Effects of 25-hydroxycholesterol and aminoglutethimide in isolated rat adrenal cells. A model for congenital lipoid adrenal hyperplasia?

• Published in: Molecular and cellular endocrinology Vol. 4; no. 2; pp. 107 - 114
• Main Authors: Falke, H.E., Degenhart, H.J., Abeln, G.J.A., Visser, H.K.A.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 1976
• Subjects: 25-hydroxycholesterol; ACTH; adrenal cells; Adrenal Glands - drug effects; Adrenal Glands - metabolism; Adrenocortical Hyperfunction - metabolism; Adrenocorticotropic Hormone - pharmacology; aminoglutethimide; Aminoglutethimide - pharmacology; Animals; Cells, Cultured; Cholesterol - analogs & derivatives; congenital lipoid adrenal hyperplasia; Corticosterone - biosynthesis; Hydroxycholesterols - metabolism; Hydroxycholesterols - pharmacology; Male; Models, Biological; Rats; ACTH; aminoglutethimide; 25-hydroxycholesterol; congenital lipoid adrenal hyperplasia; adrenal cells
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/0303-7207(76)90030-7

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 μM. AGI also inhibits ACTH-stimulated steroid production from endogeneous substrates; here half-maximal inhibition is obtained with ca. 40 μM 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-3β, 24-diol. These results may just reflect substrate competition for the side-chain cleaving system or may be due to some secondary toxic effect on the cells.