Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Thyroid hormones and skeletal muscle—new insights and potential implications

Nature Reviews Endocrinology volume 10, pages 206–214 (2014)Cite this article

Subjects

Key Points

  • Thyroid hormone signalling is required for skeletal muscle development, contractile function and muscle regeneration

  • As skeletal muscle comprises 30–40% of body mass, the altered basal metabolic rate in patients with thyroid hormone excess or deficiency is largely due to changes in skeletal muscle energy turnover

  • Functional studies indicate that the active thyroid hormone isoform T3 signals predominantly through the thyroid-hormone receptor α1 (THRA1) isoform in skeletal muscle

  • Expression of the type 2 iodothyronine deiodinase (DIO2), which converts the prohormone T4 to the active thyroid hormone isoform T3, is increased in developing or injured muscles

  • In the absence of DIO2, the muscle-specific thyroid hormone-dependent gene expression programme fails to be induced in the stem-cell-like satellite cells of skeletal muscle, resulting in impaired muscle regeneration

  • Current studies suggest that the dynamic control of thyroid hormone activity through the regulation of deiodinase expression can be harnessed to optimize myogenesis in patients with muscle diseases or injury

Abstract

Thyroid hormone signalling regulates crucial biological functions, including energy expenditure, thermogenesis, development and growth. The skeletal muscle is a major target of thyroid hormone signalling. The type 2 and 3 iodothyronine deiodinases (DIO2 and DIO3, respectively) have been identified in skeletal muscle. DIO2 expression is tightly regulated and catalyses outer-ring monodeiodination of the secreted prohormone tetraiodothyronine (T4) to generate the active hormone tri-iodothyronine (T3). T3 can remain in the myocyte to signal through nuclear receptors or exit the cell to mix with the extracellular pool. By contrast, DIO3 inactivates T3 through removal of an inner-ring iodine. Regulation of the expression and activity of deiodinases constitutes a cell-autonomous, pre-receptor mechanism for controlling the intracellular concentration of T3. This local control of T3 activity is crucial during the various phases of myogenesis. Here, we review the roles of T3 in skeletal muscle development and homeostasis, with a focus on the emerging local deiodinase-mediated control of T3 signalling. Moreover, we discuss these novel findings in the context of both muscle homeostasis and pathology, and examine how skeletal muscle deiodinase activity might be therapeutically harnessed to improve satellite-cell-mediated muscle repair in patients with skeletal muscle disorders, muscle atrophy or injury.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The role of thyroid hormone signalling in skeletal myogenesis.
Figure 2: The thyroid hormone signalling cascade in myotube differentiation.

Similar content being viewed by others

References

  1. Simonides, W. S. & van Hardeveld, C. Thyroid hormone as a determinant of metabolic and contractile phenotype of skeletal muscle. Thyroid 18, 205–216 (2008).

    CAS  PubMed  Google Scholar 

  2. Schiaffino, S. & Reggiani, C. Fiber types in mammalian skeletal muscles. Physiol. Rev. 91, 1447–1531 (2011).

    CAS  PubMed  Google Scholar 

  3. Murphy, R. M., Larkins, N. T., Mollica, J. P., Beard, N. A. & Lamb, G. D. Calsequestrin content and SERCA determine normal and maximal Ca2+ storage levels in sarcoplasmic reticulum of fast- and slow-twitch fibres of rat. J. Physiol. 587, 443–460 (2009).

    CAS  PubMed  Google Scholar 

  4. Novák, P. & Soukup, T. Calsequestrin distribution, structure and function, its role in normal and pathological situations and the effect of thyroid hormones. Physiol. Res. 60, 439–452 (2011).

    PubMed  Google Scholar 

  5. Bianco, A. C., Salvatore, D., Gereben, B., Berry, M. J. & Larsen, P. R. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr. Rev. 23, 38–89 (2002).

    CAS  PubMed  Google Scholar 

  6. Gereben, B. et al. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr. Rev. 29, 898–938 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Croteau, W., Davey, J. C., Galton, V. A. & St Germain, D. L. Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues. J. Clin. Invest. 98, 405–417 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Salvatore, D., Bartha, T., Harney, J. W. & Larsen, P. R. Molecular biological and biochemical characterization of the human type 2 selenodeiodinase. Endocrinology 137, 3308–3315 (1996).

    CAS  PubMed  Google Scholar 

  9. Peeters, R. P. et al. Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients. J. Clin. Endocrinol. Metab. 88, 3202–3211 (2003).

    CAS  PubMed  Google Scholar 

  10. Brack, A. S. & Rando, T. A. Tissue-specific stem cells: lessons from the skeletal muscle satellite cell. Cell Stem Cell 10, 504–514 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Yin, H., Price, F. & Rudnicki, M. A. Satellite cells and the muscle stem cell niche. Physiol. Rev. 93, 23–67 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Relaix, F. & Zammit, P. S. Satellite cells are essential for skeletal muscle regeneration: the cell on the edge returns centre stage. Development 139, 2845–2856 (2012).

    CAS  PubMed  Google Scholar 

  13. Yu, F. et al. Effects of thyroid hormone receptor gene disruption on myosin isoform expression in mouse skeletal muscles. Am. J. Physiol. Regul. Integr. Comp. Physiol. 278, R1545–R1554 (2000).

    CAS  PubMed  Google Scholar 

  14. Brent, G. A. Mechanisms of thyroid hormone action. J. Clin. Invest. 122, 3035–3043 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Mebis, L. et al. Expression of thyroid hormone transporters during critical illness. Eur. J. Endocrinol. 161, 243–250 (2009).

    CAS  PubMed  Google Scholar 

  16. Friesema, E. C. et al. Effective cellular uptake and efflux of thyroid hormone by human monocarboxylate transporter 10. Mol. Endocrinol. 22, 1357–1369 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Marsili, A. et al. Type 2 iodothyronine deiodinase levels are higher in slow-twitch than fast-twitch mouse skeletal muscle and are increased in hypothyroidism. Endocrinology 151, 5952–5960 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Marsili, A. et al. Type II iodothyronine deiodinase provides intracellular 3,5,3′-triiodothyronine to normal and regenerating mouse skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 301, E818–E824 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Dentice, M. et al. The FoxO3/type 2 deiodinase pathway is required for normal mouse myogenesis and muscle regeneration. J. Clin. Invest. 120, 4021–4030 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Hosoi, Y. et al. Expression and regulation of type II iodothyronine deiodinase in cultured human skeletal muscle cells. J. Clin. Endocrinol. Metab. 84, 3293–3300 (1999).

    CAS  PubMed  Google Scholar 

  21. Maia, A. L., Kim, B. W., Huang, S. A., Harney, J. W. & Larsen, P. R. Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans. J. Clin. Invest. 115, 2524–2533 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Grozovsky, R. et al. Type 2 deiodinase expression is induced by peroxisomal proliferator-activated receptor-gamma agonists in skeletal myocytes. Endocrinology 150, 1976–1983 (2009).

    CAS  PubMed  Google Scholar 

  23. Mebis, L., Langouche, L., Visser, T. J. & Van den Berghe, G. The type II iodothyronine deiodinase is up-regulated in skeletal muscle during prolonged critical illness. J. Clin. Endocrinol. Metab. 92, 3330–3333 (2007).

    CAS  PubMed  Google Scholar 

  24. Heemstra, K. A. et al. Type 2 iodothyronine deiodinase in skeletal muscle: effects of hypothyroidism and fasting. J. Clin. Endocrinol. Metab. 94, 2144–2150 (2009).

    CAS  PubMed  Google Scholar 

  25. Steinsapir, J., Harney, J. & Larsen, P. R. Type 2 iodothyronine deiodinase in rat pituitary tumor cells is inactivated in proteasomes. J. Clin. Invest. 102, 1895–1899 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Mills, I., Barge, R. M., Silva, J. E. & Larsen, P. R. Insulin stimulation of iodothyronine 5′-deiodinase in rat brown adipocytes. Biochem. Biophys. Res. Commun. 143, 81–86 (1987).

    CAS  PubMed  Google Scholar 

  27. Silva, J. E. & Larsen, P. R. Hormonal regulation of iodothyronine 5′-deiodinase in rat brown adipose tissue. Am. J. Physiol. 251, E639–E643 (1986).

    CAS  PubMed  Google Scholar 

  28. Boelen, A., Kwakkel, J., Wiersinga, W. M. & Fliers, E. Chronic local inflammation in mice results in decreased TRH and type 3 deiodinase mRNA expression in the hypothalamic paraventricular nucleus independently of diminished food intake. J. Endocrinol. 191, 707–714 (2006).

    CAS  PubMed  Google Scholar 

  29. Peeters, R. P. et al. Serum 3,3′,5′-triiodothyronine (rT3) and 3,5,3′-triiodothyronine/rT3 are prognostic markers in critically ill patients and are associated with postmortem tissue deiodinase activities. J. Clin. Endocrinol. Metab. 90, 4559–4565 (2005).

    CAS  PubMed  Google Scholar 

  30. Yen, P. M. Physiological and molecular basis of thyroid hormone action. Physiol. Rev. 81, 1097–1142 (2001).

    CAS  PubMed  Google Scholar 

  31. Simonides, W. S. et al. Characterization of the promoter of the rat sarcoplasmic endoplasmic reticulum Ca2+-ATPase 1 gene and analysis of thyroid hormone responsiveness. J. Biol. Chem. 271, 32048–32056 (1996).

    CAS  PubMed  Google Scholar 

  32. Hartong, R. et al. 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. J. Biol. Chem. 269, 13021–13029 (1994).

    CAS  PubMed  Google Scholar 

  33. Solanes, G. et al. Thyroid hormones directly activate the expression of the human and mouse uncoupling protein-3 genes through a thyroid response element in the proximal promoter region. Biochem. J. 386, 505–513 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Zorzano, A., Palacin, M. & Guma, A. Mechanisms regulating GLUT4 glucose transporter expression and glucose transport in skeletal muscle. Acta Physiol. Scand. 183, 43–58 (2005).

    CAS  PubMed  Google Scholar 

  35. Desvergne, B., Petty, K. J. & Nikodem, V. M. Functional characterization and receptor binding studies of the malic enzyme thyroid hormone response element. J. Biol. Chem. 266, 1008–1013 (1991).

    CAS  PubMed  Google Scholar 

  36. Dümmler, K., Müller, S. & Seitz, H. J. Regulation of adenine nucleotide translocase and glycerol 3-phosphate dehydrogenase expression by thyroid hormones in different rat tissues. Biochem. J. 317 (Pt 3), 913–918 (1996).

    PubMed  PubMed Central  Google Scholar 

  37. Morkin, E. Control of cardiac myosin heavy chain gene expression. Microsc. Res. Tech. 50, 522–531 (2000).

    CAS  PubMed  Google Scholar 

  38. Muscat, G. E., Mynett-Johnson, L., Dowhan, D., Downes, M. & Griggs, R. Activation of myoD gene transcription by 3,5,3′-triiodo-L-thyronine: a direct role for the thyroid hormone and retinoid X receptors. Nucleic Acids Res. 22, 583–591 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Downes, M., Griggs, R., Atkins, A., Olson, E. N. & Muscat, G. E. Identification of a thyroid hormone response element in the mouse myogenin gene: characterization of the thyroid hormone and retinoid X receptor heterodimeric binding site. Cell Growth Differ. 4, 901–909 (1993).

    CAS  PubMed  Google Scholar 

  40. Muller, A., Thelen, M. H., Zuidwijk, M. J., Simonides, W. S. & van Hardeveld, C. Expression of MyoD in cultured primary myotubes is dependent on contractile activity: correlation with phenotype-specific expression of a sarcoplasmic reticulum Ca2+-ATPase isoform. Biochem. Biophys. Res. Commun. 229, 198–204 (1996).

    CAS  PubMed  Google Scholar 

  41. Kraus, B. & Pette, D. Quantification of MyoD, myogenin, MRF4 and Id-1 by reverse-transcriptase polymerase chain reaction in rat muscles—effects of hypothyroidism and chronic low-frequency stimulation. Eur. J. Biochem. 247, 98–106 (1997).

    CAS  PubMed  Google Scholar 

  42. Wheeler, M. T., Snyder, E. C., Patterson, M. N. & Swoap, S. J. An E-box within the MHC IIB gene is bound by MyoD and is required for gene expression in fast muscle. Am. J. Physiol. 276, C1069–C1078 (1999).

    CAS  PubMed  Google Scholar 

  43. Allen, D. L., Sartorius, C. A., Sycuro, L. K. & Leinwand, L. A. Different pathways regulate expression of the skeletal myosin heavy chain genes. J. Biol. Chem. 276, 43524–43533 (2001).

    CAS  PubMed  Google Scholar 

  44. Weitzel, J. M., Iwen, K. A. & Seitz, H. J. Regulation of mitochondrial biogenesis by thyroid hormone. Exp. Physiol. 88, 121–128 (2003).

    CAS  PubMed  Google Scholar 

  45. Irrcher, I., Adhihetty, P. J., Joseph, A. M., Ljubicic, V. & Hood, D. A. Regulation of mitochondrial biogenesis in muscle by endurance exercise. Sports Med. 33, 783–793 (2003).

    PubMed  Google Scholar 

  46. Psarra, A. M., Solakidi, S. & Sekeris, C. E. The mitochondrion as a primary site of action of steroid and thyroid hormones: presence and action of steroid and thyroid hormone receptors in mitochondria of animal cells. Mol. Cell Endocrinol. 246, 21–33 (2006).

    CAS  PubMed  Google Scholar 

  47. Muscat, G. E., Downes, M. & Dowhan, D. H. Regulation of vertebrate muscle differentiation by thyroid hormone: the role of the myoD gene family. Bioessays 17, 211–218 (1995).

    CAS  PubMed  Google Scholar 

  48. White, R. B., Bierinx, A. S., Gnocchi, V. F. & Zammit, P. S. Dynamics of muscle fibre growth during postnatal mouse development. BMC Dev. Biol. 10, 21 (2010).

    PubMed  PubMed Central  Google Scholar 

  49. Braverman, L. E. & Cooper, D. S. Werner & Ingbar's The Thyroid: A Fundamental and Clinical Text, 10th edn (Lippincott, Williams & Wilkins, Philadelphia, 2012).

    Google Scholar 

  50. de Lange, P. et al. Uncoupling protein-3 is a molecular determinant for the regulation of resting metabolic rate by thyroid hormone. Endocrinology 142, 3414–3420 (2001).

    CAS  PubMed  Google Scholar 

  51. Silva, J. E. Thermogenic mechanisms and their hormonal regulation. Physiol. Rev. 86, 435–464 (2006).

    CAS  PubMed  Google Scholar 

  52. Visser, W. E. et al. Physiological thyroid hormone levels regulate numerous skeletal muscle transcripts. J. Clin. Endocrinol. Metab. 94, 3487–3496 (2009).

    CAS  PubMed  Google Scholar 

  53. Clement, K. et al. In vivo regulation of human skeletal muscle gene expression by thyroid hormone. Genome Res. 12, 281–291 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Lebon, V. et al. Effect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle. J. Clin. Invest. 108, 733–737 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Mitchell, C. S. et al. Resistance to thyroid hormone is associated with raised energy expenditure, muscle mitochondrial uncoupling, and hyperphagia. J. Clin. Invest. 120, 1345–1354 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Johannsen, D. L. et al. Effect of short-term thyroxine administration on energy metabolism and mitochondrial efficiency in humans. PLoS ONE 7, e40837 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Queiroz, M. S., Shao, Y. & Ismail-Beigi, F. Effect of thyroid hormone on uncoupling protein-3 mRNA expression in rat heart and skeletal muscle. Thyroid 14, 177–185 (2004).

    PubMed  Google Scholar 

  58. Ramadan, W., Marsili, A., Larsen, P. R., Zavacki, A. M. & Silva, J. E. Type-2 iodothyronine 5′deiodinase (D2) in skeletal muscle of C57Bl/6 mice. II. Evidence for a role of D2 in the hypermetabolism of thyroid hormone receptor alpha-deficient mice. Endocrinology 152, 3093–102 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. van Marken Lichtenbelt, W. D. et al. Cold-activated brown adipose tissue in healthy men. N. Engl. J. Med. 360, 1500–1508 (2009).

    CAS  PubMed  Google Scholar 

  60. Cypess, A. M. et al. Cold but not sympathomimetics activates human brown adipose tissue in vivo. Proc. Natl Acad. Sci. USA 109, 10001–10005 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. van der Lans, A. A. et al. Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. J. Clin. Invest. 123, 3395–3403 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Wu, J. et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150, 366–376 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Boström, P. et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481, 463–468 (2012).

    PubMed  PubMed Central  Google Scholar 

  64. Chidakel, A., Mentuccia, D. & Celi, F. S. Peripheral metabolism of thyroid hormone and glucose homeostasis. Thyroid 15, 899–903 (2005).

    CAS  PubMed  Google Scholar 

  65. Klieverik, L. P. et al. Thyroid hormone effects on whole-body energy homeostasis and tissue-specific fatty acid uptake in vivo. Endocrinology 150, 5639–5648 (2009).

    CAS  PubMed  Google Scholar 

  66. Harrison, S. A., Buxton, J. M., Clancy, B. M. & Czech, M. P. Insulin regulation of hexose transport in mouse 3T3-L1 cells expressing the human HepG2 glucose transporter. J. Biol. Chem. 265, 20106–20116 (1990).

    CAS  PubMed  Google Scholar 

  67. Marsili, A. et al. Mice with a targeted deletion of the type 2 deiodinase are insulin resistant and susceptible to diet induced obesity. PLoS ONE 6, e20832 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Mentuccia, D. et al. Association between a novel variant of the human type 2 deiodinase gene Thr92Ala and insulin resistance: evidence of interaction with the Trp64Arg variant of the β-3-adrenergic receptor. Diabetes 51, 880–883 (2002).

    CAS  PubMed  Google Scholar 

  69. Canani, L. H. et al. The type 2 deiodinase A/G. (Thr92Ala) polymorphism is associated with decreased enzyme velocity and increased insulin resistance in patients with type 2 diabetes mellitus. J. Clin. Endocrinol. Metab. 90, 3472–3478 (2005).

    CAS  PubMed  Google Scholar 

  70. Meulenbelt, I. et al. Identification of DIO2 as a new susceptibility locus for symptomatic osteoarthritis. Hum. Mol. Genet. 17, 1867–1875 (2008).

    CAS  PubMed  Google Scholar 

  71. Heemstra, K. A. et al. Thr92Ala polymorphism in the type 2 deiodinase is not associated with T4 dose in athyroid patients or patients with Hashimoto thyroiditis. Clin. Endocrinol. (Oxf.) 71, 279–283 (2009).

    CAS  Google Scholar 

  72. Charge, S. B. & Rudnicki, M. A. Cellular and molecular regulation of muscle regeneration. Physiol. Rev. 84, 209–238 (2004).

    CAS  PubMed  Google Scholar 

  73. Schultz, E. & McCormick, K. M. Skeletal muscle satellite cells. Rev. Physiol. Biochem. Pharmacol. 123, 213–257 (1994).

    CAS  PubMed  Google Scholar 

  74. Yablonka-Reuveni, Z. Development and postnatal regulation of adult myoblasts. Microsc. Res. Tech. 30, 366–380 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Olson, E. N. Interplay between proliferation and differentiation within the myogenic lineage. Dev. Biol. 154, 261–272 (1992).

    CAS  PubMed  Google Scholar 

  76. Rudnicki, M. A. & Jaenisch, R. The MyoD family of transcription factors and skeletal myogenesis. Bioessays 17, 203–209 (1995).

    CAS  PubMed  Google Scholar 

  77. Brunet, A. et al. Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor. Cell 96, 857–868 (1999).

    CAS  PubMed  Google Scholar 

  78. Bois, P. R., Brochard, V. F., Salin-Cantegrel, A. V., Cleveland, J. L. & Grosveld, G. C. FoxO1a-cyclic GMP-dependent kinase I interactions orchestrate myoblast fusion. Mol. Cell Biol. 25, 7645–7656 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Gross, D. N., van den Heuvel, A. P. & Birnbaum, M. J. The role of FoxO in the regulation of metabolism. Oncogene 27, 2320–2336 (2008).

    CAS  PubMed  Google Scholar 

  80. Mammucari, C., Schiaffino, S. & Sandri, M. Downstream of Akt: FoxO3 and mTOR in the regulation of autophagy in skeletal muscle. Autophagy 4, 524–526 (2008).

    CAS  PubMed  Google Scholar 

  81. Zhao, J. et al. FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab. 6, 472–483 (2007).

    CAS  PubMed  Google Scholar 

  82. Hu, P., Geles, K. G., Paik, J. H., DePinho, R. A. & Tjian, R. Codependent activators direct myoblast-specific MyoD transcription. Dev. Cell 15, 534–546 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Dentice, M. et al. Type 3 deiodinase is highly expressed in proliferating myoblasts and during the early phase of muscle regeneration. Presented at the 35th Annual Meeting of the European Thyroid Association (Krakow, Poland, 2011).

  84. Koenig, M., Monaco, A. P. & Kunkel, L. M. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53, 219–228 (1988).

    CAS  PubMed  Google Scholar 

  85. Partridge, T. Pathophysiology of muscular dystrophy. Br. J. Hosp. Med. 49, 26–36 (1993).

    CAS  PubMed  Google Scholar 

  86. England, S. B. et al. Very mild muscular dystrophy associated with the deletion of 46% of dystrophin. Nature 343, 180–182 (1990).

    CAS  PubMed  Google Scholar 

  87. Anderson, J. E., Liu, L. & Kardami, E. The effects of hyperthyroidism on muscular dystrophy in the mdx mouse: greater dystrophy in cardiac and soleus muscle. Muscle Nerve 17, 64–73 (1994).

    CAS  PubMed  Google Scholar 

  88. McIntosh, L. M. & Anderson, J. E. Hypothyroidism prolongs and increases mdx muscle precursor proliferation and delays myotube formation in normal and dystrophic limb muscle. Biochem. Cell Biol. 73, 181–190 (1995).

    CAS  PubMed  Google Scholar 

  89. Pernitsky, A. N., McIntosh, L. M. & Anderson, J. E. Hyperthyroidism impairs early repair in normal but not dystrophic mdx mouse tibialis anterior muscle. An in vivo study. Biochem. Cell Biol. 74, 315–324 (1996).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Work described in this Review was supported by Telethon grant GGP00185 to D. Salvatore and NIH grant DK044128 to P. R. Larsen and D. Salvatore.

Author information

Authors and Affiliations

  1. Department of Clinical Medicine and Surgery, University of Naples 'Federico II', Building 1, 1st floor, Via Pansini 5, Naples, 80131, Italy

    Domenico Salvatore & Monica Dentice

  2. Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Centre, van der Boechorststraat 7, Amsterdam, 1081 BT, Netherlands

    Warner S. Simonides

  3. Division of Endocrinology, Department of Medicine, Thyroid Section, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, HIM room 641, Boston, 02115, MA, USA

    Ann Marie Zavacki & P. Reed Larsen

Authors
  1. Domenico Salvatore
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Warner S. Simonides
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Monica Dentice
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ann Marie Zavacki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Reed Larsen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed equally to all aspects of this article.

Corresponding author

Correspondence to P. Reed Larsen.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Salvatore, D., Simonides, W., Dentice, M. et al. Thyroid hormones and skeletal muscle—new insights and potential implications. Nat Rev Endocrinol 10, 206–214 (2014). https://doi.org/10.1038/nrendo.2013.238

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrendo.2013.238

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing