Exp Clin Endocrinol Diabetes 2022; 130(05): 296-302
DOI: 10.1055/a-1716-7980
Article

What is the Role of Thyroid Hormone Receptor Alpha 2 (TRα2) in Human Physiology?

Sarah Paisdzior
1   Institute of Experimental Pediatric Endocrinology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
,
Markus Schuelke
2   NeuroCure Cluster of Excellence; Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
3   Department of Neuropediatrics, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
,
Heiko Krude
1   Institute of Experimental Pediatric Endocrinology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
› Author Affiliations
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Abstract

Thyroid hormone receptors are nuclear receptors that function as transcription factors and are regulated by thyroid hormones. To date, a number of variants and isoforms are known. This review focuses on the thyroid hormone receptor α (TRα), in particular TRα2, an isoform that arises from alternative splicing of the THRA mRNA transcript. Unlike the TRα1 isoform, which can bind T3, the TRα2 isoform lacks a ligand-binding domain but still binds to DNA thereby antagonizing the transcriptional activity of TRα1. Although a regulatory role has been proposed, the physiological function of this TRα2 antagonism is still unclear due to limited in vitro and mouse model data. Recently, the first patients with resistance to thyroid hormone due to mutations in THRA, the TRα encoding gene, affecting the antagonistic function of TRα2 were described, suggesting a significant role of this particular isoform in human physiology.

Key words

thyroid hormone receptor alpha - TRα2 - mutation - resistance to thyroid hormone - RTH - THRA


Publication History

Received: 30 September 2021
Received: 19 November 2021

Accepted: 25 November 2021

Article published online:
07 March 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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