Regulation of cyp3a gene transcription by the pregnane x receptor

Annu Rev Pharmacol Toxicol. 2002:42:1-23. doi: 10.1146/annurev.pharmtox.42.111901.111051.


The pregnane X receptor (PXR) is a promiscuous nuclear receptor that has evolved to protect the body from toxic chemicals. PXR is activated by a structurally diverse collection of xenobiotics, including several widely used prescription drugs. Various lipophilic compounds produced by the body, such as bile acids and steroids, also activate PXR. PXR stimulates the transcription of cytochrome P450 3A monooxygenases and other genes involved in the detoxification and elimination of these potentially harmful chemicals. Assays that detect PXR activation have important implications for the design of future drugs in two respects. On the one hand, PXR activation assays can be used to determine whether candidate drugs are likely to induce CYP3A gene expression and interact with other medicines. On the other hand, PXR agonists may prove useful in the treatment of diseases in which toxic metabolites accumulate, such as cholestatic liver disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases*
  • Bile Acids and Salts / metabolism
  • Binding Sites
  • Catalysis
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / genetics*
  • Gene Expression Regulation, Enzymologic* / drug effects
  • Homeostasis
  • Humans
  • Oxidoreductases, N-Demethylating / genetics*
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Receptors, Steroid / chemistry
  • Receptors, Steroid / physiology*
  • Transcription, Genetic
  • Xenobiotics / pharmacology


  • Bile Acids and Salts
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Xenobiotics
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP3A
  • Oxidoreductases, N-Demethylating