Regulation of bile acid synthesis in the rat: relationship between hepatic cholesterol 7 alpha-hydroxylase activity and portal bile acids

Bile acid biosynthesis has been believed to be regulated by negative feedback control; however, recent experiments have cast considerable doubts on the concept. The aim of the study was to examine the consensus of the negative feedback regulation of bile acids by clarifying the correlation between the portal bile acids and the rate-limiting enzyme of bile acid biosynthesis, hepatic microsomal cholesterol 7 alpha-hydroxylase. We measured the enzyme activity and the portal bile acids in male Wistar rats that were orally administered three different bile acids or cholestyramine for 2 weeks. The serum level of 7 alpha-hydroxycholesterol was also determined to verify whether it would be a parameter of bile acid synthesis rate in the rat. The activity of cholesterol 7 alpha-hydroxylase increased about threefold in rats treated with cholestyramine when compared with controls. On the other hand, in rats fed ursodeoxycholic, chenodeoxycholic, and deoxycholic acids, the enzyme activities decreased to 40%, 26%, and 28%, respectively. Treatment with cholestyramine had no significant effect on the portal bile acid concentration. Administration of ursodeoxycholic and chenodeoxycholic acids resulted in a significant increase in the concentration of portal bile acids, whereas deoxycholic acid feeding did not significantly affect it. In the control group, conjugated cholic acid constituted a major part of the portal bile acids while the administered bile acid and its metabolites became predominant in each bile acid feeding group. Treatment with ursodeoxycholic acid made the portal bile acids more hydrophilic, but, by contrast, administration of chenodeoxycholic, deoxycholic acids, and cholestyramine made the portal bile acids more hydrophobic.(ABSTRACT TRUNCATED AT 250 WORDS)