Steroid-C14 Metabolism in Bile Acid and Cholesterol-Treated Mice after Injection of Mevalonic Acid-2-C14.

Abstract

The effects of bile acid and cholesterol on the time-pattern of fecal steroid-C¹⁴ elimination was investigated in mice following a single injection of mevalonic acid-2-C¹⁴. In controls, excreted bile acid-C¹⁴ assayed 3 times sterol-C¹⁴ during the first 24 hours. This ratio reversed during the 2nd 24-hour period, and remained constant for the remainder of the 7-day experiment. Cholic acid depressed bile acid-C¹⁴ excretion, but failed to alter the time pattern of fecal sterol-C¹⁴ elimination. Cholesterol plus cholic acid depressed bile acid-C¹⁴ and increased α + β sterol-C¹⁴ excretion throughout the experiment. Hyodeoxycholic acid increased sterol-C¹⁴ excretion (shown to be of hepatic origin), had little effect on bile acid-C¹⁴ excretion, and increased total steroid-C¹⁴ eliminated. Lithocholic acid had a similar though smaller effect. After sacrifice, the livers of cholic acid-treated mice had twice the β-sterol-C¹⁴ concentration found in livers of controls, while those of mice treated with cholesterol plus cholic acid had β-sterol-C¹⁴ levels 4 times as high. Livers of lithocholic and hyodeoxycholic acid-treated animals showed reduced β-sterol-C¹⁴ levels. Carcass β-sterol-C¹⁴ levels were unaffected by any of the bile acids, but were lowered by the combination of cholesterol and cholic acid. The total amount of sterol-C¹⁴ synthesized from injected mevalonic acid was similar in all cases.