Download PDF
Int J Sports Med 2008; 29(10): 795-802
DOI: 10.1055/s-2008-1038433
Physiology & Biochemistry

© Georg Thieme Verlag KG Stuttgart · New York

Testosterone and Ca2+ Regulation in Skeletal Muscle

K. Anttila1 , S. Mänttäri1 , 2 , M. Järvilehto1
  • 1Department of Biology, University of Oulu, Oulu, Finland
  • 2Institute of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
Further Information

Publication History

accepted after revision February 11, 2008

Publication Date:
09 April 2008 (online)

Also available at
    Permissions and Reprints

Abstract

The aim of this study was to examine the effect of testosterone treatment on the expression of dihydropyridine and ryanodine receptors in skeletal muscle of mouse. Furthermore, the effects of training, a method also known to elevate the plasma testosterone level, were studied and compared to the effects of pure testosterone administration. Male mice were either administered with testosterone or trained with treadmill. After 6 weeks, hindlimb muscles were excised and the expression of receptors was measured by Western blotting. Furthermore, the alterations in myosin heavy chain phenotypes were studied. In general, both training and testosterone administration induced changes in the expression of both receptors and in myosin heavy chain composition. In testosterone treated mice the expression of dihydropyridine receptor in extensor digitorum longus was higher compared to the control ones (38.9 %, p = 0.026). In soleus the expression was quite the contrary (− 27.3 %, p = 0.044), as was the case with ryanodine receptor (− 51.4 %, p = 0.012). The amount of ryanodine receptors was higher in rectus femoris (144.0 %, p = 0.044) and plantaris (48.1 %, p = 0.037) in testosterone treated mice. In trained mice, the expression of ryanodine receptor was significantly higher in gastrocnemius (27.6 %, p = 0.018), soleus (57.2 %, p = 0.025), plantaris (28.5 %, p = 0.009) and extensor digitorum longus (94.8 %, p = 0.009) than in the control ones. No differences were observed in the dihydropyridine receptor level. To conclude, training has a more important role in skeletal muscle adaptation compared to increased plasma testosterone level. However, in postural muscles both treatments have comparable effects.

Key words

Ca2+ handling capacity - myosin heavy chain - exercise - dihydropyridine receptor - ryanodine receptor

References

  • 1 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
    CrossrefPubMedGoogle Scholar
  • 2 Anttila K, Mänttäri S, Järvilehto M. Expression of dihydropyride and ryanodine receptors in type IIA fibres of rat skeletal muscle.  Acta Histochem Cytochem. 2007;  40 35-41
    CrossrefPubMedGoogle Scholar
  • 3 Ariano M A, Armstrong R B, Edgerton V R. Hindlimb muscles fiber populations of five mammals.  J Histochem Cytochem. 1973;  21 51-55
    CrossrefPubMedGoogle Scholar
  • 4 Bamman M M, Shipp J R, Jiang J, Gower B A, Hunter G R, Goodman A, McLafferty Jr C L, Urban R J. Mechanical load increases muscle IGF‐I and androgen receptor mRNA concentrations in humans.  Am J Physiol. 2001;  280 E383-E390
    PubMedGoogle Scholar
  • 5 Bell G J, Syrotuik D, Martin T P, Burnham R, Quinney H A. Effect of concurrent strength and endurance training on skeletal muscle properties and hormone concentrations in humans.  Eur J Appl Physiol. 2000;  81 418-427
    CrossrefPubMedGoogle Scholar
  • 6 Bhasin S, Woodhouse L, Storer T W. Proof of the effect of testosterone on skeletal muscle.  J Endocrinol. 2001;  170 27-38
    CrossrefPubMedGoogle Scholar
  • 7 Bradford M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.  Anal Biochem. 1976;  72 248-254
    CrossrefPubMedGoogle Scholar
  • 8 Bricout V-A, Serrurier B D, Bigard A X, Guzennec C Y. Effects of hindlimb suspension and androgen treatment on testosterone receptors in rat skeletal muscles.  Eur J Appl Physiol. 1999;  79 443-448
    CrossrefPubMedGoogle Scholar
  • 9 Briggs F N, Lee K F, Feher J J, Wechsler A S, Ohlendieck K, Campbell K. Ca-ATPase isozymes expression in sarcoplasmic reticulum is altered by chronic stimulation of skeletal muscle.  FEBS Lett. 1990;  259 269-272
    CrossrefPubMedGoogle Scholar
  • 10 Close R I. Dynamic properties of mammalian skeletal muscles.  Physiol Rev. 1972;  52 129-197
    CrossrefPubMedGoogle Scholar
  • 11 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;  654 241-250
    CrossrefPubMedGoogle Scholar
  • 12 Díaz-Herrera P, García-Castellano J M, Torres A, Morcuende J A, Calbet J AL, Sarrat R. Effect of high-intensity running in rectus femoris muscle fiber in rats.  J Orthop Res. 2001;  19 229-232
    CrossrefPubMedGoogle Scholar
  • 13 Dudley G A, Abraham W M, Terjung R L. Influence of exercise intensity and duration on biochemical adaptations in skeletal muscle.  J Appl Physiol. 1982;  53 844-850
    CrossrefPubMedGoogle Scholar
  • 14 Exner G U, Staudte H W, Pette D. Isometric training of rats – effects upon fast and slow muscle and modification by an anabolic hormone (nandrolone decanoate).  Pflügers Arch. 1973;  345 1-14
    CrossrefPubMedGoogle Scholar
  • 15 Froemming G R, Murray B E, Harmon S, Pette D, Ohlendieck K. Comparative analysis of the isoform expression pattern of Ca2+‐regulatory membrane proteins in fast-twitch, slow-twitch, cardiac, neonatal and chronic low-frequency stimulated muscle fibers.  Biochim Biophys Acta. 2000;  1466 151-168
    CrossrefPubMedGoogle Scholar
  • 16 Golden K L, Marsh J D, Jiang Y, Brown T, Moulden J. Gonadectomy of adult male rats reduces contractility of isolated cardiac myocytes.  Am J Physiol. 2003;  285 E449-E453
    PubMedGoogle Scholar
  • 17 Goodman C, Patterson M, Stephenson G. MHC-based fiber type and EC-coupling characteristics in mechanically skinned muscle fibers of the rat.  Am J Physiol. 2003;  284 C1448-C1459
    CrossrefPubMedGoogle Scholar
  • 18 Hackney A C. Endurance training and testosterone levels.  Sports Med. 1989;  8 117-127
    CrossrefPubMedGoogle Scholar
  • 19 Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes.  Sports Med. 2004;  34 513-554
    CrossrefPubMedGoogle Scholar
  • 20 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Hyyppä S, Karvonen U, Räsänen L A, Persson S G, Pösö A R. Androgen receptors and skeletal muscle composition in trotters treated with nandrolene laureate.  Zentralbl Veterinarmed A. 1997;  44 481-491
    CrossrefPubMedGoogle Scholar
  • 22 Härkönen M, Näveri H, Kuoppasalmi K, Huhtaniemi I. Pituitary and gonadal function during physical exercise in the male rat.  J Steroid Biochem. 1990;  35 127-132
    CrossrefPubMedGoogle Scholar
  • 23 Inoue K, Yamasaki S, Fushuki T, Kano T, Moritani T, Itoh K, Sugimoto E. Rapid increase in the number of androgen receptors following electrical stimulation of the rat muscle.  Eur Appl Physiol. 1993;  66 134-140
    CrossrefPubMedGoogle Scholar
  • 24 Jorgensen A O, Shen A C, Arnold W, Leung A T, Campbell K P. Subcellular distribution of the 1,4-dihydropyridine receptor in rabbit skeletal muscle in situ: an immunofluorescence and immunocolloidal gold-labelling study.  J Cell Biol. 1989;  109 135-147
    CrossrefPubMedGoogle Scholar
  • 25 Kandarian S, O'Brien S, Thomas K, Schulte L, Navarro J. Regulation of skeletal muscle dihydropyridine receptor gene expression by biomechanical unloading.  J Appl Physiol. 1992;  72 2510-2514
    CrossrefPubMedGoogle Scholar
  • 26 Klueber K M, Feczko J D, Schmidt G, Watkins 3rd J B. Skeletal muscle in the diabetic mouse: histochemical and morphometric analysis.  Anat Rec. 1989;  225 41-45
    CrossrefPubMedGoogle Scholar
  • 27 Kraemer W J, Patton J F, Gordon S E, Harman E A, Deschenes M R, Reynolds K, Newton R U, Triplett N T, Dziados J E. Compatibility of high-intensity strength and endurance training on hormonal and skeletal muscle adaptations.  J Appl Physiol. 1995;  78 976-989
    CrossrefPubMedGoogle Scholar
  • 28 Laemmli U K. Cleavage of structural proteins during assembly of head of bacteriophage T4.  Nature. 1970;  227 680-685
    PubMedGoogle Scholar
  • 29 Lamb G D. Excitation-contraction coupling in skeletal muscle: comparison with cardiac muscle.  Clin Exp Pharmacol Physiol. 2000;  27 216-224
    CrossrefPubMedGoogle Scholar
  • 30 Lubek B M. Contractile responses of rat lateral gastrocnemius and soleus to dianabol (17β-hydroxy-17-methyl-1, 4-androstadien-3-one) and exercise.  Steroids. 1984;  44 485-495
    CrossrefPubMedGoogle Scholar
  • 31 Mänttäri S, Pyörnilä A, Harjula R, Järvilehto M. Expression of L-type calcium channels associated with postnatal development of skeletal muscle function in mouse.  J Muscle Res Cell Mot. 2001;  22 61-67
    CrossrefPubMedGoogle Scholar
  • 32 Mänttäri S, Järvilehto M. Comparative analysis of mouse skeletal muscle fibre type composition and contractile responses to calcium channel blocker.  BMC Physiol. 2005;  5 4
    CrossrefPubMedGoogle Scholar
  • 33 Nicolopoulos-Stournaras S, Iles J F. Hindlimb muscle activity during locomotion in the rat (Rattus norvegicus) (Rodentia: Muridae).  J Zool Lond. 1984;  203 427-440
    PubMedGoogle Scholar
  • 34 Ørtenblad N, Lunde P K, Levin K, Andersen J L, Pedersen P K. Enhanced sarcoplasmic reticulum Ca2+ release following intermittent sprint training.  Am J Physiol. 2000;  279 R152-R160
    PubMedGoogle Scholar
  • 35 Pansarasa O, D'Antona G, Gualea M R, Marzani B, Pellegrino M A, Marzatico F. “Oxidative stress”: effects of mild endurance training and testosterone treatment on rat gastrocnemius muscle.  Eur J Appl Physiol. 2002;  87 550-555
    CrossrefPubMedGoogle Scholar
  • 36 Péréon Y, Navarro J, Hamilton M, Booth F W, Palade P. Chronic stimulation differentially modulates expression of mRNA for dihydropyridine receptor isoforms in rat fast twitch skeletal muscle.  Biochem Biophys Res Commun. 1997;  235 217-222
    CrossrefPubMedGoogle Scholar
  • 37 Pette D, Staron R S. Transition of muscle fiber phenotypic profiles.  Histochem Cell Biol. 2001;  115 359-372
    CrossrefPubMedGoogle Scholar
  • 38 Prezant D J, Karwa M J, Kim H H, Maggiore D, Chung V, Valentine D E. Short- and long-term effects of testosterone on diaphragm in castrated and normal male rats.  J Appl Physiol. 1997;  82 134-143
    CrossrefPubMedGoogle Scholar
  • 39 Prilutsky B I, Herzog W, Allinger T L. Mechanical power and work of cat soleus, gastrocnemius and plantaris muscles during locomotion: possible functional significance of muscle design and force patterns.  J Exp Biol. 1996;  199 801-814
    PubMedGoogle Scholar
  • 40 Saborido A, Molano F, Moro G, Megías M. Regulation of dihydropyridine receptor levels in skeletal and cardiac muscle by exercise training.  Pflügers Arch. 1995;  429 364-369
    CrossrefPubMedGoogle Scholar
  • 41 Sinha-Hikim I, Artaza J, Woodhouse L, Gonzalez-Cadavid N, Singh A B, Lee M I, Storer T W, Casaburi R, Shen R, Bhasin S. Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy.  Am J Physiol. 2002;  283 E154-E164
    PubMedGoogle Scholar
  • 42 Staron R S, Karapondo D L, Kraemer W J, Fry A C, Gordon S E, Falkel J E, Hagerman F C, Hikida R S. Skeletal muscle adaptations during early phase of heavy-resistance training in men and woman.  J Appl Physiol. 1994;  76 1247-1255
    CrossrefPubMedGoogle Scholar
  • 43 Sullivan T E, Armstrong R B. Rat locomotory muscle fiber activity during trotting and galloping.  J Appl Physiol. 1978;  44 358-363
    PubMedGoogle Scholar
  • 44 Tagarakis C VM, Bloch W, Hartmann G, Hollmann W, Addicks K. Testosterone-propionate impairs the response of the cardiac capillary bed to exercise.  Med Sci Sports Exerc. 2000;  32 946-953
    PubMedGoogle Scholar
  • 45 Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.  Proc Natl Acad Sci USA. 1979;  76 4350-4354
    CrossrefPubMedGoogle Scholar
  • 46 Tsika R W, Herrick R E, Baldwin K M. Effect of anabolic steroids in skeletal muscle mass during hindlimb suspension.  J Appl Physiol. 1987;  63 2122-2127
    CrossrefPubMedGoogle Scholar
  • 47 Üstunel I, Akkoyunlu G, Demir R. The effect of testosterone on gastrocnemius muscle fibres in growing and adult male and female rats: a histochemical, morphometric and ultrastructural study.  Anat Histol Embryol. 2003;  32 70-79
    CrossrefPubMedGoogle Scholar
  • 48 Willoughby D S, Taylor L. Effects of sequential bouts of resistance exercise on androgen receptor expression.  Med Sci Sports Exerc. 2004;  36 1499-1506
    CrossrefPubMedGoogle Scholar
  • 49 Yarasheski K E, Lemon P WR, Gilloteaux J. Effect of heavy-resistance exercise training on muscle fiber composition in young rats.  J Appl Physiol. 1990;  69 434-437
    CrossrefPubMedGoogle Scholar

Dr. Satu Mänttäri

Department of Biology
University of Oulu

P. O. Box 3000

90014 Oulu

Finland

Phone: + 35 85 04 38 51 52

Fax: + 35 8 85 53 12 42

Email: satu.manttari@oulu.fi

      >