Nonisotopic method for estimating cholesterogenesis in the rat.
Influence of several compounds on sterol production was determined from serum desmosterol (D) levels in rats treated with U-18666A:3beta-(2-diethylaminoethoxy) androst-5-en-17-one HCl. U-18666A blocks biosynthesis of cholesterol (C) by inhibiting conversion from D to C. Diets containing C (2%), the bile acid sequestrant colestipol HCl (1%), clofibrate (0.2%), combination of colestipol HCl and clofibrate, or basal diet were fed to normal or U-18666A (3 mg/kg/d) mald rats for 2 weeks. In normal rats, C feeding increased serum C levels (39%), colestipol HC l had no significant effect, while clofibrate or the combination with colestipated rats, C feeding reduced D concentration (30 to 13 mg/dl) indicating inhibition of synthesis via negative feedback system. Colestipol HCl increased D level (33%) and reduced C (60%) indicating increased synthesis; results are compatible with an agent capable of binding bile acids in the rat which can compensate for loss of these acids by increasing sterol synthesis. Compared to control, clofibrate reduced serum C (33%) and D (43%); in combination with colestipol HCl it inhibited the increased synthesis caused by the latter. Clofibrate appears to be an inhibitor of C biosynthesis. Also, tests with other compounds make it apparent that the U-18666A-treated rat model system can be useful in evaluating cholesterogenesis.
D000736:Androstenes / Q000494:pharmacology; D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood / Q000494:pharmacology; D002791:Cholesterol, Dietary; D002792:Cholestyramine Resin / Q000494:pharmacology; D002994:Clofibrate / Q000494:pharmacology; D003897:Desmosterol / Q000097:blood*; D008297:Male; D008698:Mesylates / Q000494:pharmacology; D009539:Nicotinic Acids / Q000494:pharmacology; D051381:Rats; D013974:Thyroxine / Q000494:pharmacology
D000736:Androstenes; D002791:Cholesterol, Dietary; D008698:Mesylates; D009539:Nicotinic Acids; D002792:Cholestyramine Resin; C006261:3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one; D003897:Desmosterol; D002784:Cholesterol; D002994:Clofibrate; D013974:Thyroxine