Thyroid hormone receptor
|Thyroid hormone receptor alpha|
|Alt. symbols||THRA1, THRA2, ERBA1|
|Locus||Chr. 17 q11.2-17q12|
|Thyroid hormone receptor beta|
|Locus||Chr. 3 p24.1-p22|
Mechanism of action
Thyroid hormone receptors regulate gene expression by binding to hormone response elements (HREs) in DNA either as monomers, heterodimers with retinoid X receptor (RXR; which in turn is activated by binding to 9-cis-retinoic acid) or as homodimers. However TR/RXR heterodimers are the most transcriptionally active form of TR.
In the absence of hormone, TR in complex with corepressor proteins bind to HREs in a transcriptionally inactive state. Binding of thyroid hormone results in a conformational change in TR which displaces corepressor from the receptor/DNA complex and recruitment of coactivator proteins. The DNA/TR/coactivator complex then recruits RNA polymerase that transcribes downstream DNA into messenger RNA and eventually protein that results in a change in cell function.
There are three forms of the thyroid hormone receptor designated alpha-1, beta-1 and beta-2 that are able to bind thyroid hormone. There are two TR-α receptor splice variants encoded by the THRA gene and two TR-β isoform splice variants encoded by the THRB gene:
- TR-α1 (widely expressed and especially high expression in cardiac and skeletal muscles)
- TR-α2 (homologous with viral oncogene c-erb-A, also widely expressed but unable to bind hormone)
- TR-β1 (predominately expressed in brain, liver and kidney)
- TR-β2 (expression primarily limited to the hypothalamus and pituitary)
Certain mutations in the thyroid hormone receptor are associated with thyroid hormone resistance.
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- Overview at vivo.colostate.edu
- Thyroid Hormone Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)