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Int J Sports Med 2013; 34(04): 293-301
DOI: 10.1055/s-0032-1321895
Physiology & Biochemistry
© Georg Thieme Verlag KG Stuttgart · New York

Myogenin, MyoD and IGF-I Regulate Muscle Mass but not Fiber-type Conversion during Resistance Training in Rats

A. F. Aguiar
1   Morphology, Univ Estadual Paulista (UNESP), Botucatu, Brazil
,
I. J. Vechetti-Júnior
2   Morphology, Univ Estadual Paulista, Botucatu, Brazil
,
R. W. Alves de Souza
2   Morphology, Univ Estadual Paulista, Botucatu, Brazil
,
E. P. Castan
2   Morphology, Univ Estadual Paulista, Botucatu, Brazil
,
R. C. Milanezi-Aguiar
2   Morphology, Univ Estadual Paulista, Botucatu, Brazil
,
C. R. Padovani
3   Bioestatística, Universidade Estadual Paulista, Botucatu, Brazil
,
R. F. Carvalho
2   Morphology, Univ Estadual Paulista, Botucatu, Brazil
,
M.D P. Silva
4   Instituto de Biociências de Botucatu, Universidade Estadual Paulista Júlio de Mesquita Filho, Morphology, Botucatu, Brazil
› Author Affiliations
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Publication History



accepted after revision 22 June 2012

Publication Date:
11 October 2012 (online)

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Abstract

The purpose of this study was to test the hypothesis that skeletal muscle adaptations induced by long-term resistance training (RT) are associated with increased myogenic regulatory factors (MRF) and insulin-like growth factor-I (IGF-I) mRNA expression in rats skeletal muscle. Male Wistar rats were divided into 4 groups: 8-week control (C8), 8-week trained (T8), 12-week control (C12) and 12-week trained (T12). Trained rats were submitted to a progressive RT program (4 sets of 10–12 repetitions at 65–75% of the 1RM, 3 day/week), using a squat-training apparatus with electric stimulation. Muscle hypertrophy was determined by measurement of muscle fiber cross-sectional area (CSA) of the muscle fibers, and myogenin, MyoD and IGF-I mRNA expression were measured by RT-qPCR. A hypertrophic stabilization occurred between 8 and 12 weeks of RT (control-relative % area increase, T8: 29% vs. T12: 35%; p>0.05) and was accompanied by the stabilization of myogenin (control-relative % increase, T8: 44.8% vs. T12: 37.7%, p>0.05) and MyoD (control-relative % increase, T8: 22.9% vs. T12: 22.3%, p>0.05) mRNA expression and the return of IGF-I mRNA levels to the baseline (control-relative % increase, T8: 30.1% vs. T12: 1.5%, p<0.05). Moreover, there were significant positive correlations between the muscle fiber CSA and mRNA expression for MyoD (r=0.85, p=0.0001), myogenin (r=0.87, p=0.0001), and IGF-I (r=0.88, p=0.0001). The significant (p<0.05) increase in myogenin, MyoD and IGF-I mRNA expression after 8 weeks was not associated with changes in the fiber-type frequency. In addition, there was a type IIX/D-to-IIA fiber conversion at 12 weeks, even with the stabilization of MyoD and myogenin expression and the return of IGF-I levels to baseline. These results indicate a possible interaction between MRFs and IGF-I in the control of muscle hypertrophy during long-term RT and suggest that these factors are involved more in the regulation of muscle mass than in fiber-type conversion.

Key words

muscle hypertrophy - fiber-type - strength training - myogenic regulatory factor - insulin-like growth factor
 

  • References

  • 1 Adams GR, McCue SA. Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats. J Appl Physiol 1998; 84: 1716-1722
    CrossrefPubMedGoogle Scholar
  • 2 Alway SE, Degens H, Krishnamurthy G, Smith CA. Potential role for Id myogenic repressors in apoptosis and attenuation of hypertrophy in muscles of aged rats. Am J Physiol 2002; 283: C66-C76
    CrossrefPubMedGoogle Scholar
  • 3 Andersen P, Henriksson J. Training induced changes in the subgroups of human type II skeletal muscle fibres. Acta Physiol Scand 1977; 99: 123-125
    CrossrefPubMedGoogle Scholar
  • 4 Bamman MM, Shipp JR, Jiang J, Gower BA, Hunter GR, Goodman A, McLafferty Jr CL, Urban RJ. Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans. Am J Physiol 2001; 280: E383-E390
    PubMedGoogle Scholar
  • 5 Barauna VG, Batista Jr ML, Costa Rosa LF, Casarini DE, Krieger JE, Oliveira EM. Cardiovascular adaptations in rats submitted to a resistance-training model. Clin Exp Pharmacol Physiol 2005; 32: 249-254
    CrossrefPubMedGoogle Scholar
  • 6 Bickel CS, Slade JM, Haddad F, Adams GR, Dudley GA. Acute molecular responses of skeletal muscle to resistance exercise in able-bodied and spinal cord-injured subjects. J Appl Physiol 2003; 94: 2255-2262
    PubMedGoogle Scholar
  • 7 Bickel CS, Slade J, Mahoney ED, Haddad D, Dudley A, Adams GR. Time course of molecular responses of human skeletal muscle to acute bouts of resistance exercise. J Appl Physiol 2005; 98: 482-488
    PubMedGoogle Scholar
  • 8 Buckingham M. Skeletal muscle formation in vertebrates. Curr Opin Genet Dev 2001; 11: 440-448
    CrossrefPubMedGoogle Scholar
  • 9 Campos GE, Luecke TJ, Wendeln HK, Toma K, Hagerman FC, Murray TF, Ragg KE, Ratamess NA, Kraemer WJ, Staron RS. Muscular adaptations in response to three different resistance-training regimens: specificity of repetition maximum training zones. Eur J Appl Physiol 2002; 88: 50-60
    CrossrefPubMedGoogle Scholar
  • 10 Chargé SB, Rudnicki MA. Cellular and molecular regulation of muscle regeneration. Physiol Rev 2004; 84: 209-238
    CrossrefPubMedGoogle Scholar
  • 11 DeVol DL, Rotwein P. Activation of insulin-like growth factor gene expression during work-induced skeletal muscle growth. Am J Physiol 1990; 259: E89-E95
    PubMedGoogle Scholar
  • 12 Glass DL. Molecular mechanisms modulating muscle mass. Trend Mol Med 2003; 9: 344-350
    CrossrefPubMedGoogle Scholar
  • 13 Goldspink DF, Cox VM, Smith SK, Eaves LA, Osbaldeston NJ, Lee DM, Mantle D. Muscle growth in response to mechanical stimuli. Am J Physiol 1995; 268: 288-297
    PubMedGoogle Scholar
  • 14 Goldstein DS. Stress-induced activation of the sympathetic nervous system. Baillieres Clin Endocrinol Metab 1987; 1: 253-278
    PubMedGoogle Scholar
  • 15 Goodman LA. Simultaneous confidence intervals for contrasts among multinominal populations. Ann Math Stat 1964; 35: 716-725
    Google Scholar
  • 16 Goodman LA. On simultaneous confidence intervals for multinominal proportions. Technometrics 1965; 7: 247-254
    CrossrefPubMedGoogle Scholar
  • 17 Haddad F, Adams GR. Selected contribution: Acute cellular and molecular responses to resistance exercise. J Appl Physiol 2002; 93: 394-403
    PubMedGoogle Scholar
  • 18 Harriss DJ, Atkinson G. Update-ethical standards in sport and exercise science research. Int J Sports Med 2011; 32: 819-821
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Hobler SC, Williams AB, Fischer JE, Hasselgren PO. IGF-I stimulates protein synthesis but does not inhibit protein breakdown in muscle from septic rats. Am J Physiol 1998; 274: R571-R576
    PubMedGoogle Scholar
  • 20 Hughes SM, Taylor JM, Tapscott SJ, Gurley CM, Carter WJ, Peterson CA. Selective accumulation of MyoD and myogenin mRNAs in fast and slow adult skeletal muscle is controlled by innervation and hormones. Development 1993; 118: 1137-1147
    PubMedGoogle Scholar
  • 21 Hughes SM, Koishi K, Rudnicki M, Maggs AM. MyoD protein is differentially accumulated in fast and slow skeletal muscle fibres and required for normal fibre type balance in rodents. Mech Dev 1997; 61: 151-163
    CrossrefPubMedGoogle Scholar
  • 22 Institute for Laboratory Animal Research, National Research Council . Guide for the Care and Use of Laboratory Animals. Washington, D.C.: National Academy Press; 2010: 248
    Google Scholar
  • 23 Ishido M, Kami K, Masuhara M. Localization of MyoD, myogenin and cell cycle regulatory factors in hypertrophying rat skeletal muscles. Acta Physiol Scand 2004; 180: 281-289
    CrossrefPubMedGoogle Scholar
  • 24 Kesidis N, Metaxas TI, Vrabas IS, Stefanidis P, Vamvakoudis E, Christoulas K, Mandroukas A, Balasas D, Mandroukas K. Myosin heavy chain isoform distribution in single fibers of bodybuilders. Eur J Appl Physiol 2008; 103: 579-583
    CrossrefPubMedGoogle Scholar
  • 25 Klitgaard H, Zhou M, Richter EA. Myosin heavy chain composition of single fibres from m. biceps brachii of male bodybuilders. Acta Physiol Scand 1990; 140: 175-180
    CrossrefPubMedGoogle Scholar
  • 26 Kraemer WJ, Patton JF, Gordon SE, Harman EA, Deschenes MR, Reynolds K, Newton RU, Triplett NT, Dziados JE. Compatibility of high intensity strength and endurance training on hormonal and skeletal muscle adaptations. J Appl Physiol 1995; 78: 976-989
    CrossrefPubMedGoogle Scholar
  • 27 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 1997; 247: 98-106
    CrossrefPubMedGoogle Scholar
  • 28 Launay T, Armand AS, Charbonnier F, Mira JC, Donsez E, Gallien CL, Chanoine C. Expression and neural control of myogenic regulatory factor genes during regeneration of mouse soleus. J Histochem Cytochem 2001; 49: 887-899
    CrossrefPubMedGoogle Scholar
  • 29 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 − ΔΔCT method. Methods 2001; 25: 402-408
    CrossrefPubMedGoogle Scholar
  • 30 Lowe DA, Alway SE. Stretch-induced myogenin, MyoD, and MRF4 expression and acute hypertrophy in quail slow-tonic muscle are not dependent upon satellite cell proliferation. Cell Tissue Res 1999; 296: 531-539
    CrossrefPubMedGoogle Scholar
  • 31 Marsh DR, Criswell DS, Carson JA, Booth FW. Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats. J Appl Physiol 1997; 83: 1270-1275
    PubMedGoogle Scholar
  • 32 Mozdziak PE, Greaser ML, Schultz EJ. Myogenin, MyoD, and myosin expression after pharmacologically and surgically induced hypertrophy. J Appl Physiol 1998; 84: 1359-1364
    PubMedGoogle Scholar
  • 33 Musarò A, McCullagh K, Paul A, Houghton L, Dobrowolny G, Molinaro M, Barton ER, Sweeney HL, Rosenthal N. Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle. Nat Genet 27 2001; 195-200
    CrossrefPubMedGoogle Scholar
  • 34 Olson EN. Regulation of muscle transcription by the MyoD family. Circ Res 1993; 72: 1-6
    CrossrefPubMedGoogle Scholar
  • 35 Phelan JN, Gonyea WJ. Effect of radiation on satellite cell activity and protein expression in overloaded mammalian skeletal muscle. Anat Rec 1997; 247: 179-188
    CrossrefPubMedGoogle Scholar
  • 36 Psilander N, Damsgaard R, Pilegaard H. Resistance exercise alters MRF and IGF-I mRNA content in human skeletal muscle. J Appl Physiol 2003; 95: 1038-1044
    PubMedGoogle Scholar
  • 37 Raue U, Slivka D, Jemiolo B, Hollon C, Trappe S. Myogenic gene expression at rest and after a bout of resistance exercise in young (18–30 yr) and old (80–89 yr) women. J Appl Physiol 2006; 101: 53-59
    CrossrefPubMedGoogle Scholar
  • 38 Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, Yancopoulos GD, Glass DJ. Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol 2001; 3: 1009-1013
    CrossrefPubMedGoogle Scholar
  • 39 Rosenblatt JD, Yong D, Parry DJ. Satellite cell activity is required for hypertrophy of overloaded adult rat muscle. Muscle Nerve 1994; 17: 608-613
    CrossrefPubMedGoogle Scholar
  • 40 Rudnicki MA, Braun T, Hinuma S, Jaenisch R. Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development. Cell 1992; 71: 383-390
    CrossrefPubMedGoogle Scholar
  • 41 Selye H. The evolution of the stress concept. Stress and cardiovascular disease. Am J Cardiol 1970; 26: 289-299
    CrossrefPubMedGoogle Scholar
  • 42 Sharman MJ, Newton RU, Triplett-McBride T, McGuigan MR, McBride JM, Häkkinen A, Häkkinen K, Kraemer WJ. Changes in myosin heavy chain composition with heavy resistance training in 60- to 75-year-old men and women. Eur J Appl Physiol 2001; 84: 127-132
    CrossrefPubMedGoogle Scholar
  • 43 Smith CK, Janney MJ, Allen RE. Temporal expression of myogenic regulatory genes during activation, proliferation and differentiation of rat skeletal muscle satellite cells. J Cell Physiol 1994; 159: 379-385
    CrossrefPubMedGoogle Scholar
  • 44 Staron RS, Kraemer WJ, Hikida RS, Fry AC, Murray JD, Campos GE. Fiber type composition of four hindlimb muscles of adult Fisher 344 rats. Histochem Cell Biol 1999; 111: 117-123
    CrossrefPubMedGoogle Scholar
  • 45 Tamaki T, Uchiyama S, Nakano S. A weight-lifting exercise model for inducing hypertrophy in the hindlimb muscles of rats. Med Sci Sports Exerc 1992; 24: 881-886
    PubMedGoogle Scholar
  • 46 Tamaki T, Uchiyama S, Uchiyama Y, Akatsuka A, Yoshimura S, Roy RR, Edgerton VR. Limited myogenic response to a single bout of weight-lifting exercise in old rats. Am J Physiol 2000; 278: C1143-C1152
    PubMedGoogle Scholar
  • 47 Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 2002; 3 RESEARCH0034. Epub 2002
    PubMedGoogle Scholar
  • 48 Voytik LL, Przyborski MJ, Badylak SF, Konieczny SF. Differential expression of muscle regulatory factor genes in normal and denervated adult rat hindlimb muscles. Dev Dyn 1993; 198: 214-224
    CrossrefPubMedGoogle Scholar
  • 49 Willoughby DS, Nelson MJ. Myosin heavy-chain mRNA expression after a single session of heavy-resistance exercise. Med Sci Sports Exerc 2002; 34: 1262-1269
    CrossrefPubMedGoogle Scholar