Direct Effects of Gonadotropin Releasing Hormone and Its Antagonist upon Ovarian Functions Stimulated by FSH, Prolactin, and LH1

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Abstract
The role of gonadotropin releasing hormone (GnRH) and its antagonist, [D-pGlu1, D-Phe2-D-Trp3,6] GnRH, in the direct regulation of ovarian functions was studied in vivo and in vitro. Immature hypophysectomized rats were treated twice daily with FSH [follicle stimulating hormone] in the presence or absence of 30 .mu.g GnRH or 500 .mu.g antagonist or both. GnRH inhibited FSH stimulation of ovarian weight as well as LH receptor content and aromatase activity in the ovarian granulosa cells. Concomitant treatment with the antagonist blocked the inhibitory effect of GnRH. In cultured granulosa cells, GnRH treatment resulted in time-dependent inhibition of FSH-induced increase in estrogen and progesterone production; addition of the antagonist to these cells reversed the inhibitory effect of GnRH in a time-related manner. Priming with FSH for 2 days in vitro induced functional PRL [prolactin] and LH [luteinizing hormone] receptors. Subsequent treatment with PRL for 2 days stimulated progesterone production and LH receptor content of these cells in vitro. PRL stimulation of LH receptor and progesterone production was inhibited by GnRH, whereas concomitant treatment with the antagonist blocked the GnRH inhibition. The GnRH inhibition of PRL-stimulated progesterone production was time-dependent and the addition of the antagonist to cells treated with PRL and GnRH reversed the GnRH inhibition in a time-related manner. LH treatment of FSH-primed granulosa cells stimulated both estrogen and progesterone production, whereas GnRH inhibited the LH-stimulated steroidogenesis. Concomitant treatment with the antagonist blocked the GnRH inhibition of the LH effect. The antagonist blocked the GnRH inhibition of cholera toxin-induced estrogen and progesterone production in cultured granulosa cells. The direct inhibitory effect of GnRH on ovarian functions maintained by FSH, LH, PRL, and cholera toxin and the ability of a GnRH antagonist to block the GnRH inhibition in a time- and dose-related manner were demonstrated.