出版社：American Society for Biochemistry and Molecular Biology
摘要：Administration of large doses of estrogens has been shown to result in decreased conjugation and increased sulfation of bile acids as well as cholestasis. There have been no previous studies on the effects of low doses of estrogens on these parameters of bile acid metabolism. Therefore, rats were given ethinylestradiol, 0.06 to 600 micrograms/kg/day subcutaneously for up to 21 days and the in vitro activity of the hepatic conjugation and sulfation enzymes was measured. Conjugating enzyme activity was unchanged at doses below 600 micrograms/kg/day. In contrast, hepatic sulfation of conjugated bile acids increased significantly after 21 days treatment with 0.6 micrograms/kg/day. The magnitude of the increase was both time- and dose-dependent. Increased sulfotransferase activity was noted only in the liver and was specific for conjugated bile acids; there was no change in the rate of sulfation of the unconjugated bile acids or in renal sulfotransferase activity. Increased hepatic bile acid sulfotransferase activity occurred in the presence of normal bile flow and bile acid secretion. These data indicate that treatment with doses of ethinylestradiol comparable to those present in oral contraceptives may lead to readily detectable time- and dose-dependent changes in bile acid sulfation without producing cholestasis. The data also suggest that there may be significant differences in the enzymatic sulfation of conjugated and unconjugated bile acids in the liver.
