Hormonal regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA in the rat adrenal gland.

We studied the effect of ACTH on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase enzyme. Reductase activity and reductase mass were enhanced by 22- and 6.2-fold respectively in one series of experiments, whereas in another the levels of reductase activity, reductase mass, and reductase mRNA were increased 6.6-, 3.6- and 2.2-fold respectively, following daily administration of exogenous ACTH for 3 days. Daily injection of 4-aminopyrazolopyrimidine (4-APP) to rats for 3 days increased circulating ACTH level 5.4-fold, whereas adrenal HMG-CoA reductase activity, reductase mass and reductase mRNA levels were greatly increased 36-, 10- and 16-fold, respectively. To counteract the effect of elevated plasma ACTH, dexamethasone acetate (Dex) was administered to 4-APP treated rats. At 3 h post Dex administration, plasma ACTH and corticosteroids levels were effectively decreased by 58 and 59%, respectively. The levels of adrenal HMG-CoA reductase mRNA, reductase activity and reductase mass were also diminished by 38, 31 and 40%, respectively. Our results show that rat adrenal HMG-CoA reductase can respond rapidly to hormonal changes, presumably through variations in circulating ACTH levels.