Activation of the Aryl Hydrocarbon Receptor by Structurally Diverse Exogenous and Endogenous Chemicals
Abstract
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.
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Differences in receptor size, affinity, sensitivity, and stability have been used to support the idea that the AHR is an evolutionarily malleable molecule that adapts to different chemical environments.
“These differences in receptor size, affinity, sensitivity, and stability have been used to support the idea that the AHR is an evolutionarily malleable molecule that adapts to different chemical environments (M. S. Denison & Nagy, 2003; M. E. Hahn, 2002; Mark E. Hahn et al., 2017).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as M. S. Denison & Nagy, 2003
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- Authors
- Denison, M. S., & Nagy, S. R.
- Affiliations
- University of California, Davis (US)
- ORCID
- Denison, Michael S.
- Venue
- Annual Review of Pharmacology and Toxicology
- Publisher
- Annual Reviews
- Published
- 2003-04
- Volume
- 43
- Issue
- 1
- Pages
- 309-334
- ISSN
- 0362-1642 (ISSN-L)
- 1545-4304
- OpenAlex
- W1935479846
- Cited by
- 1,895
- References
- 9
- Citations by year
- 2026: 68 · 2025: 55 · 2024: 64 · 2023: 82 · 2022: 74 · 2021: 90 · 2020: 110 · 2019: 82 · 2018: 98 · 2017: 98 · 2016: 79 · 2015: 80 · 2014: 117 · 2013: 97 · 2012: 99
- FWCI
- 8.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Annual Review of Pharmacology and Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences (P42ES004699, ES07059, ES 07685, R01ES007685, ES5707, ES 04699, T32ES007059)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Keywords
- aryl hydrocarbon receptor, AhR activation, endogenous AhR ligands, xenobiotic metabolism, gene transcription, environmental chemicals
- MeSH terms
- Animals, Binding Sites, Biological Factors, Humans, Ligands, Structure-Activity Relationship, Xenobiotics, Signal Transduction, Gene Expression Regulation, Enzymologic, Receptors, Aryl Hydrocarbon, Cytochrome P-450 CYP1A1
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