Crosstalk between the AHR signaling pathway and circadian rhythm

Nov 6, 2008Biochemical pharmacology

Interaction between the AHR signaling pathway and the body’s daily biological clock

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Abstract

AHR expression levels show diurnal variation in many tissues.

Circadian rhythm influences various physiological functions, including behavior and metabolism.
BMAL1 is identified as a crucial regulator in the transcriptional feedback loop governing circadian rhythms.
The structural similarity between BMAL1 and ARNT suggests a potential link between AHR signaling and circadian regulation.
Pharmacological effects of AHR agonists may vary depending on the time of administration due to circadian variation.
AHR agonists can disrupt circadian rhythms, affecting behavior and immune cell proliferation.

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In this chapter, we review the crosstalk between the AHR signaling pathway and molecular clock system in mammals. In mammals, circadian rhythm is observed in most physiological functions including behavior, metabolism, cell growth, and immune responses. Circadian rhythm is regulated by a transcriptional feedback loop, and the transcription factor called "Brain Muscle ARNT-like protein 1 (BMAL1)" is a master regulator of this system. Because of its structural similarity to ARNT, a partner of AHR, BMAL1 is also referred as ARNT3. This structural feature of BMAL1 suggests that the activation of the AHR signaling pathway may influence the regulation of circadian rhythm. Several studies have shown that the expression levels of AHR display diurnal variation in many tissues. This circadian variation of AHR means that the pharmacological effects of AHR agonists vary according to the time of administration. AHR agonist administration results in a disruption of circadian rhythm with regard to behavior, immune cell proliferation, etc. As such, understanding the crosstalk between the AHR signaling and circadian rhythm may provide a new insight into TCDD actions.

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Crosstalk between the AHR signaling pathway and circadian rhythm

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