The economy of the enterohepatic circulation of bile acids in the baboon. 2. Regulation of bile acid synthesis by enterohepatic circulation of bile acids.

Isotope dilution within bile acid pools and radiochemical assessment of cholesterol oxidation to bile acids were methods used to measure short-term feedback regulation of bile acid synthesis in baboons with controlled enterohepatic circulations. Intraduodenal infusion of labeled endogenous bile acid pools into bile acid-depleted animals with enhanced bile acid synthesis showed that the rate of bile acid returned to the liver affected the degree of inhibition of bile acid synthesis. Infusion of prepared bile acid pools of varying composition resulted in a specific pattern of feedback inhibition of bile salt synthesis related to pool composition and mass. Individual bile salts inhibited their own synthesis more than that of other bile salts, and chenodeoxycholic and deoxycholic acids were found to have greater inhibitory effects than cholic acid. Glycine-conjugated cholic and chenodeoxycholic acids had greater inhibitory effects than did the respective free bile salts. Infusion of mixed bile acid pools showed that dihydroxy bile acids (chenodeoxycholic or deoxycholic) enhanced feedback inhibition of cholic acid. In all studies, inhibition of bile acid synthesis occurred twice as fast as its derepression.