Control of ovarian cholesterol ester biosynthesis.
1. Experimental evidence is presented for a role of progesterone and 20alpha-hydroxypregn-4-en-3-one as inhibitors of cholesterol ester synthetase in the acute depletion of ovarian cholesterol ester after trophic stimulation. 2. Luteinizing hormone in vitro decreased by 84% the rate of esterification of cholesterol with added [(14)C]oleate by slices of rabbit ovarian interstitial tissue; this effect was mimicked by cyclic AMP (adenosine 3':5'-cyclic monophosphate) in vitro, and occurred without large changes in precursor pool sizes or membrane permeability. 3. Cyclic AMP was shown to have no direct effect on cholesterol ester synthetase or cholesterol esterase in cell-free extracts of rabbit ovarian interstitial tissue, but decreased the activity of cholesterol ester synthetase (not that of cholesterol esterase) in extracts prepared from slices previously incubated with it. 4. The inhibitory effect of cyclic AMP on esterification of cholesterol with added [(14)C]-oleate was prevented by both cycloheximide and aminoglutethimide phosphate (which also inhibited steroid synthesis in response to cyclic AMP). 5. Cyclic AMP raised the intracellular concentrations of progesterone and 20alpha-hydroxypregn-4-en-3-one in incubated slices by factors of 2.8 and 3.9 respectively. 6. Cycloheximide and aminoglutethimide phosphate administered in vivo blocked cholesterol ester depletion in response to luteinizing hormone in rats; in these ovaries cycloheximide and aminoglutethimide phosphate decreased the concentrations of progesterone and 20alpha-hydroxypregn-4-en-3-one and luteinizing hormone raised them. 7. Progesterone and 20alpha-hydroxypregn-4-en-3-one added to cell-free extracts of rabbit ovarian interstitial tissue in vitro (at concentrations comparable with those found in incubated slices) inhibited cholesterol ester synthetase by up to 85%. 8. The results are discussed with reference to the acute control of cholesterol ester concentrations in the ovary and adrenal cortex.
D000123:Acetyltransferases / Q000378:metabolism; D000616:Aminoglutethimide / Q000494:pharmacology; D000818:Animals; D002247:Carbon Isotopes; D002784:Cholesterol / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004950:Esterases / Q000378:metabolism; D004952:Esters / Q000096:biosynthesis; D005110:Extracellular Space; D005260:Female; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000494:pharmacology; D009829:Oleic Acids / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism; D011817:Rabbits; D013012:Sorbitol / Q000378:metabolism; D014316:Tritium
D002247:Carbon Isotopes; D004952:Esters; D009829:Oleic Acids; D000616:Aminoglutethimide; D014316:Tritium; D011374:Progesterone; D013012:Sorbitol; D007986:Luteinizing Hormone; D002784:Cholesterol; D003513:Cycloheximide; D000242:Cyclic AMP; D000123:Acetyltransferases; D004950:Esterases