Nuclear receptor PXR, transcriptional circuits and metabolic relevance

The pregnane X receptor (PXR, NR1I2) is a ligand activated transcription factor that belongs to the nuclear hormone receptor (NR) superfamily. PXR is highly expressed in the liver and intestine, but low levels of expression have also been found in many other tissues. PXR plays an integral role in xenobiotic and endobiotic metabolism by regulating the expression of drug-metabolizing enzymes and transporters, as well as genes implicated in the metabolism of endobiotics. PXR exerts its transcriptional regulation by binding to its DNA response elements as a heterodimer with the retinoid X receptor (RXR) and recruitment of a host of coactivators. The biological and physiological implications of PXR activation are broad, ranging from drug metabolism and drug–drug interactions to the homeostasis of numerous endobiotics, such as glucose, lipids, steroids, bile acids, bilirubin, retinoic acid, and bone minerals. The purpose of this article is to provide an overview on the transcriptional circuits and metabolic relevance controlled by PXR. This article is part of a Special Issue entitled: Translating Nuclear Receptors from Health to Disease.

Research highlights
► PXR was initially cloned as a xenobiotic receptor regulating drug metabolism.
► Accumulating evidence has suggested broader transcriptional circuits controlled by this receptor.
► Moreover, the perceived function of PXR has been extended to a sensor that dictates the homeostasis of both xenobiotics and endobiotics.