Direct Inhibitory Effect of Gonadotropin-Releasing Hormone upon Luteal Luteinizing Hormone Receptor and Steroidogenesis in Hypophysectomized Rats*

Publisher Website
Google Scholar
Abstract
The effects of gonadotropin-releasing hormone (GnRH) and its potent agonist [des-Gly10, D-Leu6-(N Me) Leu7, Pro9,NHEt-GnRH (GnRH-A)] on ovarian luteal functions maintained by PRL were studied in vivo and in vitro. Hypophysectomized, diethylstilbestrol-treated female rats were primed with FSH for 2 days, followed by an ovulating dose of LH or hCG. Two days later, ovarian luteal functions were maintained by daily injections of 250 μg PRL for 3 days. PRL treatment increased the serum progesterone level from 13.0 ± 0.5 to 298 ± 24 ng/ml and increased the ovarian hCG-binding capacity from 5.8 ± 1.3 to 584 ± 86 ng bound hCG/ovary. In contrast, concomitant treatment with GnRH or GnRH-A resulted in dosedependent decreases in the PRL-induced increase of serum progesterone and ovarian LH/hCG receptor content. GnRH at 100 μg/day caused a 60% decrease in serum progesterone and an 80% decrease in ovarian LH receptor content, whereas GnRH-A was effective at a 1-μg dose level. Neither GnRH nor GnRH-A affected the binding affinity (Kd) of ovarian LH receptor. The direct inhibitory effects of GnRH and GnRH-A upon granulosaluteal cell function were also tested in vitro. FSH treatment for 2 days induced functional LH and PRL receptors in cultured granulosa cells. Subsequent treatment with LH, followed by PRL, increased (by ∼3-fold) progesterone production by these granulosa-luteal cells, whereas concomitant treatment with GnRH-A inhibited progesterone production in a dose-dependent manner. Thus, these studies demonstrated that GnRH and GnRH-A exert direct inhibition on ovarian luteal functions by decreasing LH receptor and progesterone production in vivo as well as inhibiting progesterone production by cultured granulosaluteal cells in vitro.