Thyroid hormone receptor

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Thyroid hormone receptor alpha
Identifiers
Symbol THRA
Alt. symbols THRA1, THRA2, ERBA1
Entrez 7067
HUGO 11796
OMIM 190120
RefSeq NM_199334
UniProt P10827
Other data
Locus Chr. 17 q11.2-17q12
Thyroid hormone receptor beta
Identifiers
Symbol THRB
Alt. symbols ERBA2
Entrez 7068
HUGO 11799
OMIM 190160
RefSeq NM_000461
UniProt P10828
Other data
Locus Chr. 3 p24.1-p22

The thyroid hormone receptor (TR)[1] is a type of nuclear receptor that is activated by binding thyroid hormone.[2]

Function[edit]

Amongst the most important functions of thyroid hormone receptors are regulation of metabolism and heart rate.[3][4] In addition, they play critical roles in the development of organisms.[5]

Mechanism of action[edit]

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.[6]

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.

Isoforms[edit]

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:[2]

  • 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)

Disease linkage[edit]

Certain mutations in the thyroid hormone receptor are associated with thyroid hormone resistance.[7]

References[edit]

  1. ^ Spurr NK, Solomon E, Jansson M, Sheer D, Goodfellow PN, Bodmer WF, Vennstrom B (1984). "Chromosomal localisation of the human homologues to the oncogenes erbA and B". EMBO J. 3 (1): 159–63. PMC 557313. PMID 6323162. 
  2. ^ a b Flamant F, Baxter JD, Forrest D, Refetoff S, Samuels H, Scanlan TS, Vennstrom B, Samarut J (2006). "International Union of Pharmacology. LIX. The pharmacology and classification of the nuclear receptor superfamily: thyroid hormone receptors". Pharmacol Rev 58 (4): 705–11. doi:10.1124/pr.58.4.3. PMID 17132849. 
  3. ^ Yen PM (2001). "Physiological and molecular basis of thyroid hormone action". Physiol Rev 81 (3): 1097–142. PMID 11427693. 
  4. ^ Harvey CB, Williams GR (2002). "Mechanism of thyroid hormone action". Thyroid (journal) 12 (6): 441–6. doi:10.1089/105072502760143791. PMID 12165104. 
  5. ^ Brent GA (2000). "Tissue-specific actions of thyroid hormone: insights from animal models". Rev Endocr Metab Disord 1 (1–2): 27–33. doi:10.1023/A:1010056202122. PMID 11704989. 
  6. ^ Kliewer SA, Umesono K, Mangelsdorf DJ, Evans RM (January 1992). "Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling". Nature 355 (6359): 446–9. doi:10.1038/355446a0. PMID 1310351. 
  7. ^ Olateju TO, Vanderpump MP (2006). "Thyroid hormone resistance". Ann Clin Biochem 43 (Pt 6): 431–40. doi:10.1258/000456306778904678. PMID 17132274. 

External links[edit]