Effect of Endogenous and Exogenous Cholesterol on the Feedback Control of Cholesterol Synthesis.

The feeding of cholesterol has been found to result in a prompt suppression of hepatic cholesterol synthesis in all experimental animals thus far studied (1-4). Although the animal body, therefore, has available an effective negative feedback system that can minimize the effects of excessive amounts of exogenous cholesterol, it is not known to what extent this mechanism will respond to hypercholesterolemia of endogenous synthetic origin. The present studies were designed to compare the influence of endogenous and of exogenous hypercholesterolemia upon the feedback control of cholesterol synthesis. Exogenous hypercholesterolemia was produced by feeding chickens a 1 or 2% cholesterol diet for a period of 2 days to 3 weeks. As an experimental model of an endogenous hypercholesterolemic state, use was made of chickens treated for comparable periods with stilbestrol (a,a'-diethylstilbenediol) at a dosage of 5 mg per day, a procedure that is known to produce marked hypercholesterolemia within 2 to 3 days (5). The results of this study demonstrate that the cholesterol feedback system in the chicken is promptly activated by exogenous cholesterol; in contrast, however, the comparable hypercholesterolemia produced by the administration of stilbestrol does not cause a depression in cholesterol synthesis for a period of at least 10 days. Furthermore, the administration of stilbestrol will actually inhibit the feedback response to exogenous