EFFECT OF ENDOGENOUS AND EXOGENOUS CHOLESTEROL ON THE FEEDBACK CONTROL OF CHOLESTEROL SYNTHESIS*

Abstract

The responseof the cholesterol feedback system to hypercholesterolemia of exogenous and of endogenous origins has been compared in the male chicken. Cholesterol feeding promptly inhibits cholesterol synthesis in the rooster, but stilbestrol treatment, despite the production of marked endogenous hypercholesterolemia, leads to normal or increased cholesterol synthesis for at least the first 10 days of treatment. These results suggest that the cholesterol feedback system may be more sensitive to exogenous than to endogenous cholesterol. It is concluded on the basis of crossinfusion experiments that stilbestrol administration influences the physical or chemical structure of the plasma cholesterol-lipopro-tein complex in a manner that prevents the concentration of cholesterol in the liver cell. The resulting failure of feedback control leads to increased synthesis of cholesterol which, in addition to the sequestration of the cholesterol in the blood, is responsible for stilbestrol-induced hyper cholesterolemia.