Gonadotropin-releasing hormone inhibits cyclic nucleotide accumulation in cultured rat granulosa cells.
Ovarian granulosa cells obtained from hypophysectomized, diethylstilbestrol-treated rats were cultured in the presence of ovine follicle-stimulating hormone (FSH) and gonadotropin-releasing hormone (GnRH). FSH stimulated the production and accumulation of both cAMP and cGMP, as well as progesterone, during a 48-h incubation period. Addition of GnRH or an agonist analog, [D-Ala6]des-Gly10-GnRH N-ethylamide (GnRHa), did not influence the cyclic nucleotide response to FSH in the first 6 h of incubation, but caused dose-dependent inhibition of the FSH-induced rise in cyclic nucleotide production from 24 to 48 h of incubation. Cellular production of both cyclic nucleotides and progesterone was decreased by GnRHa concentrations as low as 10(-12) M, with maximum inhibition at 10(-9) M GnRHa. These results suggest that the in vitro antigonadal actions of GnRH and related peptides are expressed through inhibition of cyclic nucleotide production.
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004054:Diethylstilbestrol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D007016:Hypophysectomy; D007700:Kinetics; D051381:Rats
D007987:Gonadotropin-Releasing Hormone; D004054:Diethylstilbestrol; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D006152:Cyclic GMP