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Molecular Basis of Thyroid Hormone Action

  • Paul M. Yen
Chapter
Part of the Endocrine Updates book series (ENDO, volume 22)

Abstract

3,3′,5-triiodothyronine (T3), the active thyroid hormone (TH) metabolite of thyroxine (T4), affects the differentiation, growth, and cellular metabolism of virtually all tissues (1–3). TH exerts its major effects at the genomic level, although it also may have activities at nongenomic sites such as the plasma membrane, cytoplasm, and mitochondrion. A general schema for TH effects on gene transcription is shown in Fig. 1.

Keywords

Thyroid Hormone Hormone Receptor Thyroid Hormone Receptor Nuclear Hormone Receptor Thyroid Hormone Action 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Yen, P.M. 2001. Physiological and molecular basis of thyroid hormone action. Physiol Rev. 81:1097–1142.PubMedGoogle Scholar
  2. 2.
    Zhang, J., and M.A. Lazar. 2000. The mechanism of action of thyroid hormones. Annu Rev Physiol. 62:439–466.PubMedCrossRefGoogle Scholar
  3. 3.
    Cheng, S.Y. 2000. Multiple mechanisms for regulation of the transcriptional activity of thyroid hormone receptors. Reviews in Endocrine and Metabolic Disorders. 1/2:9–18.PubMedCrossRefGoogle Scholar
  4. 4.
    Sap, J., A. Munoz, and K. Damm. 1986. The c-erbA protein is a high affinity receptor for thyroid hormone. Nature. 324:635–640.PubMedCrossRefGoogle Scholar
  5. 5.
    Weinberger, C., C.C. Thompson, E.S. Ong, R. Lebo, D.J. Gruol, and R.M. Evans. 1986. The c-erbA gene encodes a thyroid hormone receptor. Nature. 324:641–646.PubMedCrossRefGoogle Scholar
  6. 6.
    McKenna, N.J., R.B. Lanz, and B.W. O’Malley. 1999. Nuclear receptor coregulators: cellular and molecular biology. Endocr Rev. 20:321–344.PubMedCrossRefGoogle Scholar
  7. 7.
    Wagner, R.L., J.W. Apriletti, M.E. McGrath, B.L. West, J.D. Baxter, and R.J. Fletterick. 1995. A structural role for hormone in the thyroid hormone receptor. Nature. 378:690–697.PubMedCrossRefGoogle Scholar
  8. 8.
    Baumann, C.T., P. Maruvada, G.L. Hager, and P.M. Yen. 2001. Nuclear cytoplasmic shuttling by thyroid hormone receptors. multiple protein interactions are required for nuclear retention. J Biol Chem. 276:11237–11245.PubMedCrossRefGoogle Scholar
  9. 9.
    Dace, A., L. Zhao, K.S. Park, T. Furuno, N. Takamura, M. Nakanishi, B.L. West, J.A. Hanover, and S. Cheng. 2000. Hormone binding induces rapid proteasome-mediated degradation of thyroid hormone receptors. Proc Nall Acad Sci USA. 97:8985–8990.CrossRefGoogle Scholar
  10. 10.
    Katz, D., M.J. Reginato, and M.A. Lazar. 1995. Functional regulation of thyroid hormone receptor variant TR alpha 2 by phosphorylation. Molecular and Cellular Biology. 15:2341–2348.PubMedGoogle Scholar
  11. 11.
    Wood, W.M., J.M. Dowding, B.R. Haugen, T.M. Bright, D.F. Gordon, and E.C. Ridgway. 1994. Structural and functional characterization of the genomic locus encoding the murine beta 2 thyroid hormone receptor. Mol Endocrinol. 8:1605–1617.PubMedCrossRefGoogle Scholar
  12. 12.
    Williams, G.R. 2000. Cloning and characterization of two novel thyroid hormone receptor beta isoforms. Mol Cell Biol. 20:8329–8342.PubMedCrossRefGoogle Scholar
  13. 13.
    Chassande, O., A. Fraichard, K. Gauthier, F. Flamant, C. Legrand, P. Savatier, V. Laudet, and J. Samarut. 1997. Identification of transcripts initiated from an internal promoter in the c-erbA alpha locus that encode inhibitors of retinoic acid receptor-alpha and triiodothyronine receptor activities. Mol Endocrinol. 11:1278–1290.PubMedCrossRefGoogle Scholar
  14. 14.
    Bradley, D.J., H.C. Towle, and W.S. Young. 1992. Spatial and temporal expression of a- and 0-thyroid hormone receptor mRNAs, including the b2-subtype, in the developing mammalian system. J Neurosci. 12:2288–2302.PubMedGoogle Scholar
  15. 15.
    Hodin, R.A., M.A. Lazar, and W.W. Chin. 1990. Differential and tissue-specific regulation of the multiple rat c-erbA mRNA species by thyroid hormone. J Clin Invest. 85:101–105.PubMedCrossRefGoogle Scholar
  16. 16.
    Feng, X., Y. Jiang, P. Meltzer, and P.M. Yen. 2000. Thyroid hormone regulation of hepatic genes in vivo detected by complementary DNA microarray. Mol Endocrinol. 14:947–955.PubMedCrossRefGoogle Scholar
  17. 17.
    Williams, G.R., and G.A. Brent. 1995. Thyroid hormone response elements. In Molecular Endocrinology: Basic concepts and clinical correlations. B. Weintraub, editor. Raven Press, New York. 217–239.Google Scholar
  18. 18.
    Glass, C.K. 1994. Differential recognition of target genes by nuclear receptor monomers, dimers and heterodimers. Endo Rev. 15:391–407.Google Scholar
  19. 19.
    Brent, G.A., M.K. Dunn, J.W. Harney, T. Gulick, P.R. Larsen, and D.D. Moore. 1989. Thyroid hormone aporeceptor represses T3-inducible promoters and blocks activity of the retinoic acid receptor. New Biologist. 1:329–336.PubMedGoogle Scholar
  20. 20.
    Horlein, A.J., A.M. Naar, T. Heinzel, J. Torchia, B. Gloss, R. Kurokawa, A. Ryan, Y. Kamel, M. Soderstrotn, C.K. Glass, and M.G. Rosenfeld. 1995. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear co-repressor. Nature. 377:397–404.PubMedCrossRefGoogle Scholar
  21. 21.
    Chen, J.D., and R.M. Evans. 1995. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature. 377:454–457.PubMedCrossRefGoogle Scholar
  22. 22.
    Seol, W., H.S. Choi, and D.D. Moore. 1995. Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors. Mol Endocrinol. 9:72–85.PubMedCrossRefGoogle Scholar
  23. 23.
    Hu, I., and M.A. Lazar. 2000. Transcriptional Repression by Nuclear Hormone Receptors. Trends Endocrinol Metab. 11:6–10.PubMedCrossRefGoogle Scholar
  24. 24.
    Zhang, J., X. Hu, and M.A. Lazar. 1999. A novel role for helix 12 of retinoid X receptor in regulating repression. Mol Cell Biol. 19:6448–6457.PubMedGoogle Scholar
  25. 25.
    Wong, J., Y.B. Shi, and A.P. Wolffe. 1996. A role for nucleosome asembly in both silencing and actiation of the xenopus TR beta A gene by the thyroid hormone receptor. Genes and Development. 9:2696–1711.CrossRefGoogle Scholar
  26. 26.
    Nan, X., H.H. Ng, C.A. Johnson, C.D. Laherty, B.M. Turner, R.N. Eisenman, and A. Bird. 1998. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex [see comments]. Nature. 393:386–389.PubMedCrossRefGoogle Scholar
  27. 27.
    Baniahmad, A., I. Ha, D. Reinberg, M.J. Tsai, S.Y. Tsai, and B.W. O’Malley. 1993. Interaction of human thyroid hormone receptor b with transcription factor TFIIB may mediate target gene derepression and activation by thyroid hormone. Proc Natl Acad Sci USA. 90:8832–8836.PubMedCrossRefGoogle Scholar
  28. 28.
    Fondell, J.D., A.L. Roy, and R.G. Roeder. 1993. Unliganded thyroid hormone receptor inhibits formation of a functional preinitiation complex: implications for active repression. Genes Dev. 7:1400–1410.PubMedCrossRefGoogle Scholar
  29. 29.
    Onate, S.A., S.Y. Tsai, M.J. Tsai, and B.W. O’Malley. 1995. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science. 270:1354–1357.PubMedCrossRefGoogle Scholar
  30. 30.
    McInerney, E.M., D.W. Rose, S.E. Flynn, S. Westin, T.M. Mullen, A. Krones, J. Inostroza, J. Torchia, R.T. Nolte, N. Assa-Munt, M.V. Milburn, C.K. Glass, and M.G. Rosenfeld. 1998. Determinants of coactivator LXXLL motif specificity in nuclear receptor transcriptional activation. Genes Dev. 12:3357–3368.PubMedCrossRefGoogle Scholar
  31. 31.
    Heery, D.M., E. Kalkhoven, S. Hoare, and M.G. Parker. 1997. A signature motif in transcriptional co-activators mediates binding to nuclear receptors [see comments]. Nature. 387:733–736.PubMedCrossRefGoogle Scholar
  32. 32.
    Torchia, J., C. Glass, and M.G. Rosenfeld. 1998. Co-activators and co-repressors in the integration of transcriptional responses. Curr Opin Cell Biol. 10:373–383.PubMedCrossRefGoogle Scholar
  33. 33.
    Nakajima, T., C. Uchida, S.F. Anderson, C.G. Lee, J. Hurwitz, J.D. Parvin, and M. Montminy. 1997. RNA helicase A mediates association of CBP with RNA polymerase II. Cell. 90:1107–1112.PubMedCrossRefGoogle Scholar
  34. 34.
    Ko, L., G.R. Cardona, and W.W. Chin. 2000. Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator [In Process Citation]. Proc Natl Acad Sci USA. 97:6212–6217.PubMedCrossRefGoogle Scholar
  35. 35.
    Iwasaki, T., W.W. Chin, and L. Ko. 2001. Identification and characterization of RRMcontaining coactivator activator (CoAA) as TRBP-interacting protein, and its splice variant as a coactivator modulator (CoAM). J Biol Chem. 276:33375–33383.PubMedCrossRefGoogle Scholar
  36. 36.
    Ito, M., and R.G. Roeder. 2001. The TRAP/SMCC/Mediator complex and thyroid hormone receptor function. Trends Endocrinol Metab. 12:127–134.PubMedCrossRefGoogle Scholar
  37. 37.
    Rachez, C., and L.P. Freedman. 2001. Mediator complexes and transcription. Curr Opin Cell Biol. 13:274–280.PubMedCrossRefGoogle Scholar
  38. 38.
    Sharma, D., and J.D. Fondell. 2002. Ordered recruitment of histone acetyltransferases and the TRAP/Mediator complex to thyroid hormone-responsive promoters in vivo. Proc Natl Acad Sci USA. 99:7934–7939.PubMedCrossRefGoogle Scholar
  39. 39.
    Shang, Y., X. Hu, J. DiRenzo, M.A. Lazar, and M. Brown. 2000. Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell. 103:843–852.PubMedCrossRefGoogle Scholar
  40. 40.
    Chen, H., R.J. Lin, R.L. Schiltz, D. Chakravarti, A. Nash, L. Nagy, M.L. Privalsky, Y. Nakatani, and R.M. Evans. 1997. Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell. 90:569–580.PubMedCrossRefGoogle Scholar
  41. 41.
    DiRenzo, J., Y. Shang, M. Phelan, S. Sif, M. Myers, R. Kingston, and M. Brown. 2000. BRG-1 is recruited to estrogen-responsive promoters and cooperates with factors involved in histone acetylation. Mol Cell Biol. 20:7541–7549.PubMedCrossRefGoogle Scholar
  42. 42.
    Lim, W., N.H. Nguyen, H.Y. Yang, T.S. Scanlan, and J.D. Furlow. 2002. A thyroid hormone antagonist that inhibits thyroid hormone action in vivo. J Biol Chem. 277:35664–35670.PubMedCrossRefGoogle Scholar
  43. 43.
    Trost, S.U., E. Swanson, B. Gloss, D.B. Wang-Iverson, H. Zhang, T. Volodarsky, G.J. Grover, J.D. Baxter, G. Chiellini, T.S. Scanlan, and W.H. Dillmann. 2000. The thyroid hormone receptor-beta-selective agonist GC-1 differentially affects plasma lipids and cardiac activity. Endocrinology. 141:3057–3064.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Paul M. Yen
    • 1
  1. 1.Mol. Regulation and Neuroendocrinology Section, Clinical Endocrinology Branch, NIDDKNational Institutes of HealthBethesdaUSA

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