title: Effects of 22S-hydroxy-cholesterol and other hydroxylated sterols on the ACTH-stimulated steroid production in rat adrenal cells.
abstract: Several effects of hydroxylated sterols on cell cultures are known. Most of these can be explained by an inhibition of the cholesterol synthesis at the level of the 3-hydroxy-3-methylglutaryl CoA reductase. When studying cholesterol metabolism in rat adrenal cells, an inhibitory action of some sterols on the ACTH-stimulated corticosterone production was observed. The effects of one sterol, 22S-OH-cholesterol, were investigated further. The sterol had no effect on the ACTH-stimulated cyclic AMP production, suggesting an intact receptor-adenylate cyclase complex and cellular membrane. In the presence of ACTH and 22-OH-cholesterol particularly the free cholesterol concentration was elevated; 22S-OH-cholesterol therefore probably exerts its inhibitory effect at a step located after hydrolysis of the cholesterol esters. 22S-OH-cholesterol had no effect on the conversion of exogenous pregnenolone into corticosterone. These results make it probable, that the inhibitory effect of 22S-OH-cholesterol on the ACTH-stimulated corticosterone production is situated at the level of the cholesterol side-chain cleavage.
mesh_terms: D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002775:Cholestadienols / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology; D003345:Corticosterone / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000378:metabolism; D003897:Desmosterol / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007653:Ketocholesterols / Q000494:pharmacology; D008297:Male; D011284:Pregnenolone / Q000378:metabolism; D051381:Rats; D013261:Sterols / Q000494:pharmacology
chemical_list: D002775:Cholestadienols; D006888:Hydroxycholesterols; D007653:Ketocholesterols; D013261:Sterols; C003585:22-hydroxycholesterol; D003897:Desmosterol; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D002784:Cholesterol; D000242:Cyclic AMP; C015582:zymosterol; D003345:Corticosterone