Regulation of luteal cell lipoprotein receptors, sterol contents, and steroidogenesis by estradiol in the pregnant rat.

Although estradiol has been found to possess receptors in the luteal cell and to stimulate progesterone synthesis, its mechanism of action in the corpus luteum remains completely unknown. To determine whether estradiol modulates cellular uptake of lipoprotein substrate and intracellular cholesterol utilization, pregnant rats were hypophysectomized and hysterectomized on day 12 to reduce the luteal content of estradiol. They were treated with either 100 micrograms estradiol daily or with a 1-cm capsule filled with testosterone, which maintained luteal estradiol at levels found in intact pregnant rats. Blood was obtained 24, 48, and 72 h later for progesterone and cholesterol measurement. At 72 h, rats were killed, and corpora lutea (CL) were isolated for measurement of cholesteryl ester, free cholesterol, and [125I]iodo high density lipoprotein [( 125I]iodo-HDL)- and [125I]iodo-hCG-binding activities. In vivo treatment with estradiol or testosterone increased serum progesterone concentrations from 35 +/- 7 ng/ml in vehicle-treated rats to 128 +/- 21 and 118 +/- 16, respectively, and luteal weight from 2.1 +/- 0.2 mg/CL to 3.9 +/- 0.3 and 4.0 +/- 0.3 within 72 h. However, steroid treatment did not induce a change in luteal cell number, since the content of DNA per CL remained similar in all groups. It also did not modify levels of serum cholesterol. [125I]Iodo-HDL binding in luteal cells increased from 3.2 +/- 0.3 pg/cell in vehicle-treated rats to 9.9 +/- 0.8 and 7.9 +/- 0.6 after estradiol or testosterone treatment, while the luteal cell content of cholesteryl ester declined from 12.5 +/- 2.0 to 7.7 +/- 0.5 and 8.4 +/- 0.9 micrograms/CL, respectively. Thus, estradiol or testosterone increases luteal cell size but not cell number, depletes cholesteryl ester, and enhances HDL receptor content and progesterone synthesis. These results suggest that one possible mechanism by which estradiol and testosterone stimulate luteal cell steroidogenesis is by increasing the delivery of cholesterol substrate through a receptor-mediated process and by enhancing cholesterol utilization.