Human follicular fluid from superovulated women inhibits progesterone receptor-dependent gonadotropin-releasing hormone self-priming in an estrous cycle-dependent manner in the rat

These experiments investigated the involvement of gonadotrope progesterone receptor (PR) in the effects of the putative gonadotropin surge-attenuating factor (GnSAF) on gonadotropin (LH and FSH) secretion. Human follicular fluids (hFF) used in this study were aspirated from follicles in gonadotropin-treated women for in vitro fertilization. Samples were subjected to two-fold charcoal extraction of steroid hormones and two-fold inhibin immunoprecipitation. Gonadotropin secretion parameters were assessed by specific radioimmunoassays. In the first experiment, the effects of hFF on both basal and GnRH-stimulated gonadotropin secretion and GnRH self-priming were studied in incubated hemipituitaries from rats on each day of the 4-day estrous cycle. hFF inhibited only GnRH self-priming in pituitaries from rats in diestrus. In the second experiment, immunohistochemical PR expression and action were evaluated in pituitaries from rats in diestrus. PR-positive (PR10A9 antibody) gonadotropes were detected (4–5/field 40x), and antiprogestins added to the incubation media blocked the ligand-independent (GnRH) activation of PR effects on GnRH self-priming. Finally, the third experiment evaluated the effects of hFF on P-induced potentiation of GnRH-stimulated LH secretion. GnSAF bioactivity, as evidenced by inhibition of PR-induced potentiation of GnRH-stimulated LH secretion, was found in diestrous pituitaries incubated with hFF. The results indicate that GnSAF attenuated GnRH-dependent LH secretion in diestrus through the inhibition of PR-dependent GnRH self-priming.