The role of glucocorticoids in the regulation of the diurnal rhythm of hepatic β hydroxy β methylglutaryl coenzyme A reductase and cholesterol 7α hydroxylase

Abstract

The microsomal activities of the hepatic enzymes hydroxymethylglutaryl CoA reductase and cholesterol 7α hydroxylase exhibit a diurnal rhythm with maximum activities observed during the dark period and minimum activities around noon (12:00 hr). This diurnal rhythm was maintained for both enzymes after adrenalectomy, but the amplitude of variation for the activity of both enzymes was greatly decreased. A single injection of cortisol administered to adrenalectomized rats 3 hr before the expected maximum in enzyme activity resulted in a twofold increase in the activity of both enzymes 3 hr later, at values similar to those observed for control rats killed at the same time. This response appeared to require protein synthesis, since it was blocked by actinomycin D. However, the administration of cortisol to adrenalectomized rats 3 hr before the expected minimum did not result in significant change in the activity of hydroxymethylglutaryl CoA reductase and cholesterol 7α hydroxylase 3 hr later. Kinetic studies of cholic acid 14C metabolism in vivo demonstrated that adrenalectomy results in a significant decrease in the rate of synthesis of cholic acid and a considerable decrease in the pool size of cholic acid and its metabolic products. Treatment of adrenalectomized rats with cortisol increased the rate of synthesis of cholic acid and restored the pool size. These results are consistent with the effects of adrenalectomy and cortisol treatment on the activity of cholesterol 7α hydroxylase.