McLean M P, Puryear T K, Khan I, Azhar S, Billheimer J T, Orly J, Gibori G
Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago 60612.
Endocrinology. 1989 Sep;125(3):1337-44. doi: 10.1210/endo-125-3-1337.
A major action of estradiol in the corpus luteum of the pregnant rat is to increase the supply of cholesterol substrate for progesterone production by stimulating both cholesterol synthesis and uptake. To determine whether this steroid also affects cholesterol metabolism and transport, estradiol's action on the expression of cytochrome P450 side-chain cleavage enzyme (P450scc) and the cholesterol transport protein, sterol carrier protein-2 (SCP2), was examined. Mitochondria isolated from corpora lutea of estradiol-treated rats secreted significantly more progestagen than mitochondria of control corpora lutea. Several findings indicate that estradiol enhances cholesterol transport and availability to the P450scc rather than affects the expression of this enzyme: 1) the difference in mitochondrial progestagen synthesis induced by estradiol was obliterated by the presence of 25-hydroxycholesterol; 2) immunoblotting of P450scc indicated no stimulatory effect of estradiol on the amount of enzyme; and 3) levels of P450scc mRNA were not increased by estradiol. Whereas estradiol had no stimulatory effect on P450scc it caused a mark (3-fold) increase in the mitochondrial content of SCP2. Thus, the increase in luteal progestagen synthesis stimulated by estradiol appears to be associated with an increase in mitochondrial SCP2 and is independent of luteal P450 content or message.
雌二醇在妊娠大鼠黄体中的一个主要作用是通过刺激胆固醇合成和摄取来增加用于孕酮生成的胆固醇底物供应。为了确定这种类固醇是否也影响胆固醇代谢和转运，研究了雌二醇对细胞色素P450侧链裂解酶（P450scc）和胆固醇转运蛋白固醇载体蛋白2（SCP2）表达的作用。从经雌二醇处理的大鼠黄体中分离出的线粒体分泌的孕激素明显多于对照黄体的线粒体。几项研究结果表明，雌二醇增强了胆固醇向P450scc的转运和可用性，而不是影响该酶的表达：1）25-羟基胆固醇的存在消除了雌二醇诱导的线粒体孕激素合成差异；2）P450scc的免疫印迹表明雌二醇对酶的量没有刺激作用；3）雌二醇没有增加P450scc mRNA的水平。虽然雌二醇对P450scc没有刺激作用，但它使SCP2的线粒体含量显著增加（3倍）。因此，雌二醇刺激的黄体孕激素合成增加似乎与线粒体SCP2的增加有关，并且独立于黄体P450含量或信息。
