Androgens and skeletal muscle: cellular and molecular action mechanisms underlying the anabolic actions (original) (raw)
Yin D, Gao W, Kearbey JD, Xu H, Chung K, He Y, Marhefka CA, Veverka KA, Miller DD, Dalton JT (2003) Pharmacodynamics of selective androgen receptor modulators. J Pharmacol Exp Ther 304:1334–1340 ArticlePubMedCAS Google Scholar
Bhasin S, Woodhouse L, Storer TW (2003) Androgen effects on body composition. Growth Horm IGF Res 13 (Suppl A):S63–S71 ArticlePubMedCAS Google Scholar
Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, Bunnell TJ, Tricker R, Shirazi A, Casaburi R (1996) The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med 335:1–7 ArticlePubMedCAS Google Scholar
Bhasin S, Woodhouse L, Casaburi R, Singh AB, Mac RP, Lee M, Yarasheski KE, Sinha-Hikim I, Dzekov C, Dzekov J, Magliano L, Storer TW (2005) Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab 90:678–688 ArticlePubMedCAS Google Scholar
Sinha-Hikim I, Artaza J, Woodhouse L, Gonzalez-Cadavid N, Singh AB, Lee MI, Storer TW, Casaburi R, Shen R, Bhasin S (2002) Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy. Am J Physiol Endocrinol Metab 283:E154–E164 PubMedCAS Google Scholar
MacLean HE, Handelsman DJ (2009) Unraveling androgen action in muscle: genetic tools probing cellular mechanisms. Endocrinology 150:3437–3439 ArticlePubMedCAS Google Scholar
Cawthon PM, Ensrud KE, Laughlin GA, Cauley JA, Dam TT, Barrett-Connor E, Fink HA, Hoffman AR, Lau E, Lane NE, Stefanick ML, Cummings SR, Orwoll ES (2009) Sex hormones and frailty in older men: the osteoporotic fractures in men (MrOS) study. J Clin Endocrinol Metab 94:3806–3815 ArticlePubMedCAS Google Scholar
Srinivas-Shankar U, Roberts SA, Connolly MJ, O’Connell MD, Adams JE, Oldham JA, Wu FC (2010) Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 95:639–650 ArticlePubMedCAS Google Scholar
Bhasin S, Calof OM, Storer TW, Lee ML, Mazer NA, Jasuja R, Montori VM, Gao W, Dalton JT (2006) Drug insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging. Nat Clin Pract Endocrinol Metab 2:146–159 ArticlePubMedCAS Google Scholar
Ferrando AA, Sheffield-Moore M, Yeckel CW, Gilkison C, Jiang J, Achacosa A, Lieberman SA, Tipton K, Wolfe RR, Urban RJ (2002) Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am J Physiol Endocrinol Metab 282:E601–E607 PubMedCAS Google Scholar
Bhasin S, Storer TW, Javanbakht M, Berman N, Yarasheski KE, Phillips J, Dike M, Sinha-Hikim I, Shen R, Hays RD, Beall G (2000) Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels. JAMA 283:763–770 ArticlePubMedCAS Google Scholar
Storer TW, Woodhouse L, Magliano L, Singh AB, Dzekov C, Dzekov J, Bhasin S (2008) Changes in muscle mass, muscle strength, and power but not physical function are related to testosterone dose in healthy older men. J Am Geriatr Soc 56:1991–1999 ArticlePubMed Google Scholar
Urban RJ, Bodenburg YH, Gilkison C, Foxworth J, Coggan AR, Wolfe RR, Ferrando A (1995) Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol 269:E820–E826 PubMedCAS Google Scholar
Ferrando AA, Tipton KD, Doyle D, Phillips SM, Cortiella J, Wolfe RR (1998) Testosterone injection stimulates net protein synthesis but not tissue amino acid transport. Am J Physiol 275:E864–E871 PubMedCAS Google Scholar
Sheffield-Moore M, Urban RJ, Wolf SE, Jiang J, Catlin DH, Herndon DN, Wolfe RR, Ferrando AA (1999) Short-term oxandrolone administration stimulates net muscle protein synthesis in young men. J Clin Endocrinol Metab 84:2705–2711 ArticlePubMedCAS Google Scholar
Ferrando AA, Sheffield-Moore M, Paddon-Jones D, Wolfe RR, Urban RJ (2003) Differential anabolic effects of testosterone and amino acid feeding in older men. J Clin Endocrinol Metab 88:358–362 ArticlePubMedCAS Google Scholar
Wittert GA, Chapman IM, Haren MT, Mackintosh S, Coates P, Morley JE (2003) Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. J Gerontol A Biol Sci Med Sci 58:618–625 ArticlePubMed Google Scholar
Claessens F, Denayer S, Van Tilborgh N, Kerkhofs S, Helsen C, Haelens A (2008) Diverse roles of androgen receptor (AR) domains in AR-mediated signaling. Nucl Recept Signal 6:e008 PubMed Google Scholar
Lewis MI, Horvitz GD, Clemmons DR, Fournier M (2002) Role of IGF-I and IGF-binding proteins within diaphragm muscle in modulating the effects of nandrolone. Am J Physiol Endocrinol Metab 282:E483–E490 PubMedCAS Google Scholar
Estrada M, Liberona JL, Miranda M, Jaimovich E (2000) Aldosterone- and testosterone-mediated intracellular calcium response in skeletal muscle cell cultures. Am J Physiol Endocrinol Metab 279:E132–E139 PubMedCAS Google Scholar
Callewaert F, Sinnesael M, Gielen E, Boonen S, Vanderschueren D (2010) Skeletal sexual dimorphism: relative contribution of sex steroids, GH-IGF1, and mechanical loading. J Endocrinol 207:127–134 ArticlePubMedCAS Google Scholar
Lubischer JL, Bebinger DM (1999) Regulation of terminal Schwann cell number at the adult neuromuscular junction. J Neurosci 19: RC46
Monks DA, O’Bryant EL, Jordan CL (2004) Androgen receptor immunoreactivity in skeletal muscle: enrichment at the neuromuscular junction. J Comp Neurol 473:59–72 ArticlePubMedCAS Google Scholar
Johansen JA, Breedlove SM, Jordan CL (2007) Androgen receptor expression in the levator ani muscle of male mice. J Neuroendocrinol 19:823–826 ArticlePubMedCAS Google Scholar
Charge SB, Rudnicki MA (2004) Cellular and molecular regulation of muscle regeneration. Physiol Rev 84:209–238 ArticlePubMedCAS Google Scholar
Chen Y, Zajac JD, MacLean HE (2005) Androgen regulation of satellite cell function. J Endocrinol 186:21–31 ArticlePubMedCAS Google Scholar
Sinha-Hikim I, Taylor WE, Gonzalez-Cadavid NF, Zheng W, Bhasin S (2004) Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment. J Clin Endocrinol Metab 89:5245–5255 ArticlePubMedCAS Google Scholar
Niel L, Willemsen KR, Volante SN, Monks DA (2008) Sexual dimorphism and androgen regulation of satellite cell population in differentiating rat levator ani muscle. Dev Neurobiol 68:115–122 ArticlePubMed Google Scholar
Matsumoto A, Arai Y, Prins GS (1996) Androgenic regulation of androgen receptor immunoreactivity in motoneurons of the spinal nucleus of the bulbocavernosus of male rats. J Neuroendocrinol 8:553–559 ArticlePubMedCAS Google Scholar
Montarras D, Morgan J, Collins C, Relaix F, Zaffran S, Cumano A, Partridge T, Buckingham M (2005) Direct isolation of satellite cells for skeletal muscle regeneration. Science 309:2064–2067 ArticlePubMedCAS Google Scholar
Fukada S, Higuchi S, Segawa M, Koda K, Yamamoto Y, Tsujikawa K, Kohama Y, Uezumi A, Imamura M, Miyagoe-Suzuki Y, Takeda S, Yamamoto H (2004) Purification and cell-surface marker characterization of quiescent satellite cells from murine skeletal muscle by a novel monoclonal antibody. Exp Cell Res 296:245–255 ArticlePubMedCAS Google Scholar
Gnocchi VF, White RB, Ono Y, Ellis JA, Zammit PS (2009) Further characterisation of the molecular signature of quiescent and activated mouse muscle satellite cells. PLoS One 4:e5205 ArticlePubMedCAS Google Scholar
Hughes VA, Frontera WR, Roubenoff R, Evans WJ, Singh MA (2002) Longitudinal changes in body composition in older men and women: role of body weight change and physical activity. Am J Clin Nutr 76:473–481 PubMedCAS Google Scholar
Brooks NE, Schuenke MD, Hikida RS (2009) No change in skeletal muscle satellite cells in young and aging rat soleus muscle. J Physiol Sci 59:465–471 ArticlePubMedCAS Google Scholar
Day K, Shefer G, Shearer A, Yablonka-Reuveni Z (2010) The depletion of skeletal muscle satellite cells with age is concomitant with reduced capacity of single progenitors to produce reserve progeny. Dev Biol 340:330–343 ArticlePubMedCAS Google Scholar
Grounds MD (1998) Age-associated changes in the response of skeletal muscle cells to exercise and regeneration. Ann N Y Acad Sci 854:78–91 ArticlePubMedCAS Google Scholar
Welle S (2002) Cellular and molecular basis of age-related sarcopenia. Can J Appl Physiol 27:19–41 ArticlePubMedCAS Google Scholar
Conboy IM, Conboy MJ, Smythe GM, Rando TA (2003) Notch-mediated restoration of regenerative potential to aged muscle. Science 302:1575–1577 ArticlePubMedCAS Google Scholar
Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA (2005) Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433:760–764 ArticlePubMedCAS Google Scholar
Filippin LI, Moreira AJ, Marroni NP, Xavier RM (2009) Nitric oxide and repair of skeletal muscle injury. Nitric Oxide 21:157–163 ArticlePubMedCAS Google Scholar
Pedersen BK, Edward F (2009) Adolph distinguished lecture: muscle as an endocrine organ: IL-6 and other myokines. J Appl Physiol 107:1006–1014 ArticlePubMedCAS Google Scholar
Conboy IM, Rando TA (2002) The regulation of Notch signaling controls satellite cell activation and cell fate determination in postnatal myogenesis. Dev Cell 3:397–409 ArticlePubMedCAS Google Scholar
Buas MF, Kadesch T (2010) Regulation of skeletal myogenesis by Notch. Exp Cell Res 316:3028–3033 ArticlePubMedCAS Google Scholar
Tsivitse S (2010) Notch and Wnt signaling, physiological stimuli and postnatal myogenesis. Int J Biol Sci 6:268–281 ArticlePubMedCAS Google Scholar
Sinha-Hikim I, Roth SM, Lee MI, Bhasin S (2003) Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. Am J Physiol Endocrinol Metab 285:E197–E205 PubMedCAS Google Scholar
Sinha-Hikim I, Cornford M, Gaytan H, Lee ML, Bhasin S (2006) Effects of testosterone supplementation on skeletal muscle fiber hypertrophy and satellite cells in community-dwelling older men. J Clin Endocrinol Metab 91:3024–3033 ArticlePubMedCAS Google Scholar
Doumit ME, Cook DR, Merkel RA (1996) Testosterone up-regulates androgen receptors and decreases differentiation of porcine myogenic satellite cells in vitro. Endocrinology 137:1385–1394 ArticlePubMedCAS Google Scholar
Joubert Y, Tobin C (1989) Satellite cell proliferation and increase in the number of myonuclei induced by testosterone in the levator ani muscle of the adult female rat. Dev Biol 131:550–557 ArticlePubMedCAS Google Scholar
Joubert Y, Tobin C, Lebart MC (1994) Testosterone-induced masculinization of the rat levator ani muscle during puberty. Dev Biol 162:104–110 ArticlePubMedCAS Google Scholar
Mulvaney DR, Marple DN, Merkel RA (1988) Proliferation of skeletal muscle satellite cells after castration and administration of testosterone propionate. Proc Soc Exp Biol Med 188:40–45 PubMedCAS Google Scholar
Powers ML, Florini JR (1975) A direct effect of testosterone on muscle cells in tissue culture. Endocrinology 97:1043–1047 ArticlePubMedCAS Google Scholar
Diel P, Baadners D, Schlupmann K, Velders M, Schwarz JP (2008) C2C12 myoblastoma cell differentiation and proliferation is stimulated by androgens and associated with a modulation of myostatin and Pax7 expression. J Mol Endocrinol 40:231–241 ArticlePubMedCAS Google Scholar
Chen Y, Lee NK, Zajac JD, MacLean HE (2008) Generation and analysis of an androgen-responsive myoblast cell line indicates that androgens regulate myotube protein accretion. J Endocrinol Invest 31:910–918 PubMedCAS Google Scholar
Desler MM, Jones SJ, Smith CW, Woods TL (1996) Effects of dexamethasone and anabolic agents on proliferation and protein synthesis and degradation in C2C12 myogenic cells. J Anim Sci 74:1265–1273 PubMedCAS Google Scholar
Zhang P, Wong C, Liu D, Finegold M, Harper JW, Elledge SJ (1999) p21CIP1 and p57KIP2 control muscle differentiation at the myogenin step. Genes Dev 13:213–224 ArticlePubMedCAS Google Scholar
Schmid C, Steiner T, Froesch ER (1983) Preferential enhancement of myoblast differentiation by insulin-like growth factors (IGF I and IGF II) in primary cultures of chicken embryonic cells. FEBS Lett 161:117–121 ArticlePubMedCAS Google Scholar
Li J, Mayne R, Wu C (1999) A novel muscle-specific beta 1 integrin binding protein (MIBP) that modulates myogenic differentiation. J Cell Biol 147:1391–1398 ArticlePubMedCAS Google Scholar
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 22:2676–2689 ArticlePubMedCAS Google Scholar
Wannenes F, Caprio M, Gatta L, Fabbri A, Bonini S, Moretti C (2008) Androgen receptor expression during C2C12 skeletal muscle cell line differentiation. Mol Cell Endocrinol 292:11–19 ArticlePubMedCAS Google Scholar
Kamanga-Sollo E, White ME, Hathaway MR, Weber WJ, Dayton WR (2011) Effect of trenbolone acetate on protein synthesis and degradation rates in fused bovine satellite cell cultures. Domest Anim Endocrinol 40:60–66 ArticlePubMedCAS Google Scholar
Zammit PS, Partridge TA, Yablonka-Reuveni Z (2006) The skeletal muscle satellite cell: the stem cell that came in from the cold. J Histochem Cytochem 54:1177–1191 ArticlePubMedCAS Google Scholar
De Angelis L, Berghella L, Coletta M, Lattanzi L, Zanchi M, Cusella-De Angelis MG, Ponzetto C, Cossu G (1999) Skeletal myogenic progenitors originating from embryonic dorsal aorta coexpress endothelial and myogenic markers and contribute to postnatal muscle growth and regeneration. J Cell Biol 147:869–878 ArticlePubMed Google Scholar
LaBarge MA, Blau HM (2002) Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury. Cell 111:589–601 ArticlePubMedCAS Google Scholar
Asakura A, Seale P, Girgis-Gabardo A, Rudnicki MA (2002) Myogenic specification of side population cells in skeletal muscle. J Cell Biol 159:123–134 ArticlePubMedCAS Google Scholar
Tamaki T, Okada Y, Uchiyama Y, Tono K, Masuda M, Nitta M, Hoshi A, Akatsuka A (2008) Skeletal muscle-derived CD34 +/45- and CD34-/45- stem cells are situated hierarchically upstream of Pax7 + cells. Stem Cells Dev 17:653–667 ArticlePubMedCAS Google Scholar
Dellavalle A, Sampaolesi M, Tonlorenzi R, Tagliafico E, Sacchetti B, Perani L, Innocenzi A, Galvez BG, Messina G, Morosetti R, Li S, Belicchi M, Peretti G, Chamberlain JS, Wright WE, Torrente Y, Ferrari S, Bianco P, Cossu G (2007) Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nat Cell Biol 9:255–267 ArticlePubMedCAS Google Scholar
Mitchell KJ, Pannerec A, Cadot B, Parlakian A, Besson V, Gomes ER, Marazzi G, Sassoon DA (2010) Identification and characterization of a non-satellite cell muscle resident progenitor during postnatal development. Nat Cell Biol 12:257–266 PubMedCAS Google Scholar
Woodhouse LJ, Gupta N, Bhasin M, Singh AB, Ross R, Phillips J, Bhasin S (2004) Dose-dependent effects of testosterone on regional adipose tissue distribution in healthy young men. J Clin Endocrinol Metab 89:718–726 ArticlePubMedCAS Google Scholar
Dati E, Baroncelli GI, Mora S, Russo G, Baldinotti F, Parrini D, Erba P, Simi P, Bertelloni S (2009) Body composition and metabolic profile in women with complete androgen insensitivity syndrome. Sex Dev 3:188–193 ArticlePubMedCAS Google Scholar
Sato T, Matsumoto T, Yamada T, Watanabe T, Kawano H, Kato S (2003) Late onset of obesity in male androgen receptor-deficient (AR KO) mice. Biochem Biophys Res Commun 300:167–171 ArticlePubMedCAS Google Scholar
Lin HY, Xu Q, Yeh S, Wang RS, Sparks JD, Chang C (2005) Insulin and leptin resistance with hyperleptinemia in mice lacking androgen receptor. Diabetes 54:1717–1725 ArticlePubMedCAS Google Scholar
Callewaert F, Venken K, Ophoff J, De Gendt K, Torcasio A, van Lenthe GH, Van Oosterwyck H, Boonen S, Bouillon R, Verhoeven G, Vanderschueren D (2009) Differential regulation of bone and body composition in male mice with combined inactivation of androgen and estrogen receptor-alpha. FASEB J 23:232–240 ArticlePubMedCAS Google Scholar
Ophoff J, Callewaert F, Venken K, De Gendt K, Ohlsson C, Gayan-Ramirez G, Decramer M, Boonen S, Bouillon R, Verhoeven G, Vanderschueren D (2009) Physical activity in the androgen receptor knockout mouse: evidence for reversal of androgen deficiency on cancellous bone. Biochem Biophys Res Commun 378:139–144 ArticlePubMedCAS Google Scholar
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 150:3558–3566 ArticlePubMedCAS Google Scholar
Starkey JD, Yamamoto M, Yamamoto S, Goldhamer DJ (2011) Skeletal muscle satellite cells are committed to myogenesis and do not spontaneously adopt nonmyogenic fates. J Histochem Cytochem 59:33–46 ArticlePubMedCAS Google Scholar
Uezumi A, Fukada S, Yamamoto N, Takeda S, Tsuchida K (2010) Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle. Nat Cell Biol 12:143–152 ArticlePubMedCAS Google Scholar
Herbst KL, Bhasin S (2004) Testosterone action on skeletal muscle. Curr Opin Clin Nutr Metab Care 7:271–277 ArticlePubMedCAS Google Scholar
Grounds MD, White JD, Rosenthal N, Bogoyevitch MA (2002) The role of stem cells in skeletal and cardiac muscle repair. J Histochem Cytochem 50:589–610 ArticlePubMedCAS Google Scholar
Semirale AA, Zhang X, Wiren KM (2011) Body composition changes and inhibition of fat development in vivo implicates androgen in regulation of stem cell lineage allocation. J Cell Biochem 112:1773–1786 ArticlePubMedCAS Google Scholar
Fernando SM, Rao P, Niel L, Chatterjee D, Stagljar M, Monks DA (2010) Myocyte androgen receptors increase metabolic rate and improve body composition by reducing fat mass. Endocrinology 151:3125–3132 ArticlePubMedCAS Google Scholar
Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S (2003) Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology 144:5081–5088 ArticlePubMedCAS Google Scholar
Singh R, Bhasin S, Braga M, Artaza JN, Pervin S, Taylor WE, Krishnan V, Sinha SK, Rajavashisth TB, Jasuja R (2009) Regulation of myogenic differentiation by androgens: cross talk between androgen receptor/beta-catenin and follistatin/transforming growth factor-beta signaling pathways. Endocrinology 150:1259–1268 ArticlePubMedCAS Google Scholar
Narici MV, Maffulli N, Maganaris CN (2008) Ageing of human muscles and tendons. Disabil Rehabil 30:1548–1554 ArticlePubMed Google Scholar
Hadi Mansouri S, Siegford JM, Ulibarri C (2003) Early postnatal response of the spinal nucleus of the bulbocavernosus and target muscles to testosterone in male gerbils. Brain Res Dev Brain Res 142:129–139 ArticlePubMedCAS Google Scholar
Fraley GS, Ulibarri CM (2002) Long-term castration effects motoneuron size but not number in the spinal nucleus of the bulbocavernosus in the adult male Mongolian gerbil. Brain Res 953:265–271 ArticlePubMedCAS Google Scholar
Raskin K, de Gendt K, Duittoz A, Liere P, Verhoeven G, Tronche F, Mhaouty-Kodja S (2009) Conditional inactivation of androgen receptor gene in the nervous system: effects on male behavioral and neuroendocrine responses. J Neurosci 29:4461–4470 ArticlePubMedCAS Google Scholar
Fishman RB, Breedlove SM (1988) Neonatal androgen maintains sexually dimorphic muscles in the absence of innervation. Muscle Nerve 11:553–560 ArticlePubMedCAS Google Scholar
Rand MN, Breedlove SM (1992) Androgen locally regulates rat bulbocavernosus and levator ani size. J Neurobiol 23:17–30 ArticlePubMedCAS Google Scholar
Heemers HV, Tindall DJ (2007) Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex. Endocr Rev 28:778–808 ArticlePubMedCAS Google Scholar
Xu J, Qiu Y, DeMayo FJ, Tsai SY, Tsai MJ, O’Malley BW (1998) Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene. Science 279:1922–1925 ArticlePubMedCAS Google Scholar
Gehin M, Mark M, Dennefeld C, Dierich A, Gronemeyer H, Chambon P (2002) The function of TIF2/GRIP1 in mouse reproduction is distinct from those of SRC-1 and p/CIP. Mol Cell Biol 22:5923–5937 ArticlePubMedCAS Google Scholar
Ting HJ, Chang C (2008) Actin associated proteins function as androgen receptor coregulators: an implication of androgen receptor’s roles in skeletal muscle. J Steroid Biochem Mol Biol 111:157–163 ArticlePubMedCAS Google Scholar
Wyce A, Bai Y, Nagpal S, Thompson CC (2010) Research resource: the androgen receptor modulates expression of genes with critical roles in muscle development and function. Mol Endocrinol 24:1665–1674 ArticlePubMedCAS Google Scholar
Helsen C, Kerkhofs S, Clinckemalie L, Spans L, Laurent M, Boonen S, Vanderschueren D, Claessens F (2011) Structural basis for nuclear hormone receptor DNA binding. Mol Cell Endocrinol (Epub ahead of print)
Vlahopoulos S, Zimmer WE, Jenster G, Belaguli NS, Balk SP, Brinkmann AO, Lanz RB, Zoumpourlis VC, Schwartz RJ (2005) Recruitment of the androgen receptor via serum response factor facilitates expression of a myogenic gene. J Biol Chem 280:7786–7792 ArticlePubMedCAS Google Scholar
Amir AL, Barua M, McKnight NC, Cheng S, Yuan X, Balk SP (2003) A direct beta-catenin-independent interaction between androgen receptor and T cell factor 4. J Biol Chem 278:30828–30834 ArticlePubMedCAS Google Scholar
Igarashi K, Kashiwagi K (2000) Polyamines: mysterious modulators of cellular functions. Biochem Biophys Res Commun 271:559–564 ArticlePubMedCAS Google Scholar
Turchanowa L, Rogozkin VA, Milovic V, Feldkoren BI, Caspary WF, Stein J (2000) Influence of physical exercise on polyamine synthesis in the rat skeletal muscle. Eur J Clin Invest 30:72–78 ArticlePubMedCAS Google Scholar
Cepero M, Cubria JC, Reguera R, Balana-Fouce R, Ordonez C, Ordonez D (1998) Plasma and muscle polyamine levels in aerobically exercised rats treated with salbutamol. J Pharm Pharmacol 50:1059–1064 ArticlePubMedCAS Google Scholar
Bardocz S, Brown DS, Grant G, Pusztai A, Stewart JC, Palmer RM (1992) Effect of the beta-adrenoceptor agonist clenbuterol and phytohaemagglutinin on growth, protein synthesis and polyamine metabolism of tissues of the rat. Br J Pharmacol 106:476–482 PubMedCAS Google Scholar
Lee NK, Skinner JP, Zajac JD, Maclean HE (2011) Ornithine decarboxylase is up-regulated by the androgen receptor in skeletal muscle and regulates myoblast proliferation. Am J Physiol Endocrinol Metab 301:E172–E179 ArticlePubMedCAS Google Scholar
Crozat A, Palvimo JJ, Julkunen M, Janne OA (1992) Comparison of androgen regulation of ornithine decarboxylase and S-adenosylmethionine decarboxylase gene expression in rodent kidney and accessory sex organs. Endocrinology 130:1131–1144 ArticlePubMedCAS Google Scholar
Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM (2005) Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3′UTR evolution. Cell 123:1133–1146 ArticlePubMedCAS Google Scholar
Jinek M, Doudna JA (2009) A three-dimensional view of the molecular machinery of RNA interference. Nature 457:405–412 ArticlePubMedCAS Google Scholar
O’Rourke JR, Georges SA, Seay HR, Tapscott SJ, McManus MT, Goldhamer DJ, Swanson MS, Harfe BD (2007) Essential role for Dicer during skeletal muscle development. Dev Biol 311:359–368 ArticlePubMedCAS Google Scholar
Narayanan R, Jiang J, Gusev Y, Jones A, Kearbey JD, Miller DD, Schmittgen TD, Dalton JT (2010) MicroRNAs are mediators of androgen action in prostate and muscle. PLoS One 5:e13637 ArticlePubMedCAS Google Scholar
Williams AH, Liu N, van Rooij E, Olson EN (2009) MicroRNA control of muscle development and disease. Curr Opin Cell Biol 21:461–469 ArticlePubMedCAS Google Scholar
Lai KM, Gonzalez M, Poueymirou WT, Kline WO, Na E, Zlotchenko E, Stitt TN, Economides AN, Yancopoulos GD, Glass DJ (2004) Conditional activation of akt in adult skeletal muscle induces rapid hypertrophy. Mol Cell Biol 24:9295–9304 ArticlePubMedCAS Google Scholar
Glass DJ (2005) Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol 37:1974–1984 ArticlePubMedCAS Google Scholar
Allemand MC, Irving BA, Asmann YW, Klaus KA, Tatpati L, Coddington CC, Nair KS (2009) Effect of testosterone on insulin stimulated IRS1 Ser phosphorylation in primary rat myotubes—a potential model for PCOS-related insulin resistance. PLoS One 4:e4274 ArticlePubMedCAS Google Scholar
Jones A, Hwang DJ, Narayanan R, Miller DD, Dalton JT (2010) Effects of a novel selective androgen receptor modulator on dexamethasone-induced and hypogonadism-induced muscle atrophy. Endocrinology 151:3706–3719 ArticlePubMedCAS Google Scholar
Ibebunjo C, Eash JK, Li C, Ma Q, Glass DJ (2011) Voluntary running, skeletal muscle gene expression, and signaling inversely regulated by orchidectomy and testosterone replacement. Am J Physiol Endocrinol Metab 300:E327–E340 ArticlePubMedCAS Google Scholar
Baron S, Manin M, Beaudoin C, Leotoing L, Communal Y, Veyssiere G, Morel L (2004) Androgen receptor mediates non-genomic activation of phosphatidylinositol 3-OH kinase in androgen-sensitive epithelial cells. J Biol Chem 279:14579–14586 ArticlePubMedCAS Google Scholar
McPherron AC, Lawler AM, Lee SJ (1997) Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 387:83–90 ArticlePubMedCAS Google Scholar
McPherron AC, Lee SJ (1997) Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci USA 94:12457–12461 ArticlePubMedCAS Google Scholar
Mosher DS, Quignon P, Bustamante CD, Sutter NB, Mellersh CS, Parker HG, Ostrander EA (2007) A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs. PLoS Genet 3:e79 ArticlePubMedCAS Google Scholar
Reisz-Porszasz S, Bhasin S, Artaza JN, Shen R, Sinha-Hikim I, Hogue A, Fielder TJ, Gonzalez-Cadavid NF (2003) Lower skeletal muscle mass in male transgenic mice with muscle-specific overexpression of myostatin. Am J Physiol Endocrinol Metab 285:E876–E888 PubMedCAS Google Scholar
Thomas M, Langley B, Berry C, Sharma M, Kirk S, Bass J, Kambadur R (2000) Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation. J Biol Chem 275:40235–40243 ArticlePubMedCAS Google Scholar
Taylor WE, Bhasin S, Artaza J, Byhower F, Azam M, Willard DH Jr, Kull FC Jr, Gonzalez-Cadavid N (2001) Myostatin inhibits cell proliferation and protein synthesis in C2C12 muscle cells. Am J Physiol Endocrinol Metab 280:E221–E228 PubMedCAS Google Scholar
Rios R, Carneiro I, Arce VM, Devesa J (2002) Myostatin is an inhibitor of myogenic differentiation. Am J Physiol Cell Physiol 282:C993–C999 PubMedCAS Google Scholar
Langley B, Thomas M, Bishop A, Sharma M, Gilmour S, Kambadur R (2002) Myostatin inhibits myoblast differentiation by down-regulating MyoD expression. J Biol Chem 277:49831–49840 ArticlePubMedCAS Google Scholar
Joulia D, Bernardi H, Garandel V, Rabenoelina F, Vernus B, Cabello G (2003) Mechanisms involved in the inhibition of myoblast proliferation and differentiation by myostatin. Exp Cell Res 286:263–275 ArticlePubMedCAS Google Scholar
McFarlane C, Plummer E, Thomas M, Hennebry A, Ashby M, Ling N, Smith H, Sharma M, Kambadur R (2006) Myostatin induces cachexia by activating the ubiquitin proteolytic system through an NF-kappaB-independent, FoxO1-dependent mechanism. J Cell Physiol 209:501–514 ArticlePubMedCAS Google Scholar
Wagner KR, Liu X, Chang X, Allen RE (2005) Muscle regeneration in the prolonged absence of myostatin. Proc Natl Acad Sci USA 102:2519–2524 ArticlePubMedCAS Google Scholar
McCroskery S, Thomas M, Maxwell L, Sharma M, Kambadur R (2003) Myostatin negatively regulates satellite cell activation and self-renewal. J Cell Biol 162:1135–1147 ArticlePubMedCAS Google Scholar
McFarlane C, Hennebry A, Thomas M, Plummer E, Ling N, Sharma M, Kambadur R (2008) Myostatin signals through Pax7 to regulate satellite cell self-renewal. Exp Cell Res 314:317–329 ArticlePubMedCAS Google Scholar
Amthor H, Otto A, Vulin A, Rochat A, Dumonceaux J, Garcia L, Mouisel E, Hourde C, Macharia R, Friedrichs M, Relaix F, Zammit PS, Matsakas A, Patel K, Partridge T (2009) Muscle hypertrophy driven by myostatin blockade does not require stem/precursor-cell activity. Proc Natl Acad Sci USA 106:7479–7484 ArticlePubMedCAS Google Scholar
McPherron AC, Lee SJ (2002) Suppression of body fat accumulation in myostatin-deficient mice. J Clin Invest 109:595–601 PubMedCAS Google Scholar
Lin J, Arnold HB, Della-Fera MA, Azain MJ, Hartzell DL, Baile CA (2002) Myostatin knockout in mice increases myogenesis and decreases adipogenesis. Biochem Biophys Res Commun 291:701–706 ArticlePubMedCAS Google Scholar
Seuntjens E, Umans L, Zwijsen A, Sampaolesi M, Verfaillie CM, Huylebroeck D (2009) Transforming Growth Factor type beta and Smad family signaling in stem cell function. Cytokine Growth Factor Rev 20:449–458 ArticlePubMedCAS Google Scholar
Gilson H, Schakman O, Kalista S, Lause P, Tsuchida K, Thissen JP (2009) Follistatin induces muscle hypertrophy through satellite cell proliferation and inhibition of both myostatin and activin. Am J Physiol Endocrinol Metab 297:E157–E164 ArticlePubMedCAS Google Scholar
Amthor H, Nicholas G, McKinnell I, Kemp CF, Sharma M, Kambadur R, Patel K (2004) Follistatin complexes Myostatin and antagonises Myostatin-mediated inhibition of myogenesis. Dev Biol 270:19–30 ArticlePubMedCAS Google Scholar
Hill JJ, Davies MV, Pearson AA, Wang JH, Hewick RM, Wolfman NM, Qiu Y (2002) The myostatin propeptide and the follistatin-related gene are inhibitory binding proteins of myostatin in normal serum. J Biol Chem 277:40735–40741 ArticlePubMedCAS Google Scholar
Mendler L, Baka Z, Kovacs-Simon A, Dux L (2007) Androgens negatively regulate myostatin expression in an androgen-dependent skeletal muscle. Biochem Biophys Res Commun 361:237–242 ArticlePubMedCAS Google Scholar
Gentile MA, Nantermet PV, Vogel RL, Phillips R, Holder D, Hodor P, Cheng C, Dai H, Freedman LP, Ray WJ (2010) Androgen-mediated improvement of body composition and muscle function involves a novel early transcriptional program including IGF1, mechano growth factor, and induction of {beta}-catenin. J Mol Endocrinol 44:55–73 ArticlePubMedCAS Google Scholar
Zhao JX, Hu J, Zhu MJ, Du M (2011) Trenbolone enhances myogenic differentiation by enhancing beta-catenin signaling in muscle-derived stem cells of cattle. Domest Anim Endocrinol 40:222–229 ArticlePubMedCAS Google Scholar
Ma K, Mallidis C, Artaza J, Taylor W, Gonzalez-Cadavid N, Bhasin S (2001) Characterization of 5′-regulatory region of human myostatin gene: regulation by dexamethasone in vitro. Am J Physiol Endocrinol Metab 281:E1128–E1136 PubMedCAS Google Scholar
Laviola L, Natalicchio A, Giorgino F (2007) The IGF-I signaling pathway. Curr Pharm Des 13:663–669 ArticlePubMedCAS Google Scholar
Shavlakadze T, Winn N, Rosenthal N, Grounds MD (2005) Reconciling data from transgenic mice that overexpress IGF-I specifically in skeletal muscle. Growth Horm IGF Res 15:4–18 ArticlePubMedCAS Google Scholar
Florini JR, Ewton DZ, Coolican SA (1996) Growth hormone and the insulin-like growth factor system in myogenesis. Endocr Rev 17:481–517 PubMedCAS Google Scholar
Frost RA, Lang CH (2003) Regulation of insulin-like growth factor-I in skeletal muscle and muscle cells. Minerva Endocrinol 28:53–73 PubMedCAS Google Scholar
Sacheck JM, Ohtsuka A, McLary SC, Goldberg AL (2004) IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. Am J Physiol Endocrinol Metab 287:E591–E601 ArticlePubMedCAS Google Scholar
Hameed M, Lange KH, Andersen JL, Schjerling P, Kjaer M, Harridge SD, Goldspink G (2004) The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men. J Physiol 555:231–240 ArticlePubMedCAS Google Scholar
Yang SY, Goldspink G (2002) Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation. FEBS Lett 522:156–160 ArticlePubMedCAS Google Scholar
Keenan BS, Richards GE, Ponder SW, Dallas JS, Nagamani M, Smith ER (1993) Androgen-stimulated pubertal growth: the effects of testosterone and dihydrotestosterone on growth hormone and insulin-like growth factor-I in the treatment of short stature and delayed puberty. J Clin Endocrinol Metab 76:996–1001 ArticlePubMedCAS Google Scholar
Ulloa-Aguirre A, Blizzard RM, Garcia-Rubi E, Rogol AD, Link K, Christie CM, Johnson ML, Veldhuis JD (1990) Testosterone and oxandrolone, a nonaromatizable androgen, specifically amplify the mass and rate of growth hormone (GH) secreted per burst without altering GH secretory burst duration or frequency or the GH half-life. J Clin Endocrinol Metab 71:846–854 ArticlePubMedCAS Google Scholar
Bhasin S, Woodhouse L, Casaburi R, Singh AB, Bhasin D, Berman N, Chen X, Yarasheski KE, Magliano L, Dzekov C, Dzekov J, Bross R, Phillips J, Sinha-Hikim I, Shen R, Storer TW (2001) Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab 281:E1172–E1181 PubMedCAS Google Scholar
Serra C, Bhasin S, Tangherlini F, Barton ER, Ganno M, Zhang A, Shansky J, Vandenburgh HH, Travison TG, Jasuja R, Morris C (2011) The role of GH and IGF-I in mediating anabolic effects of testosterone on androgen-responsive muscle. Endocrinology 152:193–206 ArticlePubMedCAS Google Scholar
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 92:447–454 ArticlePubMedCAS Google Scholar
Kamanga-Sollo E, Pampusch MS, Xi G, White ME, Hathaway MR, Dayton WR (2004) IGF-I mRNA levels in bovine satellite cell cultures: effects of fusion and anabolic steroid treatment. J Cell Physiol 201:181–189 ArticlePubMedCAS Google Scholar
Wu Y, Zhao W, Zhao J, Pan J, Wu Q, Zhang Y, Bauman WA, Cardozo CP (2007) Identification of androgen response elements in the insulin-like growth factor I upstream promoter. Endocrinology 148:2984–2993 ArticlePubMedCAS Google Scholar
Chambon C, Duteil D, Vignaud A, Ferry A, Messaddeq N, Malivindi R, Kato S, Chambon P, Metzger D (2010) Myocytic androgen receptor controls the strength but not the mass of limb muscles. Proc Natl Acad Sci USA 107:14327–14332 ArticlePubMedCAS Google Scholar
Dardevet D, Sornet C, Vary T, Grizard J (1996) Phosphatidylinositol 3-kinase and p70 s6 kinase participate in the regulation of protein turnover in skeletal muscle by insulin and insulin-like growth factor I. Endocrinology 137:4087–4094 ArticlePubMedCAS Google Scholar
Kim HJ, Lee WJ (2009) Insulin-like growth factor-I induces androgen receptor activation in differentiating C2C12 skeletal muscle cells. Mol Cells 28:189–194 ArticlePubMedCAS Google Scholar
Lee WJ (2009) Insulin-like growth factor-I-induced androgen receptor activation is mediated by the PI3 K/Akt pathway in C2C12 skeletal muscle cells. Mol Cells 28:495–499 ArticlePubMedCAS Google Scholar
Brown D, Hikim AP, Kovacheva EL, Sinha-Hikim I (2009) Mouse model of testosterone-induced muscle fiber hypertrophy: involvement of p38 mitogen-activated protein kinase-mediated Notch signaling. J Endocrinol 201:129–139 ArticlePubMedCAS Google Scholar
Kovacheva EL, Hikim AP, Shen R, Sinha I, Sinha-Hikim I (2010) Testosterone supplementation reverses sarcopenia in aging through regulation of myostatin, c-Jun NH2-terminal kinase, Notch, and Akt signaling pathways. Endocrinology 151:628–638 ArticlePubMedCAS Google Scholar
Bedogni B, Warneke JA, Nickoloff BJ, Giaccia AJ, Powell MB (2008) Notch1 is an effector of Akt and hypoxia in melanoma development. J Clin Invest 118:3660–3670 ArticlePubMedCAS Google Scholar
Wehling M (1997) Specific, nongenomic actions of steroid hormones. Annu Rev Physiol 59:365–393 ArticlePubMedCAS Google Scholar
Cato AC, Nestl A, Mink S (2002) Rapid actions of steroid receptors in cellular signaling pathways. Sci STKE 2002(138): re9
Migliaccio A, Castoria G, Di Domenico M, de Falco A, Bilancio A, Lombardi M, Barone MV, Ametrano D, Zannini MS, Abbondanza C, Auricchio F (2000) Steroid-induced androgen receptor-oestradiol receptor beta-Src complex triggers prostate cancer cell proliferation. EMBO J 19:5406–5417 ArticlePubMedCAS Google Scholar
Kousteni S, Bellido T, Plotkin LI, O’Brien CA, Bodenner DL, Han L, Han K, DiGregorio GB, Katzenellenbogen JA, Katzenellenbogen BS, Roberson PK, Weinstein RS, Jilka RL, Manolagas SC (2001) Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell 104:719–730 PubMedCAS Google Scholar
Nakhla AM, Rosner W (1996) Stimulation of prostate cancer growth by androgens and estrogens through the intermediacy of sex hormone-binding globulin. Endocrinology 137:4126–4129 ArticlePubMedCAS Google Scholar
Kampa M, Papakonstanti EA, Hatzoglou A, Stathopoulos EN, Stournaras C, Castanas E (2002) The human prostate cancer cell line LNCaP bears functional membrane testosterone receptors that increase PSA secretion and modify actin cytoskeleton. FASEB J 16:1429–1431 PubMedCAS Google Scholar
Benten WP, Lieberherr M, Giese G, Wrehlke C, Stamm O, Sekeris CE, Mossmann H, Wunderlich F (1999) Functional testosterone receptors in plasma membranes of T cells. FASEB J 13:123–133 PubMedCAS Google Scholar
Yeh S, Lin HK, Kang HY, Thin TH, Lin MF, Chang C (1999) From HER2/Neu signal cascade to androgen receptor and its coactivators: a novel pathway by induction of androgen target genes through MAP kinase in prostate cancer cells. Proc Natl Acad Sci USA 96:5458–5463 ArticlePubMedCAS Google Scholar
Lopez GN, Turck CW, Schaufele F, Stallcup MR, Kushner PJ (2001) Growth factors signal to steroid receptors through mitogen-activated protein kinase regulation of p160 coactivator activity. J Biol Chem 276:22177–22182 ArticlePubMedCAS Google Scholar
Schneider MD, Olson EN (1988) Control of myogenic differentiation by cellular oncogenes. Mol Neurobiol 2:1–39 ArticlePubMedCAS Google Scholar
Falcone G, Alema S, Tato F (1991) Transcription of muscle-specific genes is repressed by reactivation of pp60v-src in postmitotic quail myotubes. Mol Cell Biol 11:3331–3338 PubMedCAS Google Scholar
Hamdi MM, Mutungi G (2010) Dihydrotestosterone activates the MAPK pathway and modulates maximum isometric force through the EGF receptor in isolated intact mouse skeletal muscle fibres. J Physiol 588:511–525 ArticlePubMedCAS Google Scholar
Siiteri PK, Murai JT, Hammond GL, Nisker JA, Raymoure WJ, Kuhn RW (1982) The serum transport of steroid hormones. Recent Prog Horm Res 38:457–510 PubMedCAS Google Scholar
Krupenko SA, Krupenko NI, Danzo BJ (1994) Interaction of sex hormone-binding globulin with plasma membranes from the rat epididymis and other tissues. J Steroid Biochem Mol Biol 51:115–124 ArticlePubMedCAS Google Scholar
Nazareth LV, Weigel NL (1996) Activation of the human androgen receptor through a protein kinase A signaling pathway. J Biol Chem 271:19900–19907 ArticlePubMedCAS Google Scholar
Sadar MD (1999) Androgen-independent induction of prostate-specific antigen gene expression via cross-talk between the androgen receptor and protein kinase A signal transduction pathways. J Biol Chem 274:7777–7783 ArticlePubMedCAS Google Scholar
Fortunati N (1999) Sex hormone-binding globulin: not only a transport protein. What news is around the corner? J Endocrinol Invest 22:223–234 PubMedCAS Google Scholar
Rosner W, Hryb DJ, Kahn SM, Nakhla AM, Romas NA (2010) Interactions of sex hormone-binding globulin with target cells. Mol Cell Endocrinol 316:79–85 ArticlePubMedCAS Google Scholar
Benten WP, Lieberherr M, Stamm O, Wrehlke C, Guo Z, Wunderlich F (1999) Testosterone signaling through internalizable surface receptors in androgen receptor-free macrophages. Mol Biol Cell 10:3113–3123 PubMedCAS Google Scholar
Estrada M, Espinosa A, Muller M, Jaimovich E (2003) Testosterone stimulates intracellular calcium release and mitogen-activated protein kinases via a G protein-coupled receptor in skeletal muscle cells. Endocrinology 144:3586–3597 ArticlePubMedCAS Google Scholar
Mellstrom B, Naranjo JR (2001) Mechanisms of Ca(2 +)-dependent transcription. Curr Opin Neurobiol 11:312–319 ArticlePubMedCAS Google Scholar
Fu R, Liu J, Fan J, Li R, Li D, Yin J, Cui S (2011) Novel evidence that testosterone promotes cell proliferation and differentiation via G protein-coupled receptors in the rat L6 skeletal muscle myoblast cell line. J Cell Physiol 227:98–107 ArticleCAS Google Scholar
Thum T, Springer J (2011) Breakthrough in cachexia treatment through a novel selective androgen receptor modulator?! J Cachex Sarcopenia Muscle 2:121–123 Article Google Scholar
Whittemore LA, Song K, Li X, Aghajanian J, Davies M, Girgenrath S, Hill JJ, Jalenak M, Kelley P, Knight A, Maylor R, O’Hara D, Pearson A, Quazi A, Ryerson S, Tan XY, Tomkinson KN, Veldman GM, Widom A, Wright JF, Wudyka S, Zhao L, Wolfman NM (2003) Inhibition of myostatin in adult mice increases skeletal muscle mass and strength. Biochem Biophys Res Commun 300:965–971 ArticlePubMedCAS Google Scholar
Rose FF Jr, Mattis VB, Rindt H, Lorson CL (2009) Delivery of recombinant follistatin lessens disease severity in a mouse model of spinal muscular atrophy. Hum Mol Genet 18:997–1005 ArticlePubMedCAS Google Scholar
Mohler ML, Bohl CE, Jones A, Coss CC, Narayanan R, He Y, Hwang DJ, Dalton JT, Miller DD (2009) Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit. J Med Chem 52:3597–3617 ArticlePubMedCAS Google Scholar
Wright AS, Douglas RC, Thomas LN, Lazier CB, Rittmaster RS (1999) Androgen-induced regrowth in the castrated rat ventral prostate: role of 5alpha-reductase. Endocrinology 140:4509–4515 ArticlePubMedCAS Google Scholar
Kazmin D, Prytkova T, Cook CE, Wolfinger R, Chu TM, Beratan D, Norris JD, Chang CY, McDonnell DP (2006) Linking ligand-induced alterations in androgen receptor structure to differential gene expression: a first step in the rational design of selective androgen receptor modulators. Mol Endocrinol 20:1201–1217 ArticlePubMedCAS Google Scholar
Narayanan R, Coss CC, Yepuru M, Kearbey JD, Miller DD, Dalton JT (2008) Steroidal androgens and nonsteroidal, tissue-selective androgen receptor modulator, S-22, regulate androgen receptor function through distinct genomic and nongenomic signaling pathways. Mol Endocrinol 22:2448–2465 ArticlePubMedCAS Google Scholar
Dalton JT, Barnette KG, Bohl CE, Hancock ML, Rodriguez D, Dodson ST, Morton RA, Steiner MS (2011) The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. J Cachex Sarcopenia Muscle 2:153–161 Article Google Scholar