Effects of bile acid conjugates on biliary excretion of estradiol-17 beta-glucuronide in the rat

Estradiol-17 beta-glucuronide is a cholestatic agent and is considered to be related to the pathogenesis of intrahepatic cholestasis of pregnancy. We previously reported that biliary estradiol-17 beta-glucuronide excretion was delayed in Eisai hyperbililubinemic rats (EI-IBR) and inhibited by sulfobromophthalein whereas dibromosulfophthalein had not effect on biliary estradiol-17 beta-glucuronide excretion. In the present study, we examined the affects of bile acid conjugates on biliary excretion of tracer doses of [H-3]lestradiol-17 beta-glucuronide and [C-14]estradiol intravenously injected to rats. Biliary excretion of estradiol-17 beta-glucuronide and estradiol metabolites was significantly delayed by the infusion of taurolithocholate-3-sulfate or ursodeoxycholate-3-0-glucuronide. but not by ursudeoxycholate-3.7-disulfate. These findings indicate that estradiol-17 beta-glucuronide is excreted into bile at least partially by the canalicular multispecific organic anion transporter which is common for sulfobromophthaleinglutathione and some bile acid sulfates and glucuronides. (C) 1997 Elsevier Science Ireland Ltd.