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

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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.