Differential Feedback Regulation by 17?-Estradiol of LH Production and LHRH-Responsiveness in Adenohypophyseal Cell Cultures

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Abstract
To evaluate the direct effects of 17β-estradiol (E2) on pituitary LH release, cellular LH content, and LHRH-gesponsive-ness, physiological doses of E2 (10−10, 10−9, or 10−8M) were tested in pituitary monolayer cultures of female rats. The effects of E2 appeared to be dose-related. After a4 h incubation, basal LH release was significantly stimulated by lO−10M E2 (176% of control level) whereas 10−10M or 10−8M had no effect. The cellular LH content was significantly stimulated by 10−8M E2 (127% of control level) but not by the lower doses of E2. Both 10−8M and 10−9m E2 but not 10−10M E2 stimulated LH production (sum of LH contents in medium and cells). When the cultures were incubated with 10−8M LHRH, cellular LH content was depressed (76% of control level) by 10−8M E2 coincubation, whereas LH release was not altered. To further explore the interaction between E2 and LHRH, extended preincubation times with 10−8M E2 were used to test its effect on the subsequent LHRH-responsiveness. After a lag period, preincubation with 10−10E2 for 48 or 72 h decreased the subsequent LH release in response to 10−8M LHRH with a coincident increase in cellular LH content. These data indicate that depending on the concentration, the duration of exposure, and its interaction with LHRH, E2 exerts either stimulatory or inhibitory effects on LH-producing cells. The evidence of multiple levels of E2 feedback on the pituitary LH release, production, or response to LHRH, which may be regulated independently by E2, provides the means for biphasic E2 actions on LH secretion.