Conversion of 22S-hydroxy-cholesterol and its effects on the metabolism of other sterols in rat adrenal cells and bovine adrenal mitochondria.
This study provides evidence that 22S-OH-cholesterol inhibits the conversion of 25-OH-cholesterol but has no effect on the conversion of 22R-OH-cholesterol. The latter sterol is an intermediate in the cholesterol side-chain cleavage, whereas for the conversion of 25-OH-cholesterol into pregnenolone the complete side-chain cleaving enzyme system is necessary. This complements a previous study in which it was shown, that 22S-OH-cholesterol has an inhibitory effect on the ACTH-induced conversion of cholesterol into corticosterone in isolated rat adrenal cells. The available evidence thus suggests an inhibition by 22S-OH-cholesterol of the first step in the cholesterol side-chain cleavage. The results, obtained from the experiments with rat adrenal cells and with bovine adrenal mitochondria, allow the hypothesis, that a causal relationship exists between conversion of 22S-OH-cholesterol and production of corticosterone, respectively pregnenolone. We conclude, that 22S-OH-cholesterol is a substrate for steroid production in the adrenal cell. This sterol inhibits the ACTH-stimulated corticosterone production. The site of this inhibition is located at one of the first steps in the cholesterol side-chain cleavage, probably the binding of cholesterol to the cytochrome P450-complex.
D000311:Adrenal Glands / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D002849:Chromatography, Gas; D003345:Corticosterone / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006888:Hydroxycholesterols / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D011284:Pregnenolone / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D006888:Hydroxycholesterols; C003585:22-hydroxycholesterol; C035465:22-ketocholesterol; D011284:Pregnenolone; C007997:25-hydroxycholesterol; D000324:Adrenocorticotropic Hormone; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D003345:Corticosterone