Gonadotropin-releasing hormone-induced desensitization may account for the decrease in pituitary responsiveness after...

The LH secretory response of gonadotropes to GnRH varies during the estrous cycle of the rat. The increased secretion of estrogens during the 24-48 h before the preovulatory surge of LH secretion and the enhanced quantities of progesterone secreted acutely during the surge elevate the responsiveness of hypophysial gonadotropes to GnRH. However, the cause of the massive decline in GnRH responsiveness that occurs during or after the surge remains unknown. In the present studies, we investigated the possibility that it is due to GnRH-induced desensitization of gonadotropes. Dispersed pituitary cells from proestrous and estrous rats were preincubated with GnRH (3 or 6 h, 10(- 10) or 10(-9) M), progesterone (13 h, 100 or 200 nM), GnRH plus progesterone, or medium alone. Then, the cells were retrypsinized to permit performance of the reverse hemolytic plaque assay for measurement of LH secretin, during which they were treated with GnRH(0,10(-11),10(-10), and 10(-8)M) for 2 h. The cells from estrous animals showed the large decline in GnRH responsiveness typical of that day of the cycle compared to those from proestrous animals (the total amount of LH secreted decreased by 50-70%). Preincubation of cells from proestrous rat pituitary glands with GnRH in concentrations and for durations that were designed to mimic the physiological situation induced a decline in GnRH responsiveness similar to that observed at estrus. Preincubation with progesterone also reduced the pituitary responsiveness to GnRH in a dose-dependent manner, but did not show additive effects with GnRH. Our results suggest that the major increase in GnRH secretion that induces the preovulatory surge of LH secretion may also participate in inducing the major decrease in pituitary responsiveness to GnRH that occurs from proestrus to estrus.