The effect of hypocholesterolemic drug treatment on adrenocortical cell function

• Published in: Biochimica et biophysica acta Vol. 751; no. 3; pp. 375 - 383
• Main Authors: McNamara, Brian C., Boyd, George S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 16.05.1983
• Subjects: Adrenal Cortex - drug effects; Adrenal Cortex Hormones - biosynthesis; Adrenocorticotropic Hormone - pharmacology; Animals; Anticholesteremic Agents - pharmacology; Cholesterol - blood; Hypocholesterolemic drug; In Vitro Techniques; Lipoprotein; Lipoproteins - metabolism; Rat adrenal cell; Rats; Steroidogenesis; ACTH; Steroidogenesis; Rat adrenal cell; Lipoprotein; Hypocholesterolemic drug; Hepes
• ISSN: 0005-2760; 0006-3002; 1879-145X
• DOI: 10.1016/0005-2760(83)90296-5

The role of exogenous lipoprotein cholesterol versus endogenous cholesteryl esters as substrates in adrenal Steroidogenesis was studied in isolated rat adrenal cells. Hypocholesterolemic drugs were used in rats to depress the plasma cholesterol concentration and the adrenal cholesterol concentration. Adrenal cortical cells were prepared in the usual way. The steroidogenic response to ACTH in normal adrenal cells and in cells which have been cholesterol-depleted was studied. Normal adrenal cells responded specifically over a 6 h incubation period to low doses of ACTH (half-maximal response equivalent to 40 μunits ACTH). These normal cells exhibited no altered response over a 3 h period to ACTH in the presence of serum or serum lipoproteins. The hypocholesterolemic drugs, 4-aminopyrazolo-[3,4-d]-pyrimidine, hexestrol and 17α-ethinyl estradiol were used to lower plasma cholesterol, and after 1 day of 4-aminopyrazolo-[3,4-d]-pyrimidine and 5 days of hexestrol or 17α-ethinyl estradiol treatment the plasma total cholesterol concentrations were similar. After 3 days of 4-aminopyrazolo-[3,4-d]-pyrimidine treatment the adrenal total cholesterol content was lower than after 1 day of this treatment, or 5 days of hexestrol treatment or 5 days of 17α-ethinyl extradiol treatment. Lipoproteins had no significant effect on ACTH-stimulated Steroidogenesis in cells isolated from rats treated for 1 day with 4-aminopyrazolo-[3,4-d]-pyrimidine, or for 5 days with hexestrol or 17α-ethinyl estradiol. However, lipoproteins did stimulate Steroidogenesis in cells from rats treated for 3 days with 4-aminopyrazolo-[3,4-d]-pyrimidine. The results show that normal adrenal cells contain a reserve of intracellular cholesterol so that the supply of endogenous cholesterol for Steroidogenesis does not limit the response to ACTH and exogenous lipoproteins have no effect on Steroidogenesis. However, if the cells are severely depleted of cholesterol then exogenous lipoproteins must be added for maximal Steroidogenesis to occur.