thyroid hormone receptors


Summary: Specific high affinity binding proteins for THYROID HORMONES in target cells. They are usually found in the nucleus and regulate DNA transcription. These receptors are activated by hormones that leads to transcription, cell differentiation, and growth suppression. Thyroid hormone receptors are encoded by two genes (GENES, ERBA): erbA-alpha and erbA-beta for alpha and beta thyroid hormone receptors, respectively.

Top Publications

  1. Privalsky M, Lee S, Hahm J, Young B, Fong R, Chan I. The p160 coactivator PAS-B motif stabilizes nuclear receptor binding and contributes to isoform-specific regulation by thyroid hormone receptors. J Biol Chem. 2009;284:19554-63 pubmed publisher
    b>Thyroid hormone receptors (TRs) are hormone-regulated transcription factors that play multiple roles in vertebrate endocrinology and development...
  2. Flamant F, Baxter J, Forrest D, Refetoff S, Samuels H, Scanlan T, et al. International Union of Pharmacology. LIX. The pharmacology and classification of the nuclear receptor superfamily: thyroid hormone receptors. Pharmacol Rev. 2006;58:705-11 pubmed
  3. Konno Y, Kodama S, Moore R, Kamiya N, Negishi M. Nuclear xenobiotic receptor pregnane X receptor locks corepressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) onto the CYP24A1 promoter to attenuate vitamin D3 activation. Mol Pharmacol. 2009;75:265-71 pubmed publisher
    ..D(3) activates the CYP24A1 promoter by dissociating the corepressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) from the vitamin D receptor (VDR) on those VDREs...
  4. Ichiyama K, Yoshida H, Wakabayashi Y, Chinen T, Saeki K, Nakaya M, et al. Foxp3 inhibits RORgammat-mediated IL-17A mRNA transcription through direct interaction with RORgammat. J Biol Chem. 2008;283:17003-8 pubmed publisher
    ..We propose that induction of Foxp3 is the mechanism for the suppression of Th17 and polarization into inducible Treg. ..
  5. Chen R, Huang Y, Yeh C, Liao C, Lin K. Thyroid hormone receptors suppress pituitary tumor transforming gene 1 activity in hepatoma. Cancer Res. 2008;68:1697-706 pubmed publisher
    ..Together, these findings indicate that PTTG1 gene expression is mediated by Sp1 and is indirectly down-regulated by T(3). Finally, overexpression of PTTG1 or SP1 in HCCs is TR-dependent and crucial in the development of HCC. ..
  6. Hogan N, Crump K, Duarte P, Lean D, Trudeau V. Hormone cross-regulation in the tadpole brain: developmental expression profiles and effect of T3 exposure on thyroid hormone- and estrogen-responsive genes in Rana pipiens. Gen Comp Endocrinol. 2007;154:5-15 pubmed
    ..action and potential cross-regulation between thyroid hormone and estrogen, we examined changes in thyroid hormone receptors (TRalpha and TRbeta) and the estrogen receptor (ERalpha) in the brain of Rana pipiens throughout ..
  7. Shin D, Plateroti M, Samarut J, Osborne T. Two uniquely arranged thyroid hormone response elements in the far upstream 5' flanking region confer direct thyroid hormone regulation to the murine cholesterol 7alpha hydroxylase gene. Nucleic Acids Res. 2006;34:3853-61 pubmed
    ..These two independent TR-binding sites are closely spaced and both are required for full induction of the CYP7A1 promoter by thyroid hormone, although the DR-0 site was more crucial. ..
  8. Chen Y, Coulter S, Jetten A, Goldstein J. Identification of human CYP2C8 as a retinoid-related orphan nuclear receptor target gene. J Pharmacol Exp Ther. 2009;329:192-201 pubmed publisher
  9. Michel M, Mendes da Cruz D, Keller A, Lochner M, Schneider E, Dy M, et al. Critical role of ROR-?t in a new thymic pathway leading to IL-17-producing invariant NKT cell differentiation. Proc Natl Acad Sci U S A. 2008;105:19845-50 pubmed publisher
    ..In conclusion, our findings demonstrate an alternative thymic pathway leading to the development of iNKT17 cells that requires ROR-gammat expression. ..

More Information


  1. Kawakami Y, Nozaki J, Seoka M, Kumai H, Ohta H. Characterization of thyroid hormones and thyroid hormone receptors during the early development of Pacific bluefin tuna (Thunnus orientalis). Gen Comp Endocrinol. 2008;155:597-606 pubmed
    We studied the profiles of 3,5,3'-l-triiodothyronine (T3), thyroxine (T4), and thyroid hormone receptors (TRs) in Pacific bluefin tuna (Thunnus orientalis) during embryonic and post-embryonic development...
  2. Raichur S, Lau P, Staels B, Muscat G. Retinoid-related orphan receptor gamma regulates several genes that control metabolism in skeletal muscle cells: links to modulation of reactive oxygen species production. J Mol Endocrinol. 2007;39:29-44 pubmed
    ..Surprisingly, the investigation revealed a function for RORgamma in the pathway that regulates production of reactive oxygen species. ..
  3. Tilley S, Jaradat M, Stapleton C, Dixon D, Hua X, Erikson C, et al. Retinoid-related orphan receptor gamma controls immunoglobulin production and Th1/Th2 cytokine balance in the adaptive immune response to allergen. J Immunol. 2007;178:3208-18 pubmed
    ..These data reveal a critical role for RORgamma in the regulation of Ig production and Th1/Th2 balance in adaptive immunity. ..
  4. Matsushita A, Sasaki S, Kashiwabara Y, Nagayama K, Ohba K, Iwaki H, et al. Essential role of GATA2 in the negative regulation of thyrotropin beta gene by thyroid hormone and its receptors. Mol Endocrinol. 2007;21:865-84 pubmed
  5. Zhu X, Zhao L, Willingham M, Cheng S. Thyroid hormone receptors are tumor suppressors in a mouse model of metastatic follicular thyroid carcinoma. Oncogene. 2010;29:1909-19 pubmed publisher
    ..Thus, TRs could function as tumor suppressors in a mouse model of metastatic follicular thyroid cancer. ..
  6. Nannipieri M, Cecchetti F, Anselmino M, Camastra S, Niccolini P, Lamacchia M, et al. Expression of thyrotropin and thyroid hormone receptors in adipose tissue of patients with morbid obesity and/or type 2 diabetes: effects of weight loss. Int J Obes (Lond). 2009;33:1001-6 pubmed publisher
    ..The reversal of these changes with major weight loss and the reciprocal changes in plasma TSH and FT(3) levels suggest a role for adipocytes in the regulation of TSH and thyroid hormones. ..
  7. Ivanov I, McKenzie B, Zhou L, Tadokoro C, Lepelley A, Lafaille J, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126:1121-33 pubmed
    ..Together, these studies suggest that RORgammat is a key regulator of immune homeostasis and highlight its potential as a therapeutic target in inflammatory diseases. ..
  8. Cupedo T, Crellin N, Papazian N, Rombouts E, Weijer K, Grogan J, et al. Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells. Nat Immunol. 2009;10:66-74 pubmed publisher
    ..Our data indicate that lymph node organogenesis is controlled by an NK cell precursor population with adaptive immune features and demonstrate a previously unappreciated link between the innate and adaptive immune systems. ..
  9. Manchado M, Infante C, Rebordinos L, Cañavate J. Molecular characterization, gene expression and transcriptional regulation of thyroid hormone receptors in Senegalese sole. Gen Comp Endocrinol. 2009;160:139-47 pubmed publisher
    ..Their genomic effects are mediated by thyroid hormone receptors (TRs)...
  10. Pearen M, Myers S, Raichur S, Ryall J, Lynch G, Muscat G. The orphan nuclear receptor, NOR-1, a target of beta-adrenergic signaling, regulates gene expression that controls oxidative metabolism in skeletal muscle. Endocrinology. 2008;149:2853-65 pubmed publisher
    ..In conclusion, NOR-1 is necessary for oxidative metabolism in skeletal muscle. ..
  11. Chen Z, Laurence A, O Shea J. Signal transduction pathways and transcriptional regulation in the control of Th17 differentiation. Semin Immunol. 2007;19:400-8 pubmed publisher
    ..Precisely how cytokines produced by this lineage are selectively expressed and selectively extinguished through epigenetic modifications is an area of great importance, but considerable uncertainty. ..
  12. Au W, Payne V, O Rahilly S, Rochford J. The NR4A family of orphan nuclear receptors are not required for adipogenesis. Int J Obes (Lond). 2008;32:388-92 pubmed
    ..Thus, while members of the NR4A subfamily of nuclear receptors may have important metabolic roles in skeletal muscle and liver, we demonstrate that they are dispensable for normal adipocyte development. ..
  13. Gauger K, Giera S, Sharlin D, Bansal R, Iannacone E, Zoeller R. Polychlorinated biphenyls 105 and 118 form thyroid hormone receptor agonists after cytochrome P4501A1 activation in rat pituitary GH3 cells. Environ Health Perspect. 2007;115:1623-30 pubmed
  14. Davis P, Leonard J, Davis F. Mechanisms of nongenomic actions of thyroid hormone. Front Neuroendocrinol. 2008;29:211-8 pubmed
  15. Lu C, Cheng S. Thyroid hormone receptors regulate adipogenesis and carcinogenesis via crosstalk signaling with peroxisome proliferator-activated receptors. J Mol Endocrinol. 2010;44:143-54 pubmed publisher
    Peroxisome proliferator-activated receptors (PPARs) and thyroid hormone receptors (TRs) are members of the nuclear receptor superfamily...
  16. Kawakami Y, Shin D, Kitano T, Adachi S, Yamauchi K, Ohta H. Transactivation activity of thyroid hormone receptors in fish (Conger myriaster) in response to thyroid hormones. Comp Biochem Physiol B Biochem Mol Biol. 2006;144:503-9 pubmed
    ..Therefore, we conclude that cTRs can act in concert with THs in fish metamorphosis. ..
  17. Palmer M, Weaver C. Immunology: narcissistic helpers. Nature. 2007;448:416-8 pubmed
  18. Yang X, Pappu B, Nurieva R, Akimzhanov A, Kang H, Chung Y, et al. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity. 2008;28:29-39 pubmed publisher
    ..Therefore, Th17 differentiation is directed by two lineage-specific nuclear receptors, ROR alpha and ROR gamma. ..
  19. Wagner M, Helbing C. Multiple ING1 and ING2 genes in Xenopus laevis and evidence for differential association of thyroid hormone receptors and ING proteins to their promoters. Biochim Biophys Acta. 2008;1779:152-63 pubmed publisher
  20. Sato I, Miyado M, Miwa Y, Sunohara M. Expression of nuclear and mitochondrial thyroid hormone receptors in postnatal rat tongue muscle. Cells Tissues Organs. 2006;183:195-205 pubmed
    In this quantitative study, a competitive RT-PCR analysis was used to measure the level of the thyroid hormone receptors (TRs) in rat tongue muscle during the development of male Wistar rats aged 0, 5, 10, 15 and 21 postnatal days...
  21. Manel N, Unutmaz D, Littman D. The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol. 2008;9:641-9 pubmed publisher
    ..Our studies identify RORgammat as having a central function in the differentiation of human T(H)-17 cells from naive CD4+ T cells and suggest that similar cytokine pathways are involved in this process in mice and humans. ..
  22. Pantos C, Xinaris C, Mourouzis I, Kokkinos A, Cokkinos D. TNF-alpha administration in neonatal cardiomyocytes is associated with differential expression of thyroid hormone receptors: a response prevented by T3. Horm Metab Res. 2008;40:731-4 pubmed publisher
  23. Bernal J. Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab. 2007;3:249-59 pubmed
    ..The actions of thyroid hormones are mediated through nuclear thyroid hormone receptors (TRs) and regulation of gene expression...
  24. Zhou L, Ivanov I, Spolski R, Min R, Shenderov K, Egawa T, et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol. 2007;8:967-74 pubmed
    ..IL-6 therefore orchestrates a series of 'downstream' cytokine-dependent signaling pathways that, in concert with TGF-beta, amplify RORgammat-dependent differentiation of T(H)-17 cells. ..
  25. Zhao B, Chen H, Lei N, Li G, Zhao W, Zhan Y, et al. p53 mediates the negative regulation of MDM2 by orphan receptor TR3. EMBO J. 2006;25:5703-15 pubmed
  26. Tsuji M, Suzuki K, Kitamura H, Maruya M, Kinoshita K, Ivanov I, et al. Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. Immunity. 2008;29:261-71 pubmed publisher
    ..These findings provide insight into the crosstalk between bacteria, ROR gamma t(+)LTi cells, SCs, DCs, and B cells required for ILF formation and establish a critical role of ILFs in T cell-independent IgA synthesis in gut. ..
  27. Wang X, Matsuda H, Shi Y. Developmental regulation and function of thyroid hormone receptors and 9-cis retinoic acid receptors during Xenopus tropicalis metamorphosis. Endocrinology. 2008;149:5610-8 pubmed publisher
    ..laevis development and the genetic and sequence superiority of X. tropicalis to dissect the molecular pathways governing tissue/organ-specific transformations during vertebrate postembryonic development...
  28. Casas F, Pessemesse L, Grandemange S, Seyer P, Gueguen N, Baris O, et al. Overexpression of the mitochondrial T3 receptor p43 induces a shift in skeletal muscle fiber types. PLoS ONE. 2008;3:e2501 pubmed publisher
    ..These data indicate that the direct mitochondrial T3 pathway is deeply involved in the acquisition of contractile and metabolic features of muscle fibers in particular by regulating PGC-1alpha and PPARdelta. ..
  29. Furuzawa Carballeda J, Vargas Rojas M, Cabral A. Autoimmune inflammation from the Th17 perspective. Autoimmun Rev. 2007;6:169-75 pubmed
    ..The IL-17/23 axis of inflammation and related molecules may rise as therapeutic targets for treating these and perhaps other autoimmune diseases. ..
  30. Gu Y, Yang J, Ouyang X, Liu W, Li H, Yang J, et al. Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells. Eur J Immunol. 2008;38:1807-13 pubmed publisher
    ..These data demonstrate that Th17 cytokines and RORgammat are also expressed in macrophages and that IL-10 negatively regulates the expression of Th17 cytokines and RORgammat by both macrophages and T cells. ..
  31. Lema S, Dickey J, Schultz I, Swanson P. Thyroid hormone regulation of mRNAs encoding thyrotropin beta-subunit, glycoprotein alpha-subunit, and thyroid hormone receptors alpha and beta in brain, pituitary gland, liver, and gonads of an adult teleost, Pimephales promelas. J Endocrinol. 2009;202:43-54 pubmed publisher
    ..Here, we characterized TH regulation of mRNAs encoding thyrotropin subunits and thyroid hormone receptors (TRs) in an adult teleost fish model, the fathead minnow (Pimephales promelas)...
  32. Luci C, Reynders A, Ivanov I, Cognet C, Chiche L, Chasson L, et al. Influence of the transcription factor RORgammat on the development of NKp46+ cell populations in gut and skin. Nat Immunol. 2009;10:75-82 pubmed publisher
    ..Our data show that lymphoid tissue-inducer cells and natural killer cells shared unanticipated similarities and emphasize the heterogeneity of NKp46+CD3- cells in innate immunity, lymphoid organization and local tissue repair. ..
  33. Nurieva R, Yang X, Martinez G, Zhang Y, Panopoulos A, Ma L, et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature. 2007;448:480-3 pubmed
    ..IL-21 is therefore an autocrine cytokine that is sufficient and necessary for T(H)17 differentiation, and serves as a target for treating inflammatory diseases. ..
  34. Zoeller R. Environmental chemicals impacting the thyroid: targets and consequences. Thyroid. 2007;17:811-7 pubmed
  35. Shi Y. Dual functions of thyroid hormone receptors in vertebrate development: the roles of histone-modifying cofactor complexes. Thyroid. 2009;19:987-99 pubmed publisher
    ..Furthermore, the concentrations of coactivators appear to regulate the rate of metamorphic progression. Studies in mammals also suggest that the dual function model for TR is conserved across vertebrates. ..
  36. Sanos S, Bui V, Mortha A, Oberle K, Heners C, Johner C, et al. RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat Immunol. 2009;10:83-91 pubmed publisher
    ..IL-22 released by these cells promoted the production of antimicrobial molecules important in the maintenance of mucosal homeostasis. ..
  37. Furuya F, Lu C, Guigon C, Cheng S. Nongenomic activation of phosphatidylinositol 3-kinase signaling by thyroid hormone receptors. Steroids. 2009;74:628-34 pubmed publisher
    ..Recent studies suggest that thyroid hormone receptors (TRs) not only mediate the biological activities of T3 via nucleus-initiated transcription, but also ..
  38. Zhou L, Lopes J, Chong M, Ivanov I, Min R, Victora G, et al. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature. 2008;453:236-40 pubmed publisher
    ..Therefore, the decision of antigen-stimulated cells to differentiate into either T(H)17 or T(reg) cells depends on the cytokine-regulated balance of RORgammat and Foxp3. ..
  39. Leppkes M, Becker C, Ivanov I, Hirth S, Wirtz S, Neufert C, et al. RORgamma-expressing Th17 cells induce murine chronic intestinal inflammation via redundant effects of IL-17A and IL-17F. Gastroenterology. 2009;136:257-67 pubmed publisher
    ..Reagents that target RORgamma or a combination of anti-IL-17A and anti-IL-17F might be developed as therapeutics for chronic colitis. ..
  40. Huang Z, Xie H, Wang R, Sun Z. Retinoid-related orphan receptor gamma t is a potential therapeutic target for controlling inflammatory autoimmunity. Expert Opin Ther Targets. 2007;11:737-43 pubmed
    ..RORgamma t is thus potentially an excellent therapeutic target for the intervention of inflammatory autoimmunity. ..
  41. Huber M, Brüstle A, Reinhard K, Guralnik A, Walter G, Mahiny A, et al. IRF4 is essential for IL-21-mediated induction, amplification, and stabilization of the Th17 phenotype. Proc Natl Acad Sci U S A. 2008;105:20846-51 pubmed publisher
    ..These data highlight IRF4 as a decisive factor during the IL-21-mediated steps of Th17 development by influencing the balance of Foxp3, RORalpha, and RORgammat. ..
  42. Ivanov I, Diehl G, Littman D. Lymphoid tissue inducer cells in intestinal immunity. Curr Top Microbiol Immunol. 2006;308:59-82 pubmed
    ..The potential functional implications of the organization of LTi-like cells, DCs, and lymphocytes in the lamina propria are discussed in the context of maintenance of homeostasis and of infectious diseases, particularly HIV infection. ..
  43. Psarra A, Sekeris C. Steroid and thyroid hormone receptors in mitochondria. IUBMB Life. 2008;60:210-23 pubmed publisher
  44. Duarte Guterman P, Langlois V, Pauli B, Trudeau V. Expression and T3 regulation of thyroid hormone- and sex steroid-related genes during Silurana (Xenopus) tropicalis early development. Gen Comp Endocrinol. 2010;166:428-35 pubmed publisher
    ..In addition, T3 also affected androgen-related gene expression, supporting our hypothesis that THs are involved in male development in frogs. ..
  45. Lochner M, Peduto L, Cherrier M, Sawa S, Langa F, Varona R, et al. In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORgamma t+ T cells. J Exp Med. 2008;205:1381-93 pubmed publisher
  46. Zhang F, Meng G, Strober W. Interactions among the transcription factors Runx1, RORgammat and Foxp3 regulate the differentiation of interleukin 17-producing T cells. Nat Immunol. 2008;9:1297-306 pubmed publisher
    ..Thus, our data support a model in which the differential association of Runx1 with Foxp3 and with RORgammat regulates T(H)-17 differentiation. ..
  47. Martinez L, Polikarpov I, Skaf M. Only subtle protein conformational adaptations are required for ligand binding to thyroid hormone receptors: simulations using a novel multipoint steered molecular dynamics approach. J Phys Chem B. 2008;112:10741-51 pubmed publisher
    b>Thyroid hormone receptors (TR) are hormone-dependent transcription regulators that play a major role in human health, development, and metabolic functions...
  48. Park S, Hu X, Gupta P, Lin Y, Ha S, Wei L. SUMOylation of Tr2 orphan receptor involves Pml and fine-tunes Oct4 expression in stem cells. Nat Struct Mol Biol. 2007;14:68-75 pubmed
  49. Naito T, Shiohara T, Hibi T, Suematsu M, Ishikawa H. ROR gamma t is dispensable for the development of intestinal mucosal T cells. Mucosal Immunol. 2008;1:198-207 pubmed publisher
    ..These results clearly reassert the intraintestinal differentiation of the body's largest peripheral T cell subpopulation. ..
  50. Acosta Rodriguez E, Napolitani G, Lanzavecchia A, Sallusto F. Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol. 2007;8:942-9 pubmed
  51. Wei L, Laurence A, Elias K, O Shea J. IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner. J Biol Chem. 2007;282:34605-10 pubmed
    ..These data argue that IL-21 serves as an autocrine factor secreted by Th17 cells that promotes or sustains Th17 lineage commitment. ..
  52. Acosta Rodriguez E, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, et al. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol. 2007;8:639-46 pubmed
    ..Our results demonstrate that human T(H)-17 cells have distinct migratory capacity and antigenic specificities and establish a link between microbial products, T helper cell differentiation and homing in response to fungal antigens. ..
  53. Xu X, Liu Y, Sadamatsu M, Tsutsumi S, Akaike M, Ushijima H, et al. Perinatal bisphenol A affects the behavior and SRC-1 expression of male pups but does not influence on the thyroid hormone receptors and its responsive gene. Neurosci Res. 2007;58:149-55 pubmed
    Bisphenol A (BPA) has been shown to interfere with thyroid hormone receptors (THRs) and to influence the expression of THR-responsive elements in vivo and in vitro, while some studies reported hyperactivity induced by BPA treatment...