Dissociation of bile flow and biliary lipid secretion from biliary lysosomal enzyme output in experimental cholestasis.

Although the cellular mechanisms controlling bile flow and biliary lipid secretion are unclear, morphologic data suggest that intracellular vesicles may be involved. Therefore, to investigate the role of hepatocyte lysosomes in bile flow and biliary lipid secretion, we studied the effect of cholestasis on biliary lipid output and on lysosomal enzyme activities and total protein concentration in liver and bile. Castrated male rats were treated with ethinyl estradiol at 0.5 or 5 mg/kg per day for 5 days; bile was collected through a complete bile fistula hourly for 4 hours, and then liver homogenates were prepared. Bile acids, cholesterol, and phospholipid were measured in bile, and three lysosomal glycosidases (beta-glucuronidase, beta-galactosidase, and N-acetyl-beta-glucosaminidase) and total protein were measured in bile and liver. Ethinyl estradiol inhibited bile flow in a dose-dependent fashion; it also inhibited bile acid and phospholipid outputs. In contrast, a marked and parallel increase in the biliary outputs of all three lysosomal hydrolases was observed after high-dose ethinyl estradiol; no change in the biliary concentration of total protein was found. Our data suggest that bile flow and biliary lipid secretion involve cellular mechanisms other than vesicular transport by lysosomes.