Relationship between hepatic cholesterol synthesis and biliary cholesterol secretion in man: hepatic cholesterol synthesis is not a major regulator of biliary lipid secretion.

1. To examine the role of newly synthesized cholesterol as a determinant of bile lipid secretion, both hepatic cholesterol synthesis (as judged by the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, EC 1.1.1.34; HMGCoAR) and steady state biliary cholesterol output were measured in nine patients. 2. HMGCoAR levels varied four fold (9-40 pmol min-1 mg-1) and biliary cholesterol secretion 2.5-fold (0.60-1.15 mumol h-1 kg-1) but there was no correlation between these two variables (r = 0.18; P greater than 0.05) nor between biliary bile acid output and HMGCoAR activity (r = 0.34; P greater than 0.05). 3. There was, however, a linear relationship between bile acid and phospholipid secretion (r = 0.77; P less than 0.001) and between bile acid and cholesterol secretion (r = 0.69; P less than 0.05). 4. These results suggest that HMGCoAR activity is not a major determinant of cholesterol secretion nor at these secretion rates is HMGCoAR activity related to bile acid return to the liver.