Biphasic effect of estradiol on mechanisms regulating LH release in ovariectomized sheep

Single injections of 50 mug estradiol-17beta (E2beta) into overiectomized sheep caused biphasic changes in plasma luteinizing hormone (LH). An initial 8-h period of LH inhibition was followed by a period (12-20 h after E2beta) of facilitated LH release. Pituitary LH responsiveness to small dosages of synthetic gonadotropin-releasing hormone (GnRH) was tested repeatedly at 2-h intervals during the time periods when plasma LH was inhibited and when it was facilitated. Reduced sensitivity to GnRH (91% decrease) characterized only the initial 4 h of the inhibitory period, suggesting that E2beta suppressed endogenous LH-releasing factor (LRF) during the latter part of the inhibitory period. Hypersensitivity (2-fold increase) to GnRH was briefly observed at the beginning of the period of E2beta-facilitated LH release. This transient and modest hypersensitivity does not completely account for the very large E2beta-induced increases in plasma LH. Therefore, E2beta probably increased endogenous LRF during the period of facilitated LH release.