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Department of Physiology and Biophysics, University of Illinois College of Medicine Chicago, Illinois 60612
the Department of Medicine, Stanford University School of Medicine and Geriatric Research Education and Clinical Centers, Veterans Administration Medical Center Palo Alto, California 94304
Experimental Station, Department of Central Research and Development, E. I. DuPont de Nemours and Co Wilmington, Delaware 19898
the Department of Biological Chemistry, Institute of Life Sciences, Hebrew University of Jerusalem Jerusalem 91904, Israel
Address all correspondence and requests for reprints to: Dr. Geula Gibori, Department of Physiology and Biophysics, University of Illinois, 835 South Wolcott, Chicago, Illinois 60612.
Abstract
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 P450BCC 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 P450BCC indicated no stimulatory effect of estradiol on the amount of enzyme; and 3) levels of P450BCC mRNA were not increased by estradiol. Whereas estradiol had no stimulatory effect on P450BCC, it caused a marked (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 P450BCC content or message.
Footnotes
* This work was supported by NIH Grant HD-11119 (to G.G.) and National Research Scientist Award HD-6982 (to M.P.M.).
Received April 4, 1989.
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