Effect of feeding cholesterol and sitosterol on hepatic steroid 12 alpha-hydroxylase activity in female hamsters.

The effects of dietary cholesterol and sitosterol on the activity of the hepatic steroid 12 alpha-hydroxylase, gallbladder bile acid composition, and serum and liver cholesterol concentrations were studied in female hamsters. The 12 alpha-hydroxylase activity was inhibited by 63% in cholesterol-fed animals and by 30% in sitosterol-fed animals. Cholesterol feeding increased percentages of chenodeoxycholic and lithocholic acids in gallbladder bile with reciprocal decrease of cholic acid, while sitosterol feeding had no significant effect on bile acid composition. Cholesterol feeding increased levels of serum and liver cholesterol, on the contrary, sitosterol decreased both concentrations. A positive correlation between the 12 alpha-hydroxylase activity and the ratio of cholic acid plus its metabolites to chenodeoxycholic acid plus its metabolite was also observed. These results support the proposal that steroid 12 alpha-hydroxylase is a major factor in determining the relative proportion of cholic acid and chenodeoxycholic acid synthesized in the liver and indicate that cholesterol feeding increased percentage of chenodeoxycholic acid by inhibiting the activity of steroid 12 alpha-hydroxylase.