Presence of a low molecular weight inhibitor of succinate-supported cholesterol side chain cleavage in rat ovaries.
1. Low molecular weight fractions (mol. wt. 3500-10 000) prepared from cytosols of luteinized rat ovaries inhibited succinate-supported cholesterol side chain cleavage by intact ovarian mitochondria utilizing endogenous or exogenous sterol as substrate. 2. The low molecular weight fractions inhibited steroid secretion by collagenase-dispersed ovarian cells stimulated with lutropin or dibutyryl cyclic AMP. 3. Steroidogenesis by intact mitochondria incubated with NADPH was enhanced by the low molecular weight ovarian fraction, but cholesterol side chain cleavage carried out by sonicated mitochondria incubated with NADPH was unaffected. 4. Succinate-supported mitochondrial respiration was stimulated by the low molecular weight factor, apparently by uncoupling of oxidative phosphorylation. The uncoupling seems to be the mechanism by which steroid synthesis is inhibited. 5. The low molecular weight factor was heat-labile and not extracted by activated charcoal. Similar heat-labile material capable of inhibiting succinate-supported mitochondrial steroid synthesis was not found in low molecular weight fractions prepared from rat kidney, liver, spleen, brain, plasma and bovine corpus luteum. 6. Treatment of rats with cycloheximide 1 h before killing resulted in a reduction of inhibitory activity in ovarian low molecular weight cytosolic fractions. 7. We conclude that ovarian cytosols contain a low molecular weight factor, presumably a protein, which inhibits mitochondrial cholesterol side chain cleavage by uncoupling oxidative phosphorylation. The physiological function of this factor remains to be determined.
D006907:17-alpha-Hydroxypregnenolone / Q000096:biosynthesis; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors*; D003513:Cycloheximide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000302:isolation & purification*; D005260:Female; D006358:Hot Temperature; D007986:Luteinizing Hormone / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D008970:Molecular Weight; D010053:Ovary / Q000201:enzymology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010101:Oxygen Consumption; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D013386:Succinates / Q000378:metabolism*
D004791:Enzyme Inhibitors; D013386:Succinates; D006907:17-alpha-Hydroxypregnenolone; D011374:Progesterone; D003994:Bucladesine; D007986:Luteinizing Hormone; D003513:Cycloheximide; D010088:Oxidoreductases; D002786:Cholesterol Side-Chain Cleavage Enzyme