Feedback Control of Cholesterol Biosynthesis in the Mouse. ∗

Summary

Effects of cholic acid on biosynthesis of hepatic cholesterol and bile acids were studied. Mice maintained on a basal diet, or this diet supplemented with 0.5% cholic acid, received single intraperitoneal injections of mevalonic acid-2-C¹⁴ or choles-terol-4-C¹⁴. Feces were collected at 24-hour intervals, fecal steroid-C¹⁴ was isolated and fractionated, α + β-sterol-C¹⁴ and bile acid-C¹⁴ were determined. In control mice the distribution of C¹⁴ activity in fecal steroids was 60% in the sterol fraction and 40% in the bile acid fraction. This ratio was constant with time after the first 24-hour interval, regardless of the substance injected. It was shown that cholic acid brings about equal decreases in the rates of both hepatic cholesterol and bile acid biosyntheses. Since a preceding study had shown that the rate of bile acid synthesis in mouse liver is inhibited by cholic acid independently of its effect on cholesterol synthesis, it was concluded that the rate of hepatic cholesterol biosynthesis in mice is controlled by cholic acid and its conjugates by means of a double feedback reaction.