Effect of Bile Acid Synthesis Rate on Cholesterol Secretion Rate in the Steady State

In order to discover the effect of bile acid synthesis on cholesterol secretion into the bile, 7 rhesus monkeys were studied at various stable interruptions of the enterohepatic circulation of bile acids. In 4 animals, 2.5 and 7.5% interruptions were compared; 2.5 and 15% interruptions were compared in 5 animals. There was a significant decrease in the cholesterol secretion rate, 0.048 mmoles per 24 hr ± 0.016 (SD), and a significant increase in bile acid synthesis rate, 0.62 mmoles per 24 hr ± 0.03 (SD) at the 7.5% interruption. No significant changes in bile acid or phospholipid secretion rates occurred. Therefore, bile acid synthesis rate influences the cholesterol secretion rate in the chronic stable state. At 15% interruption there was a significant decrease in the bile acid secretion rate from 13.4 mmoles per 24 hr ± 1.8 (SD) to 8.0 mmoles per 24 hr ± 2.4 (SD), suggesting that the maximum percentage interruption of the enterohepatic circulation of bile acids, at which the bile acid synthesis rate is maintained in this species, has been overestimated. A large variation in cholesterol secretion rate was found in the 7 animals when the 2.5% interruption was examined alone. Bile acid secretion and synthesis rates were considerably more stable at this interruption. Additional determinants of cholesterol secretion into the bile which are independent of bile acid metabolism probably exist.