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Published Online: 7 August 2020

Central Hypothyroidism Impairs Heart Rate Stability and Prevents Thyroid Hormone-Induced Cardiac Hypertrophy and Pyrexia

Publication: Thyroid
Volume 30, Issue Number 8

Abstract

Background: Tachycardia, cardiac hypertrophy, and elevated body temperature are major signs of systemic hyperthyroidism, which are considered to reflect the excessive thyroid hormone (TH) action in the respective peripheral tissues. However, recent observations indicate that the central actions of TH also contribute substantially to cardiovascular regulation and thermogenesis.
Methods: In this study, we dissect the individual contributions of peripheral TH action versus the central effects in body temperature regulation and cardiovascular functions by taking advantage of mice lacking the TH transporters monocarboxylate transporter 8 (MCT8) and organic anion transporting polypeptide 1C1 (OATP1C1) (M/O double knock-out [dko]), which exhibit elevated serum triiodothyronine (T3) levels while their brain is in a profoundly hypothyroid state. We compared these animals with wild-type (WT) mice that were treated orally with T3 to achieve similarly elevated serum T3 levels, but are centrally hyperthyroid. For the studies, we used radiotelemetry, infrared thermography, gene expression profiling, Western blot analyses, and enzyme linked immunosorbent assays (ELISA) assays.
Results: Our analyses revealed mild hyperthermia and cardiac hypertrophy in T3-treated WT mice but not in M/O dko animals, suggesting that central actions of TH are required for these hyperthyroid phenotypes. Although the average heart rate was unaffected in either model, the M/O dko exhibited an altered heart rate frequency distribution with tachycardic bursts in active periods and bradycardic episodes during resting time, demonstrating that the stabilization of heart rate by the autonomic nervous system can be impaired in centrally hypothyroid animals.
Conclusions: Our studies unravel distinct phenotypical traits of hyperthyroidism that depend on an intact central nervous system, and provide valuable insight into the cardiovascular pathology of the Allan–Herndon–Dudley syndrome, a condition caused by the lack of MCT8 in humans.

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cover image Thyroid®
Thyroid
Volume 30Issue Number 8August 2020
Pages: 1205 - 1216
PubMed: 32188347

History

Published online: 7 August 2020
Published in print: August 2020
Published ahead of print: 24 April 2020
Published ahead of production: 18 March 2020

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    Affiliations

    Beate Herrmann
    Department of Molecular Endocrinology, Institute for Endocrinology and Diabetes, Center of Brain Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.
    Lisbeth Harder
    Department of Molecular Endocrinology, Institute for Endocrinology and Diabetes, Center of Brain Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.
    Rebecca Oelkrug
    Department of Molecular Endocrinology, Institute for Endocrinology and Diabetes, Center of Brain Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.
    Jiesi Chen
    Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany.
    Sogol Gachkar
    Department of Molecular Endocrinology, Institute for Endocrinology and Diabetes, Center of Brain Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.
    Sebastian Nock
    Department of Molecular Endocrinology, Institute for Endocrinology and Diabetes, Center of Brain Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.
    Julia Resch
    Department of Molecular Endocrinology, Institute for Endocrinology and Diabetes, Center of Brain Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.
    Markus Korkowski
    Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany.
    Department of Endocrinology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
    Heike Heuer
    Leibniz Research Institute for Environmental Medicine (IUF), Düsseldorf, Germany.
    Department of Endocrinology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
    Jens Mittag [email protected]
    Department of Molecular Endocrinology, Institute for Endocrinology and Diabetes, Center of Brain Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.

    Notes

    Address correspondence to: Jens Mittag, PhD, Department of Molecular Endocrinology, Institute for Endocrinology and Diabetes, Center of Brain Behavior and Metabolism (CBBM), University of Lübeck, Ratzeburger Allee 160, Lübeck 23562, Germany [email protected]

    Author Disclosure Statement

    No competing financial interests exist.

    Funding Information

    The study was funded by the Deutsche Forschungsgemeinschaft (Heisenberg Program MI1242/2-2 to J.M.; SPP1629 “Thyroid TransAct” MI1242/6-1 to J.M. and HE3418/8-1 to H.H.) and the Medical Facility of the University of Lübeck (J14-2018) to R.O.; B.H., L.H., S.G., and S.N. are students of the DFG funded GRK1957 “Adipocyte-Brain-Crosstalk.”

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