title: Thermoregulatory and Cardiovascular Consequences of a Transient Thyrotoxicosis and Recovery in Male Mice.
abstract: Thyroid hormones play a major role in body homeostasis, regulating energy expenditure and cardiovascular function. Given that obese people or athletes might consider rapid weight loss as beneficial, voluntary intoxication with T4 preparations is a growing cause for thyrotoxicosis. However, the long-lasting effects of transient thyrotoxicosis are poorly understood. Here we examined metabolic, thermoregulatory, and cardiovascular function upon induction and recovery from a 2-week thyrotoxicosis in male C57BL/6J mice. Our results showed that T4 treatment caused tachycardia, decreased hepatic glycogen stores, and higher body temperature as expected; however, we did not observe an increase in brown fat thermogenesis or decreased tail heat loss, suggesting that these tissues do not contribute to the hyperthermia induced by thyroid hormone. Most interestingly, when the T4 treatment was ended, a pronounced bradycardia was observed in the animals, which was likely caused by a rapid decline of T3 even below baseline levels. On the molecular level, this was accompanied by an overexpression of cardiac phospholamban and Serca2a mRNA, supporting the hypothesis that the heart depends more on T3 than T4. Our findings therefore demonstrate that a transient thyrotoxicosis can have pathological effects that even persist beyond the recovery of serum T4 levels, and in particular the observed bradycardia could be of clinical relevance when treating hyperthyroid patients.
authors.affiliation: Department of Cell and Molecular Biology (C.S.H., L.H., M.M., B.V., J.M.), Karolinska Institutet, Stockholm, Sweden 17177; Institute of Experimental Endocrinology (C.S.H.), Charité-University Hospital Berlin, Berlin, Germany 13353; Center of Brain, Behavior and Metabolism CBBM/Medizinische Klinik I (L.H., R.O., G.B., J.M.), University of Lübeck, Lübeck, Germany 23562; and Medizinische Klinik II (M.M.), University of Lübeck, Lübeck, Germany 23562.
authors.forename: Carolin S
authors.initials: CS
authors.lastname: Hoefig
authors.affiliation: Department of Cell and Molecular Biology (C.S.H., L.H., M.M., B.V., J.M.), Karolinska Institutet, Stockholm, Sweden 17177; Institute of Experimental Endocrinology (C.S.H.), Charité-University Hospital Berlin, Berlin, Germany 13353; Center of Brain, Behavior and Metabolism CBBM/Medizinische Klinik I (L.H., R.O., G.B., J.M.), University of Lübeck, Lübeck, Germany 23562; and Medizinische Klinik II (M.M.), University of Lübeck, Lübeck, Germany 23562.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Harder
authors.affiliation: Department of Cell and Molecular Biology (C.S.H., L.H., M.M., B.V., J.M.), Karolinska Institutet, Stockholm, Sweden 17177; Institute of Experimental Endocrinology (C.S.H.), Charité-University Hospital Berlin, Berlin, Germany 13353; Center of Brain, Behavior and Metabolism CBBM/Medizinische Klinik I (L.H., R.O., G.B., J.M.), University of Lübeck, Lübeck, Germany 23562; and Medizinische Klinik II (M.M.), University of Lübeck, Lübeck, Germany 23562.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Oelkrug
authors.affiliation: Department of Cell and Molecular Biology (C.S.H., L.H., M.M., B.V., J.M.), Karolinska Institutet, Stockholm, Sweden 17177; Institute of Experimental Endocrinology (C.S.H.), Charité-University Hospital Berlin, Berlin, Germany 13353; Center of Brain, Behavior and Metabolism CBBM/Medizinische Klinik I (L.H., R.O., G.B., J.M.), University of Lübeck, Lübeck, Germany 23562; and Medizinische Klinik II (M.M.), University of Lübeck, Lübeck, Germany 23562.
authors.forename: Moritz
authors.initials: M
authors.lastname: Meusel
authors.affiliation: Department of Cell and Molecular Biology (C.S.H., L.H., M.M., B.V., J.M.), Karolinska Institutet, Stockholm, Sweden 17177; Institute of Experimental Endocrinology (C.S.H.), Charité-University Hospital Berlin, Berlin, Germany 13353; Center of Brain, Behavior and Metabolism CBBM/Medizinische Klinik I (L.H., R.O., G.B., J.M.), University of Lübeck, Lübeck, Germany 23562; and Medizinische Klinik II (M.M.), University of Lübeck, Lübeck, Germany 23562.
authors.forename: Björn
authors.initials: B
authors.lastname: Vennström
authors.affiliation: Department of Cell and Molecular Biology (C.S.H., L.H., M.M., B.V., J.M.), Karolinska Institutet, Stockholm, Sweden 17177; Institute of Experimental Endocrinology (C.S.H.), Charité-University Hospital Berlin, Berlin, Germany 13353; Center of Brain, Behavior and Metabolism CBBM/Medizinische Klinik I (L.H., R.O., G.B., J.M.), University of Lübeck, Lübeck, Germany 23562; and Medizinische Klinik II (M.M.), University of Lübeck, Lübeck, Germany 23562.
authors.forename: Georg
authors.initials: G
authors.lastname: Brabant
authors.affiliation: Department of Cell and Molecular Biology (C.S.H., L.H., M.M., B.V., J.M.), Karolinska Institutet, Stockholm, Sweden 17177; Institute of Experimental Endocrinology (C.S.H.), Charité-University Hospital Berlin, Berlin, Germany 13353; Center of Brain, Behavior and Metabolism CBBM/Medizinische Klinik I (L.H., R.O., G.B., J.M.), University of Lübeck, Lübeck, Germany 23562; and Medizinische Klinik II (M.M.), University of Lübeck, Lübeck, Germany 23562.
authors.forename: Jens
authors.initials: J
authors.lastname: Mittag
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D001831:Body Temperature / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D013610:Tachycardia / Q000209:etiology / Q000503:physiopathology*; D022722:Thermogenesis / Q000502:physiology*; D013971:Thyrotoxicosis / Q000139:chemically induced / Q000150:complications*; D013974:Thyroxine; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D006003:Glycogen; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013974:Thyroxine; D000099211:Phospholamban