title: 3-Iodothyronamine Induces Tail Vasodilation Through Central Action in Male Mice.
abstract: 3-Iodothyronamine (3-T1AM) is an endogenous thyroid hormone (TH)-derived metabolite that induces severe hypothermia in mice after systemic administration; however, the underlying mechanisms have remained enigmatic. We show here that the rapid 3-T1AM-induced loss in body temperature is a consequence of peripheral vasodilation and subsequent heat loss (e.g., over the tail surface). The condition is subsequently intensified by hypomotility and a lack of brown adipose tissue activation. Although the possible 3-T1AM targets trace amine-associated receptor 1 or α2a-adrenergic receptor were detected in tail artery and aorta respectively, myograph studies did not show any direct effect of 3-T1AM on vasodilation, suggesting that its actions are likely indirect. Intracerebroventricular application of 3-T1AM, however, replicated the phenotype of tail vasodilation and body temperature decline and led to neuronal activation in the hypothalamus, suggesting that the metabolite causes tail vasodilation through a hypothalamic signaling pathway. Consequently, the 3-T1AM response constitutes anapyrexia rather than hypothermia and closely resembles the heat-stress response mediated by hypothalamic temperature-sensitive neurons. Our results thus underline the well-known role of the hypothalamus as the body's thermostat and suggest an additional molecular link between TH signaling and the central control of body temperature.
authors.affiliation: Center of Brain, Behavior and Metabolism, Medizinische Klinik I, University of Lübeck, 23562 Lübeck, Germany.
authors.forename: Sogol
authors.initials: S
authors.lastname: Gachkar
authors.affiliation: Center of Brain, Behavior and Metabolism, Medizinische Klinik I, University of Lübeck, 23562 Lübeck, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Oelkrug
authors.affiliation: NeurObesity Group, Department of Physiology, Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela-Instituto de Investigación Sanitaria, 15782 Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706 Santiago de Compostela, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Martinez-Sanchez
authors.affiliation: NeurObesity Group, Department of Physiology, Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela-Instituto de Investigación Sanitaria, 15782 Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706 Santiago de Compostela, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Rial-Pensado
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
authors.forename: Amy
authors.initials: A
authors.lastname: Warner
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden.|Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin, 13353 Berlin, Germany.
authors.forename: Carolin S
authors.initials: CS
authors.lastname: Hoefig
authors.affiliation: NeurObesity Group, Department of Physiology, Center for Research in Molecular Medicine and Chronic Diseases, University of Santiago de Compostela-Instituto de Investigación Sanitaria, 15782 Santiago de Compostela, Spain.|CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706 Santiago de Compostela, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: López
authors.affiliation: Center of Brain, Behavior and Metabolism, Medizinische Klinik I, University of Lübeck, 23562 Lübeck, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Mittag
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D057967:Infusions, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects; D013623:Tail / Q000098:blood supply* / Q000187:drug effects; D013970:Thyronines / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: C487948:3-iodothyronamine; D013970:Thyronines