The direct role of estradiol and progesterone in sensitizing the adenohypophysis to the releasing action of LHRH (luteinizing hormone-releasing hormone) has been examined in rats bearing pituitary homografts. Groups (10-14/group) of virgin female rats (CDF) strain) were hypophysectomized, ovariectomized, and pituitaries obtained from long-term ovariectomized donors were implanted under the kidney capsule. The animals were treated on the sixth day after transplantation with sesame oil vehicle, estradiol (1.6 mug/100 g BW), progesterone (0.6 mg/100 g BW), or estradiol plus progesterone. This injection regimen was repeated 12 h later. Ninety minutes after the steroid injection on day 7 half of the animals in each group received LHRH (ip) and half received saline. Basal levels of LH in the steroid-treated groups not injected with LHRH were, in general, elevated as compared to the oil-injected group. Following LHRH, blood samples were collected by cardiac puncture under light ether anesthesia at 5, 15, 30, 60, and 90 min postinjection. Animals receiving LHRH responded with significant elevations of LH both in the presence and absence of steroids while saline was without effect. However, the magnitude of the LH peak was found to be significantly blunted by estrogen treatment. Moreover, the peak LH response to LHRH occurred 30 min following injection in all groups except the progesterone primed animals. In this group the peak LH was delayed by 30 min. These results suggest that estradiol directly inhibits the release of LH at the level of the pituitary and that the ovarian steroids, estradiol and progesterone probably interact to determine the time of optimal pituitary sensitivity to LHRH.

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