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Search: (WFRF:(Arner Anders)) srt2:(2020-2024) > Resistance to thyro...

  • Dore, RiccardoBritish Columbia Children's Hospital (author)

Resistance to thyroid hormone induced tachycardia in RTHα syndrome

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2023

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:e47370ac-5f40-4716-8100-506bb6eb7e24
  • https://lup.lub.lu.se/record/e47370ac-5f40-4716-8100-506bb6eb7e24URI
  • https://doi.org/10.1038/s41467-023-38960-1DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Watson, LauraAddenbrooke's Hospital (author)
  • Hollidge, StefanieUniversity of Cambridge (author)
  • Krause, ChristinBritish Columbia Children's Hospital (author)
  • Sentis, Sarah ChristineBritish Columbia Children's Hospital (author)
  • Oelkrug, RebeccaBritish Columbia Children's Hospital (author)
  • Geißler, CathleenBritish Columbia Children's Hospital (author)
  • Johann, KorneliaBritish Columbia Children's Hospital (author)
  • Pedaran, MehdiBritish Columbia Children's Hospital (author)
  • Lyons, GretaUniversity of Cambridge (author)
  • Lopez-Alcantara, NuriaBritish Columbia Children's Hospital (author)
  • Resch, JuliaBritish Columbia Children's Hospital (author)
  • Sayk, FriedhelmUniversity Medical Center Schleswig-Holstein (author)
  • Iwen, Karl AlexanderUniversity Medical Center Schleswig-Holstein,British Columbia Children's Hospital (author)
  • Franke, AndreUniversity of Kiel (author)
  • Boysen, Teide JensUniversity of Kiel (author)
  • Dalley, Jeffrey W.University of Cambridge (author)
  • Lorenz, KristinaLeibniz Institute For Analytical Sciences (ISAS),Julius Maximilian University of Würzburg (author)
  • Moran, CarlaUniversity College Dublin,University of Cambridge (author)
  • Rennie, Kirsten L.University of Cambridge (author)
  • Arner, AndersLund University,Lunds universitet,Thoraxkirurgi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Thoracic Surgery,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Igelösa Life Science AB(Swepub:lu)an8151ar (author)
  • Kirchner, HenrietteBritish Columbia Children's Hospital (author)
  • Chatterjee, KrishnaUniversity of Cambridge (author)
  • Mittag, JensBritish Columbia Children's Hospital (author)
  • British Columbia Children's HospitalAddenbrooke's Hospital (creator_code:org_t)

Related titles

  • In:Nature Communications14:12041-1723

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