Studies on isolated rat adrenal cells metabolism of hydroxylated sterols

Corticosterone production by isolated rat adrenal cells in the absence of ACTH is stimulated by 20alpha-hydroxycholesterol, 22R-hydroxycholesterol and 25-hydroxycholesterol. This effect is also seen at sub-maximal ACTH concentrations. Aminoglutethimide (AGI) inhibits the stimulation caused by the three hydroxylated cholesterols. In the presence of ACTH, AGI also inhibits steroid production both under control conditions and in the presence of the sterols. The stimulation by 25-hydroxycholesterol is dose-dependent, both in the presence and absence of a sub-maximal ACTH concentration. At maximal ACTH concentrations 25-hydroxycholesterol does not give additional stimulation. Cycloheximide has no effect on corticosterone production from 25-hydroxycholesterol whether ACTH is present or not. Our results indicate that 25-hydroxycholesterol is a good substrate for the study of the cholesterol side-chain cleaving system and the mechanism of action of ACTH at the levels of the intact cell.