Molecular basis for hepatic multidrug resistance associated protein 3 induction by ethynylestradiol

RUIZ ML; RIGALLI JP; ARIAS A; VILLANUEVA SSM; BANCHIO C; VORE M; MOTTINO AD; CATANIA VA

Barcelona

Congreso; 47th annual meeting of the European Association for the study of the Liver; 2012

European Association for the Study of the Liver (EASL)

Multidrug resistance-associated protein 3 (Mrp3, Abcc3) expression and activity are up-regulated in rat liver after in vivo repeated administration of ethynylestradiol (EE), a cholestatic synthetic estrogen, whereas Mrp2 is down-regulated. Our aim was to determine if Mrp3 induction results from a direct effect of EE, independent of accumulation of any endogenous common Mrp2/Mrp3 substrates resulting from cholestasis. Male rats were given a single dose of EE (5 mg/kg, s.c.) and basal bile flow, biliary excretion rate of bile salts, and glutathione and serum alkaline phosphatase, were measured 5 h later. This treatment increased Mrp3 mRNA (Control: 100±13 vs EE: 431±147 % p