Concentration of unsulfated lithocholic acid in portal and systemic venous plasma: evidence that lithocholic acid does not down regulate the hepatic cholesterol 7α-hydroxylase activity in gallstone patients

Abstract

It has been proposed that lithocholic acid may have a physiological role for the regulation of bile acid synthesis in humans. In this study, the portal venous concentration and hepatic uptake of unsulfated lithocholic acid was determined in 21 gallstone patients - untreated, cholestyramine-treated and chenodeoxycholic acid-treated — at cholecystectomy. Lithocholic acid was analyzed by a combined gas-liquid mass-fragmentographic technique. In most of the patients a liver biopsy was obtained for assay of the cholesterol 7α-hydroxylase activity. The portal venous concentration of unsulfated lithocholic acid averaged 0.32 μmol/1 in untreated patients, constituting about 4% of the total bile acids. The apparent hepatic uptake of lithocholic acid averaged 78%, being as high as that of cholic acid. No significant correlation was obtained between the portal venous concentration of unsulfated lithocholic acid and the hepatic cholesterol 7α-hydroxylase activity. This study thus confirms an enterohepatic circulation of lithocholic acid in humans. No evidence was obtained that the portal venous inflow of small amounts of lithocholic acid to the liver is of regulatory importance for the cholesterol 7α-hydroxylase activity.