CYP3A induction by liver x receptor ligands in primary cultured rat and mouse hepatocytes is mediated by the pregnane X receptor.

The effects of oxysterol and drug ligands of the liver X receptor (LXR) on cytochrome P450 expression were evaluated in primary cultured rodent hepatocytes. Treatment of rat hepatocyte cultures with either 25-hydroxycholesterol or 24(S),25-epoxycholesterol (10(-5) to 5 x 10(-5) M) produced concentration-dependent elevations in CYP3A mRNA and immunoreactive protein levels but did not increase the amounts of CYP1A1, CYP2B, or CYP4A gene products. The effects of 24(S),25-epoxycholesterol on CYP3A content were much greater than were those of 25-hydroxycholesterol, consistent with the relative abilities of these sterols to bind and activate LXR.