Fifty Years of Aryl Hydrocarbon Receptor Research as Reflected in the Pages of Drug Metabolism and Disposition

The induction of multiple drug-metabolizing enzymes by halogenated and polycyclic aromatic hydrocarbon toxicants is mediated by the aryl hydrocarbon receptor (AHR). This fascinating receptor also has natural dietary and endogenous ligands, and much is now appreciated about the AHR's developmental and physiologic roles, as well as its impor-tance in cancer and other diseases. The past several years has wit-nessed increasing emphasis on understanding the multifaceted roles of the AHR in the immune system. Most would agree that the discovery of the AHR occurred in 1976, with the report of specific binding of a high affinity radioligand in mouse liver, just three years after the launch of the journal Drug Metabolism and Disposition (DMD) in 1973. Over the ensuing 50 years, the AHR and DMD have led parallel and often intersecting lives. The overall goal of this mini-review is to provide a decade-by-decade overview of major historical landmark discoveries in the AHR field and to highlight the numerous contribu-tions made by publications appearing in the pages of DMD. It is hoped that this historical tour might inspire current and future research in the AHR field. SIGNIFICANCE STATEMENT With the launch of Drug Metabolism and Disposition (DMD) in 1973 and the discovery of the aryl hydrocarbon receptor (AHR) in 1976, the journal and the receptor have led parallel and often intersecting lives over the past 50 years. Tracing the history of the AHR can re-veal how knowledge in the field has evolved to the present and highlight the important contributions made by discoveries re-ported in DMD. This may inspire additional DMD papers reporting future AHR landmark discoveries.

Automated summary

The induction of drug-metabolizing enzymes by halogenated and polycyclic aromatic hydrocarbon toxicants is mediated by the aryl hydrocarbon receptor (AHR). AHR has natural and endogenous ligands and plays important roles in development, physiology, cancer, and other diseases. Understanding the multifaceted roles of AHR in the immune system has gained increasing emphasis in recent years.