The alternatively spliced murine pregnane X receptor isoform, mPXR(delta171-211) exhibits a repressive action.

The orphan nuclear receptor pregnane X receptor regulates enzymes and transport proteins involved in the detoxification and clearance of numerous endobiotic and xenobiotic compounds, including pharmaceutical agents. Multiple alternatively spliced pregnane X receptor isoforms have been identified which are significantly expressed in humans and mice (up to 30% of the total pregnane X receptor transcript), however, little is known about their biological action. We explored functional differences between the major mouse pregnane X receptor isoforms mPXR(431) and mPXR(Delta171-211) that lacks 41 amino acids adjacent to the ligand-binding pocket.

Pregnane X receptor: promiscuous regulator of detoxification pathways.

The Pregnane X Receptor (PXR) is pivotal for the body's response to toxic xenobiotics and endogenous metabolites. By acting as a ligand-activated transcription factor, PXR regulates all stages of xenobiotic metabolism and transport and is responsible for important inductive drug interactions. Screening assays to assess the PXR activation potential of new and existing drugs are becoming integral components of drug discovery programs.