Effect of catecholamines on the hepatic rate-limiting enzymes of cholesterol metabolism in normally fed and cholesterol-fed rabbits.

Adrenergic control of liver cholesterol metabolism was studied in the rabbit. The effects of noradrenaline (alpha 1, alpha 2, beta 2 agonist) and isoprenaline (beta 1, beta 2 agonist) on 3-hydroxy-3-methylglutaryl coenzyme A reductase, acyl-coenzyme A: cholesterol-o-acyltransferase (cholesterol acyltransferase) and cholesterol 7 alpha-hydroxylase, the rate-limiting enzymes of cholesterol biosynthesis and esterification and bile acid synthesis, respectively, were examined in the normally fed and cholesterol-fed male New Zealand White rabbit. Isoprenaline increased the activities of hydroxymethylglutaryl CoA reductase and cholesterol acyltransferase approx. 12-fold and 5-fold, respectively, in normally fed rabbits. Noradrenaline, by contrast, produced an effect only on hydroxymethylglutaryl CoA reductase, the activity of which was increased 3-fold in these animals. Neither catecholamine had an effect on hydroxymethylglutaryl CoA reductase in the cholesterol-fed rabbit. Isoprenaline decreased the activity of cholesterol acyltransferase by approx. 40% and increased the activity of cholesterol 7 alpha-hydroxylase 2-fold in the cholesterol-fed rabbit compared to cholesterol-fed controls. Noradrenaline had no effect on either cholesterol acyltransferase or cholesterol 7 alpha-hydroxylase in either the normally fed or the cholesterol-fed rabbit. We suggest that beta 2-adrenergic stimulation by isoprenaline in the normally fed rabbit may enhance cholesterol synthesis and storage, but that in the cholesterol-fed rabbit, it facilitates the elimination of cholesterol from the body by increasing the rate of bile acid synthesis.