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Glucocorticoids and Skeletal Muscle

  • Chapter
Glucocorticoid Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 872))

Abstract

Glucocorticoids are known to regulate protein metabolism in skeletal muscle, producing a catabolic effect that is opposite that of insulin. In many catabolic diseases, such as sepsis, starvation, and cancer cachexia, endogenous glucocorticoids are elevated contributing to the loss of muscle mass and function. Further, exogenous glucocorticoids are often given acutely and chronically to treat inflammatory conditions such as asthma, chronic obstructive pulmonary disease, and rheumatoid arthritis, resulting in muscle atrophy. This chapter will detail the nature of glucocorticoid-induced muscle atrophy and discuss the mechanisms thought to be responsible for the catabolic effects of glucocorticoids on muscle.

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References

  1. Pereira RM, Freire de Carvalho J. Glucocorticoid-induced myopathy. Joint Bone Spine. 2011;78:41–4.

    CAS  PubMed  Google Scholar 

  2. Overman RA, Yeh JY, Deal CL. Prevalence of oral glucocorticoid usage in the United States: a general population perspective. Arthritis Care Res (Hoboken). 2013;65:294–8.

    Google Scholar 

  3. Schiaffino S, Reggiani C. Fiber types in mammalian skeletal muscles. Physiol Rev. 2011;91:1447–531.

    CAS  PubMed  Google Scholar 

  4. Goldberg AL. Protein turnover in skeletal muscle. II. Effects of denervation and cortisone on protein catabolism in skeletal muscle. J Biol Chem. 1969;244:3223–9.

    CAS  PubMed  Google Scholar 

  5. Kelly FJ, Goldspink DF. The differing responses of four muscle types to dexamethasone treatment in the rat. Biochem J. 1982;208:147–51.

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Gardiner PF, Montanaro G, Simpson DR, Edgerton VR. Effects of glucocorticoid treatment and food restriction on rat hindlimb muscles. Am J Physiol. 1980;238:E124–30.

    CAS  PubMed  Google Scholar 

  7. Roy RR, Gardiner PF, Simpson DR, Edgerton VR. Glucocorticoid-induced atrophy in different fibre types of selected rat jaw and hind-limb muscles. Arch Oral Biol. 1983;28:639–43.

    CAS  PubMed  Google Scholar 

  8. Dekhuijzen PN, Gayan-Ramirez G, Bisschop A, De Bock V, Dom R, Decramer M. Corticosteroid treatment and nutritional deprivation cause a different pattern of atrophy in rat diaphragm. J Appl Physiol. 1995;78:629–37.

    CAS  PubMed  Google Scholar 

  9. Gardiner PF, Botterman BR, Eldred E, Simpson DR, Edgerton VR. Metabolic and contractile changes in fast and slow muscles of the cat after glucocorticoid-induced atrophy. Exp Neurol. 1978;62:241–55.

    CAS  PubMed  Google Scholar 

  10. Bullock GR, Carter EE, Elliott P, Peters RF, Simpson P, White AM. Relative changes in the function of muscle ribosomes and mitochondria during the early phase of steroid-induced catabolism. Biochem J. 1972;127:881–92.

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Anagnos A, Ruff RL, Kaminski HJ. Endocrine neuromyopathies. Neurol Clin. 1997;15:673–96.

    CAS  PubMed  Google Scholar 

  12. Baehr LM, Furlow JD, Bodine SC. Muscle sparing in muscle RING finger 1 null mice: response to synthetic glucocorticoids. J Physiol. 2011;589:4759–76.

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Zhao W, Pan J, Zhao Z, Wu Y, Bauman WA, Cardozo CP. Testosterone protects against dexamethasone-induced muscle atrophy, protein degradation and MAFbx upregulation. J Steroid Biochem Mol Biol. 2008;110:125–9.

    CAS  PubMed  Google Scholar 

  14. Ragnarsson O, Burt MG, Ho KK, Johannsson G. Effect of short-term GH and testosterone administration on body composition and glucose homoeostasis in men receiving chronic glucocorticoid therapy. Eur J Endocrinol. 2013;168:243–51.

    CAS  PubMed  Google Scholar 

  15. Capaccio JA, Kurowski TT, Czerwinski SM, Chatterton Jr RT, Hickson RC. Testosterone fails to prevent skeletal muscle atrophy from glucocorticoids. J Appl Physiol. 1987;63:328–34.

    CAS  PubMed  Google Scholar 

  16. Batchelor TT, Taylor LP, Thaler HT, Posner JB, DeAngelis LM. Steroid myopathy in cancer patients. Neurology. 1997;48:1234–8.

    CAS  PubMed  Google Scholar 

  17. Levin OS, Polunina AG, Demyanova MA, Isaev FV. Steroid myopathy in patients with chronic respiratory diseases. J Neurol Sci. 2014;338:96–101.

    CAS  PubMed  Google Scholar 

  18. Decramer M, de Bock V, Dom R. Functional and histologic picture of steroid-induced myopathy in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996;153:1958–64.

    CAS  PubMed  Google Scholar 

  19. Hatakenaka M, Soeda H, Okafuji T, et al. Steroid myopathy: evaluation of fiber atrophy with T2 relaxation time—rabbit and human study. Radiology. 2006;238:650–7.

    PubMed  Google Scholar 

  20. Khaleeli AA, Edwards RH, Gohil K, et al. Corticosteroid myopathy: a clinical and pathological study. Clin Endocrinol (Oxf). 1983;18:155–66.

    CAS  Google Scholar 

  21. Horber FF, Scheidegger JR, Grunig BE, Frey FJ. Thigh muscle mass and function in patients treated with glucocorticoids. Eur J Clin Invest. 1985;15:302–7.

    CAS  PubMed  Google Scholar 

  22. Decramer M, Stas KJ. Corticosteroid-induced myopathy involving respiratory muscles in patients with chronic obstructive pulmonary disease or asthma. Am Rev Respir Dis. 1992;146:800–2.

    CAS  PubMed  Google Scholar 

  23. Danneskiold-Samsoe B, Grimby G. Isokinetic and isometric muscle strength in patients with rheumatoid arthritis. The relationship to clinical parameters and the influence of corticosteroid. Clin Rheumatol. 1986;5:459–67.

    CAS  PubMed  Google Scholar 

  24. Rossignol B, Gueret G, Pennec JP, et al. Effects of chronic sepsis on contractile properties of fast twitch muscle in an experimental model of critical illness neuromyopathy in the rat. Crit Care Med. 2008;36:1855–63.

    PubMed  Google Scholar 

  25. Alamdari N, Toraldo G, Aversa Z, et al. Loss of muscle strength during sepsis is in part regulated by glucocorticoids and is associated with reduced muscle fiber stiffness. Am J Physiol Regul Integr Comp Physiol. 2012;303:R1090–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Supinski GS, Wang L, Song XH, Moylan JS, Callahan LA. Muscle-specific calpastatin overexpression prevents diaphragm weakness in cecal ligation puncture-induced sepsis. J Appl Physiol. 2014;117:921–9.

    CAS  PubMed  Google Scholar 

  27. Robinson AJ, Clamann HP. Effects of glucocorticoids on motor units in cat hindlimb muscles. Muscle Nerve. 1988;11:703–13.

    CAS  PubMed  Google Scholar 

  28. Gardiner PF, Edgerton VR. Contractile responses of rat fast-twitch and slow-twitch muscles to glucocorticoid treatment. Muscle Nerve. 1979;2:274–81.

    CAS  PubMed  Google Scholar 

  29. Ruff RL, Martyn D, Gordon AM. Glucocorticoid-induced atrophy is not due to impaired excitability of rat muscle. Am J Physiol. 1982;243:E512–21.

    CAS  PubMed  Google Scholar 

  30. Van Balkom RH, Zhan WZ, Prakash YS, Dekhuijzen PN, Sieck GC. Corticosteroid effects on isotonic contractile properties of rat diaphragm muscle. J Appl Physiol. 1997;83:1062–7.

    PubMed  Google Scholar 

  31. Manzur AY, Kuntzer T, Pike M, Swan A. Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev 2008;CD003725.

    Google Scholar 

  32. Hanaoka BY, Peterson CA, Horbinski C, Crofford LJ. Implications of glucocorticoid therapy in idiopathic inflammatory myopathies. Nat Rev Rheumatol. 2012;8:448–57.

    CAS  PubMed  Google Scholar 

  33. Sali A, Guerron AD, Gordish-Dressman H, et al. Glucocorticoid-treated mice are an inappropriate positive control for long-term preclinical studies in the mdx mouse. PLoS One. 2012;7:e34204.

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Janssen PM, Murray JD, Schill KE, et al. Prednisolone attenuates improvement of cardiac and skeletal contractile function and histopathology by lisinopril and spironolactone in the mdx mouse model of Duchenne muscular dystrophy. PLoS One. 2014;9:e88360.

    PubMed Central  PubMed  Google Scholar 

  35. Baltgalvis KA, Call JA, Nikas JB, Lowe DA. Effects of prednisolone on skeletal muscle contractility in mdx mice. Muscle Nerve. 2009;40:443–54.

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Fisher I, Abraham D, Bouri K, Hoffman EP, Muntoni F, Morgan J. Prednisolone-induced changes in dystrophic skeletal muscle. FASEB J. 2005;19:834–6.

    CAS  PubMed  Google Scholar 

  37. Hershey JW, Sonenberg N, Mathews MB. Principles of translational control: an overview. Cold Spring Harb Perspect Biol. 2012;4. pii: a011528.

    Google Scholar 

  38. Gordon BS, Kelleher AR, Kimball SR. Regulation of muscle protein synthesis and the effects of catabolic states. Int J Biochem Cell Biol. 2013;45:2147–57.

    CAS  PubMed Central  PubMed  Google Scholar 

  39. Ma XM, Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol. 2009;10:307–18.

    PubMed  Google Scholar 

  40. Marcotte GR, West DW, Baar K. The molecular basis for load-induced skeletal muscle hypertrophy. Calcif Tissue Int. 2015;96(3):196–210.

    CAS  PubMed  Google Scholar 

  41. Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol. 2011;12:21–35.

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Millward DJ, Garlick PJ, Nnanyelugo DO, Waterlow JC. The relative importance of muscle protein synthesis and breakdown in the regulation of muscle mass. Biochem J. 1976;156:185–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Rannels SR, Rannels DE, Pegg AE, Jefferson LS. Glucocorticoid effects on peptide-chain initiation in skeletal muscle and heart. Am J Physiol. 1978;235:E134–9.

    CAS  PubMed  Google Scholar 

  44. Short KR, Nygren J, Bigelow ML, Nair KS. Effect of short-term prednisone use on blood flow, muscle protein metabolism, and function. J Clin Endocrinol Metab. 2004;89:6198–207.

    CAS  PubMed  Google Scholar 

  45. Liu Z, Li G, Kimball SR, Jahn LA, Barrett EJ. Glucocorticoids modulate amino acid-induced translation initiation in human skeletal muscle. Am J Physiol Endocrinol Metab. 2004;287:E275–81.

    CAS  PubMed  Google Scholar 

  46. Mayer M, Shafrir E, Kaiser N, Milholland RJ, Rosen F. Interaction of glucocorticoid hormones with rat skeletal muscle: catabolic effects and hormone binding. Metabolism. 1976;25:157–67.

    CAS  PubMed  Google Scholar 

  47. Kostyo JL, Redmond AF. Role of protein synthesis in the inhibitory action of adrenal steroid hormones on amino acid transport by muscle. Endocrinology. 1966;79:531–40.

    CAS  PubMed  Google Scholar 

  48. Young VR, Chen SC, Macdonald J. The sedimentation of rat skeletal-muscle ribosomes. Effect of hydrocortisone, insulin and diet. Biochem J. 1968;106:913–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Peters RF, Richardson MC, Small M, White AM. Some biochemical effects of triamcinolone acetonide on rat liver and muscle. Biochem J. 1970;116:349–55.

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Rannels DE, Rannels SR, Li JB, Pegg AE, Morgan HE, Jefferson LS. Effects of glucocorticoids on peptide chain initiation in heart and skeletal muscle. Adv Myocardiol. 1980;1:493–501.

    CAS  PubMed  Google Scholar 

  51. Shah OJ, Kimball SR, Jefferson LS. Acute attenuation of translation initiation and protein synthesis by glucocorticoids in skeletal muscle. Am J Physiol Endocrinol Metab. 2000;278:E76–82.

    CAS  PubMed  Google Scholar 

  52. Shah OJ, Kimball SR, Jefferson LS. Glucocorticoids abate p70(S6k) and eIF4E function in L6 skeletal myoblasts. Am J Physiol Endocrinol Metab. 2000;279:E74–82.

    CAS  PubMed  Google Scholar 

  53. Tomas FM, Munro HN, Young VR. Effect of glucocorticoid administration on the rate of muscle protein breakdown in vivo in rats, as measured by urinary excretion of N tau-methylhistidine. Biochem J. 1979;178:139–46.

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Nagasawa T, Funabiki R. Quantitative determination of urinary N-tau-methylhistidine output as an index of myofibrillar protein degradation. J Biochem. 1981;89:1155–61.

    CAS  PubMed  Google Scholar 

  55. Millward DJ, Bates PC. 3-Methylhistidine turnover in the whole body, and the contribution of skeletal muscle and intestine to urinary 3-methylhistidine excretion in the adult rat. Biochem J. 1983;214:607–15.

    CAS  PubMed Central  PubMed  Google Scholar 

  56. Mitch WE, Clark AS, May RC. Relationships between protein degradation and glucose metabolism in skeletal muscle. Prog Clin Biol Res. 1985;180:623–5.

    CAS  PubMed  Google Scholar 

  57. Mitch WE, Goldberg AL. Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway. N Engl J Med. 1996;335:1897–905.

    CAS  PubMed  Google Scholar 

  58. Wing SS, Goldberg AL. Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting. Am J Physiol. 1993;264:E668–76.

    CAS  PubMed  Google Scholar 

  59. Mitch WE, Medina R, Grieber S, et al. Metabolic acidosis stimulates muscle protein degradation by activating the adenosine triphosphate-dependent pathway involving ubiquitin and proteasomes. J Clin Invest. 1994;93:2127–33.

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Price SR, Bailey JL, England BK. Necessary but not sufficient: the role of glucocorticoids in the acidosis-induced increase in levels of mRNAs encoding proteins of the ATP-dependent proteolytic pathway in rat muscle. Miner Electrolyte Metab. 1996;22:72–5.

    CAS  PubMed  Google Scholar 

  61. Price SR, Mitch WE. Mechanisms stimulating protein degradation to cause muscle atrophy. Curr Opin Clin Nutr Metab Care. 1998;1:79–83.

    CAS  PubMed  Google Scholar 

  62. Medina R, Wing SS, Haas A, Goldberg AL. Activation of the ubiquitin-ATP-dependent proteolytic system in skeletal muscle during fasting and denervation atrophy. Biomed Biochim Acta. 1991;50:347–56.

    CAS  PubMed  Google Scholar 

  63. Lecker SH, Solomon V, Mitch WE, Goldberg AL. Muscle protein breakdown and the critical role of the ubiquitin-proteasome pathway in normal and disease states. J Nutr. 1999;129:227S–37S.

    CAS  PubMed  Google Scholar 

  64. Chau V, Tobias JW, Bachmair A, et al. A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science. 1989;243:1576–83.

    CAS  PubMed  Google Scholar 

  65. D’Azzo A, Bongiovanni A, Nastasi T. E3 ubiquitin ligases as regulators of membrane protein trafficking and degradation. Traffic. 2005;6:429–41.

    PubMed  Google Scholar 

  66. Tisdale MJ. The ubiquitin-proteasome pathway as a therapeutic target for muscle wasting. J Support Oncol. 2005;3:209–17.

    CAS  PubMed  Google Scholar 

  67. Xie Y. Structure, assembly and homeostatic regulation of the 26S proteasome. J Mol Cell Biol. 2010;2:308–17.

    CAS  PubMed  Google Scholar 

  68. Lecker SH, Goldberg AL, Mitch WE. Protein degradation by the ubiquitin-proteasome pathway in normal and disease states. J Am Soc Nephrol. 2006;17:1807–19.

    CAS  PubMed  Google Scholar 

  69. Deshaies RJ, Joazeiro CA. RING domain E3 ubiquitin ligases. Annu Rev Biochem. 2009;78:399–434.

    CAS  PubMed  Google Scholar 

  70. Metzger MB, Hristova VA, Weissman AM. HECT and RING finger families of E3 ubiquitin ligases at a glance. J Cell Sci. 2012;125:531–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Auclair D, Garrel DR, Chaouki Zerouala A, Ferland LH. Activation of the ubiquitin pathway in rat skeletal muscle by catabolic doses of glucocorticoids. Am J Physiol. 1997;272:C1007–16.

    CAS  PubMed  Google Scholar 

  72. Combaret L, Taillandier D, Dardevet D, et al. Glucocorticoids regulate mRNA levels for subunits of the 19S regulatory complex of the 26S proteasome in fast-twitch skeletal muscles. Biochem J. 2004;378:239–46.

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Britto FA, Begue G, Rossano B, et al. REDD1 deletion prevents dexamethasone-induced skeletal muscle atrophy. Am J Physiol Endocrinol Metab. 2014;307:E983–93.

    CAS  PubMed  Google Scholar 

  74. Price SR, Bailey JL, Wang X, et al. Muscle wasting in insulinopenic rats results from activation of the ATP-dependent, ubiquitin-proteasome proteolytic pathway by a mechanism including gene transcription. J Clin Invest. 1996;98:1703–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Tawa Jr NE, Odessey R, Goldberg AL. Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles. J Clin Invest. 1997;100:197–203.

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Wing SS, Haas AL, Goldberg AL. Increase in ubiquitin-protein conjugates concomitant with the increase in proteolysis in rat skeletal muscle during starvation and atrophy denervation. Biochem J. 1995;307(Pt 3):639–45.

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Tiao G, Hobler S, Wang JJ, et al. Sepsis is associated with increased mRNAs of the ubiquitin-proteasome proteolytic pathway in human skeletal muscle. J Clin Invest. 1997;99:163–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Voisin L, Breuille D, Combaret L, et al. Muscle wasting in a rat model of long-lasting sepsis results from the activation of lysosomal, Ca2+-activated, and ubiquitin-proteasome proteolytic pathways. J Clin Invest. 1996;97:1610–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  79. Tiao G, Fagan JM, Samuels N, et al. Sepsis stimulates nonlysosomal, energy-dependent proteolysis and increases ubiquitin mRNA levels in rat skeletal muscle. J Clin Invest. 1994;94:2255–64.

    CAS  PubMed Central  PubMed  Google Scholar 

  80. Baracos VE, DeVivo C, Hoyle DH, Goldberg AL. Activation of the ATP-ubiquitin-proteasome pathway in skeletal muscle of cachectic rats bearing a hepatoma. Am J Physiol. 1995;268:E996–1006.

    CAS  PubMed  Google Scholar 

  81. Bodine SC, Baehr LM. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am J Physiol Endocrinol Metab. 2014;307:E469–84.

    CAS  PubMed  Google Scholar 

  82. Centner T, Yano J, Kimura E, et al. Identification of muscle specific ring finger proteins as potential regulators of the titin kinase domain. J Mol Biol. 2001;306:717–26.

    CAS  PubMed  Google Scholar 

  83. Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A. 2001;98:14440–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Bodine SC, Latres E, Baumhueter S, et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science. 2001;294:1704–8.

    CAS  PubMed  Google Scholar 

  85. Files DC, D’Alessio FR, Johnston LF, et al. A critical role for muscle ring finger-1 in acute lung injury-associated skeletal muscle wasting. Am J Respir Crit Care Med. 2012;185:825–34.

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Frost RA, Lang CH. Multifaceted role of insulin-like growth factors and mammalian target of rapamycin in skeletal muscle. Endocrinol Metab Clin North Am. 2012;41:297–322.

    CAS  PubMed Central  PubMed  Google Scholar 

  87. Gayan-Ramirez G, Vanderhoydonc F, Verhoeven G, Decramer M. Acute treatment with corticosteroids decreases IGF-1 and IGF-2 expression in the rat diaphragm and gastrocnemius. Am J Respir Crit Care Med. 1999;159:283–9.

    CAS  PubMed  Google Scholar 

  88. Inder WJ, Jang C, Obeyesekere VR, Alford FP. Dexamethasone administration inhibits skeletal muscle expression of the androgen receptor and IGF-1–implications for steroid-induced myopathy. Clin Endocrinol (Oxf). 2010;73:126–32.

    CAS  Google Scholar 

  89. Schakman O, Gilson H, de Coninck V, et al. Insulin-like growth factor-I gene transfer by electroporation prevents skeletal muscle atrophy in glucocorticoid-treated rats. Endocrinology. 2005;146:1789–97.

    CAS  PubMed  Google Scholar 

  90. Schakman O, Kalista S, Bertrand L, et al. Role of Akt/GSK-3beta/beta-catenin transduction pathway in the muscle anti-atrophy action of insulin-like growth factor-I in glucocorticoid-treated rats. Endocrinology. 2008;149:3900–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Sacheck JM, Ohtsuka A, McLary SC, Goldberg AL. IGF-1 stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin-ligases, atrogin-1 and MuRF1. Am J Physiol Endocrinol Metab. 2004;287(4):E591–601.

    CAS  PubMed  Google Scholar 

  92. Stitt TN, Drujan D, Clarke BA, et al. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell. 2004;14:395–403.

    CAS  PubMed  Google Scholar 

  93. Fournier M, Huang ZS, Li H, Da X, Cercek B, Lewis MI. Insulin-like growth factor I prevents corticosteroid-induced diaphragm muscle atrophy in emphysematous hamsters. Am J Physiol Regul Integr Comp Physiol. 2003;285:R34–43.

    CAS  PubMed  Google Scholar 

  94. Chrysis D, Underwood LE. Regulation of components of the ubiquitin system by insulin-like growth factor I and growth hormone in skeletal muscle of rats made catabolic with dexamethasone. Endocrinology. 1999;140:5635–41.

    CAS  PubMed  Google Scholar 

  95. Kanda F, Takatani K, Okuda S, Matsushita T, Chihara K. Preventive effects of insulin like growth factor-I on steroid-induced muscle atrophy. Muscle Nerve. 1999;22:213–7.

    CAS  PubMed  Google Scholar 

  96. Schakman O, Kalista S, Barbe C, Loumaye A, Thissen JP. Glucocorticoid-induced skeletal muscle atrophy. Int J Biochem Cell Biol. 2013;45:2163–72.

    CAS  PubMed  Google Scholar 

  97. Armstrong DD, Esser KA. Wnt/beta-catenin signaling activates growth-control genes during overload-induced skeletal muscle hypertrophy. Am J Physiol Cell Physiol. 2005;289:C853–9.

    CAS  PubMed  Google Scholar 

  98. Nakao R, Hirasaka K, Goto J, et al. Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading. Mol Cell Biol. 2009;29:4798–811.

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Morgan SA, Sherlock M, Gathercole LL, et al. 11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle. Diabetes. 2009;58:2506–15.

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Zheng B, Ohkawa S, Li H, Roberts-Wilson TK, Price SR. FOXO3a mediates signaling crosstalk that coordinates ubiquitin and atrogin-1/MAFbx expression during glucocorticoid-induced skeletal muscle atrophy. FASEB J. 2010;24:2660–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  101. Koh A, Lee MN, Yang YR, et al. C1-Ten is a protein tyrosine phosphatase of insulin receptor substrate 1 (IRS-1), regulating IRS-1 stability and muscle atrophy. Mol Cell Biol. 2013;33:1608–20.

    CAS  PubMed Central  PubMed  Google Scholar 

  102. Kuo T, Lew MJ, Mayba O, Harris CA, Speed TP, Wang JC. Genome-wide analysis of glucocorticoid receptor-binding sites in myotubes identifies gene networks modulating insulin signaling. Proc Natl Acad Sci U S A. 2012;109:11160–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  103. Furlow JD, Watson ML, Waddell DS, et al. Altered gene expression patterns in muscle ring finger 1 null mice during denervation- and dexamethasone-induced muscle atrophy. Physiol Genomics. 2013;45:1168–85.

    CAS  PubMed Central  PubMed  Google Scholar 

  104. Wang H, Kubica N, Ellisen LW, Jefferson LS, Kimball SR. Dexamethasone represses signaling through the mammalian target of rapamycin in muscle cells by enhancing expression of REDD1. J Biol Chem. 2006;281:39128–34.

    CAS  PubMed  Google Scholar 

  105. Kumari R, Willing LB, Jefferson LS, Simpson IA, Kimball SR. REDD1 (regulated in development and DNA damage response 1) expression in skeletal muscle as a surrogate biomarker of the efficiency of glucocorticoid receptor blockade. Biochem Biophys Res Commun. 2011;412:644–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  106. Dennis MD, Coleman CS, Berg A, Jefferson LS, Kimball SR. REDD1 enhances protein phosphatase 2A-mediated dephosphorylation of Akt to repress mTORC1 signaling. Sci Signal. 2014;7:ra68.

    PubMed Central  PubMed  Google Scholar 

  107. Kadmiel M, Cidlowski JA. Glucocorticoid receptor signaling in health and disease. Trends Pharmacol Sci. 2013;34:518–30.

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Duma D, Jewell CM, Cidlowski JA. Multiple glucocorticoid receptor isoforms and mechanisms of post-translational modification. J Steroid Biochem Mol Biol. 2006;102:11–21.

    CAS  PubMed  Google Scholar 

  109. Schaaf MJ, Champagne D, van Laanen IH, et al. Discovery of a functional glucocorticoid receptor beta-isoform in zebrafish. Endocrinology. 2008;149:1591–9.

    CAS  PubMed  Google Scholar 

  110. Shimizu N, Yoshikawa N, Ito N, et al. Crosstalk between glucocorticoid receptor and nutritional sensor mTOR in skeletal muscle. Cell Metab. 2011;13:170–82.

    CAS  PubMed  Google Scholar 

  111. Oakley RH, Cidlowski JA. Homologous down regulation of the glucocorticoid receptor: the molecular machinery. Crit Rev Eukaryot Gene Expr. 1993;3:63–88.

    CAS  PubMed  Google Scholar 

  112. Yao Z, DuBois DC, Almon RR, Jusko WJ. Modeling circadian rhythms of glucocorticoid receptor and glutamine synthetase expression in rat skeletal muscle. Pharm Res. 2006;23:670–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Witchel SF, DeFranco DB. Mechanisms of disease: regulation of glucocorticoid and receptor levels–impact on the metabolic syndrome. Nat Clin Pract Endocrinol Metab. 2006;2:621–31.

    CAS  PubMed  Google Scholar 

  114. Aubry EM, Odermatt A. Retinoic acid reduces glucocorticoid sensitivity in C2C12 myotubes by decreasing 11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor activities. Endocrinology. 2009;150:2700–8.

    CAS  PubMed  Google Scholar 

  115. Wang SC, Myers S, Dooms C, Capon R, Muscat GE. An ERRbeta/gamma agonist modulates GRalpha expression, and glucocorticoid responsive gene expression in skeletal muscle cells. Mol Cell Endocrinol. 2010;315:146–52.

    CAS  PubMed  Google Scholar 

  116. Almon RR, DuBois DC, Yao Z, Hoffman EP, Ghimbovschi S, Jusko WJ. Microarray analysis of the temporal response of skeletal muscle to methylprednisolone: comparative analysis of two dosing regimens. Physiol Genomics. 2007;30:282–99.

    CAS  PubMed Central  PubMed  Google Scholar 

  117. Lecker SH, Jagoe RT, Gilbert A, et al. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J. 2004;18:39–51.

    CAS  PubMed  Google Scholar 

  118. Carraro L, Ferraresso S, Cardazzo B, et al. Expression profiling of skeletal muscle in young bulls treated with steroidal growth promoters. Physiol Genomics. 2009;38:138–48.

    CAS  PubMed  Google Scholar 

  119. Kukreti H, Amuthavalli K, Harikumar A, et al. Muscle-specific microRNA1 (miR1) targets heat shock protein 70 (HSP70) during dexamethasone-mediated atrophy. J Biol Chem. 2013;288:6663–78.

    CAS  PubMed Central  PubMed  Google Scholar 

  120. Busillo JM, Cidlowski JA. The five Rs of glucocorticoid action during inflammation: ready, reinforce, repress, resolve, and restore. Trends Endocrinol Metab. 2013;24:109–19.

    CAS  PubMed Central  PubMed  Google Scholar 

  121. Yang H, Menconi MJ, Wei W, Petkova V, Hasselgren PO. Dexamethasone upregulates the expression of the nuclear cofactor p300 and its interaction with C/EBPbeta in cultured myotubes. J Cell Biochem. 2005;94:1058–67.

    CAS  PubMed  Google Scholar 

  122. Tobimatsu K, Noguchi T, Hosooka T, et al. Overexpression of the transcriptional coregulator Cited2 protects against glucocorticoid-induced atrophy of C2C12 myotubes. Biochem Biophys Res Commun. 2009;378:399–403.

    CAS  PubMed  Google Scholar 

  123. Yang H, Wei W, Menconi M, Hasselgren PO. Dexamethasone-induced protein degradation in cultured myotubes is p300/HAT dependent. Am J Physiol Regul Integr Comp Physiol. 2007;292:R337-4.

    PubMed  Google Scholar 

  124. Alamdari N, Aversa Z, Castillero E, Hasselgren PO. Acetylation and deacetylation—novel factors in muscle wasting. Metabolism. 2013;62:1–11.

    CAS  PubMed Central  PubMed  Google Scholar 

  125. Proserpio V, Fittipaldi R, Ryall JG, Sartorelli V, Caretti G. The methyltransferase SMYD3 mediates the recruitment of transcriptional cofactors at the myostatin and c-Met genes and regulates skeletal muscle atrophy. Genes Dev. 2013;27:1299–312.

    CAS  PubMed Central  PubMed  Google Scholar 

  126. Kim H, Heo K, Kim JH, Kim K, Choi J, An W. Requirement of histone methyltransferase SMYD3 for estrogen receptor-mediated transcription. J Biol Chem. 2009;284:19867–77.

    CAS  PubMed Central  PubMed  Google Scholar 

  127. Furuyama T, Kitayama K, Yamashita H, Mori N. Forkhead transcription factor FOXO1 (FKHR)-dependent induction of PDK4 gene expression in skeletal muscle during energy deprivation. Biochem J. 2003;375:365–71.

    CAS  PubMed Central  PubMed  Google Scholar 

  128. Cho JE, Fournier M, Da X, Lewis MI. Time course expression of Foxo transcription factors in skeletal muscle following corticosteroid administration. J Appl Physiol. 2010;108:137–45.

    CAS  PubMed Central  PubMed  Google Scholar 

  129. Sun H, Gong Y, Qiu J, Chen Y, Ding F, Zhao Q. TRAF6 inhibition rescues dexamethasone-induced muscle atrophy. Int J Mol Sci. 2014;15:11126–41.

    CAS  PubMed Central  PubMed  Google Scholar 

  130. Webb AE, Brunet A. FOXO transcription factors: key regulators of cellular quality control. Trends Biochem Sci. 2014;39:159–69.

    CAS  PubMed Central  PubMed  Google Scholar 

  131. Gross DN, Wan M, Birnbaum MJ. The role of FOXO in the regulation of metabolism. Curr Diab Rep. 2009;9:208–14.

    CAS  PubMed  Google Scholar 

  132. Zhao J, Brault JJ, Schild A, et al. FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab. 2007;6:472–83.

    CAS  PubMed  Google Scholar 

  133. Mammucari C, Milan G, Romanello V, et al. FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab. 2007;6:458–71.

    CAS  PubMed  Google Scholar 

  134. Waddell DS, Baehr LM, van den Brandt J, et al. The glucocorticoid receptor and FOXO1 synergistically activate the skeletal muscle atrophy-associated MuRF1 gene. Am J Physiol Endocrinol Metab. 2008;295:E785–97.

    CAS  PubMed Central  PubMed  Google Scholar 

  135. Reed SA, Sandesara PB, Senf SM, Judge AR. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy. FASEB J. 2012;26:987–1000.

    CAS  PubMed Central  PubMed  Google Scholar 

  136. Senf SM, Sandesara PB, Reed SA, Judge AR. p300 Acetyltransferase activity differentially regulates the localization and activity of the FOXO homologues in skeletal muscle. Am J Physiol Cell Physiol. 2011;300:C1490–501.

    CAS  PubMed Central  PubMed  Google Scholar 

  137. Beharry AW, Sandesara PB, Roberts BM, Ferreira LF, Senf SM, Judge AR. HDAC1 activates FoxO and is both sufficient and required for skeletal muscle atrophy. J Cell Sci. 2014;127:1441–53.

    CAS  PubMed Central  PubMed  Google Scholar 

  138. Yang H, Mammen J, Wei W, et al. Expression and activity of C/EBPbeta and delta are upregulated by dexamethasone in skeletal muscle. J Cell Physiol. 2005;204:219–26.

    CAS  PubMed  Google Scholar 

  139. Gonnella P, Alamdari N, Tizio S, Aversa Z, Petkova V, Hasselgren PO. C/EBPbeta regulates dexamethasone-induced muscle cell atrophy and expression of atrogin-1 and MuRF1. J Cell Biochem. 2011;112:1737–48.

    CAS  PubMed Central  PubMed  Google Scholar 

  140. Bruscoli S, Donato V, Velardi E, et al. Glucocorticoid-induced leucine zipper (GILZ) and long GILZ inhibit myogenic differentiation and mediate anti-myogenic effects of glucocorticoids. J Biol Chem. 2010;285:10385–96.

    CAS  PubMed Central  PubMed  Google Scholar 

  141. Ayroldi E, Riccardi C. Glucocorticoid-induced leucine zipper (GILZ): a new important mediator of glucocorticoid action. FASEB J. 2009;23:3649–58.

    CAS  PubMed  Google Scholar 

  142. Kaestner KH. The FoxA factors in organogenesis and differentiation. Curr Opin Genet Dev. 2010;20:527–32.

    CAS  PubMed Central  PubMed  Google Scholar 

  143. Revollo JR, Cidlowski JA. Mechanisms generating diversity in glucocorticoid receptor signaling. Ann N Y Acad Sci. 2009;1179:167–78.

    CAS  PubMed  Google Scholar 

  144. Hu Z, Wang H, Lee IH, Du J, Mitch WE. Endogenous glucocorticoids and impaired insulin signaling are both required to stimulate muscle wasting under pathophysiological conditions in mice. J Clin Invest. 2009;119:3059–69.

    CAS  PubMed Central  PubMed  Google Scholar 

  145. Fang CH, Li BG, James JH, et al. Protein breakdown in muscle from burned rats is blocked by insulin-like growth factor i and glycogen synthase kinase-3beta inhibitors. Endocrinology. 2005;146:3141–9.

    CAS  PubMed  Google Scholar 

  146. Rubio-Patino C, Palmeri CM, Perez-Perarnau A, et al. Glycogen synthase kinase-3beta is involved in ligand-dependent activation of transcription and cellular localization of the glucocorticoid receptor. Mol Endocrinol. 2012;26:1508–20.

    CAS  PubMed  Google Scholar 

  147. Sarabdjitsingh RA, Joels M, de Kloet ER. Glucocorticoid pulsatility and rapid corticosteroid actions in the central stress response. Physiol Behav. 2012;106:73–80.

    CAS  PubMed  Google Scholar 

  148. Tasker JG, Di S, Malcher-Lopes R. Minireview: rapid glucocorticoid signaling via membrane-associated receptors. Endocrinology. 2006;147:5549–56.

    CAS  PubMed Central  PubMed  Google Scholar 

  149. Perez MH, Cormack J, Mallinson D, Mutungi G. A membrane glucocorticoid receptor mediates the rapid/non-genomic actions of glucocorticoids in mammalian skeletal muscle fibres. J Physiol. 2013;591:5171–85.

    CAS  PubMed Central  PubMed  Google Scholar 

  150. Kewalramani G, Puthanveetil P, Kim MS, et al. Acute dexamethasone-induced increase in cardiac lipoprotein lipase requires activation of both Akt and stress kinases. Am J Physiol Endocrinol Metab. 2008;295:E137–47.

    CAS  PubMed  Google Scholar 

  151. Lee SR, Kim HK, Youm JB, et al. Non-genomic effect of glucocorticoids on cardiovascular system. Pflugers Arch. 2012;464:549–59.

    CAS  PubMed  Google Scholar 

  152. Stitt TN, Drujan D, Clarke BA, et al. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin liganses by inhibiting FOXO transcription factors. Mol Cell. 2004;14:1–14.

    Google Scholar 

  153. Latres E, Amini AR, Amini AA, et al. Insulin-like growth factor-1 (IGF-1) inversely regulates atrophy-induced genes via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. J Biol Chem. 2005;280:2737–44.

    CAS  PubMed  Google Scholar 

  154. Chapman K, Holmes M, Seckl J. 11beta-hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action. Physiol Rev. 2013;93:1139–206.

    CAS  PubMed Central  PubMed  Google Scholar 

  155. Short KR, Bigelow ML, Nair KS. Short-term prednisone use antagonizes insulin's anabolic effect on muscle protein and glucose metabolism in young healthy people. Am J Physiol Endocrinol Metab. 2009;297:E1260–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  156. Almon RR, Dubois DC, Jin JY, Jusko WJ. Temporal profiling of the transcriptional basis for the development of corticosteroid-induced insulin resistance in rat muscle. J Endocrinol. 2005;184:219–32.

    CAS  PubMed Central  PubMed  Google Scholar 

  157. Patel R, Bookout AL, Magomedova L, et al. Glucocorticoids regulate the metabolic hormone FGF21 in a feed-forward loop. Mol Endocrinol. 2015;29(2):213–23.

    PubMed  Google Scholar 

  158. Mazziotti G, Giustina A. Glucocorticoids and the regulation of growth hormone secretion. Nat Rev Endocrinol. 2013;9:265–76.

    CAS  PubMed  Google Scholar 

  159. Wurtman RJ. Stress and the adrenocortical control of epinephrine synthesis. Metabolism. 2002;51:11–4.

    CAS  PubMed  Google Scholar 

  160. la Fleur SE. The effects of glucocorticoids on feeding behavior in rats. Physiol Behav. 2006;89:110–4.

    PubMed  Google Scholar 

  161. Watson ML, Baehr LM, Reichardt HM, Tuckermann JP, Bodine SC, Furlow JD. A cell-autonomous role for the glucocorticoid receptor in skeletal muscle atrophy induced by systemic glucocorticoid exposure. Am J Physiol Endocrinol Metab. 2012;302:E1210–20.

    CAS  PubMed Central  PubMed  Google Scholar 

  162. Braun TP, Grossberg AJ, Krasnow SM, et al. Cancer- and endotoxin-induced cachexia require intact glucocorticoid signaling in skeletal muscle. FASEB J. 2013;27:3572–82.

    CAS  PubMed Central  PubMed  Google Scholar 

  163. Braun TP, Szumowski M, Levasseur PR, et al. Muscle atrophy in response to cytotoxic chemotherapy is dependent on intact glucocorticoid signaling in skeletal muscle. PLoS One. 2014;9:e106489.

    PubMed Central  PubMed  Google Scholar 

  164. Zhao W, Qin W, Pan J, Wu Y, Bauman WA, Cardozo C. Dependence of dexamethasone-induced Akt/FOXO1 signaling, upregulation of MAFbx, and protein catabolism upon the glucocorticoid receptor. Biochem Biophys Res Commun. 2009;378:668–72.

    CAS  PubMed  Google Scholar 

  165. Nesan D, Kamkar M, Burrows J, Scott IC, Marsden M, Vijayan MM. Glucocorticoid receptor signaling is essential for mesoderm formation and muscle development in zebrafish. Endocrinology. 2012;153:1288–300.

    CAS  PubMed  Google Scholar 

  166. Segal DJ, Meckler JF. Genome engineering at the dawn of the golden age. Annu Rev Genomics Hum Genet. 2013;14:135–58.

    CAS  PubMed  Google Scholar 

  167. Sandri M, Sandri C, Gilbert A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell. 2004;117:399–412.

    CAS  PubMed Central  PubMed  Google Scholar 

  168. Qin W, Pan J, Qin Y, Lee DN, Bauman WA, Cardozo C. Identification of functional glucocorticoid response elements in the mouse FoxO1 promoter. Biochem Biophys Res Commun. 2014;450:979–83.

    CAS  PubMed  Google Scholar 

  169. Ma K, Mallidis C, Bhasin S, et al. Glucocorticoid-induced skeletal muscle atrophy is associated with upregulation of myostatin gene expression. Am J Physiol Endocrinol Metab. 2003;285:E363–71.

    CAS  PubMed  Google Scholar 

  170. Qin J, Du R, Yang YQ, et al. Dexamethasone-induced skeletal muscle atrophy was associated with upregulation of myostatin promoter activity. Res Vet Sci. 2013;94:84–9.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurobiology, Physiology and Behavior, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA

    Sue C. Bodine Ph.D. & J. David Furlow Ph.D.

  2. Department of Physiology and Membrane Biology, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA

    Sue C. Bodine Ph.D.

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  1. Sue C. Bodine Ph.D.
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  2. J. David Furlow Ph.D.
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Correspondence to Sue C. Bodine Ph.D. .

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  1. Department of Nutritional Science & Toxicology, University of California Berkeley, Berkeley, California, USA

    Jen-Chywan Wang

  2. Division of Endocrinology Metabolism & Lipid Research, Department of Internal Medicine, Washington University School of Medicine Division of Endocrinology, St. Louis, Missouri, USA

    Charles Harris

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Bodine, S.C., Furlow, J.D. (2015). Glucocorticoids and Skeletal Muscle. In: Wang, JC., Harris, C. (eds) Glucocorticoid Signaling. Advances in Experimental Medicine and Biology, vol 872. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2895-8_7

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