Effects of 25-hydroxycholesterol and aminoglutethimide in isolated rat adrenal cells. A model for congenital lipoid adrenal hyperplasia?
The production of corticosterone from 25-hydroxycholesterol by isolated rat adrenal cells is inhibited by aminoglutethimide phosphate (AGI); half-maximal inhibition is obtained at ca. 10 muM. AGI also inhibits ACTH-stimulated steroid production from endogeneous substrates; here half-maximal inhibition is obtained with ca. 40 muM AGI. In the presence of ACTH + AGI, 25-hydroxycholesterol causes additive inhibition. This effect of 25-hydroxycholesterol is dose-dependent. ACTH-stimulated steroid production from endogeneous substrates is partially inhibited by 5-cholene-3 beta,24-diol. These results may just reflect substrate competition for the side-chain cleaving system or may be due to some seocndary toxic effect on the cells.
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000308:Adrenocortical Hyperfunction / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000616:Aminoglutethimide / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives*; D003345:Corticosterone / Q000096:biosynthesis; D006888:Hydroxycholesterols / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008954:Models, Biological; D051381:Rats
D006888:Hydroxycholesterols; D000616:Aminoglutethimide; D000324:Adrenocorticotropic Hormone; D002784:Cholesterol; D003345:Corticosterone