Effect of Voluntary Exercise on the Expression of IGF-I and Androgen Receptor in Three Rat Skeletal Muscles and on Serum IGF-I and Testosterone Levels

Abstract

The effects of anabolic agents and training on skeletal muscle are believed to be mediated by a variety of growth and transcription factors. Among these regulatory proteins, insulin-like growth factor-I (IGF-Ι) and androgen receptor (AR) play a crucial role. The purpose of this study was to investigate the effects of wheel running on IGF-I and AR mRNA expression in three distinct rat skeletal muscles (i.e., gastrocnemius, vastus lateralis, and soleus), as well as on the serum levels of IGF-I and testosterone. Twenty male Wistar rats were housed in cages with free access to running wheels for 12 weeks, while nine rats served as controls. Analysis of the mRNA expression of IGF-I and AR using real time RT-PCR revealed no significant differences between the trained and untrained rats in any of the muscles studied. Enzyme immunoassay showed significantly lower serum levels of IGF-I and testosterone in the trained compared to the untrained animals. These results suggest that chronic exercise in wheels does not affect IGF-I and AR mRNA levels in rat skeletal muscle, while decreasing the circulating levels of two anabolic factors, i.e., IGF-I and testosterone. It is concluded that IGF-I, AR and testosterone seem to play a marginal role during the adaptation process of rat skeletal muscle to long-term wheel running.

Gene expression - serum hormones - real time RT-PCR

References

• 1 Adams G R. Role of insulin-like growth factor-I in the regulation of skeletal muscle adaptation to increased loading.  Exerc Sports Sci Rev. 1998;  26 31-60
• 2 Allen D L, Harrison B C, Maass A, Bell M L, Byrnes W C, Leinwand L A. Cardiac and skeletal muscle adaptations to voluntary wheel running in the mouse.  J Appl Physiol. 2001;  90 1900-1908
• 3 Bamman M M, Shipp J R, Jiang J, Gower B A, Hunter G R, Goodman A, McLafferty C L, Urban R J. Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans.  Am J Physiol. 2001;  280 383-390
• 4 Banu M J, Orhii P B, Mejia W, McCarter R J, Mosekilde L, Thomsen J S, Kalu D N. Analysis of the effects of growth hormone, voluntary exercise, and food restriction on diaphyseal bone in female F344 rats.  Bone. 1999;  25 469-480
• 5 Booth F W, Thomason D B. Molecular and cellular adaptation of muscle in response to exercise: perspectives of various models.  Physiol Rev. 1991;  71 541-585
• 6 Boss O, Samec S, Desplanches D, Mayet M H, Seydoux J, Muzzin P, Giacobino J P. Effect of endurance training on mRNA expression of uncoupling proteins 1, 2, and 3 in the rat.  FASEB J. 1998;  12 335-339
• 7 Bravenboer N, Engelbregt M J, Visser N A, Popp-Snijders C, Lips P. The effect of exercise on systemic and bone concentrations of growth factors in rats.  J Orthop Res. 2001;  19 945-949
• 8 Brinkmann A O, Blok L J, de Ruiter P E, Doesburg P, Steketee K, Berrevoets C A, Trapman J. Mechanisms of androgen receptor activation and function.  J Steroid Biochem Mol Biol. 1999;  69 307-313
• 9 Cooper D M, Moromisato D, Zanconato S, Moromisato M, Jensen S, Brasel J A. Effect of growth hormone suppression on exercise training and growth responses in young rats.  Pediatr Res. 1994;  35 223-227
• 10 de Leon R, Hodgson J A, Roy R R, Edgerton V R. Extensor- and flexor-like modulation within motor pools of the rat hindlimb during treadmill locomotion and swimming.  Brain Res. 1994;  22 241-250
• 11 Delp M D, Duan C. Composition and size of type I, IIA, IID/X, and IIB fibers and citrate synthase activity of rat muscle.  J Appl Physiol. 1996;  80 261-270
• 12 Deschenes M R, Maresh C M, Armstrong L E, Covault J, Kraemer W J, Crivello J F. Endurance and resistance exercise induce muscle fibre type specific responses in androgen binding capacity.  J Steroid Biochem Mol Biol. 1994;  50 175-179
• 13 Dishman R K. Brain monoamines, exercise, and behavioral stress: animal models.  Med Sci Sports Exerc. 1997;  29 63-74
• 14 Eliakim A, Moromisato M, Moromisato D, Brasel J A, Roberts C, Cooper D M. Increase in muscle IGF-I protein but not IGF-I mRNA after 5 days of endurance training in young rats.  Am J Physiol. 1997;  42 1557-1561
• 15 Gerra G, Zaimovic A, Zambelli U, Timpano M, Reali N, Bernasconi S, Brambilla F. Neuroendocrine responses to psychological stress in adolescents with anxiety disorder.  Neuropsychobiology. 2000;  42 82-92
• 16 Guezennec C Y, Ferre P, Serrurier B, Merino D, Pesquies P C. Effects of prolonged physical exercise and fasting upon plasma testosterone level in rats.  Eur J Appl Physiol. 1982;  49 159-168
• 17 Guglielmini C, Paolini A R, Conconi F. Variations of serum testosterone concentrations after physical exercises of different duration.  Int J Sports Med. 1984;  5 246-249
• 18 Gulve E A, Rodnick K J, Henriksen E J, Holloszy J O. Effects of wheel running on glucose transporter (GLUT4) concentration in skeletal muscle of young adult and old rats.  Mech Ageing Dev. 1993;  67 187-200
• 19 Hamilton M T, Etienne J, McClure W C, Pavey B S, Holloway A K. Role of local contractile activity and muscle fiber type on LPL regulation during exercise.  Am J Physiol. 1998;  275 1016-1022
• 20 Harkonen M, Naveri H, Kuoppasalmi K, Huhtaniemi I. Pituitary and gonadal function during physical exercise in the male rat.  J Steroid Biochem. 1990;  35 127-132
• 21 Hu Y, Asano K, Mizuno K, Usuki S, Kawakura Y. Comparisons of serum testosterone and corticosterone between exercise training during normoxia and hypobaric hypoxia in rats.  Eur J Appl Physiol. 1998;  78 417-421
• 22 Hu Y, Asano K, Mizuno K, Usuki S, Kawakura Y. Serum testosterone responses to continuous and intermittent exercise training in male rats.  Int J Sports Med. 1999;  20 12-16
• 23 Klein D. Quantification using real-time PCR technology: applications and limitations.  Trends Mol Med. 2002;  8 257-260
• 24 Kubo H, Libonati J R, Kendrick Z V, Paolone A, Gaughan J P, Houser S R. Differential effects of exercise training on skeletal muscle SERCA gene expression.  Med Sci Sports Exerc. 2003;  35 27-31
• 25 Kuhn C M. Anabolic steroids.  Recent Prog Horm Res. 2002;  57 411-434
• 26 Kuoppasalmi K, Naveri H, Harkonen M, Adlecreutz H. Plasma cortisol, androstenedione, testosterone and luteinizing hormone in running exercise of different intensities.  Scand J Clin Lab Invest. 1980;  40 403-409
• 27 Lee J S, Bruce C R, Tunstall R J, Cameron-Smith D, Hugel H, Hawley J A. Interaction of exercise and diet on GLUT-4 protein and gene expression in type I and type II rat skeletal muscle.  Acta Physiol Scand. 2002;  175 37-44
• 28 Michelson D, Amsterdam J, Apter J, Fava M, Londborg P, Tamura R, Pagh L. Hormonal markers of stress response following interruption of selective serotonin reuptake inhibitor treatment.  Psychoneuroendocrinology. 2000;  25 169-177
• 29 Murphy R M, Watt K K, Cameron-Smith D, Gibbons C J, Snow R J. Effects of creatine supplementation on housekeeping genes in human skeletal muscle using real-time RT-PCR.  Physiol Genomics. 2003;  12 163-174
• 30 Neufer P D. Contractile activity and skeletal muscle gene expression. Hargreaves M, Thompson M Biochemistry of Exercise X. Champaign, IL; Human Kinetics 1999: 291-300
• 31 Noble E G, Moraska A, Mazzeo R S, Roth D A, Olsson M C, Moore R L, Fleshner M. Differential expression of stress proteins in rat myocardium after free wheel or treadmill run training.  J Appl Physiol. 1999;  86 1696-1701
• 32 Oxlund H, Andersen N B, Ortoft G, Orskov H, Andreassen T T. Growth hormone and mild exercise in combination markedly enhance cortical bone formation and strength in old rats.  Endocrinology. 1998;  139 1899-1904
• 33 Rosen J C, Pollak M. Circulating IGF-1: New perspectives for a new century.  Trends Endocrinol Metab. 1999;  10 136-141
• 34 Roy R R, Hutchison D L, Pierotti D J, Hodgson J A, Edgerton V R. EMG patterns of rat ankle extensors and flexors during treadmill locomotion and swimming.  J Appl Physiol. 1991;  70 2522-2529
• 35 Salo D C, Donovan C M, Davies K J. HSP70 and other possible heat shock or oxidative stress proteins are induced in skeletal muscle, heart, and liver during exercise.  Free Radic Biol Med. 1991;  11 239-246
• 36 Sveistrup H, Chan R Y, Jasmin B J. Chronic enhancement of neuromuscular activity increases acetylcholinesterase gene expression in skeletal muscle.  Am J Physiol. 1995;  269 856-862
• 37 Woody C J, Weber S L, Laubach H E, Ingram-Willey V, Amini-Alashti P, Sturbaum B A. The effects of chronic exercise on metabolic and reproductive functions in male rats.  Life Sci. 1998;  62 327-332
• 38 Yeh J K, Aloia J F, Chen M, Ling N, Koo H C, Millard W J. Effect of growth hormone administration and treadmill exercise on serum and skeletal IGF-I in rats.  Am J Physiol. 1994;  266 129-135
• 39 Zanconato S, Moromisato D Y, Moromisato M Y, Woods J, Brasel J A, Leroith D, Roberts Jr C T, Cooper D M. Effect of training and growth hormone suppression on insulin-like growth factor I mRNA in young rats.  J Appl Physiol. 1994;  76 2204-2209