Bilirubin and bile acids may modulate their own metabolism via regulating uridine diphosphate-glucuronosyltransferase expression in the rat.

Abstract

BACKGROUND AND AIMS: Uridine diphosphate (UDP)-glucuronosyltransferase (UGT) is a critical enzyme in the elimination of bilirubin and it also plays a role in the metabolism of bile acids. The aim of this study was to determine whether bilirubin and bile acids could modulate their own metabolism by regulating UGT levels in cultured rat hepatocytes. METHODS AND RESULTS: Incubation of hepatocytes with bilirubin (48 micromol/L) for 24 h significantly increased the mRNA expression of UGT1A1 and UGT1A5, two UGT isoforms responsible for the conjugation of bilirubin. The induction of UGT1A1 and UGT1A5 by bilirubin was concentration and time dependent. Treatment with chenodeoxycholic acid, cholic aci..