title: The mammalian circadian system is resistant to dioxin.
abstract: The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that is bound and activated by many toxic ubiquitous environmental contaminants, including the halogenated aromatic hydrocarbon, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The AhR belongs to a family of proteins that contain basic helix-loop-helix/Per-ARNT-SIM (bHLH/PAS) domains. The circadian clock protein, BMAL1, is also a bHLH-PAS transcription factor and has been shown to interact with the AhR. AhRs are expressed in nearly every mammalian tissue, including the suprachiasmatic nuclei (SCN), and previous studies have suggested that activation of the AhR with dioxins affects rhythmicity in circadian clocks. In this study, the authors tested the hypothesis that activation of the aryl hydrocarbon receptor with the potent dioxin, TCDD, alters the organization of the mammalian circadian system by measuring bioluminescence from tissues explanted from PER2::LUCIFERASE mice. They found that in vitro treatment of explanted tissues with TCDD did not alter the periods, amplitudes, or damping rates of the PER2::LUC rhythms compared with controls. Likewise, in vivo treatment with TCDD had no effect on the phase relationship between central and peripheral oscillators. Together, these data demonstrate that activation of the AhR with TCDD does not directly or systemically alter the mouse circadian system.
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA.
authors.forename: Julie S
authors.initials: JS
authors.lastname: Pendergast
authors.forename: Shin
authors.initials: S
authors.lastname: Yamazaki
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D057906:Circadian Clocks / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004785:Environmental Pollutants / Q000633:toxicity; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D004785:Environmental Pollutants; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D008156:Luciferases; D019363:Cytochrome P-450 CYP1A1