Effect of gonadotrophin-releasing hormone (GnRH) and GnRH agonists upon accumulation of progesterone, cAMP and prostaglandin in isolated preovulatory rat follicles

Abstract

To study the acute and direct effects of GnRH [gonadotropin releasing hormone] agonists preovulatory follicles were isolated from PMSG[pregnant mare serum gonadotropin]-treated immature rats and incubated for 15-360 min in modified Kreb''s bicarbonate buffer. The levels of cAMP, prostaglandin (PG) E, and progesterone were analyzed in the tissue and/or incubation media. GnRH and 2 GnRH agonists produced a dose-dependent stimulation of progesterone production with maximal levels 5- to 6-fold higher than in the control group. As compared to LH [luteinizing hormone] the magnitude of this effect was small and was detected only after 240-360 min of incubation. GnRH also stimulated PGE accumulation; this effect was as pronounced as for LH. There were no detectable changes in cAMP levels for any concentration of GnRH when the incubation time varied between 15 and 120 min whether a phosphodiesterase inhibitor was present, but after 240 min of incubation a 2-fold increase in cAMP was found. Consistent with previous results, LH caused a pronounced (40- to 50-fold) increase in follicular cAMP which was already detectable after 15 min of incubation. Indomethacin abolished the rise in PGE induced either by GnRH or LH but did not affect the response in terms of cAMP or progesterone, and did not affect the stimulation of meiotic maturation of the follicle-enclosed oocytes caused by the hormones. GnRH can exert acute and LH-like stimulatory effects on the preovulatory rat follicle but the mechanism of GnRH action is different from that of LH.