NR1H4 and cholestasis: The farsenoid X receptor (FXR) acts as a sensor for intracellular bile acid levels (Makishima et al. 1999), and activation of FXR (NR1H4) induces adaptive gene expression changes in response to accumulation of bile acids in cholestasis such as inhibition of bile acid synthesis, upregulation of phase I bile acid hydroxylation, phase II conjugation enzymes, and induction of the expression of canalicular and basolateral bile acid transporters.