IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38960-1.html
   My bibliography  Save this article

Resistance to thyroid hormone induced tachycardia in RTHα syndrome

Author

Listed:
  • Riccardo Dore

    (University of Lübeck)

  • Laura Watson

    (National Institute Health and Care Research Cambridge Clinical Research Facility, Addenbrooke’s Hospital)

  • Stefanie Hollidge

    (University of Cambridge)

  • Christin Krause

    (University of Lübeck)

  • Sarah Christine Sentis

    (University of Lübeck)

  • Rebecca Oelkrug

    (University of Lübeck)

  • Cathleen Geißler

    (University of Lübeck)

  • Kornelia Johann

    (University of Lübeck)

  • Mehdi Pedaran

    (University of Lübeck)

  • Greta Lyons

    (University of Cambridge)

  • Nuria Lopez-Alcantara

    (University of Lübeck)

  • Julia Resch

    (University of Lübeck)

  • Friedhelm Sayk

    (Internal Medicine I, Universitätsklinikum Schleswig-Holstein)

  • Karl Alexander Iwen

    (University of Lübeck
    Internal Medicine I, Universitätsklinikum Schleswig-Holstein)

  • Andre Franke

    (Christian-Albrechts-University of Kiel)

  • Teide Jens Boysen

    (Christian-Albrechts-University of Kiel)

  • Jeffrey W. Dalley

    (University of Cambridge
    University of Cambridge)

  • Kristina Lorenz

    (University of Würzburg
    Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V.)

  • Carla Moran

    (University of Cambridge
    University College Dublin)

  • Kirsten L. Rennie

    (University of Cambridge)

  • Anders Arner

    (Lund University)

  • Henriette Kirchner

    (University of Lübeck)

  • Krishna Chatterjee

    (University of Cambridge)

  • Jens Mittag

    (University of Lübeck)

Abstract

Mutations in thyroid hormone receptor α1 (TRα1) cause Resistance to Thyroid Hormone α (RTHα), a disorder characterized by hypothyroidism in TRα1-expressing tissues including the heart. Surprisingly, we report that treatment of RTHα patients with thyroxine to overcome tissue hormone resistance does not elevate their heart rate. Cardiac telemetry in male, TRα1 mutant, mice indicates that such persistent bradycardia is caused by an intrinsic cardiac defect and not due to altered autonomic control. Transcriptomic analyses show preserved, thyroid hormone (T3)-dependent upregulation of pacemaker channels (Hcn2, Hcn4), but irreversibly reduced expression of several ion channel genes controlling heart rate. Exposure of TRα1 mutant male mice to higher maternal T3 concentrations in utero, restores altered expression and DNA methylation of ion channels, including Ryr2. Our findings indicate that target genes other than Hcn2 and Hcn4 mediate T3-induced tachycardia and suggest that treatment of RTHα patients with thyroxine in high dosage without concomitant tachycardia, is possible.

Suggested Citation

  • Riccardo Dore & Laura Watson & Stefanie Hollidge & Christin Krause & Sarah Christine Sentis & Rebecca Oelkrug & Cathleen Geißler & Kornelia Johann & Mehdi Pedaran & Greta Lyons & Nuria Lopez-Alcantara, 2023. "Resistance to thyroid hormone induced tachycardia in RTHα syndrome," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38960-1
    DOI: 10.1038/s41467-023-38960-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38960-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38960-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Valentin Brusseau & Igor Tauveron & Reza Bagheri & Ukadike Chris Ugbolue & Valentin Magnon & Jean-Baptiste Bouillon-Minois & Valentin Navel & Frédéric Dutheil, 2022. "Heart Rate Variability in Hyperthyroidism: A Systematic Review and Meta-Analysis," IJERPH, MDPI, vol. 19(6), pages 1-13, March.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Hangjin Byeon & Yesol Moon & Seoeun Lee & Gwang-Ic Son & Eunil Lee, 2023. "Effect of the Marine Exercise Retreat Program on Thyroid-Related Hormones in Middle-Aged Euthyroid Women," IJERPH, MDPI, vol. 20(2), pages 1-17, January.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38960-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.