Harper Patricia A, Riddick David S, Okey Allan B
Program in Developmental Biology, The Hospital for Sick Children, Toronto, Ont., Canada.
Biochem Pharmacol. 2006 Jul 28;72(3):267-79. doi: 10.1016/j.bcp.2006.01.007. Epub 2006 Feb 20.
The aryl hydrocarbon receptor (AHR) participates in a wide range of critical cellular events in response to endogenous signals or xenobiotic chemicals. Hence, it is important that AHR levels and activity themselves be well controlled in target tissues. The AHR is essentially ubiquitous in its distribution in mammalian tissues. However, levels of the receptor vary widely across different tissues and among different cell types. AHR levels and activity are modulated by exposure to the receptor's own ligands and are influenced by other xenobiotic chemicals. Many different factors impinge on AHR levels and AHR activity. These factors may alter responsiveness of downstream pathways, thereby affecting normal physiologic functions as well as responses to toxic environmental chemicals such as dioxins. Our commentary appraises the current literature on factors that regulate AHR levels/activity and attempts to identify fruitful strategies towards discovery of key pathways by which AHR levels are modulated in response to endogenous signals and in response to xenobiotic chemicals. An extraordinarily large number of agents alter the level or activity of the AHR. We have not yet entered an age of enlightenment sufficient to achieve true understanding of the interplay of mechanisms that regulate AHR expression in space and in time.
芳烃受体（AHR）参与多种关键的细胞事件，以响应内源性信号或外源性化学物质。因此，在靶组织中，AHR的水平和活性本身得到良好控制非常重要。AHR在哺乳动物组织中的分布基本无处不在。然而，该受体的水平在不同组织和不同细胞类型之间差异很大。AHR的水平和活性受受体自身配体暴露的调节，并受到其他外源性化学物质的影响。许多不同的因素影响AHR的水平和活性。这些因素可能会改变下游途径的反应性，从而影响正常生理功能以及对二恶英等有毒环境化学物质的反应。我们的评论评估了当前关于调节AHR水平/活性的因素的文献，并试图确定富有成效的策略，以发现AHR水平响应内源性信号和外源性化学物质而被调节的关键途径。大量的物质会改变AHR的水平或活性。我们尚未进入一个足以真正理解调节AHR在空间和时间上表达的机制之间相互作用的启蒙时代。
