follicles. We have previously reported that progestins inhibit FSH-stimulated estrogen production by cultured granulosa cells by inhibiting the FSH induction of the aromatase enzyme. We now report that progestins can inhibit another FSH action on rat granulosa cells; the induction of LH/hCG receptors. The concomitant administration of 10(-5) M R5020, a potent synthetic progestin, with 10 ng/ml FSH during a 2-day culture period inhibits the FSH induction of LH/hCG receptors by 75 +/- 6% (mean +/- S.E.) The progestin inhibition of the induction of LH/hCG receptors is not mediated by its inhibitory action on the induction of aromatase. Scatchard analysis indicates that progestin decreases the number of LH/hCG receptors per cell but has no effect on receptor affinity. Both R5020 and progesterone have a dose-dependent inhibitory effect on the FSH induction of LH/hCG receptors, causing a 30 and 85% decrease in receptor number at concentrations of 10(-6) and 10(-5) M, respectively. The concomitant administration of R5020 with FSH also leads to a significant decrease in the ability of LH to stimulate cAMP production, indicating that progestin is inhibiting the induction of 'functional' LH/hCG receptors. R5020 (10(-5) M) also inhibits by 90% the induction of LH/hCG receptors by cholera toxin and dibutyryl cAmP, indicating that the progestin effect is at a post-cAMP site. Since the induction of LH/hCG receptors by FSH is a necessary event in follicular maturation, these results offer another mechanism by which progestins, at high concentrations, can inhibit follicular growth and development.