What is the Origin of PXR?

PXR is part of the nuclear receptor superfamily, a group of intracellular proteins that directly modulate gene expression upon binding a ligand. It was named for its ability to be activated by pregnane derivatives, a class of steroid hormones. Its evolutionary role is detoxification, acting as a broad-spectrum sensor for potentially harmful substances.

What is the Mechanism of PXR?

When an exogenous ligand, such as a pharmaceutical agent or a dietary compound, binds to PXR in the cytoplasm, the receptor undergoes a conformational change, dimerizes with the Retinoid X Receptor (RXR), and translocates to the nucleus. The PXR/RXR heterodimer then binds to response elements in the promoter regions of target genes, significantly increasing their transcription. This results in the upregulation of drug-metabolizing enzymes like CYP3A4 and various efflux transporters.

PXR ∞ Area

PXR

Meaning

PXR, or Pregnane X Receptor, is a ligand-activated nuclear receptor that functions as a master transcriptional regulator of numerous genes involved in xenobiotic and endobiotic metabolism, including many Cytochrome P450 enzymes and drug transporters. Clinically, PXR activation is a primary mechanism underlying drug-drug interactions, as it senses the presence of foreign compounds and initiates a robust detoxification response. Its activity is crucial for the clearance of both drugs and certain endogenous steroids.