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European Journal of Applied Physiology

Erschienen in:

01.04.2014 | Original Article

Androgenic and estrogenic regulation of Atrogin-1, MuRF1 and myostatin expression in different muscle types of male mice

verfasst von: H. De Naeyer, S. Lamon, A. P. Russell, I. Everaert, A. De Spaey, B. Vanheel, Y. Taes, W. Derave

Erschienen in: European Journal of Applied Physiology | Ausgabe 4/2014

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Abstract

Purpose

The molecular factors targeted by androgens and estrogens on muscle mass are not fully understood. The current study aimed to explore gene and protein expression of Atrogin-1, MuRF1, and myostatin in an androgen deprivation-induced muscle atrophy model.

Methods

We examined the effects of Orx either with or without testosterone (T) or estradiol (E₂) administration on Atrogin-1 gene expression, and MuRF1 and myostatin gene and protein expression. Measurements were made in soleus (SOL), extensor digitorum longus (EDL) and levator ani/bulbocavernosus (LA/BC) of male C57BL/6 mice.

Results

Thirty days of Orx resulted in a reduction in weight gain and muscle mass. These effects were prevented by T. In LA/BC, Atrogin-1 and MuRF1 mRNA was increased throughout 30 days of Orx, which was fully reversed by T and partially by E₂ administration. In EDL and SOL, a less pronounced upregulation of both genes was only detectable at the early stages of Orx. Myostatin mRNA levels were downregulated in LA/BC and upregulated in EDL following Orx. T, but not E₂, reversed these effects. No changes in protein levels of MuRF1 and myostatin were found in EDL at any time point following Orx.

Conclusions

The atrophy in SOL and EDL in response to androgen deprivation, and its restoration by T, is accompanied by only minimal changes in atrogenes and myostatin gene expression. The marked differences in muscle atrophy and atrogene and myostatin mRNA between LA/BC and the locomotor muscles suggest that the murine LA/BC is not an optimal model to study Orx-induced muscle atrophy.

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Ahtiainen M, Pollanen E, Ronkainen PH, Alen M, Puolakka J, Kaprio J, Sipila S, Kovanen V (2012) Age and estrogen-based hormone therapy affect systemic and local IL-6 and IGF-1 pathways in women. Age 34:1249–1260PubMedCentralPubMedCrossRef

Allan CA, Strauss BJ, Burger HG, Forbes EA, McLachlan RI (2008) Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. J Clin Endocrinol Metab 93:139–146PubMedCrossRef

Auyeung TW, Lee JS, Kwok T, Leung J, Ohlsson C, Vandenput L, Leung PC, Woo J (2011) Testosterone but not estradiol level is positively related to muscle strength and physical performance independent of muscle mass: a cross-sectional study in 1489 older men. Eur J Endocrinol 164:811–817PubMedCrossRef

Axell AM, MacLean HE, Plant DR, Harcourt LJ, Davis JA, Jimenez M, Handelsman DJ, Lynch GS, Zajac JD (2006) Continuous testosterone administration prevents skeletal muscle atrophy and enhances resistance to fatigue in orchidectomized male mice. Am J Physiol Endocrinol Metab 291:E506–E516PubMedCrossRef

Bhasin S, Storer TW, Berman N, Yarasheski KE, Clevenger B, Phillips J, Lee WP, Bunnell TJ, Casaburi R (1997) Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. J Clin Endocrinol Metab 82:407–413PubMed

Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K et al (2001) Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294:1704–1708PubMedCrossRef

Centner T, Yano J, Kimura E, McElhinny AS, Pelin K, Witt CC, Bang M-L, Trombitas K, Granzier H, Gregorio CC, Sorimachi H, Labeit S (2001) Identification of muscle specific ring finger proteins as potential regulators of the titin kinase domain. J Mol Biol 306:717–726PubMedCrossRef

Cohen S, Brault JJ, Gygi SP, Glass DJ, Valenzuela DM, Gartner C, Latres E, Goldberg AL (2009) During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation. J Cell Biol 185:1083–1095PubMedCentralPubMedCrossRef

Couse JF, Lindzey J, Grandien K, Gustafsson JA, Korach KS (1997) Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) messenger ribonucleic acid in the wild-type and ERalpha-knockout mouse. Endocrinology 138:4613–4621PubMed

Derave W, Eijnde BO, Ramaekers M, Hespel P (2005) Soleus muscles of SAMP8 mice provide an accelerated model of skeletal muscle senescence. Exp Gerontol 40:562–572PubMedCrossRef

Derveaux S, Vandesompele J, Hellemans J (2010) How to do successful gene expression analysis using real-time PCR. Methods 50:227–230PubMedCrossRef

Drummond MJ, Glynn EL, Lujan HL, Dicarlo SE, Rasmussen BB (2008) Gene and protein expression associated with protein synthesis and breakdown in paraplegic skeletal muscle. Muscle Nerve 37:505–513PubMedCentralPubMedCrossRef

Fielitz J, Kim MS, Shelton JM, Latif S, Spencer JA, Glass DJ, Richardson JA, Bassel-Duby R, Olson EN (2007) Myosin accumulation and striated muscle myopathy result from the loss of muscle RING finger 1 and 3. J Clin Invest 117:2486–2495PubMedCentralPubMedCrossRef

Foletta VC, White LJ, Larsen AE, Leger B, Russell AP (2011) The role and regulation of MAFbx/atrogin-1 and MuRF1 in skeletal muscle atrophy. Pflugers Arch 461:325–335PubMedCrossRef

Glass D, Roubenoff R (2010) Recent advances in the biology and therapy of muscle wasting. Ann NY Acad of Sci 1211:25–36CrossRef

Gold J, Batterham MJ, Rekers H, Harms MK, Geurts TB, Helmyr PM, Silva de Mendonca J, Falleiros Carvalho LH, Panos G, Pinchera A et al (2006) Effects of nandrolone decanoate compared with placebo or testosterone on HIV-associated wasting. HIV Med 7:146–155PubMedCrossRef

Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL (2001) Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci USA 98:14440–14445PubMedCentralPubMedCrossRef

Haren MT, Siddiqui AM, Armbrecht HJ, Kevorkian RT, Kim MJ, Haas MJ, Mazza A, Kumar VB, Green M, Banks WA et al (2011) Testosterone modulates gene expression pathways regulating nutrient accumulation, glucose metabolism and protein turnover in mouse skeletal muscle. Int J Androl 34:55–68PubMedCrossRef

Hart DW, Wolf SE, Ramzy PI, Chinkes DL, Beauford RB, Ferrando AA, Wolfe RR, Herndon DN (2001) Anabolic effects of oxandrolone after severe burn. Ann Surg 233:556–564PubMedCentralPubMedCrossRef

Hellemans J, Mortier G, De Paepe A, Speleman F, Vandesompele J (2007) qBase relative quantification framework and software for management and automated analysis of real-time quantitative PCR data. Genome Biol 8:R19PubMedCentralPubMedCrossRef

Hulmi JJ, Ahtiainen JP, Selanne H, Volek JS, Hakkinen K, Kovanen V, Mero AA (2008) Androgen receptors and testosterone in men—effects of protein ingestion, resistance exercise and fiber type. J Steroid Biochem and Mol Biol 110:130–137CrossRef

Ibebunjo C, Eash JK, Li C, Ma Q, Glass DJ (2011) Voluntary running, skeletal muscle gene expression, and signaling inversely regulated by Orx and testosterone replacement. Am J Physiol Endocrinol Metab 300:E327–E340PubMedCrossRef

Lagirand-Cantaloube J, Offner N, Csibi A, Leibovitch MP, Batonnet-Pichon S, Tintignac LA, Segura CT, Leibovitch SA (2008) The initiation factor eIF3-f is a major target for atrogin1/MAFbx function in skeletal muscle atrophy. EMBO J 27:1266–1276PubMedCentralPubMedCrossRef

Lee HJ, Chang C (2003) Recent advances in androgen receptor action. Cell Mol Life Sci 60:1613–1622PubMedCrossRef

Li HH, Kedar V, Zhang C, McDonough H, Arya R, Wang DZ, Patterson C (2004) Atrogin-1/muscle atrophy F-box inhibits calcineurin-dependent cardiac hypertrophy by participating in an SCF ubiquitin ligase complex. J Clin Invest 114:1058–1071PubMedCentralPubMedCrossRef

Lokireddy S, Mouly V, Butler-Browne G, Gluckman PD, Sharma M, Kambadur R, McFarlane C (2011) Myostatin promotes the wasting of human myoblast cultures through promoting ubiquitin-proteasome pathway-mediated loss of sarcomeric proteins. Am J Physiol Cell Physiol 301:C1316–C1324PubMedCrossRef

MacLean HE, Chiu WS, Notini AJ, Axell AM, Davey RA, McManus JF, Ma C, Plant DR, Lynch GS, Zajac JD (2008) Impaired skeletal muscle development and function in male, but not female, genomic androgen receptor knockout mice. FASEB J 22:2676–2689PubMedCrossRef

Mauras N, Hayes V, Welch S, Rini A, Helgeson K, Dokler M, Veldhuis JD, Urban RJ (1998) Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength, and adiposity. J Clin Endocrinol 83:1886–1892

McPherron AC, Lawler AM, Lee SJ (1997) Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 387:83–90PubMedCrossRef

Mendler L, Baka Z, Kovacs-Simon A, Dux L (2007) Androgens negatively regulate myostatin expression in an androgen-dependent skeletal muscle. Biochem Biophys Res Comm 361:237–242PubMedCrossRef

Messier V, Rabasa-Lhoret R, Barbat-Artigas S, Elisha B, Karelis AD, ubertin-Leheudre M (2011) Menopause and sarcopenia: a potential role for sex hormones. Maturitas 68:331–336PubMedCrossRef

Ophoff J, Van Proeyen K, Callewaert F, De Gendt K, De Bock K, Vanden Bosch A, Verhoeven G, Hespel P, Vanderschueren D (2009) Androgen signaling in myocytes contributes to the maintenance of muscle mass and fiber type regulation but not to muscle strength or fatigue. Endocrinology 150:3558–3566PubMedCrossRef

Pires-Oliveira M, Maragno AL, Parreiras-E-Silva LT, Chiavegatti T, Gomes MD, Godinho RO (2010) Testosterone represses ubiquitin ligases atrogin-1 and Murf-1 expression in an androgen-sensitive rat skeletal muscle in vivo. J Appl Physiol 108:266–273PubMedCrossRef

Rhoden EL, Morgentaler A (2004) Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med 350:482–492PubMedCrossRef

Sakuma K, Yamaguchi A (2010) Molecular mechanisms in aging and current strategies to counteract sarcopenia. Curr Aging Sci 3:90–101PubMedCrossRef

Serra C, Bhasin S, Tangherlini F, Barton ER, Ganno M, Zhang A, Shansky J, Vandenburgh HH, Travison TG, Jasuja R et al (2011) The role of GH and IGF-I in mediating anabolic effects of testosterone on androgen-responsive muscle. Endocrinology 152:193–206PubMedCentralPubMedCrossRef

Sipilä S, Narici M, Kjaer M, Pöllänen E, Atkinson RA, Hansen M, Kovanen V (2013) Sex hormones and skeletal muscle weakness. Biogerontology 14:231–245PubMedCrossRef

Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Lenrow DA, Holmes JH, Dlewati A, Santanna J, Rosen CJ et al (1999) Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 84:2647–2653PubMed

Svensson J, Moverare-Skrtic S, Windahl S, Swanson C, Sjogren K (2010) Stimulation of both estrogen and androgen receptors maintains skeletal muscle mass in gonadectomized male mice but mainly via different pathways. J Mol Endocrinol 45:45–57PubMedCrossRef

Tang K, Wagner PD, Breen EC (2010) TNF-alpha-mediated reduction in PGC-1alpha may impair skeletal muscle function after cigarette smoke exposure. J Cell Physiol 222:320–327PubMedCrossRef

Tintignac LA, Lagirand J, Batonnet S, Sirri V, Leibovitch MP, Leibovitch SA (2005) Degradation of MyoD mediated by the SCF (MAFbx) ubiquitin ligase. J Biol Chem 280:2847–2856PubMedCrossRef

Trendelenburg AU, Meyer A, Rohner D, Boyle J, Hatakeyama S, Glass DJ (2009) Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size. Am J Physiol Cell Physiol 296:C1258–C1270PubMedCrossRef

Ustunel I, Akkoyunlu G, Demir R (2003) 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 32:70–79PubMedCrossRef

Vandenput L, Mellstrom D, Karlsson MK, Orwoll E, Labrie F, Ljunggren O, Ohlsson C (2010) Serum estradiol is associated with lean mass in elderly Swedish men. Eur J Endocrinol 162:737–745PubMedCrossRef

Vanderschueren D, Vandenput L, Boonen S, Van HE, Swinnen JV, Bouillon R (2000) An aged rat model of partial androgen deficiency: prevention of both loss of bone and lean body mass by low-dose androgen replacement. Endocrinology 141:1642–1647PubMed

Vandesompele J, de Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3:RESEARCH0034

Wallace MA, Hock MB, Hazen BC, Kralli A, Snow RJ, Russell AP (2011) Striated muscle activator of Rho signalling (STARS) is a PGC-1alpha/oestrogen-related receptor-alpha target gene and is upregulated in human skeletal muscle after endurance exercise. J Physiol 589:2027–2039PubMedCentralPubMedCrossRef

White JP, Gao S, Puppa MJ, Sato S, Welle SL, Carson JA (2013) Testosterone regulation of Akt/mTORC1/FoxO3a signalling in skeletal muscle. Mol Cell Endocrinol 365:174–186PubMedCentralPubMedCrossRef

Wiik A, Ekman M, Johansson O, Jansson E, Esbjörnsson M (2009) Expression of both oestrogen receptor alpha and beta in human skeletal muscle tissue. Histochem Cell Biol 131:181–189PubMedCrossRef

Xu T, Shen Y, Pink H, Triantafillou J, Stimpson SA, Turnbull P, Han B (2004) Phosphorylation of p70s6 kinase is implicated in androgen-induced levator ani muscle anabolism in castrated rats. J Steroid Biochem Mol Biol 92:447–454PubMedCrossRef

Titel: Androgenic and estrogenic regulation of Atrogin-1, MuRF1 and myostatin expression in different muscle types of male mice
verfasst von: H. De Naeyer
S. Lamon
A. P. Russell
I. Everaert
A. De Spaey
B. Vanheel
Y. Taes
W. Derave
Publikationsdatum: 01.04.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Applied Physiology / Ausgabe 4/2014
Print ISSN: 1439-6319
Elektronische ISSN: 1439-6327
DOI: https://doi.org/10.1007/s00421-013-2800-y

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Abstract

Purpose

Methods

Results

Conclusions

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