Sports Medicine

, Volume 43, Issue 3, pp 179–194 | Cite as

Potential Mechanisms for a Role of Metabolic Stress in Hypertrophic Adaptations to Resistance Training

  • Brad J. SchoenfeldEmail author
Review Article


It is well established that regimented resistance training can promote increases in muscle hypertrophy. The prevailing body of research indicates that mechanical stress is the primary impetus for this adaptive response and studies show that mechanical stress alone can initiate anabolic signalling. Given the dominant role of mechanical stress in muscle growth, the question arises as to whether other factors may enhance the post-exercise hypertrophic response. Several researchers have proposed that exercise-induced metabolic stress may in fact confer such an anabolic effect and some have even suggested that metabolite accumulation may be more important than high force development in optimizing muscle growth. Metabolic stress pursuant to traditional resistance training manifests as a result of exercise that relies on anaerobic glycolysis for adenosine triphosphate production. This, in turn, causes the subsequent accumulation of metabolites, particularly lactate and H+. Acute muscle hypoxia associated with such training methods may further heighten metabolic buildup. Therefore, the purpose of this paper will be to review the emerging body of research suggesting a role for exercise-induced metabolic stress in maximizing muscle development and present insights as to the potential mechanisms by which these hypertrophic adaptations may occur. These mechanisms include increased fibre recruitment, elevated systemic hormonal production, alterations in local myokines, heightened production of reactive oxygen species and cell swelling. Recommendations are provided for potential areas of future research on the subject.


Resistance Training Satellite Cell Resistance Exercise Phosphatidic Acid Muscle Hypertrophy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This review was not funded by any outside organization. Brad Schoenfeld is the sole author of this work. There are no conflicts of interest present that are directly relevant to the content of this review.


  1. 1.
    Goldberg AL, Etlinger JD, Goldspink DF, et al. Mechanism of work-induced hypertrophy of skeletal muscle. Med Sci Sports. 1975 Fall;7(3):185–98.Google Scholar
  2. 2.
    Witkowski S, Lovering RM, Spangenburg EE. High-frequency electrically stimulated skeletal muscle contractions increase p70s6k phosphorylation independent of known IGF-I sensitive signaling pathways. FEBS Lett. 2010;584(13):2891–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Spangenburg EE, Le Roith D, Ward CW, et al. A functional insulin-like growth factor receptor is not necessary for load-induced skeletal muscle hypertrophy. J Physiol. 2008;586(1):283–91.PubMedCrossRefGoogle Scholar
  4. 4.
    Hornberger TA, Stuppard R, Conley KE, et al. Mechanical stimuli regulate rapamycin-sensitive signalling by a phosphoinositide 3-kinase-, protein kinase B- and growth factor-independent mechanism. Biochem J. 2004;380(Pt 3):795–804.PubMedCrossRefGoogle Scholar
  5. 5.
    Vandenburgh H, Kaufman S. In vitro model for stretch-induced hypertrophy of skeletal muscle. Science. 1979;203(4377):265–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Miyazaki M, McCarthy JJ, Fedele MJ, et al. Early activation of mTORC1 signalling in response to mechanical overload is independent of phosphoinositide 3-kinase/Akt signalling. J Physiol. 2011;589(Pt 7):1831–46.PubMedCrossRefGoogle Scholar
  7. 7.
    Toigo M, Boutellier U. New fundamental resistance exercise determinants of molecular and cellular muscle adaptations. Eur J Appl Physiol. 2006;97(6):643–63.PubMedCrossRefGoogle Scholar
  8. 8.
    Mayhew DL, Hornberger TA, Lincoln HC, et al. Eukaryotic initiation factor 2B epsilon induces cap-dependent translation and skeletal muscle hypertrophy. J Physiol. 2011;589(Pt 12):3023–37.PubMedCrossRefGoogle Scholar
  9. 9.
    Tidball JG. Mechanical signal transduction in skeletal muscle growth and adaptation. J Appl Physiol. 2005;98(5):1900–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Bassel-Duby R, Olson EN. Signaling pathways in skeletal muscle remodeling. Annu Rev Biochem. 2006;75:19–37.PubMedCrossRefGoogle Scholar
  11. 11.
    Miyazaki M, Esser KA. Cellular mechanisms regulating protein synthesis and skeletal muscle hypertrophy in animals. J Appl Physiol. 2009;106(4):1367–73.PubMedCrossRefGoogle Scholar
  12. 12.
    Glass DJ. Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol. 2005;37(10):1974–84.PubMedCrossRefGoogle Scholar
  13. 13.
    Hornberger TA, Chu WK, Mak YW, et al. The role of phospholipase D and phosphatidic acid in the mechanical activation of mTOR signaling in skeletal muscle. Proc Natl Acad Sci USA. 2006;103(12):4741–6.PubMedCrossRefGoogle Scholar
  14. 14.
    O’Neil TK, Duffy LR, Frey JW, et al. The role of phosphoinositide 3-kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions. J Physiol. 2009;587(Pt 14):3691–701.PubMedCrossRefGoogle Scholar
  15. 15.
    Lehman N, Ledford B, Di Fulvio M, et al. Phospholipase D2-derived phosphatidic acid binds to and activates ribosomal p70 S6 kinase independently of mTOR. FASEB J. 2007;21(4):1075–87.PubMedCrossRefGoogle Scholar
  16. 16.
    Rooney KJ, Herbert RD, Balnave RJ. Fatigue contributes to the strength training stimulus. Med Sci Sports Exerc. 1994;26(9):1160–4.PubMedGoogle Scholar
  17. 17.
    Schott J, McCully K, Rutherford OM. The role of metabolites in strength training. II. Short versus long isometric contractions. Eur J Appl Physiol Occup Physiol. 1995;71(4):337–41.PubMedCrossRefGoogle Scholar
  18. 18.
    Smith RC, Rutherford OM. The role of metabolites in strength training. I. A comparison of eccentric and concentric contractions. Eur J Appl Physiol Occup Physiol. 1995;71(4):332–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Shinohara M, Kouzaki M, Yoshihisa T, et al. Efficacy of tourniquet ischemia for strength training with low resistance. Eur J Appl Physiol Occup Physiol. 1998;77(1–2):189–91.PubMedGoogle Scholar
  20. 20.
    Folland JP, Irish CS, Roberts JC, et al. Fatigue is not a necessary stimulus for strength gains during resistance training. Br J Sports Med. 2002;36(5):370–3.PubMedCrossRefGoogle Scholar
  21. 21.
    Tesch PA, Colliander EB, Kaiser P. Muscle metabolism during intense, heavy-resistance exercise. Eur J Appl Physiol Occup Physiol. 1986;55(4):362–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Suga T, Okita K, Morita N, et al. Intramuscular metabolism during low-intensity resistance exercise with blood flow restriction. J Appl Physiol. 2009;106(4):1119–24.PubMedCrossRefGoogle Scholar
  23. 23.
    Pierce JR, Clark BC, Ploutz-Snyder LL, et al. Growth hormone and muscle function responses to skeletal muscle ischemia. J Appl Physiol. 2006;101(6):1588–95.PubMedCrossRefGoogle Scholar
  24. 24.
    Schoenfeld BJ. The mechanisms of muscle hypertrophy and their application to resistance training. J Strength Cond Res. 2010;24(10):2857–72.PubMedCrossRefGoogle Scholar
  25. 25.
    Fry AC. The role of resistance exercise intensity on muscle fibre adaptations. Sports Med. 2004;34(10):663–79.PubMedCrossRefGoogle Scholar
  26. 26.
    Lambert CP, Flynn MG. Fatigue during high-intensity intermittent exercise: application to bodybuilding. Sports Med. 2002;32(8):511–22.PubMedCrossRefGoogle Scholar
  27. 27.
    Kraemer WJ, Fleck SJ, Dziados JE, et al. Changes in hormonal concentrations after different heavy-resistance exercise protocols in women. J Appl Physiol. 1993;75(2):594–604.PubMedGoogle Scholar
  28. 28.
    Kraemer WJ, Marchitelli L, Gordon SE, et al. Hormonal and growth factor responses to heavy resistance exercise protocols. J Appl Physiol. 1990;69(4):1442–50.PubMedGoogle Scholar
  29. 29.
    Kraemer WJ, Gordon SE, Fleck SJ, et al. Endogenous anabolic hormonal and growth factor responses to heavy resistance exercise in males and females. Int J Sports Med. 1991;12(2):228–35.PubMedCrossRefGoogle Scholar
  30. 30.
    Katch VL, Katch FI, Moffatt R, et al. Muscular development and lean body weight in body builders and weight lifters. Med Sci Sports Exerc. 1980;12(5):340–4.PubMedGoogle Scholar
  31. 31.
    Schmidtbleicher D, Buehrle M. Neuronal adaptation and increase of cross-sectional area studying different strength training methods. In: Jonsson GB, editor. Biomechanics X-B volume 6-B. Champaign: Human Kinetics; 1987. p. 615–20.Google Scholar
  32. 32.
    Choi J, Takahashi H, Itai Y. The difference between effects of ‘power-up type’ and ‘bulk-up type’ strength training exercises: with special reference to muscle cross-sectional area. Jpn J Phys Fitness Sports Med. 1998;47(1):119–29.Google Scholar
  33. 33.
    Masuda K, Choi JY, Shimojo H, et al. Maintenance of myoglobin concentration in human skeletal muscle after heavy resistance training. Eur J Appl Physiol Occup Physiol. 1999;79(4):347–52.PubMedCrossRefGoogle Scholar
  34. 34.
    Campos GER, Luecke TJ, Wendeln HK, et al. Muscular adaptations in response to three different resistance-training regimens: specificity of repetition maximum training zones. Eur J Appl Physiol. 2002;88(1–2):50–60.PubMedCrossRefGoogle Scholar
  35. 35.
    Robbins DW, Goodale TL, Docherty D, et al. The effects of load and training pattern on acute neuromuscular responses in the upper body. J Strength Cond Res. 2010;24(11):2996–3007.PubMedCrossRefGoogle Scholar
  36. 36.
    MacDougall JD, Ray S, Sale DG, et al. Muscle substrate utilization and lactate production. Can J Appl Physiol. 1999;24(3):209–15.PubMedCrossRefGoogle Scholar
  37. 37.
    Tamaki T, Uchiyama S, Tamura T, et al. Changes in muscle oxygenation during weight-lifting exercise. Eur J Appl Physiol Occup Physiol. 1994;68(6):465–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Suga T, Okita K, Morita N, Yokota T, et al. Dose effect on intramuscular metabolic stress during low-intensity resistance exercise with blood flow restriction. J Appl Physiol. 2010;108(6):1563–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Fry CS, Glynn EL, Drummond MJ, et al. Blood flow restriction exercise stimulates mTORC1 signaling and muscle protein synthesis in older men. J Appl Physiol. 2010;108(5):1199–209.PubMedCrossRefGoogle Scholar
  40. 40.
    Loenneke JP, Wilson JM, Marin PJ, et al. Low intensity blood flow restriction training: a meta-analysis. Eur J Appl Physiol. 2012;112(5):1849–59.PubMedCrossRefGoogle Scholar
  41. 41.
    Kraemer WJ, Adams K, Cafarelli E, et al. American College of Sports Medicine position stand: progression models in resistance training for healthy adults. Med Sci Sports Exerc. 2002;34(2):364–80.PubMedCrossRefGoogle Scholar
  42. 42.
    Loenneke JP, Wilson GJ, Wilson JM. A mechanistic approach to blood flow occlusion. Int J Sports Med. 2010;31(1):1–4.PubMedCrossRefGoogle Scholar
  43. 43.
    Abe T, Kearns CF, Sato Y. Muscle size and strength are increased following walk training with restricted venous blood flow from the leg muscle, Kaatsu-walk training. J Appl Physiol. 2006;100(5):1460–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Kon M, Ikeda T, Homma T, et al. Effects of low-intensity resistance exercise under acute systemic hypoxia on hormonal responses. J Strength Cond Res. 2012;26(3):611–7.PubMedGoogle Scholar
  45. 45.
    Nishimura A, Sugita M, Kato K, et al. Hypoxia increases muscle hypertrophy induced by resistance training. Int J Sports Physiol Perform. 2010;5(4):497–508.PubMedGoogle Scholar
  46. 46.
    Goto K, Ishii N, Kizuka T, et al. The impact of metabolic stress on hormonal responses and muscular adaptations. Med Sci Sports Exerc. 2005;37(6):955–63.PubMedGoogle Scholar
  47. 47.
    Gordon SE, Kraemer WJ, Vos NH, et al. Effect of acid-base balance on the growth hormone response to acute high-intensity cycle exercise. J Appl Physiol. 1994;76(2):821–9.PubMedGoogle Scholar
  48. 48.
    Takarada Y, Nakamura Y, Aruga S, et al. Rapid increase in plasma growth hormone after low-intensity resistance exercise with vascular occlusion. J Appl Physiol. 2000;88(1):61–5.PubMedGoogle Scholar
  49. 49.
    Henneman E, Somjen G, Carpenter DO. Functional significance of cell size in spinal motoneurons. J Neurophysiol. 1965;28:560–80.PubMedGoogle Scholar
  50. 50.
    Kraemer WJ, Ratamess NA. Fundamentals of resistance training: progression and exercise prescription. Med Sci Sports Exerc. 2004;36(4):674–88.PubMedCrossRefGoogle Scholar
  51. 51.
    Houtman CJ, Stegeman DF, Van Dijk JP, et al. Changes in muscle fiber conduction velocity indicate recruitment of distinct motor unit populations. J Appl Physiol. 2003;95(3):1045–54.PubMedGoogle Scholar
  52. 52.
    Sahlin K, Soderlund K, Tonkonogi M, et al. Phosphocreatine content in single fibers of human muscle after sustained submaximal exercise. Am J Physiol. 1997;273(1 Pt 1):C172–8.PubMedGoogle Scholar
  53. 53.
    Vollestad NK, Vaage O, Hermansen L. Muscle glycogen depletion patterns in type I and subgroups of type II fibres during prolonged severe exercise in man. Acta Physiol Scand. 1984;122(4):433–41.PubMedCrossRefGoogle Scholar
  54. 54.
    Takarada Y, Takazawa H, Sato Y, et al. Effects of resistance exercise combined with moderate vascular occlusion on muscular function in humans. J Appl Physiol. 2000;88(6):2097–106.PubMedGoogle Scholar
  55. 55.
    Ingemann-Hansen T, Halkjaer-Kristensen J, Halskov O. Skeletal muscle phosphagen and lactate concentrations in ischaemic dynamic exercise. Eur J Appl Physiol Occup Physiol. 1981;46(3):261–70.PubMedCrossRefGoogle Scholar
  56. 56.
    Loenneke JP, Fahs CA, Wilson JM, et al. Blood flow restriction: the metabolite/volume threshold theory. Med Hypotheses. 2011;77(5):748–52.PubMedCrossRefGoogle Scholar
  57. 57.
    Meyer RA. Does blood flow restriction enhance hypertrophic signaling in skeletal muscle? J Appl Physiol. 2006;100(5):1443–4.PubMedCrossRefGoogle Scholar
  58. 58.
    Miller KJ, Garland SJ, Ivanova T, et al. Motor-unit behavior in humans during fatiguing arm movements. J Neurophysiol. 1996;75(4):1629–36.PubMedGoogle Scholar
  59. 59.
    Debold EP. Recent insights into the molecular basis of muscular fatigue. Med Sci Sports Exerc. 2012;44(8):1440–52.PubMedCrossRefGoogle Scholar
  60. 60.
    Moritani T, Sherman WM, Shibata M, et al. Oxygen availability and motor unit activity in humans. Eur J Appl Physiol Occup Physiol. 1992;64(6):552–6.PubMedCrossRefGoogle Scholar
  61. 61.
    Sundberg CJ. Exercise and training during graded leg ischaemia in healthy man with special reference to effects on skeletal muscle. Acta Physiol Scand Suppl. 1994;615:1–50.PubMedGoogle Scholar
  62. 62.
    Yasuda T, Abe T, Sato Y, et al. Muscle fiber cross-sectional area is increased after two weeks of twice daily KAATSU-resistance training. Int J KAATSU Train Res. 2005;1(2):65–70.CrossRefGoogle Scholar
  63. 63.
    Laurentino GC, Ugrinowitsch C, Roschel H, et al. Strength training with blood flow restriction diminishes myostatin gene expression. Med Sci Sports Exerc. 2012;44(3):406–12.PubMedCrossRefGoogle Scholar
  64. 64.
    Manini TM, Clark BC. Blood flow restricted exercise and skeletal muscle health. Exerc Sport Sci Rev. 2009;37(2):78–85.PubMedCrossRefGoogle Scholar
  65. 65.
    Hansen S, Kvorning T, Kjaer M, et al. The effect of short-term strength training on human skeletal muscle: the importance of physiologically elevated hormone levels. Scand J Med Sci Sports. 2001;11(6):347–54.PubMedCrossRefGoogle Scholar
  66. 66.
    Crewther B, Keogh J, Cronin J, et al. Possible stimuli for strength and power adaptation: acute hormonal responses. Sports Med. 2006;36(3):215–38.PubMedCrossRefGoogle Scholar
  67. 67.
    Kraemer WJ, Ratamess NA. Hormonal responses and adaptations to resistance exercise and training. Sports Med. 2005;35(4):339–61.PubMedCrossRefGoogle Scholar
  68. 68.
    Haddad F, Adams GR. Inhibition of MAP/ERK kinase prevents IGF-I-induced hypertrophy in rat muscles. J Appl Physiol. 2004;96(1):203–10.PubMedCrossRefGoogle Scholar
  69. 69.
    Stewart CE, Pell JM. Point:Counterpoint: IGF is/is not the major physiological regulator of muscle mass. Point: IGF is the major physiological regulator of muscle mass. J Appl Physiol. 2010;108(6):1820,1; discussion 1823-4; author reply 1832.Google Scholar
  70. 70.
    Hameed M, Lange KH, Andersen JL, et al. The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men. J Physiol. 2004;555(Pt 1):231–40.PubMedGoogle Scholar
  71. 71.
    Kostek MC, Delmonico MJ, Reichel JB, et al. Muscle strength response to strength training is influenced by insulin-like growth factor 1 genotype in older adults. J Appl Physiol. 2005;98(6):2147–54.PubMedCrossRefGoogle Scholar
  72. 72.
    Philippou A, Papageorgiou E, Bogdanis G, et al. Expression of IGF-1 isoforms after exercise-induced muscle damage in humans: characterization of the MGF E peptide actions in vitro. In Vivo. 2009;23(4):567–75.PubMedGoogle Scholar
  73. 73.
    Goldspink G. Mechanical signals, IGF-I gene splicing, and muscle adaptation. Physiology (Bethesda). 2005;20:232–8.CrossRefGoogle Scholar
  74. 74.
    Velloso CP, Harridge SD. Insulin-like growth factor-I E peptides: implications for aging skeletal muscle. Scand J Med Sci Sports. 2010;20(1):20–7.PubMedCrossRefGoogle Scholar
  75. 75.
    Velloso CP. Regulation of muscle mass by growth hormone and IGF-I. Br J Pharmacol. 2008;154(3):557–68.PubMedCrossRefGoogle Scholar
  76. 76.
    Timmons JA. Variability in training-induced skeletal muscle adaptation. J Appl Physiol. 2011;110(3):846–53.PubMedCrossRefGoogle Scholar
  77. 77.
    Petrella JK, Kim J, Mayhew DL, et al. Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell-mediated myonuclear addition: a cluster analysis. J Appl Physiol. 2008;104(6):1736–42.PubMedCrossRefGoogle Scholar
  78. 78.
    O’Connor RS, Pavlath GK. Point:counterpoint: satellite cell addition is/is not obligatory for skeletal muscle hypertrophy. J Appl Physiol. 2007;103(3):1099–100.PubMedCrossRefGoogle Scholar
  79. 79.
    McCarthy JJ, Esser KA. Counterpoint: satellite cell addition is not obligatory for skeletal muscle hypertrophy. J Appl Physiol. 2007;103:1100–2.PubMedCrossRefGoogle Scholar
  80. 80.
    Owino V, Yang SY, Goldspink G. Age-related loss of skeletal muscle function and the inability to express the autocrine form of insulin-like growth factor-1 (MGF) in response to mechanical overload. FEBS Lett. 2001;505(2):259–63.PubMedCrossRefGoogle Scholar
  81. 81.
    Sandri M. Signaling in muscle atrophy and hypertrophy. Physiology (Bethesda). 2008;23:160–70.CrossRefGoogle Scholar
  82. 82.
    Barton ER. Viral expression of insulin-like growth factor-I isoforms promotes different responses in skeletal muscle. J Appl Physiol. 2006;100(6):1778–84.PubMedCrossRefGoogle Scholar
  83. 83.
    Bamman MM, Petrella JK, Kim JS, et al. Cluster analysis tests the importance of myogenic gene expression during myofiber hypertrophy in humans. J Appl Physiol. 2007;102(6):2232–9.PubMedCrossRefGoogle Scholar
  84. 84.
    Hill M, Wernig A, Goldspink G. Muscle satellite (stem) cell activation during local tissue injury and repair. J Anat. 2003;203(1):89–99.PubMedCrossRefGoogle Scholar
  85. 85.
    Yang SY, Goldspink G. Different roles of the IGF-I ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation. FEBS Lett. 2002;522(1–3):156–60.PubMedCrossRefGoogle Scholar
  86. 86.
    Philippou A, Maridaki M, Halapas A, et al. The role of the insulin-like growth factor 1 (IGF-1) in skeletal muscle physiology. In Vivo. 2007;21(1):45–54.PubMedGoogle Scholar
  87. 87.
    Rubin MR, Kraemer WJ, Maresh CM, et al. High-affinity growth hormone binding protein and acute heavy resistance exercise. Med Sci Sports Exerc. 2005;37(3):395–403.PubMedCrossRefGoogle Scholar
  88. 88.
    Kraemer WJ, Aguilera BA, Terada M, et al. Responses of IGF-I to endogenous increases in growth hormone after heavy-resistance exercise. J Appl Physiol. 1995;79(4):1310–5.PubMedGoogle Scholar
  89. 89.
    Abe T, Yasuda T, Midorikawa T, et al. Skeletal muscle size and circulating IGF-1 are increased after two weeks of twice daily KAATSU resistance training. Int J Kaatsu Train Res. 2005;1:6–12.CrossRefGoogle Scholar
  90. 90.
    Takano H, Morita T, Iida H, et al. Hemodynamic and hormonal responses to a short-term low-intensity resistance exercise with the reduction of muscle blood flow. Eur J Appl Physiol. 2005;95(1):65–73.PubMedCrossRefGoogle Scholar
  91. 91.
    Fujita S, Abe T, Drummond MJ, et al. Blood flow restriction during low-intensity resistance exercise increases S6K1 phosphorylation and muscle protein synthesis. J Appl Physiol. 2007;103(3):903–10.PubMedCrossRefGoogle Scholar
  92. 92.
    Drummond MJ, Fujita S, Abe T, et al. Human muscle gene expression following resistance exercise and blood flow restriction. Med Sci Sports Exerc. 2008;40(4):691–8.PubMedCrossRefGoogle Scholar
  93. 93.
    Buresh R, Berg K, French J. The effect of resistive exercise rest interval on hormonal response, strength, and hypertrophy with training. J Strength Cond Res. 2009;23(1):62–71.PubMedCrossRefGoogle Scholar
  94. 94.
    Kadi F. Cellular and molecular mechanisms responsible for the action of testosterone on human skeletal muscle: a basis for illegal performance enhancement. Br J Pharmacol. 2008;154(3):522–8.PubMedCrossRefGoogle Scholar
  95. 95.
    Bhasin S, Woodhouse L, Storer TW. Proof of the effect of testosterone on skeletal muscle. J Endocrinol. 2001;170(1):27–38.PubMedCrossRefGoogle Scholar
  96. 96.
    Zhao W, Pan J, Zhao Z, et al. Testosterone protects against dexamethasone-induced muscle atrophy, protein degradation and MAFbx upregulation. J Steroid Biochem Mol Biol. 2008;110(1–2):125–9.PubMedCrossRefGoogle Scholar
  97. 97.
    Urban RJ, Bodenburg YH, Gilkison C, et al. Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol. 1995;269(5 Pt 1):E820–6.PubMedGoogle Scholar
  98. 98.
    Vingren JL, Kraemer WJ, Ratamess NA, et al. Testosterone physiology in resistance exercise and training: the up-stream regulatory elements. Sports Med. 2010;40(12):1037–53.PubMedCrossRefGoogle Scholar
  99. 99.
    Sculthorpe N, Solomon AM, Sinanan AC, et al. Androgens affect myogenesis in vitro and increase local IGF-1 expression. Med Sci Sports Exerc. 2012;44(4):610–5.PubMedCrossRefGoogle Scholar
  100. 100.
    Sinha-Hikim I, Cornford M, Gaytan H, et al. Effects of testosterone supplementation on skeletal muscle fiber hypertrophy and satellite cells in community-dwelling older men. J Clin Endocrinol Metab. 2006;91(8):3024–33.PubMedCrossRefGoogle Scholar
  101. 101.
    Ahtiainen JP, Pakarinen A, Alen M, et al. Muscle hypertrophy, hormonal adaptations and strength development during strength training in strength-trained and untrained men. Eur J Appl Physiol. 2003;89(6):555–63.PubMedCrossRefGoogle Scholar
  102. 102.
    Tremblay MS, Copeland JL, Van Helder W. Effect of training status and exercise mode on endogenous steroid hormones in men. J Appl Physiol. 2004;96(2):531–9.PubMedCrossRefGoogle Scholar
  103. 103.
    Kraemer WJ, Fry AC, Warren BJ, et al. Acute hormonal responses in elite junior weightlifters. Int J Sports Med. 1992;13(2):103–9.PubMedCrossRefGoogle Scholar
  104. 104.
    Loenneke JP, Wilson JM, Pujol TJ, et al. Acute and chronic testosterone response to blood flow restricted exercise. Horm Metab Res. 2011;43(10):669–73.PubMedCrossRefGoogle Scholar
  105. 105.
    Gotshalk LA, Loebel CC, Nindl BC, et al. Hormonal responses of multiset versus single-set heavy-resistance exercise protocols. Can J Appl Physiol. 1997;22(3):244–55.PubMedCrossRefGoogle Scholar
  106. 106.
    Hakkinen K, Pakarinen A. Acute hormonal responses to two different fatiguing heavy-resistance protocols in male athletes. J Appl Physiol. 1993;74(2):882–7.PubMedGoogle Scholar
  107. 107.
    Smilios I, Pilianidis T, Karamouzis M, et al. Hormonal responses after various resistance exercise protocols. Med Sci Sports Exerc. 2003;35(4):644–54.PubMedCrossRefGoogle Scholar
  108. 108.
    McCaulley GO, McBride JM, Cormie P, et al. Acute hormonal and neuromuscular responses to hypertrophy, strength and power type resistance exercise. Eur J Appl Physiol. 2009;105(5):695–704.PubMedCrossRefGoogle Scholar
  109. 109.
    Reeves GV, Kraemer RR, Hollander DB, et al. Comparison of hormone responses following light resistance exercise with partial vascular occlusion and moderately difficult resistance exercise without occlusion. J Appl Physiol. 2006;101(6):1616–22.PubMedCrossRefGoogle Scholar
  110. 110.
    Viru M, Jansson E, Viru A, et al. Effect of restricted blood flow on exercise-induced hormone changes in healthy men. Eur J Appl Physiol Occup Physiol. 1998;77(6):517–22.PubMedCrossRefGoogle Scholar
  111. 111.
    Vierck J, O’Reilly B, Hossner K, et al. Satellite cell regulation following myotrauma caused by resistance exercise. Cell Biol Int. 2000;24(5):263–72.PubMedCrossRefGoogle Scholar
  112. 112.
    Doessing S, Heinemeier KM, Holm L, et al. Growth hormone stimulates the collagen synthesis in human tendon and skeletal muscle without affecting myofibrillar protein synthesis. J Physiol. 2010;588(Pt 2):341–51.PubMedCrossRefGoogle Scholar
  113. 113.
    Sotiropoulos A, Ohanna M, Kedzia C, et al. Growth hormone promotes skeletal muscle cell fusion independent of insulin-like growth factor 1 up-regulation. Proc Natl Acad Sci USA. 2006;103(19):7315–20.PubMedCrossRefGoogle Scholar
  114. 114.
    Aperghis M, Velloso CP, Hameed M, et al. Serum IGF-I levels and IGF-I gene splicing in muscle of healthy young males receiving rhGH. Growth Horm IGF Res. 2009;19(1):61–7.PubMedCrossRefGoogle Scholar
  115. 115.
    Ehrnborg C, Rosen T. Physiological and pharmacological basis for the ergogenic effects of growth hormone in elite sports. Asian J Androl. 2008;10(3):373–83.PubMedCrossRefGoogle Scholar
  116. 116.
    Kraemer WJ, Dunn-Lewis C, Comstock BA, et al. Growth hormone, exercise, and athletic performance: a continued evolution of complexity. Curr Sports Med Rep. 2010;9(4):242–52.PubMedGoogle Scholar
  117. 117.
    Phillips SM. Physiologic and molecular bases of muscle hypertrophy and atrophy: impact of resistance exercise on human skeletal muscle (protein and exercise dose effects). Appl Physiol Nutr Metab. 2009;34(3):403–10.PubMedCrossRefGoogle Scholar
  118. 118.
    West DW, Phillips SM. Anabolic processes in human skeletal muscle: restoring the identities of growth hormone and testosterone. Phys Sportsmed. 2010;38(3):97–104.PubMedCrossRefGoogle Scholar
  119. 119.
    Lange KH, Andersen JL, Beyer N, et al. GH administration changes myosin heavy chain isoforms in skeletal muscle but does not augment muscle strength or hypertrophy, either alone or combined with resistance exercise training in healthy elderly men. J Clin Endocrinol Metab. 2002;87(2):513–23.PubMedCrossRefGoogle Scholar
  120. 120.
    Yarasheski KE, Campbell JA, Smith K, et al. Effect of growth hormone and resistance exercise on muscle growth in young men. Am J Physiol. 1992;262(3 Pt 1):E261–7.PubMedGoogle Scholar
  121. 121.
    Yarasheski KE, Zachwieja JJ, Campbell JA, et al. Effect of growth hormone and resistance exercise on muscle growth and strength in older men. Am J Physiol. 1995;268(2 Pt 1):E268–76.PubMedGoogle Scholar
  122. 122.
    Nindl BC, Hymer WC, Deaver DR, et al. Growth hormone pulsatility profile characteristics following acute heavy resistance exercise. J Appl Physiol. 2001;91(1):163–72.PubMedGoogle Scholar
  123. 123.
    West DW, Kujbida GW, Moore DR, et al. Resistance exercise-induced increases in putative anabolic hormones do not enhance muscle protein synthesis or intracellular signalling in young men. J Physiol. 2009;587(Pt 21):5239–47.PubMedCrossRefGoogle Scholar
  124. 124.
    Coffey VG, Shield A, Canny BJ, et al. Interaction of contractile activity and training history on mRNA abundance in skeletal muscle from trained athletes. Am J Physiol Endocrinol Metab. 2006;290(5):E849–55.PubMedCrossRefGoogle Scholar
  125. 125.
    Madarame H, Neya M, Ochi E, et al. Cross-transfer effects of resistance training with blood flow restriction. Med Sci Sports Exerc. 2008;40(2):258–63.PubMedCrossRefGoogle Scholar
  126. 126.
    West DW, Burd NA, Tang JE, et al. Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors. J Appl Physiol. 2010;108(1):60–7.PubMedCrossRefGoogle Scholar
  127. 127.
    Ronnestad BR, Nygaard H, Raastad T. Physiological elevation of endogenous hormones results in superior strength training adaptation. Eur J Appl Physiol. 2011;111(9):2249–59.PubMedCrossRefGoogle Scholar
  128. 128.
    Nielsen AR, Pedersen BK. The biological roles of exercise-induced cytokines: IL-6, IL-8, and IL-15. Appl Physiol Nutr Metab. 2007;32(5):833–9.PubMedCrossRefGoogle Scholar
  129. 129.
    Quinn LS. Interleukin-15: a muscle-derived cytokine regulating fat-to-lean body composition. J Anim Sci. 2008;86(14 Suppl.):E75–83.PubMedGoogle Scholar
  130. 130.
    Serrano AL, Baeza-Raja B, Perdiguero E, et al. Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab. 2008;7(1):33–44.PubMedCrossRefGoogle Scholar
  131. 131.
    Pedersen BK, Edward F. Adolph distinguished lecture: muscle as an endocrine organ: IL-6 and other myokines. J Appl Physiol. 2009;107(4):1006–14.PubMedCrossRefGoogle Scholar
  132. 132.
    Febbraio MA, Pedersen BK. Contraction-induced myokine production and release: is skeletal muscle an endocrine organ? Exerc Sport Sci Rev. 2005;33(3):114–9.PubMedCrossRefGoogle Scholar
  133. 133.
    Fujita T, Brechue WF, Kurita K, et al. Increased muscle volume and strength following six days of low-intensity resistance training with restricted muscle blood flow. Int J Kaatsu Train Res. 2008;4:1–8.CrossRefGoogle Scholar
  134. 134.
    Abe T, Beekley MD, Hinata S, et al. Day-to-day change in muscle strength and MRI-measured skeletal muscle size during 7 days KAATSU resistance training: a case study. Int J Kaatsu Train Res. 2005;1:71–6.CrossRefGoogle Scholar
  135. 135.
    Roth SM, Walsh S. Myostatin: a therapeutic target for skeletal muscle wasting. Curr Opin Clin Nutr Metab Care. 2004;7(3):259–63.PubMedCrossRefGoogle Scholar
  136. 136.
    Kawada S, Ishii N. Skeletal muscle hypertrophy after chronic restriction of venous blood flow in rats. Med Sci Sports Exerc. 2005;37(7):1144–50.PubMedCrossRefGoogle Scholar
  137. 137.
    Manini TM, Vincent KR, Leeuwenburgh CL, et al. Myogenic and proteolytic mRNA expression following blood flow restricted exercise. Acta Physiol (Oxf). 2011;201(2):255–63.CrossRefGoogle Scholar
  138. 138.
    Farooqui T. Iron-induced oxidative stress modulates olfactory learning and memory in honeybees. Behav Neurosci. 2008;122(2):433–47.PubMedCrossRefGoogle Scholar
  139. 139.
    Alessio HM, Hagerman AE, Fulkerson BK, et al. Generation of reactive oxygen species after exhaustive aerobic and isometric exercise. Med Sci Sports Exerc. 2000;32(9):1576–81.PubMedGoogle Scholar
  140. 140.
    Powers SK, Talbert EE, Adhihetty PJ. Reactive oxygen and nitrogen species as intracellular signals in skeletal muscle. J Physiol. 2011;589(Pt 9):2129–38.PubMedCrossRefGoogle Scholar
  141. 141.
    Jackson MJ. Reactive oxygen species and redox-regulation of skeletal muscle adaptations to exercise. Philos Trans R Soc Lond B Biol Sci. 2005;360(1464):2285–91.PubMedCrossRefGoogle Scholar
  142. 142.
    Simpson PJ, Lucchesi BR. Free radicals and myocardial ischemia and reperfusion injury. J Lab Clin Med. 1987;110(1):13–30.PubMedGoogle Scholar
  143. 143.
    Fulle S, Protasi F, Di Tano G, et al. The contribution of reactive oxygen species to sarcopenia and muscle ageing. Exp Gerontol. 2004;39(1):17–24.PubMedCrossRefGoogle Scholar
  144. 144.
    Jackson MJ. Free radicals generated by contracting muscle: by-products of metabolism or key regulators of muscle function? Free Radic Biol Med. 2008;44(2):132–41.PubMedCrossRefGoogle Scholar
  145. 145.
    Gomez-Cabrera MC, Domenech E, Vina J. Moderate exercise is an antioxidant: upregulation of antioxidant genes by training. Free Radic Biol Med. 2008;44(2):126–31.PubMedCrossRefGoogle Scholar
  146. 146.
    Ji LL, Gomez-Cabrera MC, Vina J. Exercise and hormesis: activation of cellular antioxidant signaling pathway. Ann N Y Acad Sci. 2006;1067:425–35.PubMedCrossRefGoogle Scholar
  147. 147.
    Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol. 2000;279(6):L1005–28.PubMedGoogle Scholar
  148. 148.
    Suzuki YJ, Ford GD. Redox regulation of signal transduction in cardiac and smooth muscle. J Mol Cell Cardiol. 1999;31(2):345–53.PubMedCrossRefGoogle Scholar
  149. 149.
    Hornberger TA, McLoughlin TJ, Leszczynski JK, et al. Selenoprotein-deficient transgenic mice exhibit enhanced exercise-induced muscle growth. J Nutr. 2003;133(10):3091–7.PubMedGoogle Scholar
  150. 150.
    Kefaloyianni E, Gaitanaki C, Beis I. ERK1/2 and p38-MAPK signalling pathways, through MSK1, are involved in NF-kappaB transactivation during oxidative stress in skeletal myoblasts. Cell Signal. 2006;18(12):2238–51.PubMedCrossRefGoogle Scholar
  151. 151.
    Tappia PS, Dent MR, Dhalla NS. Oxidative stress and redox regulation of phospholipase D in myocardial disease. Free Radic Biol Med. 2006;41(3):349–61.PubMedCrossRefGoogle Scholar
  152. 152.
    Handayaningsih A, Iguchi G, Fukuoka H, et al. Reactive oxygen species play an essential role in IGF-I signaling and IGF-I-induced myocyte hypertrophy in C2C12 myocytes. Endocrinology. 2011;152(3):912–21.PubMedCrossRefGoogle Scholar
  153. 153.
    Korthuis RJ, Granger DN, Townsley MI, et al. The role of oxygen-derived free radicals in ischemia-induced increases in canine skeletal muscle vascular permeability. Circ Res. 1985;57(4):599–609.PubMedCrossRefGoogle Scholar
  154. 154.
    Clanton TL. Hypoxia-induced reactive oxygen species formation in skeletal muscle. J Appl Physiol. 2007;102(6):2379–88.PubMedCrossRefGoogle Scholar
  155. 155.
    Goldfarb AH, Garten RS, Chee PD, et al. Resistance exercise effects on blood glutathione status and plasma protein carbonyls: influence of partial vascular occlusion. Eur J Appl Physiol. 2008;104(5):813–9.PubMedCrossRefGoogle Scholar
  156. 156.
    Smith LW, Smith JD, Criswell DS. Involvement of nitric oxide synthase in skeletal muscle adaptation to chronic overload. J Appl Physiol. 2002;92(5):2005–11.PubMedGoogle Scholar
  157. 157.
    Sellman JE, DeRuisseau KC, Betters JL, et al. In vivo inhibition of nitric oxide synthase impairs upregulation of contractile protein mRNA in overloaded plantaris muscle. J Appl Physiol. 2006;100(1):258–65.PubMedCrossRefGoogle Scholar
  158. 158.
    Anderson JE. A role for nitric oxide in muscle repair: nitric oxide-mediated activation of muscle satellite cells. Mol Biol Cell. 2000;11(5):1859–74.PubMedGoogle Scholar
  159. 159.
    Tatsumi R, Hattori A, Ikeuchi Y, et al. Release of hepatocyte growth factor from mechanically stretched skeletal muscle satellite cells and role of pH and nitric oxide. Mol Biol Cell. 2002;13(8):2909–18.PubMedCrossRefGoogle Scholar
  160. 160.
    Kiang JG, Tsokos GC. Heat shock protein 70 kDa: molecular biology, biochemistry, and physiology. Pharmacol Ther. 1998;80(2):183–201.PubMedCrossRefGoogle Scholar
  161. 161.
    Simar D, Malatesta D, Badiou S, et al. Physical activity modulates heat shock protein-72 expression and limits oxidative damage accumulation in a healthy elderly population aged 60 90 years. J Gerontol A Biol Sci Med Sci. 2007;62(12):1413–9.PubMedCrossRefGoogle Scholar
  162. 162.
    Locke M. Heat shock protein accumulation and heat shock transcription factor activation in rat skeletal muscle during compensatory hypertrophy. Acta Physiol (Oxf). 2008;192(3):403–11.CrossRefGoogle Scholar
  163. 163.
    Kregel KC. Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. J Appl Physiol. 2002;92(5):2177–86.PubMedGoogle Scholar
  164. 164.
    Paulsen G, Hanssen KE, Ronnestad BR, et al. Strength training elevates HSP27, HSP70 and alphaB-crystallin levels in musculi vastus lateralis and trapezius. Eur J Appl Physiol. 2012;112(5):1773–82.PubMedCrossRefGoogle Scholar
  165. 165.
    Morton JP, Kayani AC, McArdle A, et al. The exercise-induced stress response of skeletal muscle, with specific emphasis on humans. Sports Med. 2009;39(8):643–62.PubMedCrossRefGoogle Scholar
  166. 166.
    Haussinger D, Lang F, Gerok W. Regulation of cell function by the cellular hydration state. Am J Physiol. 1994;267(3 Pt 1):E343–55.PubMedGoogle Scholar
  167. 167.
    Haussinger D. The role of cellular hydration in the regulation of cell function. Biochem J. 1996;313(Pt 3):697–710.PubMedGoogle Scholar
  168. 168.
    Lang F, Busch GL, Ritter M, et al. Functional significance of cell volume regulatory mechanisms. Physiol Rev. 1998;78(1):247–306.PubMedGoogle Scholar
  169. 169.
    Dangott B, Schultz E, Mozdziak PE. Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy. Int J Sports Med. 2000;21(1):13–6.PubMedCrossRefGoogle Scholar
  170. 170.
    Lang F. Mechanisms and significance of cell volume regulation. J Am Coll Nutr. 2007;26(5 Suppl.):613S–23S.PubMedGoogle Scholar
  171. 171.
    Low SY, Rennie MJ, Taylor PM. Signaling elements involved in amino acid transport responses to altered muscle cell volume. FASEB J. 1997;11(13):1111–7.PubMedGoogle Scholar
  172. 172.
    Clarke MS, Feeback DL. Mechanical load induces sarcoplasmic wounding and FGF release in differentiated human skeletal muscle cultures. FASEB J. 1996;10(4):502–9.PubMedGoogle Scholar
  173. 173.
    Lambert IH, Hoffmann EK, Pedersen SF. Cell volume regulation: physiology and pathophysiology. Acta Physiol (Oxf). 2008;194(4):255–82.CrossRefGoogle Scholar
  174. 174.
    Schliess F, Richter L, vom Dahl S, et al. Cell hydration and mTOR-dependent signalling. Acta Physiol (Oxf). 2006;187(1–2):223–9.CrossRefGoogle Scholar
  175. 175.
    Finkenzeller G, Newsome W, Lang F, et al. Increase of c-jun mRNA upon hypo-osmotic cell swelling of rat hepatoma cells. FEBS Lett. 1994;340(3):163–6.PubMedCrossRefGoogle Scholar
  176. 176.
    Schliess F, Schreiber R, Haussinger D. Activation of extracellular signal-regulated kinases erk-1 and erk-2 by cell swelling in H4IIE hepatoma cells. Biochem J. 1995;309(Pt 1):13–7.PubMedGoogle Scholar
  177. 177.
    Sjogaard G. Water and electrolyte fluxes during exercise and their relation to muscle fatigue. Acta Physiol Scand Suppl. 1986;556:129–36.PubMedGoogle Scholar
  178. 178.
    Sjogaard G, Adams RP, Saltin B. Water and ion shifts in skeletal muscle of humans with intense dynamic knee extension. Am J Physiol. 1985;248(2 Pt 2):R190–6.PubMedGoogle Scholar
  179. 179.
    Frigeri A, Nicchia GP, Verbavatz JM, et al. Expression of aquaporin-4 in fast-twitch fibers of mammalian skeletal muscle. J Clin Invest. 1998;102(4):695–703.PubMedCrossRefGoogle Scholar
  180. 180.
    Kosek DJ, Kim JS, Petrella JK, et al. Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic mechanisms in young vs. older adults. J Appl Physiol. 2006;101(2):531–44.PubMedCrossRefGoogle Scholar
  181. 181.
    Gundermann DM, Fry CS, Dickinson JM, et al. Reactive hyperemia is not responsible for stimulating muscle protein synthesis following blood flow restriction exercise. J Appl Physiol. 2012.Google Scholar
  182. 182.
    MacDougall JD, Ward GR, Sale DG, et al. Biochemical adaptation of human skeletal muscle to heavy resistance training and immobilization. J Appl Physiol. 1977;43(4):700–3.PubMedGoogle Scholar
  183. 183.
    Chan ST, Johnson AW, Moore MH, et al. Early weight gain and glycogen-obligated water during nutritional rehabilitation. Hum Nutr Clin Nutr. 1982;36(3):223–32.PubMedGoogle Scholar
  184. 184.
    Widegren U, Ryder JW, Zierath JR. Mitogen-activated protein kinase signal transduction in skeletal muscle: effects of exercise and muscle contraction. Acta Physiol Scand. 2001;172(3):227–38.PubMedCrossRefGoogle Scholar
  185. 185.
    Tanimoto M, Sanada K, Yamamoto K, et al. Effects of whole-body low-intensity resistance training with slow movement and tonic force generation on muscular size and strength in young men. J Strength Cond Res. 2008;22(6):1926–38.PubMedCrossRefGoogle Scholar
  186. 186.
    Mitchell CJ, Churchward-Venne TA, West DD, et al. Resistance exercise load does not determine training-mediated hypertrophic gains in young men. J Appl Physiol. 2012.Google Scholar
  187. 187.
    Holm L, Reitelseder S, Pedersen TG, et al. Changes in muscle size and MHC composition in response to resistance exercise with heavy and light loading intensity. J Appl Physiol. 2008;105(5):1454–61.PubMedCrossRefGoogle Scholar
  188. 188.
    Schoenfeld BJ. Does exercise-induced muscle damage play a role in skeletal muscle hypertrophy? J Strength Cond Res. 2012;26(5):1441–53.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  1. 1.Department of Health SciencesProgram of Exercise Science, APEX Building, Room # 265, Lehman College, CUNYBronxUSA

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