The aryl hydrocarbon receptor sans xenobiotics: Endogenous function in genetic model systems

For more than 30 years, the aryl hydrocarbon receptor [ Ah receptor ( AHR)] has been extensively scrutinized as the cellular receptor for numerous environmental contaminants, including polychlorinated dioxins, dibenzofurans, and biphenyls. Recent evidence argues that this description is incomplete and perhaps myopic. Ah receptor orthologs have been demonstrated to mediate diverse endogenous functions in our close vertebratrelatives as well as our distant invertebrate ancestors. Moreover, these endogenous functions suggest that xenobiotic toxicity may be best understood in the context of intrinsic AHR physiology. In this literature review, we survey the emerging picture of endogenous AHR biology from work in the vertebrate and invertebrate model systems Mus musculus, Caenorhabditis elegans, and Drosophila melanogaster.