Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals

Annu Rev Pharmacol Toxicol. 2003:43:309-34. doi: 10.1146/annurev.pharmtox.43.100901.135828. Epub 2002 Jan 10.


The induction of expression of genes for xenobiotic metabolizing enzymes in response to chemical insult is an adaptive response found in most organisms. In vertebrates, the AhR is one of several chemical/ligand-dependent intracellular receptors that can stimulate gene transcription in response to xenobiotics. The ability of the AhR to bind and be activated by a range of structurally divergent chemicals suggests that the AhR contains a rather promiscuous ligand binding site. In addition to synthetic and environmental chemicals, numerous naturally occurring dietary and endogenous AhR ligands have also been identified. In this review, we describe evidence for the structural promiscuity of AhR ligand binding and discuss the current state of knowledge with regards to the activation of the AhR signaling pathway by naturally occurring exogenous and endogenous ligands.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Biological Factors / chemistry
  • Biological Factors / metabolism*
  • Biological Factors / pharmacology
  • Cytochrome P-450 CYP1A1 / biosynthesis
  • Cytochrome P-450 CYP1A1 / genetics
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Ligands
  • Receptors, Aryl Hydrocarbon / agonists
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Signal Transduction
  • Structure-Activity Relationship
  • Xenobiotics / chemistry
  • Xenobiotics / metabolism*
  • Xenobiotics / pharmacology


  • Biological Factors
  • Ligands
  • Receptors, Aryl Hydrocarbon
  • Xenobiotics
  • Cytochrome P-450 CYP1A1