Pregnane X receptor-mediated transcription.
The pregnane X receptor (PXR, receptor NR1I2) is a ligand-activated transcription factor that is activated by structurally diverse endogenous steroids and foreign chemicals and serves as an important steroid and xenobiotic sensor. This member of the nuclear receptor superfamily is highly expressed in liver and in the gastrointestinal tract, where it regulates transcription of a large set of genes that contribute to foreign compound metabolism and to the metabolism and transcellular transport of steroid hormones, bile acids, and other endogenous substances. This chapter summarizes studies of PXR and its biological functions and describes a cell culture-based luciferase reporter gene assay for determination of PXR transcriptional activity. This assay can be used to identify novel drugs and environmental chemicals that serve as PXR ligands and thereby modulate PXR activity and may aid in the prediction of drug-drug interactions and foreign chemical-induced toxicities associated with the activation of PXR transcriptional responses.
Chang
Thomas K H
TK
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
Waxman
David J
DJ
D000818:Animals; D001681:Biological Assay / Q000379:methods*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D017930:Genes, Reporter; D006801:Humans; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D015533:Transcriptional Activation
C000625852:NR1I2 protein, human; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid