Feedback Control of Cholesterol Biosynthesis in the Mouse.

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Abstract
The effects of cholic acid on biosynthesis of hepatic cholesterol and bile acids were studied. Control mice and mice maintained on a diet supplemented with cholic acid were given single injections of mevalonic acid-2-C-14 or cholesterol-4-C-14. Feces were collected at 24-hour intervals, fecal steroid-C-14 fractionated, and [alpha] + [beta] sterol-C-14 and bile acids-C-14 determined. In control mice, C-14 activity in fecal steroids was distributed 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. Cholic acid affected an equal decrease in the rates of biosyntheses of hepatic cholesterol and bile acids. Under certain conditions, cholic acid decreased bile acid synthesis 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 through a double feedback reaction.[image].