The pregnane X receptor: from bench to bedside

Expert Opin Drug Metab Toxicol. 2008 Jul;4(7):895-908. doi: 10.1517/17425255.4.7.895.

Abstract

Background: The pregnane X receptor (PXR; NR1I2), a member of the nuclear receptor superfamily, regulates the expression of metabolic enzymes and transporters involved in the response of mammals to their chemical environment.

Objective: To summarize the functions and clinical implications of PXR.

Methods: In the current review, the clinical implications of PXR are discussed, and the use of genetically engineered PXR mouse models is highlighted.

Results/conclusion: Recent advances in mouse models, including Pxr-null and PXR-humanized mice, provide in vivo tools for evaluating the physiological functions of PXR and its role in controlling xenobiotic metabolism and transport. By using the PXR knockout and humanized mouse models, PXR was found to influence drug-drug interactions, hepatic steatosis, and the homeostasis of vitamin D, bile acids, and steroid hormones. PXR was also shown to influence inflammatory bowel diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism
  • Drug Interactions
  • Homeostasis / physiology
  • Humans
  • Irritable Bowel Syndrome / genetics
  • Irritable Bowel Syndrome / metabolism
  • Liver Diseases / genetics
  • Liver Diseases / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Pharmaceutical Preparations / metabolism
  • Pregnane X Receptor
  • Receptors, Steroid / genetics*
  • Receptors, Steroid / physiology*
  • Steroids / metabolism
  • Vitamin D / physiology

Substances

  • Bile Acids and Salts
  • NR1I2 protein, human
  • Nr1i2 protein, mouse
  • Pharmaceutical Preparations
  • Pregnane X Receptor
  • Receptors, Steroid
  • Steroids
  • Vitamin D