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Sterol balance measurements using isotopic and chromatographic techniques were carried out in rats fed diets containing beta-sitosterol (0.8%) and cholesterol (1.2%). The activities of the rate-limiting enzymes of cholesterol synthesis (beta-hydroxy-beta-methylglutaryl-CoA reductase, EC 1.1.1.34) and bile acid synthesis (cholesterol 7 alpha-hydroxylase) were determined in the same animals. Cholesterol feeding increased cholesterol absorption from 1.2 to 70 mg/day. The increased absorption was compensated for by inhibition of hepatic cholesterol synthesis, enhanced conversion of cholesterol to bile acids (from 13.7 to 27.3 mg/day) and a slight increase in the excretion of endogenous neutral steroids (from 7.7 to 11.2 mg/day). Despite the adaptation there was accumulation of cholesterol in the liver (from 2.2 to 9.2 mg/g). Beta-Sitosterol feeding inhibited cholesterol absorption (calculated absorption was zero). In these rats there was enhanced cholesterol synthesis (from 20.0 to 28.8 mg/day, but no change in the rates of bile acid formation. Measurements of the activities of the rate-limiting enzymes showed fair correlation with cholesterol-bile acid balance. In cholesterol fed animals, beta-hydroxy-beta-methylglutaryl-CoA reductase was inhibited 80% and cholesterol 7 alpha-hydroxylase was enhanced 61%. In beta-sitosterol-fed animals, the reductase was increased 2-fold and cholesterol 7 alpha-hydroxylase was not significantly different from controls.

The 17-keto function of phenolic steroids is reduced by the following intestinal bacteria: Eubacterium lentum, Clostridium paraputrificum, Clostridium J-1 and Clostridium innocuum. The 17-keto group of androstenedione is reduced solely by Bacteroides fragilis.

Certain oxygenated derivatives of cholesterol have dramatic effects on cholesterol synthesis. The present study compared the effects of cholesterol and an oxygenated metabolite, cholesterol-alpha-epoxide, on sterol metabolism in rats. Sterol balance measurements using isotopic and chromatographic techniques were carried out in rats fed liquid control diets, control diets + cholesterol (1 mg/ml), and control diets + cholesterol-alpha-epoxide (1 mg/ml). Sterol metabolism was affected by both cholesterol and cholesterol-alpha-epoxide. Cholesterol feeding decreased cholesterol synthesis (-9.57 +/- 7.23 mg/day), increased endogenous bile acid synthesis (7.71 +/- 1.18 mg/day), and increased cholesterol turnover (7.78 +/- 2.33 mg/day) compared to controls. Cholesterol-alpha-epoxide had no effect on cholesterol synthesis, endogenous bile acid synthesis and cholesterol turnover compared to controls. However, animals fed cholesterol-alpha-epoxide had large increases in total acidic steroid output (determined by chromatographic analysis, 12.33 +/- 4.05 mg/day). This finding suggests that cholesterol-alpha-epoxide is absorbed and converted to bile acids. Apparently, the epoxide enters the bile acid biosynthetic pathway distal to the rate-limiting step of 7 alpha-hydroxylation. As a result, large amounts of bile acids are formed from the epoxide without affecting endogenous cholesterol or bile acid synthesis. This was confirmed in a separate experiment by feeding [4-14C]cholesterol-alpha-epoxide and recovering labeled bile acids (hyodeoxycholic acid and lithyocholic acid) as well as the starting radioactively labeled epoxide in the feces.

Sterol balance studies using isotopic and chromatographic techniques were performed in rats fed diets supplemented with ursodeoxycholic acid. Compared to controls, ursodeoxycholic acid dramatically altered sterol metabolism. Ursodeoxycholic acid was absorbed and circulated in the enterohepatic circulation. The biliary bile acid composition was significantly altered with ursodeoxycholic acid the predominant biliary bile acid (67%). Cholesterol absorption was depressed by 34%; bile acid synthesis was depressed by 30%; however, cholesterol balance was significantly increased. It is apparent that the effects of ursodeoxycholic acid on sterol metabolism are different in several respects from chenodeoxycholic acid.

Using isotope-ratio mass spectrometry, newly synthesized 26-hydroxycholesterol and its derivative, 3 beta-hydroxy-5-cholenoic acid, were detected in the liver and bile of animals within 2 h following intravenous administration of [5-13C]mevalonic acid. The findings indicate that 26-hydroxycholesterol merits further consideration as an in vivo modulator of HMG-CoA reductase activity.