551. Differential effects of 17 alpha-ethinylestradiol on the neutral and acidic pathways of bile salt synthesis in the rat
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Koopen, Nr, Post, Sm, Wolters, H., Havinga, R., Stellaard, F., Boverhof, R., Kuipers, F., Hans Princen, Groningen University Institute for Drug Exploration (GUIDE), and Center for Liver, Digestive and Metabolic Diseases (CLDM)
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BILIARY DRAINAGE ,CHOLIC-ACID ,FOOD-INTAKE ,LIVER ,sterol-27-hydroxylase ,bile ,METABOLISM ,CHOLESTEROL 7-ALPHA-HYDROXYLASE ,ETHINYL ESTRADIOL ,enterohepatic circulation ,LIPOPROTEIN RECEPTOR ,Delta(22)-beta-muri-cholate ,cholesterol-7 alpha-hydroxylase ,cholestasis ,STEROL 27-HYDROXYLASE ,MESSENGER-RNA ,estrogens - Abstract
Effects of 17 alpha-ethinylestradiol (EE) on the neutral and acidic biosynthetic pathways of bile salt (BS) synthesis were evaluated in rats with an intact enterohepatic circulation and in rats with long-term bile diversion to induce BS synthesis, For this purpose, bile salt pool composition, synthesis of individual BS in vivo, hepatic activities, and expression levels of cholesterol 7 alpha-hydroxylase (CYP7A), and sterol 27-hydroxylase (CYP27), as well as of other enzymes involved in BS synthesis, were analyzed in rats treated with EE (5 mg/kg, 3 days) or its vehicle, BS pool size was decreased by 27% but total BS synthesis was not affected by EE in intact rats. Synthesis of cholate was reduced by 68% in EE-treated rats, while that of chenodeoxycholate was increased by 60%, The recently identified Delta(22)-isomer of beta-muricholate contributed for 5.4% and 18.3% (P