Regulation of hamster adrenal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity.

Abstract

In the adrenal gland of the hamster, the activity of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase [mevalonate:NADP+ oxidoreductase (acylating CoA); EC 1.1.1.34] is mainly located in the postmitochondria fraction. This enzyme exhibits a diurnal rhythm, with a maximum at 1900 h. Peak activity levels are about 1667 pmol/mg protein . min, roughly 8 times the minimum levels. Plasma corticosteroid concentrations closely parallel reductase activity levels. The administration of ACTH or metyrapone (a drug which increases in vivo ACTH secretion) to hamsters enhanced the adrenal reductase activity, whereas aminoglutethimide, an inhibitor of the side chain cleavage of cholesterol, diminished it. The feeding of a 5% cholesterol diet and treatment with 4-aminopyrazolopyrimidine resulted in an increase and a decrease in plasma cholesterol, respectively. Neither treatment significantly altered adrenal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity or the cholesterol content of the gland. Hamster adrenals contain very little free cholesterol (7-11 microgram/mg protein) and even less esterified cholesterol (0.5-2.0 microgram/mg protein). These findings suggest that in the hamster the adrenal gland may be largely autonomous in cholesterol production.