Thyroid hormone receptor

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

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

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

Function[edit | edit source]

Among 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 | edit source]

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 | edit source]

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 | edit source]

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

References[edit | edit source]

↑ 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.
↑ ^2.0 ^2.1 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.
↑ Yen PM (2001). "Physiological and molecular basis of thyroid hormone action". Physiol Rev. 81 (3): 1097–142. PMID 11427693.
↑ Harvey CB, Williams GR (2002). "Mechanism of thyroid hormone action". Thyroid. 12 (6): 441–6. doi:10.1089/105072502760143791. PMID 12165104.
↑ 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.
↑ 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.
↑ 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 | edit source]

Overview at vivo.colostate.edu
Thyroid+Hormone+Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)

[pmid6323162-1] 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.

[Flamant_2006-2] 2.0 ^2.1 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.

[Yen_2001-3] Yen PM (2001). "Physiological and molecular basis of thyroid hormone action". Physiol Rev. 81 (3): 1097–142. PMID 11427693.

[Harvey_2002-4] Harvey CB, Williams GR (2002). "Mechanism of thyroid hormone action". Thyroid. 12 (6): 441–6. doi:10.1089/105072502760143791. PMID 12165104.

[pmid11704989-5] 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.

[pmid1310351-6] 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.

[Olateju_2006-7] Olateju TO, Vanderpump MP (2006). "Thyroid hormone resistance". Ann Clin Biochem. 43 (Pt 6): 431–40. doi:10.1258/000456306778904678. PMID 17132274.

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