Timing is everything: Consequences of transient and sustained AhR activity

The aryl hydrocarbon receptor (AhR) was implicated as a mediator of xenobiotic toxicity over three decades ago. Although a complete picture continues to elude us, investigations by many laboratories during the ensuing period have revealed much about AhR biology in normal physiological processes, as well as the toxicities induced by the dioxins and related polychlorinated aromatic hydrocarbons. The findings are captured in numerous excellent reviews. This commentary attempts to inject a new perspective on some new as well as frequently overlooked observations in the context of established receptor properties. Specifically, we examine the impact of transient versus sustained receptor activation on AhR biology, and explore the potential role for cytochrome P450 expression in regulating AhR activity amongst various tissues. The growing recognition that AhR action functions through multiple mechanisms serves to further highlight the importance of limiting prolonged receptor activation.