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. 2011 May 26;2(5):358–368. doi: 10.1007/s13238-011-1046-x

Thyroid hormone action in metabolic regulation

Yiyun Song 1, Xuan Yao 1, Hao Ying 1,✉
PMCID: PMC4875336  PMID: 21614672

Abstract

Thyroid hormone plays pivotal roles in growth, differentiation, development and metabolic homeostasis via thyroid hormone receptors (TRs) by controlling the expression of TR target genes. The transcriptional activity of TRs is modulated by multiple factors including various TR isoforms, diverse thyroid hormone response elements, different heterodimeric partners, coregulators, and the cellular location of TRs. In the present review, we summarize recent advance in understanding the molecular mechanisms of thyroid hormone action obtained from human subject research, thyroid hormone mimetics application, TR isoform-specific knock-in mouse models, and mitochondrion study with highlights in metabolic regulations. Finally, as future perspectives, we share our thoughts about current challenges and possible approaches to promote our knowledge of thyroid hormone action in metabolism.

Keywords: thyroid hormone, thyroid hormone receptor, metabolic regulation, central and peripheral effect, thyroid diseases

References

  1. Andersson M.L., Vennström B. Chicken thyroid hormone receptor alpha requires the N-terminal amino acids for exclusive nuclear localization. FEBS Lett. 1997;416:291–296. doi: 10.1016/S0014-5793(97)01223-4. [DOI] [PubMed] [Google Scholar]
  2. Araki O., Ying H., Furuya F., Zhu X., Cheng S.Y. Thyroid hormone receptor beta mutants: Dominant negative regulators of peroxisome proliferator-activated receptor gamma action. Proc Natl Acad Sci U S A. 2005;102:16251–16256. doi: 10.1073/pnas.0508556102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Araki O., Ying H., Zhu X.G., Willingham M.C., Cheng S.Y. Distinct dysregulation of lipid metabolism by unliganded thyroid hormone receptor isoforms. Mol Endocrinol. 2009;23:308–315. doi: 10.1210/me.2008-0311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bogazzi F., Hudson L.D., Nikodem V.M. A novel heterodimerization partner for thyroid hormone receptor. Peroxisome proliferator-activated receptor. J Biol Chem. 1994;269:11683–11686. [PubMed] [Google Scholar]
  5. Bradley D.J., Towle H.C., Young W.S., 3rd Alpha and beta thyroid hormone receptor (TR) gene expression during auditory neurogenesis: evidence for TR isoform-specific transcriptional regulation in vivo. Proc Natl Acad Sci U S A. 1994;91:439–443. doi: 10.1073/pnas.91.2.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Branco M., Ribeiro M., Negrão N., Bianco A.C. 3,5,3′-Triiodothyronine actively stimulates UCP in brown fat under minimal sympathetic activity. Am J Physiol. 1999;276:E179–E187. doi: 10.1152/ajpendo.1999.276.1.E179. [DOI] [PubMed] [Google Scholar]
  7. Brand M.D. The efficiency and plasticity of mitochondrial energy transduction. Biochem Soc Trans. 2005;33:897–904. doi: 10.1042/BST0330897. [DOI] [PubMed] [Google Scholar]
  8. Braverman L.E., Ingbar S.H., Sterling K. Conversion of thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects. J Clin Invest. 1970;49:855–864. doi: 10.1172/JCI106304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Brucker-Davis F., Skarulis M.C., Pikus A., Ishizawar D., Mastroianni M.A., Koby M., Weintraub B.D. Prevalence and mechanisms of hearing loss in patients with resistance to thyroid hormone. J Clin Endocrinol Metab. 1996;81:2768–2772. doi: 10.1210/jcem.81.8.8768826. [DOI] [PubMed] [Google Scholar]
  10. Casas F., Rochard P., Rodier A., Cassar-Malek I., Marchal-Victorion S., Wiesner R.J., Cabello G., Wrutniak C. A variant form of the nuclear triiodothyronine receptor c-ErbAalpha1 plays a direct role in regulation of mitochondrial RNA synthesis. Mol Cell Biol. 1999;19:7913–7924. doi: 10.1128/MCB.19.12.7913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cettour-Rose P., Theander-Carrillo C., Asensio C., Klein M., Visser T.J., Burger A.G., Meier C.A., Rohner-Jeanrenaud F. Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion. Diabetologia. 2005;48:624–633. doi: 10.1007/s00125-005-1696-4. [DOI] [PubMed] [Google Scholar]
  12. Chen J.D., Evans R.M. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature. 1995;377:454–457. doi: 10.1038/377454a0. [DOI] [PubMed] [Google Scholar]
  13. Cheng S.Y. Multiple mechanisms for regulation of the transcriptional activity of thyroid hormone receptors. Rev Endocr Metab Disord. 2000;1:9–18. doi: 10.1023/A:1010052101214. [DOI] [PubMed] [Google Scholar]
  14. Cook C.B., Kakucska I., Lechan R.M., Koenig R.J. Expression of thyroid hormone receptor beta 2 in rat hypothalamus. Endocrinology. 1992;130:1077–1079. doi: 10.1210/endo.130.2.1733708. [DOI] [PubMed] [Google Scholar]
  15. Decherf S., Seugnet I., Kouidhi S., Lopez-Juarez A., Clerget-Froidevaux M.S., Demeneix B.A. Thyroid hormone exerts negative feedback on hypothalamic type 4 melanocortin receptor expression. Proc Natl Acad Sci U S A. 2010;107:4471–4476. doi: 10.1073/pnas.0905190107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dimitriadis G., Mitrou P., Lambadiari V., Boutati E., Maratou E., Panagiotakos D.B., Koukkou E., Tzanela M., Thalassinos N., Raptis S.A. Insulin action in adipose tissue and muscle in hypothyroidism. J Clin Endocrinol Metab. 2006;91:4930–4937. doi: 10.1210/jc.2006-0478. [DOI] [PubMed] [Google Scholar]
  17. Fisher R.P., Lisowsky T., Parisi M.A., Clayton D.A. DNA wrapping and bending by a mitochondrial high mobility group-like transcriptional activator protein. J Biol Chem. 1992;267:3358–3367. [PubMed] [Google Scholar]
  18. Flamant F., Samarut J. Thyroid hormone receptors: lessons from knockout and knock-in mutant mice. Trends Endocrinol Metab. 2003;14:85–90. doi: 10.1016/S1043-2760(02)00043-7. [DOI] [PubMed] [Google Scholar]
  19. Forman B.M., Casanova J., Raaka B.M., Ghysdael J., Samuels H.H. Half-site spacing and orientation determines whether thyroid hormone and retinoic acid receptors and related factors bind to DNA response elements as monomers, homodimers, or heterodimers. Mol Endocrinol. 1992;6:429–442. doi: 10.1210/mend.6.3.1316541. [DOI] [PubMed] [Google Scholar]
  20. Forrest D., Erway L.C., Ng L., Altschuler R., Curran T. Thyroid hormone receptor beta is essential for development of auditory function. Nat Genet. 1996;13:354–357. doi: 10.1038/ng0796-354. [DOI] [PubMed] [Google Scholar]
  21. Furuya F., Ying H., Zhao L., Cheng S.Y. Novel functions of thyroid hormone receptor mutants: beyond nucleus-initiated transcription. Steroids. 2007;72:171–179. doi: 10.1016/j.steroids.2006.11.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Garstka H.L., Fäcke M., Escribano J.R., Wiesner R.J. Stoichiometry of mitochondrial transcripts and regulation of gene expression by mitochondrial transcription factor A. Biochem Biophys Res Commun. 1994;200:619–626. doi: 10.1006/bbrc.1994.1493. [DOI] [PubMed] [Google Scholar]
  23. Gauthier K., Billon C., Bissler M., Beylot M., Lobaccaro J.M., Vanacker J.M., Samarut J. Thyroid hormone receptor beta (TRbeta) and liver X receptor (LXR) regulate carbohydrateresponse element-binding protein (ChREBP) expression in a tissue-selective manner. J Biol Chem. 2010;285:28156–28163. doi: 10.1074/jbc.M110.146241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Guadaño-Ferraz A., Benavides-Piccione R., Venero C., Lancha C., Vennström B., Sandi C., DeFelipe J., Bernal J. Lack of thyroid hormone receptor alpha1 is associated with selective alterations in behavior and hippocampal circuits. Mol Psychiatry. 2003;8:30–38. doi: 10.1038/sj.mp.4001196. [DOI] [PubMed] [Google Scholar]
  25. Harper M.E., Seifert E.L. Thyroid hormone effects on mitochondrial energetics. Thyroid. 2008;18:145–156. doi: 10.1089/thy.2007.0250. [DOI] [PubMed] [Google Scholar]
  26. Hashimoto K., Ishida E., Matsumoto S., Okada S., Yamada M., Satoh T., Monden T., Mori M. Carbohydrate response element binding protein gene expression is positively regulated by thyroid hormone. Endocrinology. 2009;150:3417–3424. doi: 10.1210/en.2009-0059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hiroi Y., Kim H.H., Ying H., Furuya F., Huang Z., Simoncini T., Noma K., Ueki K., Nguyen N.H., Scanlan T.S., et al. Rapid nongenomic actions of thyroid hormone. Proc Natl Acad Sci U S A. 2006;103:14104–14109. doi: 10.1073/pnas.0601600103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Hodin R.A., Lazar M.A., Chin W.W. Differential and tissue-specific regulation of the multiple rat c-erbA messenger RNA species by thyroid hormone. J Clin Invest. 1990;85:101–105. doi: 10.1172/JCI114398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hodin R.A., Lazar M.A., Wintman B.I., Darling D.S., Koenig R.J., Larsen P.R., Moore D.D., Chin W.W. Identification of a thyroid hormone receptor that is pituitary-specific. Science. 1989;244:76–79. doi: 10.1126/science.2539642. [DOI] [PubMed] [Google Scholar]
  30. Hörlein A.J., Näär A.M., Heinzel T., Torchia J., Gloss B., Kurokawa R., Ryan A., Kamei Y., Söderström M., Glass C.K., et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature. 1995;377:397–404. doi: 10.1038/377397a0. [DOI] [PubMed] [Google Scholar]
  31. Hwang J.H., Pan J.W., Heydari S., Hetherington H.P., Stein D. T. Regional differences in intramyocellular lipids in humans observed by in vivo 1H-MR spectroscopic imaging. J Appl Physiol. 2001;90:1267–1274. doi: 10.1152/jappl.2001.90.4.1267. [DOI] [PubMed] [Google Scholar]
  32. Itoh Y., Esaki T., Kaneshige M., Suzuki H., Cook M., Sokoloff L., Cheng S.Y., Nunez J. Brain glucose utilization in mice with a targeted mutation in the thyroid hormone alpha or beta receptor gene. Proc Natl Acad Sci U S A. 2001;98:9913–9918. doi: 10.1073/pnas.171319498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Izumo S., Mahdavi V. Thyroid hormone receptor alpha isoforms generated by alternative splicing differentially activate myosin HC gene transcription. Nature. 1988;334:539–542. doi: 10.1038/334539a0. [DOI] [PubMed] [Google Scholar]
  34. Jackson I.M., Prentice C.R., McKiddie M.T. The effect of hypothyroidism on glucose tolerance and insulin metabolism. J Endocrinol. 1970;47:257–258. doi: 10.1677/joe.0.0470257. [DOI] [PubMed] [Google Scholar]
  35. Jansen M.S., Cook G.A., Song S., Park E.A. Thyroid hormone regulates carnitine palmitoyltransferase Ialpha gene expression through elements in the promoter and first intron. J Biol Chem. 2000;275:34989–34997. doi: 10.1074/jbc.M001752200. [DOI] [PubMed] [Google Scholar]
  36. Kaneshige M., Kaneshige K., Zhu X., Dace A., Garrett L., Carter T. A., Kazlauskaite R., Pankratz D.G., Wynshaw-Boris A., Refetoff S., et al. Mice with a targeted mutation in the thyroid hormone beta receptor gene exhibit impaired growth and resistance to thyroid hormone. Proc Natl Acad Sci U S A. 2000;97:13209–13214. doi: 10.1073/pnas.230285997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kaneshige M., Suzuki H., Kaneshige K., Cheng J., Wimbrow H., Barlow C., Willingham M.C., Cheng S. A targeted dominant negative mutation of the thyroid hormone alpha 1 receptor causes increased mortality, infertility, and dwarfism in mice. Proc Natl Acad Sci U S A. 2001;98:15095–15100. doi: 10.1073/pnas.261565798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Kim B. Thyroid hormone as a determinant of energy expenditure and the basal metabolic rate. Thyroid. 2008;18:141–144. doi: 10.1089/thy.2007.0266. [DOI] [PubMed] [Google Scholar]
  39. Köhrle J. The selenoenzyme family of deiodinase isozymes controls local thyroid hormone availability. Rev Endocr Metab Disord. 2000;1:49–58. doi: 10.1023/A:1010012419869. [DOI] [PubMed] [Google Scholar]
  40. Krssak M., Falk Petersen K., Dresner A., DiPietro L., Vogel S.M., Rothman D.L., Roden M., Shulman G.I. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia. 1999;42:113–116. doi: 10.1007/s001250051123. [DOI] [PubMed] [Google Scholar]
  41. Lebon V., Dufour S., Petersen K.F., Ren J., Jucker B.M., Slezak L. A., Cline G.W., Rothman D.L., Shulman G.I. Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle. J Clin Invest. 2001;108:733–737. doi: 10.1172/JCI200111775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Ledesma, A., de Lacoba, M.G., and Rial, E. (2002). The mitochondrial uncoupling proteins. Genome Biol 3, REVIEW S3015. [DOI] [PMC free article] [PubMed]
  43. Liu Y.Y., Schultz J.J., Brent G.A. A thyroid hormone receptor alpha gene mutation (P398H) is associated with visceral adiposity and impaired catecholamine-stimulated lipolysis in mice. J Biol Chem. 2003;278:38913–38920. doi: 10.1074/jbc.M306120200. [DOI] [PubMed] [Google Scholar]
  44. López M., Varela L., Vázquez M.J., Rodríguez-Cuenca S., González C.R., Velagapudi V.R., Morgan D.A., Schoenmakers E., Agassandian K., Lage R., et al. Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat Med. 2010;16:1001–1008. doi: 10.1038/nm.2207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Macchia P.E., Takeuchi Y., Kawai T., Cua K., Gauthier K., Chassande O., Seo H., Hayashi Y., Samarut J., Murata Y., et al. Increased sensitivity to thyroid hormone in mice with complete deficiency of thyroid hormone receptor alpha. Proc Natl Acad Sci U S A. 2001;98:349–354. doi: 10.1073/pnas.011306998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Marin-Garcia J., Ananthakrishnan R., Goldenthal M.J. Heart mitochondrial DNA and enzyme changes during early human development. Mol Cell Biochem. 2000;210:47–52. doi: 10.1023/A:1007031919298. [DOI] [PubMed] [Google Scholar]
  47. Marrif H., Schifman A., Stepanyan Z., Gillis M.A., Calderone A., Weiss R.E., Samarut J., Silva J.E. Temperature homeostasis in transgenic mice lacking thyroid hormone receptoralpha gene products. Endocrinology. 2005;146:2872–2884. doi: 10.1210/en.2004-1544. [DOI] [PubMed] [Google Scholar]
  48. McKenna N.J., Lanz R.B., O’Malley B.W. Nuclear receptor coregulators: cellular and molecular biology. Endocr Rev. 1999;20:321–344. doi: 10.1210/edrv.20.3.0366. [DOI] [PubMed] [Google Scholar]
  49. Meier-Heusler S.C., Zhu X., Juge-Aubry C., Pernin A., Burger A. G., Cheng S.Y., Meier C.A. Modulation of thyroid hormone action by mutant thyroid hormone receptors, c-erbA alpha 2 and peroxisome proliferator-activated receptor: evidence for different mechanisms of inhibition. Mol Cell Endocrinol. 1995;107:55–66. doi: 10.1016/0303-7207(94)03422-P. [DOI] [PubMed] [Google Scholar]
  50. Mitsuhashi T., Tennyson G.E., Nikodem V.M. Alternative splicing generates messages encoding rat c-erbA proteins that do not bind thyroid hormone. Proc Natl Acad Sci U S A. 1988;85:5804–5808. doi: 10.1073/pnas.85.16.5804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Moeller L.C., Dumitrescu A.M., Refetoff S. Cytosolic action of thyroid hormone leads to induction of hypoxia-inducible factor-1alpha and glycolytic genes. Mol Endocrinol. 2005;19:2955–2963. doi: 10.1210/me.2004-0542. [DOI] [PubMed] [Google Scholar]
  52. Nagy L., Kao H.Y., Chakravarti D., Lin R.J., Hassig C.A., Ayer D. E., Schreiber S.L., Evans R.M. Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. Cell. 1997;89:373–380. doi: 10.1016/S0092-8674(00)80218-4. [DOI] [PubMed] [Google Scholar]
  53. Nunez J., Celi F.S., Ng L., Forrest D. Multigenic control of thyroid hormone functions in the nervous system. Mol Cell Endocrinol. 2008;287:1–12. doi: 10.1016/j.mce.2008.03.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Okajima F., Ui M. Metabolism of glucose in hyper- and hypo-thyroid rats in vivo. Glucose-turnover values and futile-cycle activities obtained with 14C- and 3H-labelled glucose. Biochem J. 1979;182:565–575. doi: 10.1042/bj1820565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Oppenheimer J.H., Schwartz H.L., Lane J.T., Thompson M.P. Functional relationship of thyroid hormone-induced lipogenesis, lipolysis, and thermogenesis in the rat. J Clin Invest. 1991;87:125–132. doi: 10.1172/JCI114961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Pagliarini D.J., Calvo S.E., Chang B., Sheth S.A., Vafai S.B., Ong S.E., Walford G.A., Sugiana C., Boneh A., Chen W.K., et al. A mitochondrial protein compendium elucidates complex I disease biology. Cell. 2008;134:112–123. doi: 10.1016/j.cell.2008.06.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Parrilla R., Mixson A.J., McPherson J.A., McClaskey J.H., Weintraub B.D. Characterization of seven novel mutations of the c-erbA beta gene in unrelated kindreds with generalized thyroid hormone resistance. Evidence for two “hot spot” regions of the ligand binding domain. J Clin Invest. 1991;88:2123–2130. doi: 10.1172/JCI115542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Petersen K.F., Blair J.B., Shulman G.I. Triiodothyronine treatment increases substrate cycling between pyruvate carboxylase and malic enzyme in perfused rat liver. Metabolism. 1995;44:1380–1383. doi: 10.1016/0026-0495(95)90133-7. [DOI] [PubMed] [Google Scholar]
  59. Petersen K.F., Cline G.W., Blair J.B., Shulman G.I. Substrate cycling between pyruvate and oxaloacetate in awake normal and 3,3′-5-triiodo-L-thyronine-treated rats. Am J Physiol. 1994;267:E273–E277. doi: 10.1152/ajpendo.1994.267.2.E273. [DOI] [PubMed] [Google Scholar]
  60. Pihlajamäki J., Boes T., Kim E.Y., Dearie F., Kim B.W., Schroeder J., Mun E., Nasser I., Park P.J., Bianco A.C., et al. Thyroid hormone-related regulation of gene expression in human fatty liver. J Clin Endocrinol Metab. 2009;94:3521–3529. doi: 10.1210/jc.2009-0212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Raboudi N., Arem R., Jones R.H., Chap Z., Pena J., Chou J., Field J.B. Fasting and postabsorptive hepatic glucose and insulin metabolism in hyperthyroidism. Am J Physiol. 1989;256:E159–E166. doi: 10.1152/ajpendo.1989.256.1.E159. [DOI] [PubMed] [Google Scholar]
  62. Randin J.P., Scazziga B., Jéquier E., Felber J.P. Study of glucose and lipid metabolism by continuous indirect calorimetry in Graves’ disease: effect of an oral glucose load. J Clin Endocrinol Metab. 1985;61:1165–1171. doi: 10.1210/jcem-61-6-1165. [DOI] [PubMed] [Google Scholar]
  63. Ribeiro M.O., Bianco S.D., Kaneshige M., Schultz J.J., Cheng S. Y., Bianco A.C., Brent G.A. Expression of uncoupling protein 1 in mouse brown adipose tissue is thyroid hormone receptor-beta isoform specific and required for adaptive thermogenesis. Endocrinology. 2010;151:432–440. doi: 10.1210/en.2009-0667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Ribeiro M.O., Carvalho S.D., Schultz J.J., Chiellini G., Scanlan T. S., Bianco A.C., Brent G.A. Thyroid hormone—sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform—specific. J Clin Invest. 2001;108:97–105. doi: 10.1172/JCI200112584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Roos A., Bakker S.J., Links T.P., Gans R.O., Wolffenbuttel B. H. Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J Clin Endocrinol Metab. 2007;92:491–496. doi: 10.1210/jc.2006-1718. [DOI] [PubMed] [Google Scholar]
  66. Rubio A., Raasmaja A., Maia A.L., Kim K.R., Silva J.E. Effects of thyroid hormone on norepinephrine signaling in brown adipose tissue. I. Beta 1- and beta 2-adrenergic receptors and cyclic adenosine 3′,5′-monophosphate generation. Endocrinology. 1995;136:3267–3276. doi: 10.1210/endo.136.8.7628360. [DOI] [PubMed] [Google Scholar]
  67. Sap J., Muñoz A., Damm K., Goldberg Y., Ghysdael J., Leutz A., Beug H., Vennstrñm B. The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature. 1986;324:635–640. doi: 10.1038/324635a0. [DOI] [PubMed] [Google Scholar]
  68. Schoonjans K., Peinado-Onsurbe J., Lefebvre A.M., Heyman R.A., Briggs M., Deeb S., Staels B., Auwerx J. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J. 1996;15:5336–5348. [PMC free article] [PubMed] [Google Scholar]
  69. Schräder M., Müller K.M., Nayeri S., Kahlen J.P., Carlberg C. Vitamin D3-thyroid hormone receptor heterodimer polarity directs ligand sensitivity of transactivation. Nature. 1994;370:382–386. doi: 10.1038/370382a0. [DOI] [PubMed] [Google Scholar]
  70. Shen D.C., Davidson M.B., Kuo S.W., Sheu W.H. Peripheral and hepatic insulin antagonism in hyperthyroidism. J Clin Endocrinol Metab. 1988;66:565–569. doi: 10.1210/jcem-66-3-565. [DOI] [PubMed] [Google Scholar]
  71. Shibusawa N., Hashimoto K., Nikrodhanond A.A., Liberman M.C., Applebury M.L., Liao X.H., Robbins J.T., Refetoff S., Cohen R. N., Wondisford F.E. Thyroid hormone action in the absence of thyroid hormone receptor DNA-binding in vivo. J Clin Invest. 2003;112:588–597. doi: 10.1172/JCI18377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Sinha R., Dufour S., Petersen K.F., LeBon V., Enoksson S., Ma Y. Z., Savoye M., Rothman D.L., Shulman G.I., Caprio S. Assessment of skeletal muscle triglyceride content by (1)H nuclear magnetic resonance spectroscopy in lean and obese adolescents: relationships to insulin sensitivity, total body fat, and central adiposity. Diabetes. 2002;51:1022–1027. doi: 10.2337/diabetes.51.4.1022. [DOI] [PubMed] [Google Scholar]
  73. Sjögren M., Alkemade A., Mittag J., Nordström K., Katz A., Rozell B., Westerblad H., Arner A., Vennström B. Hypermetabolism in mice caused by the central action of an unliganded thyroid hormone receptor alpha1. EMBO J. 2007;26:4535–4545. doi: 10.1038/sj.emboj.7601882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Ting Y.T., Bhat M.K., Wong R., Cheng S. Tissuespecific stabilization of the thyroid hormone beta1 nuclear receptor by phosphorylation. J Biol Chem. 1997;272:4129–4134. doi: 10.1074/jbc.272.7.4129. [DOI] [PubMed] [Google Scholar]
  75. Ting Y.T., Cheng S.Y. Hormone-activated phosphorylation of human beta1 thyroid hormone nuclear receptor. Thyroid. 1997;7:463–469. doi: 10.1089/thy.1997.7.463. [DOI] [PubMed] [Google Scholar]
  76. Tinnikov A., Nordström K., Thorén P., Kindblom J.M., Malin S., Rozell B., Adams M., Rajanayagam O., Pettersson S., Ohlsson C., et al. Retardation of post-natal development caused by a negatively acting thyroid hormone receptor alpha1. EMBO J. 2002;21:5079–5087. doi: 10.1093/emboj/cdf523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Venero C., Guadaño-Ferraz A., Herrero A.I., Nordström K., Manzano J., de Escobar G.M., Bernal J., Vennström B. Anxiety, memory impairment, and locomotor dysfunction caused by a mutant thyroid hormone receptor alpha1 can be ameliorated by T3 treatment. Genes Dev. 2005;19:2152–2163. doi: 10.1101/gad.346105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Wagner B.K., Kitami T., Gilbert T.J., Peck D., Ramanathan A., Schreiber S.L., Golub T.R., Mootha V.K. Large-scale chemical dissection of mitochondrial function. Nat Biotechnol. 2008;26:343–351. doi: 10.1038/nbt1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Wagner R.L., Apriletti J.W., McGrath M.E., West B.L., Baxter J.D., Fletterick R.J. A structural role for hormone in the thyroid hormone receptor. Nature. 1995;378:690–697. doi: 10.1038/378690a0. [DOI] [PubMed] [Google Scholar]
  80. Weinberger C., Thompson C.C., Ong E.S., Lebo R., Gruol D.J., Evans R.M. The c-erb-A gene encodes a thyroid hormone receptor. Nature. 1986;324:641–646. doi: 10.1038/324641a0. [DOI] [PubMed] [Google Scholar]
  81. Wilcoxon J.S., Nadolski G.J., Samarut J., Chassande O., Redei E.E. Behavioral inhibition and impaired spatial learning and memory in hypothyroid mice lacking thyroid hormone receptor alpha. Behav Brain Res. 2007;177:109–116. doi: 10.1016/j.bbr.2006.10.030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Wrutniak C., Cassar-Malek I., Marchal S., Rascle A., Heusser S., Keller J.M., Fléchon J., Dauça M., Samarut J., Ghysdael J., et al. A 43-kDa protein related to c-Erb A alpha 1 is located in the mitochondrial matrix of rat liver. J Biol Chem. 1995;270:16347–16354. doi: 10.1074/jbc.270.27.16347. [DOI] [PubMed] [Google Scholar]
  83. Wu Z., Puigserver P., Andersson U., Zhang C., Adelmant G., Mootha V., Troy A., Cinti S., Lowell B., Scarpulla R.C., et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 1999;98:115–124. doi: 10.1016/S0092-8674(00)80611-X. [DOI] [PubMed] [Google Scholar]
  84. Yen P.M. Physiological and molecular basis of thyroid hormone action. Physiol Rev. 2001;81:1097–1142. doi: 10.1152/physrev.2001.81.3.1097. [DOI] [PubMed] [Google Scholar]
  85. Yen P.M., Sunday M.E., Darling D.S., Chin W.W. Isoform-specific thyroid hormone receptor antibodies detect multiple thyroid hormone receptors in rat and human pituitaries. Endocrinology. 1992;130:1539–1546. doi: 10.1210/endo.130.3.1537303. [DOI] [PubMed] [Google Scholar]
  86. Ying H., Araki O., Furuya F., Kato Y., Cheng S.Y. Impaired adipogenesis caused by a mutated thyroid hormone alpha1 receptor. Mol Cell Biol. 2007;27:2359–2371. doi: 10.1128/MCB.02189-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Yoshikawa T., Shimano H., Amemiya-Kudo M., Yahagi N., Hasty A.H., Matsuzaka T., Okazaki H., Tamura Y., Iizuka Y., Ohashi K., et al. Identification of liver X receptor-retinoid X receptor as an activator of the sterol regulatory element-binding protein 1c gene promoter. Mol Cell Biol. 2001;21:2991–3000. doi: 10.1128/MCB.21.9.2991-3000.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Zhang X.K., Pfahl M. Hetero- and homodimeric receptors in thyroid hormone and vitamin A action. Receptor. 1993;3:183–191. [PubMed] [Google Scholar]
  89. Zhu X.G., McPhie P., Cheng S.Y. Differential sensitivity of thyroid hormone receptor isoform homodimers and mutant heterodimers to hormone-induced dissociation from deoxyribonucleic acid: its role in dominant negative action. Endocrinology. 1997;138:1456–1463. doi: 10.1210/endo.138.4.5067. [DOI] [PubMed] [Google Scholar]

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