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Gene Review

Thrb  -  thyroid hormone receptor beta

Rattus norvegicus

Synonyms: C-erba-beta, ERBA2, Erba2, Nr1a2, Nuclear receptor subfamily 1 group A member 2, ...
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Disease relevance of Thrb

  • CONCLUSIONS: Treatment of hypothyroid rats with the TRbeta-specific agonist GC-1 partially reverts the skeletal development and maturation defects resultant of hypothyroidism [1].
  • Transient cotransfection of P450R promoter/chloramphenicol acetyl transferase (CAT) constructs and the thyroid hormone receptor beta1 (TR beta1) expression plasmid into rat hepatoma H4IIE cells resulted in a 2.4-fold induction of promoter activity that was both T3 and TR beta1 dependent [2].
  • The purpose of this study was to determine whether modest (5-10%) increases in metabolic rate could also be observed with minimal tachycardia after TRbeta stimulation [3].
  • Therefore, selective TRbeta activation may be a potentially usefully treatment for obesity and reduction of low density lipoprotein cholesterol and reduction of the atherogenic risk factor lipoprotein (a) [3].
  • We conclude that chronic, selective activation of the TR beta isoform does not result in bone loss typical of T3-induced thyrotoxicosis, suggesting that the TR beta isoform is not critical in this process [4].

High impact information on Thrb

  • Since there are two major thyroid hormone receptor (TR) isoforms, TR alpha and TR beta, it is not known how the mutant receptor mediates a dominant negative effect [5].
  • Here, we present direct molecular evidence for potassium channel stimulation in a rat pituitary cell line (GH(4)C(1)) by a nuclear receptor for thyroid hormone, TRbeta, acting rapidly at the plasma membrane through phosphatidylinositol 3-kinase (PI3K) to slow the deactivation of KCNH2 channels already in the membrane [6].
  • We found an inserted cREL binding sequence in the 5' flanking sequence of the Abca4 gene associated with an increased expression level of that gene, and we found a mutation of the gene encoding thyroid hormone receptor beta2 associated with a decreased expression level of the gene encoding short-wavelength sensitive opsin (Opn1sw) [7].
  • T3 acts through nuclear receptors (TR) of two types, TRalpha1 and TRbeta, that either repress or activate gene expression [8].
  • Rat c-erbA beta 1 mRNA rises in cerebrum during the first 10 days of life, coincident with an increase in tissue triiodothyronine (T3) levels and T3-dependent brain development [9].

Chemical compound and disease context of Thrb


Biological context of Thrb


Anatomical context of Thrb


Associations of Thrb with chemical compounds

  • In the presence of the transcriptional inhibitor, actinomycin D, the half-life of TR beta 2 mRNA was approximately 3 h in the presence or absence of sodium butyrate [12].
  • The reduction of receptor caused by retinoic acid is accompanied by a decreased expression of c-erbA alpha 1 and alpha 2 mRNAs, but the retinoid did not reduce the abundance of c-erbA beta mRNA [16].
  • Moreover, when various ligand binding forms of mouse or chicken TRbeta and TRalpha were expressed with TRH-luciferase, all forms of TRbeta gave T3-dependent regulation of TRH transcription, whereas transcription was T3 insensitive with each TRalpha tested [17].
  • The Northern analyses showed that MtT/S cells express retinoic acid receptor alpha2 mRNA and thyroid hormone receptor beta2 mRNA, and DEX did not affect the levels of these mRNAs [18].
  • Additional dose-response studies in hypercholesteremic rats confirmed the preferential effect of GC-1 on TRbeta-mediated parameters by showing a much higher potency to influence cholesterol and TSH than heart rate [19].

Physical interactions of Thrb


Other interactions of Thrb


Analytical, diagnostic and therapeutic context of Thrb


  1. The thyroid hormone receptor beta-specific agonist GC-1 selectively affects the bone development of hypothyroid rats. Freitas, F.R., Capelo, L.P., O'Shea, P.J., Jorgetti, V., Moriscot, A.S., Scanlan, T.S., Williams, G.R., Zorn, T.M., Gouveia, C.H. J. Bone Miner. Res. (2005) [Pubmed]
  2. Thyroid regulation of NADPH:cytochrome P450 oxidoreductase: identification of a thyroid-responsive element in the 5'-flank of the oxidoreductase gene. O'Leary, K.A., Li, H.C., Ram, P.A., McQuiddy, P., Waxman, D.J., Kasper, C.B. Mol. Pharmacol. (1997) [Pubmed]
  3. Effects of the thyroid hormone receptor agonist GC-1 on metabolic rate and cholesterol in rats and primates: selective actions relative to 3,5,3'-triiodo-L-thyronine. Grover, G.J., Egan, D.M., Sleph, P.G., Beehler, B.C., Chiellini, G., Nguyen, N.H., Baxter, J.D., Scanlan, T.S. Endocrinology (2004) [Pubmed]
  4. Spared bone mass in rats treated with thyroid hormone receptor TR beta-selective compound GC-1. Freitas, F.R., Moriscot, A.S., Jorgetti, V., Soares, A.G., Passarelli, M., Scanlan, T.S., Brent, G.A., Bianco, A.C., Gouveia, C.H. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  5. New insights on the mechanism(s) of the dominant negative effect of mutant thyroid hormone receptor in generalized resistance to thyroid hormone. Yen, P.M., Sugawara, A., Refetoff, S., Chin, W.W. J. Clin. Invest. (1992) [Pubmed]
  6. Rapid signaling at the plasma membrane by a nuclear receptor for thyroid hormone. Storey, N.M., Gentile, S., Ullah, H., Russo, A., Muessel, M., Erxleben, C., Armstrong, D.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Regulation of gene expression in the mammalian eye and its relevance to eye disease. Scheetz, T.E., Kim, K.Y., Swiderski, R.E., Philp, A.R., Braun, T.A., Knudtson, K.L., Dorrance, A.M., Dibona, G.F., Huang, J., Casavant, T.L., Sheffield, V.C., Stone, E.M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Deletion of the thyroid hormone receptor alpha 1 prevents the structural alterations of the cerebellum induced by hypothyroidism. Morte, B., Manzano, J., Scanlan, T., Vennström, B., Bernal, J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  9. Immunofluorescence localization of thyroid hormone receptor protein beta 1 and variant alpha 2 in selected tissues: cerebellar Purkinje cells as a model for beta 1 receptor-mediated developmental effects of thyroid hormone in brain. Strait, K.A., Schwartz, H.L., Seybold, V.S., Ling, N.C., Oppenheimer, J.H. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  10. Cloning and characterization of two novel thyroid hormone receptor beta isoforms. Williams, G.R. Mol. Cell. Biol. (2000) [Pubmed]
  11. Diurnal variation in rat liver thyroid hormone receptor (TR)-alpha messenger ribonucleic acid (mRNA) is dependent on the biological clock in the suprachiasmatic nucleus, whereas diurnal variation of TR beta 1 mRNA is modified by food intake. Zandieh Doulabi, B., Platvoet-Ter Schiphorst, M., Kalsbeek, A., Fliers, E., Bakker, O., Wiersinga, W.M. Endocrinology (2004) [Pubmed]
  12. Sodium butyrate selectively alters thyroid hormone receptor gene expression in GH3 cells. Lazar, M.A. J. Biol. Chem. (1990) [Pubmed]
  13. The thyroid hormone receptor-beta agonist GC-1 induces cell proliferation in rat liver and pancreas. Columbano, A., Pibiri, M., Deidda, M., Cossu, C., Scanlan, T.S., Chiellini, G., Muntoni, S., Ledda-Columbano, G.M. Endocrinology (2006) [Pubmed]
  14. Differential expression of thyroid hormone receptor isoforms in neurons and astroglial cells. Leonard, J.L., Farwell, A.P., Yen, P.M., Chin, W.W., Stula, M. Endocrinology (1994) [Pubmed]
  15. Role of thyroid hormone receptors in timing oligodendrocyte differentiation. Billon, N., Tokumoto, Y., Forrest, D., Raff, M. Dev. Biol. (2001) [Pubmed]
  16. Retinoic acid decreases thyroid hormone receptor expression in pituitary GH1 cells. Pérez, P., Sánchez-Pacheco, A., Pascual, A., Aranda, A. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  17. Physiological regulation of hypothalamic TRH transcription in vivo is T3 receptor isoform specific. Guissouma, H., Ghorbel, M.T., Seugnet, I., Ouatas, T., Demeneix, B.A. FASEB J. (1998) [Pubmed]
  18. Retinoic acids and thyroid hormone act synergistically with dexamethasone to increase growth hormone-releasing hormone receptor messenger ribonucleic acid expression. Nogami, H., Matsubara, M., Harigaya, T., Katayama, M., Kawamura, K. Endocrinology (2000) [Pubmed]
  19. The thyroid hormone receptor-beta-selective agonist GC-1 differentially affects plasma lipids and cardiac activity. Trost, S.U., Swanson, E., Gloss, B., Wang-Iverson, D.B., Zhang, H., Volodarsky, T., Grover, G.J., Baxter, J.D., Chiellini, G., Scanlan, T.S., Dillmann, W.H. Endocrinology (2000) [Pubmed]
  20. The CCAAT box binding factor, NF-Y, is required for thyroid hormone regulation of rat liver S14 gene transcription. Jump, D.B., Badin, M.V., Thelen, A. J. Biol. Chem. (1997) [Pubmed]
  21. Regulation of two c-erbA messenger ribonucleic acids in rat GH3 cells by thyroid hormone. Lazar, M.A., Chin, W.W. Mol. Endocrinol. (1988) [Pubmed]
  22. Thyroid hormone regulates heparan sulfate proteoglycan expression in the growth plate. Bassett, J.H., Swinhoe, R., Chassande, O., Samarut, J., Williams, G.R. Endocrinology (2006) [Pubmed]
  23. Hepatic HNF4alpha deficiency induces periportal expression of glutamine synthetase and other pericentral enzymes. Stanulović, V.S., Kyrmizi, I., Kruithof-de Julio, M., Hoogenkamp, M., Vermeulen, J.L., Ruijter, J.M., Talianidis, I., Hakvoort, T.B., Lamers, W.H. Hepatology (2007) [Pubmed]
  24. In vitro transcriptional studies of the roles of the thyroid hormone (T3) response elements and minimal promoters in T3-stimulated gene transcription. Suen, C.S., Yen, P.M., Chin, W.W. J. Biol. Chem. (1994) [Pubmed]
  25. Delineation of three different thyroid hormone-response elements in promoter of rat sarcoplasmic reticulum Ca2+ATPase gene. Demonstration that retinoid X receptor binds 5' to thyroid hormone receptor in response element 1. Hartong, R., Wang, N., Kurokawa, R., Lazar, M.A., Glass, C.K., Apriletti, J.W., Dillmann, W.H. J. Biol. Chem. (1994) [Pubmed]
  26. Genetic dissection of thyroid hormone receptor beta: identification of mutations that separate hormone binding and transcriptional activation. Uppaluri, R., Towle, H.C. Mol. Cell. Biol. (1995) [Pubmed]
  27. Widespread distribution of immunoreactive thyroid hormone beta 2 receptor (TR beta 2) in the nuclei of extrapituitary rat tissues. Schwartz, H.L., Lazar, M.A., Oppenheimer, J.H. J. Biol. Chem. (1994) [Pubmed]
  28. Ontogeny of hepatic nuclear triiodothyronine receptor isoforms in the rat. Rodd, C., Schwartz, H.L., Strait, K.A., Oppenheimer, J.H. Endocrinology (1992) [Pubmed]
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