Biphasic Effect of Estradiol on Mechanisms Regulating LH Release in Ovariectomized Sheep

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Abstract
Single injections of 50 µ g estradiol-17β (E2β) into ovariectomized 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 E2β) 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 E2β 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 E2β-facilitated LH release. This transient and modest hypersensitivity does not completely account for the very large E2β-induced increases in plasma LH. Therefore, E2β probably increased endogenous LRF during the period of facilitated LH release.