title: Adrenergic regulation of clock gene expression in mouse liver.
abstract: A main oscillator in the suprachiasmatic nucleus (SCN) conveys circadian information to the peripheral clock systems for the regulation of fundamental physiological functions. Although polysynaptic autonomic neural pathways between the SCN and the liver were observed in rats, whether activation of the sympathetic nervous system entrains clock gene expression in the liver has yet to be understood. To assess sympathetic innervation from the SCN to liver tissue, we investigated whether injection of adrenaline/noradrenaline (epinephrine/norepinephrine) or sympathetic nerve stimulation could induce mPer gene expression in mouse liver. Acute administration of adrenaline or noradrenaline increased mPer1 but not mPer2 expression in the liver of mice in vivo and in hepatic slices in vitro. Electrical stimulation of the sympathetic nerves or adrenaline injection caused an elevation of bioluminescence in the liver area of transgenic mice carrying mPer1 promoter-luciferase. Under a light-dark cycle, destruction of the SCN flattened the daily rhythms of not only mPer1, mPer2, and mBmal1 genes but also noradrenaline content in the liver. Daily injection of adrenaline, administered at a fixed time for 6 days, recovered oscillations of mPer2 and mBmal1 gene expression in the liver of mice with SCN lesion on day 7. Sympathetic nerve denervation by 6-hydroxydopamine flattened the daily rhythm of mPer1 and mPer2 gene expression. Thus, on the basis of the present results, activation of the sympathetic nerves through noradrenaline and/or adrenaline release was a factor controlling the peripheral clock.
authors.affiliation: Department of Pharmacology and Brain Science, School of Human Sciences, Waseda University, Tokorozawa, Saitama 359-1192, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Terazono
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Mutoh
authors.forename: Shun
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Rhyuta
authors.initials: R
authors.lastname: Udo
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Ohdo
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okamura
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Shibata
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D004837:Epinephrine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C104631:ORFA protein, Corynebacterium; D016627:Oxidopamine; D009638:Norepinephrine; D004837:Epinephrine