Effects of ethinyl estradiol on bile secretion and liver microsomal mixed function oxidase system in the mouse

In the search for an animal model suitable for the study of ethinyl estradiol (EE) induced alterations of bile secretion, we have investigated the effects of three different doses (50-500-5000 microg/kg body wt., orally for 10 days) of EE on bile flow and composition and on liver microsomal mixed function oxidase system in female Albino-Swiss mice. No difference of bile flow was found between control and EE-treated mice. The decrease of bile acid secretion was dose-related and significant in animals treated with 500 and 5000 microg/kg of EE. Cholesterol output was similar in control and EE-treated animals. The molar ratio of bile acid to biliary cholesterol was significantly lower in all groups of EE-treated mice as compared with controls. The specific activities of 3,4-benzpyrene hydroxylase, aniline hydroxylase and NADPH cytochrome-c-reductase, as well as the content of cytochromes P-450 and b(5) decreased proportionally, in a dose dependent manner and significantly after 500 and 5000 microg/kg of EE. Our data indicate that mice, following EE, develop a lithogenic bile without obvious cholestasis. Moreover, they demonstrate a decrease of liver microsomal enzyme activities and cytochromes and suggest a relationship between the impairment of liver microsomal mixed function oxidase system and the changes of bile lipid composition.