{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:18:50Z","timestamp":1792196330816,"version":"4.4.0"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T00:00:00Z","timestamp":1481760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo Nacional de Ciencia y Tecnologia","award":["1151118"],"award-info":[{"award-number":["1151118"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0168255","type":"journal-article","created":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T18:59:22Z","timestamp":1481828362000},"page":"e0168255","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":43,"title":["GSK-3\u03b2\/NFAT Signaling Is Involved in Testosterone-Induced Cardiac Myocyte Hypertrophy"],"prefix":"10.1371","volume":"11","author":[{"given":"Javier","family":"Duran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Oyarce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Pavez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisse","family":"Valladares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Basualto-Alarcon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Lagos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genaro","family":"Barrientos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayarling Francisca","family":"Troncoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Ibarra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7877-8160","authenticated-orcid":true,"given":"Manuel","family":"Estrada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,12,15]]},"reference":[{"issue":"13","key":"ref1","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1161\/01.CIR.0000120390.68287.BB","article-title":"Hypertrophy of the heart: a new therapeutic target?","volume":"109","author":"N Frey","year":"2004","journal-title":"Circulation"},{"issue":"15","key":"ref2","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1096\/fasebj.5.15.1835945","article-title":"Regulation of cardiac gene expression during myocardial growth and hypertrophy: molecular studies of an adaptive physiologic response","volume":"5","author":"KR Chien","year":"1991","journal-title":"Faseb J"},{"issue":"8","key":"ref3","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/nrm1983","article-title":"Regulation of cardiac hypertrophy by intracellular signalling pathways","volume":"7","author":"J Heineke","year":"2006","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"3","key":"ref4","doi-asserted-by":"crossref","first-page":"213","DOI":"10.3109\/08037059309077553","article-title":"Pathologic remodeling of the myocardium in a weightlifter taking anabolic steroids","volume":"2","author":"SE Campbell","year":"1993","journal-title":"Blood pressure"},{"issue":"3","key":"ref5","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1161\/01.CIR.98.3.256","article-title":"Androgen receptors mediate hypertrophy in cardiac myocytes","volume":"98","author":"JD Marsh","year":"1998","journal-title":"Circulation"},{"issue":"3","key":"ref6","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1210\/en.2005-1139","article-title":"Testosterone induces an intracellular calcium increase by a nongenomic mechanism in cultured rat cardiac myocytes","volume":"147","author":"JM Vicencio","year":"2006","journal-title":"Endocrinology"},{"issue":"2","key":"ref7","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1677\/JOE-09-0044","article-title":"Testosterone induces cardiomyocyte hypertrophy through mammalian target of rapamycin complex 1 pathway","volume":"202","author":"F Altamirano","year":"2009","journal-title":"J Endocrinol"},{"issue":"8","key":"ref8","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1210\/me.2010-0138","article-title":"Research Resource: The androgen receptor modulates expression of genes with critical roles in muscle development and function","volume":"24","author":"A Wyce","year":"2010","journal-title":"Mol Endocrinol"},{"issue":"2","key":"ref9","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.yfrne.2007.08.004","article-title":"Rapid actions of androgens","volume":"29","author":"G Michels","year":"2008","journal-title":"Front Neuroendocrinol"},{"issue":"8","key":"ref10","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1210\/en.2002-0164","article-title":"Testosterone stimulates intracellular calcium release and mitogen-activated protein kinases via a G protein-coupled receptor in skeletal muscle cells","volume":"144","author":"M Estrada","year":"2003","journal-title":"Endocrinology"},{"key":"ref11","article-title":"Testosterone replacement therapy: new data on efficacy and cardiovascular safety","author":"RA Kloner","year":"2016","journal-title":"J Cardiovasc Pharmacol Ther"},{"issue":"5","key":"ref12","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.jacc.2015.12.005","article-title":"Testosterone and cardiovascular disease","volume":"67","author":"RA Kloner","year":"2016","journal-title":"J Am Coll Cardiol"},{"issue":"3","key":"ref13","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1210\/er.2003-0005","article-title":"Androgens and cardiovascular disease","volume":"24","author":"PY Liu","year":"2003","journal-title":"Endocrine reviews"},{"issue":"2","key":"ref14","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0092-8674(00)81573-1","article-title":"A calcineurin-dependent transcriptional pathway for cardiac hypertrophy","volume":"93","author":"JD Molkentin","year":"1998","journal-title":"Cell"},{"issue":"2","key":"ref15","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1073\/pnas.231619298","article-title":"Activated glycogen synthase-3 beta suppresses cardiac hypertrophy in vivo","volume":"99","author":"CL Antos","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"19","key":"ref16","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1038\/sj.onc.1204386","article-title":"Partners in transcription: NFAT and AP-1","volume":"20","author":"F Macian","year":"2001","journal-title":"Oncogene"},{"issue":"5","key":"ref17","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S0092-8674(00)80571-1","article-title":"Generic signals and specific outcomes: signaling through Ca<sup>2+<\/sup>, calcineurin, and NF-AT","volume":"96","author":"GR Crabtree","year":"1999","journal-title":"Cell"},{"issue":"Suppl","key":"ref18","doi-asserted-by":"crossref","first-page":"S67","DOI":"10.1016\/S0092-8674(02)00699-2","article-title":"NFAT signaling: choreographing the social lives of cells","volume":"109","author":"GR Crabtree","year":"2002","journal-title":"Cell"},{"issue":"18","key":"ref19","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1101\/gad.1102703","article-title":"Transcriptional regulation by calcium, calcineurin, and NFAT","volume":"17","author":"PG Hogan","year":"2003","journal-title":"Genes Dev"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.mce.2014.09.025","article-title":"Anabolic steroids activate calcineurin-NFAT signaling and thereby increase myotube size and reduce denervation atrophy","volume":"399","author":"W Qin","year":"2015","journal-title":"Mol Cell Endocrinol"},{"issue":"10","key":"ref21","doi-asserted-by":"crossref","first-page":"4716","DOI":"10.1210\/en.2007-0145","article-title":"The immunophilin ligands cyclosporin A and FK506 suppress prostate cancer cell growth by androgen receptor-dependent and -independent mechanisms","volume":"148","author":"S Periyasamy","year":"2007","journal-title":"Endocrinology"},{"issue":"1","key":"ref22","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1083\/jcb.151.1.117","article-title":"Glycogen synthase kinase-3beta is a negative regulator of cardiomyocyte hypertrophy","volume":"151","author":"S Haq","year":"2000","journal-title":"J Cell Biol"},{"issue":"11","key":"ref23","doi-asserted-by":"crossref","first-page":"3609","DOI":"10.1172\/JCI36245","article-title":"Deletion of GSK-3beta in mice leads to hypertrophic cardiomyopathy secondary to cardiomyoblast hyperproliferation","volume":"118","author":"R Kerkela","year":"2008","journal-title":"J Clin Invest"},{"issue":"5308","key":"ref24","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1126\/science.275.5308.1930","article-title":"Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3","volume":"275","author":"CR Beals","year":"1997","journal-title":"Science"},{"issue":"3","key":"ref25","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.cardiores.2004.03.015","article-title":"Negative regulators of cardiac hypertrophy","volume":"63","author":"SE Hardt","year":"2004","journal-title":"Cardiovasc Res"},{"issue":"6","key":"ref26","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1016\/S1097-2765(01)00253-2","article-title":"A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation","volume":"7","author":"S Frame","year":"2001","journal-title":"Mol Cell"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2012.11.047","article-title":"Both PI3K\/Akt and ERK1\/2 pathways participate in the protection by dexmedetomidine against transient focal cerebral ischemia\/reperfusion injury in rats","volume":"1494","author":"YM Zhu","year":"2013","journal-title":"Brain Res"},{"issue":"1\u20132","key":"ref28","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/S0014-5793(99)01434-9","article-title":"Role of protein kinase B and the MAP kinase cascade in mediating the EGF-dependent inhibition of glycogen synthase kinase 3 in Swiss 3T3 cells","volume":"461","author":"M Shaw","year":"1999","journal-title":"FEBS Lett"},{"issue":"Pt 3","key":"ref29","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1042\/bj3030701","article-title":"Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation","volume":"303","author":"V Stambolic","year":"1994","journal-title":"Biochem J"},{"issue":"1","key":"ref30","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.cellsig.2007.10.004","article-title":"Glycogen synthase kinases 3alpha and 3beta in cardiac myocytes: regulation and consequences of their inhibition","volume":"20","author":"T Markou","year":"2008","journal-title":"Cell Signal"},{"issue":"3","key":"ref31","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1253\/circj.68.247","article-title":"Glycogen synthase kinase-3beta is involved in the process of myocardial hypertrophy stimulated by insulin-like growth factor-1","volume":"68","author":"SK Seimi","year":"2004","journal-title":"Circ J"},{"issue":"19","key":"ref32","doi-asserted-by":"crossref","first-page":"14466","DOI":"10.1074\/jbc.275.19.14466","article-title":"The Akt-glycogen synthase kinase 3beta pathway regulates transcription of atrial natriuretic factor induced by beta-adrenergic receptor stimulation in cardiac myocytes","volume":"275","author":"C Morisco","year":"2000","journal-title":"J Biol Chem"},{"issue":"3","key":"ref33","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/cvr\/cvn223","article-title":"Tissue kallikrein promotes neovascularization and improves cardiac function by the Akt-glycogen synthase kinase-3beta pathway","volume":"80","author":"YY Yao","year":"2008","journal-title":"Cardiovasc Res"},{"issue":"1","key":"ref34","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.cardiores.2006.10.014","article-title":"Tissue kallikrein protects against pressure overload-induced cardiac hypertrophy through kinin B2 receptor and glycogen synthase kinase-3beta activation","volume":"73","author":"HJ Li","year":"2007","journal-title":"Cardiovasc Res"},{"issue":"12","key":"ref35","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1101\/gad.10.12.1443","article-title":"The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3","volume":"10","author":"C Yost","year":"1996","journal-title":"Genes Dev"},{"issue":"2","key":"ref36","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1161\/CIRCRESAHA.112.273839","article-title":"Local control of nuclear calcium signaling in cardiac myocytes by perinuclear microdomains of sarcolemmal insulin-like growth factor 1 receptors","volume":"112","author":"C Ibarra","year":"2013","journal-title":"Circ Res"},{"issue":"30","key":"ref37","doi-asserted-by":"crossref","first-page":"20666","DOI":"10.1074\/jbc.M512671200","article-title":"Thyroid hormone stimulates protein synthesis in the cardiomyocyte by activating the Akt-mTOR and p70S6K pathways","volume":"281","author":"A Kenessey","year":"2006","journal-title":"J Biol Chem"},{"issue":"6","key":"ref38","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/nrd1415","article-title":"GSK3 inhibitors: development and therapeutic potential","volume":"3","author":"P Cohen","year":"2004","journal-title":"Nat Rev Drug Discov"},{"issue":"8","key":"ref39","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nrd2193","article-title":"Small-molecule therapies for cardiac hypertrophy: moving beneath the cell surface","volume":"6","author":"TA McKinsey","year":"2007","journal-title":"Nat Rev Drug Discov"},{"issue":"1\u20132","key":"ref40","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.mce.2011.08.007","article-title":"Androgen receptor coregulators: recruitment via the coactivator binding groove","volume":"352","author":"DJ van de Wijngaart","year":"2012","journal-title":"Mol Cell Endocrinol"},{"issue":"1","key":"ref41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1530\/JOE-12-0126","article-title":"Effects of androgens on cardiovascular remodeling","volume":"214","author":"Y Ikeda","year":"2012","journal-title":"The Journal of endocrinology"},{"issue":"Pt 4","key":"ref42","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1242\/jcs.02775","article-title":"Ca<sup>2+<\/sup> oscillations induced by testosterone enhance neurite outgrowth","volume":"119","author":"M Estrada","year":"2006","journal-title":"J Cell Sci"},{"issue":"1","key":"ref43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2003.10.008","article-title":"Calcineurin signaling and NFAT activation in cardiovascular and skeletal muscle development","volume":"266","author":"RA Schulz","year":"2004","journal-title":"Dev Biol"},{"issue":"10","key":"ref44","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1172\/JCI8551","article-title":"CaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo","volume":"105","author":"R Passier","year":"2000","journal-title":"J Clin Invest"},{"issue":"12","key":"ref45","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1210\/mend.13.12.0396","article-title":"Determinants of DNA sequence specificity of the androgen, progesterone, and glucocorticoid receptors: evidence for differential steroid receptor response elements","volume":"13","author":"CC Nelson","year":"1999","journal-title":"Mol Endocrinol"},{"issue":"2","key":"ref46","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/pros.20172","article-title":"Induction of AP-1 activity by androgen activation of the androgen receptor in LNCaP human prostate carcinoma cells","volume":"63","author":"DR Church","year":"2005","journal-title":"Prostate"},{"issue":"Suppl 1","key":"ref47","doi-asserted-by":"crossref","first-page":"S137","DOI":"10.1038\/sj.bjp.0707659","article-title":"Glycogen synthase kinase 3 (GSK3) in the heart: a point of integration in hypertrophic signalling and a therapeutic target? A critical analysis","volume":"153","author":"PH Sugden","year":"2008","journal-title":"Br J Pharmacol"},{"issue":"10","key":"ref48","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1161\/01.RES.0000018952.70505.F1","article-title":"Glycogen synthase kinase-3beta: a novel regulator of cardiac hypertrophy and development","volume":"90","author":"SE Hardt","year":"2002","journal-title":"Circ Res"},{"issue":"2","key":"ref49","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0014-5793(97)01548-2","article-title":"Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase-3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin","volume":"421","author":"GI Welsh","year":"1998","journal-title":"FEBS Lett"},{"issue":"3","key":"ref50","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1073\/pnas.032646799","article-title":"Testosterone prevents the heat shock-induced overactivation of glycogen synthase kinase-3 beta but not of cyclin-dependent kinase 5 and c-Jun NH2-terminal kinase and concomitantly abolishes hyperphosphorylation of tau: implications for Alzheimer&apos;s disease","volume":"99","author":"S Papasozomenos","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"ref51","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1210\/en.2008-0858","article-title":"Regulation of myogenic differentiation by androgens: cross talk between androgen receptor\/ beta-catenin and follistatin\/transforming growth factor-beta signaling pathways","volume":"150","author":"R Singh","year":"2009","journal-title":"Endocrinology"},{"issue":"13","key":"ref52","doi-asserted-by":"crossref","first-page":"11336","DOI":"10.1074\/jbc.M111962200","article-title":"Linking beta-catenin to androgen-signaling pathway","volume":"277","author":"F Yang","year":"2002","journal-title":"J Biol Chem"},{"issue":"5","key":"ref53","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1074\/jbc.M004888200","article-title":"Glycogen synthase kinase-3 inhibits the DNA binding activity of NFATc","volume":"276","author":"JW Neal","year":"2001","journal-title":"J Biol Chem"},{"issue":"8","key":"ref54","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1111\/j.1742-4658.2005.04614.x","article-title":"14-3-3 proteins regulate glycogen synthase 3beta phosphorylation and inhibit cardiomyocyte hypertrophy","volume":"272","author":"W Liao","year":"2005","journal-title":"FEBS J"},{"issue":"2","key":"ref55","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.bbrc.2009.09.101","article-title":"beta-Catenin\/TCF\/LEF1 can directly regulate phenylephrine-induced cell hypertrophy and Anf transcription in cardiomyocytes","volume":"390","author":"CG Zhang","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"issue":"4","key":"ref56","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1159\/000366346","article-title":"Membrane androgen receptor down-regulates c-src-activity and beta-catenin transcription and triggers GSK-3beta-phosphorylation in colon tumor cells","volume":"34","author":"S Gu","year":"2014","journal-title":"Cell Physiol Biochem"},{"issue":"12","key":"ref57","doi-asserted-by":"crossref","first-page":"4462","DOI":"10.1128\/MCB.02157-05","article-title":"The beta-catenin\/T-cell factor\/lymphocyte enhancer factor signaling pathway is required for normal and stress-induced cardiac hypertrophy","volume":"26","author":"X Chen","year":"2006","journal-title":"Molecular and cellular biology"},{"issue":"8","key":"ref58","doi-asserted-by":"crossref","first-page":"4610","DOI":"10.1073\/pnas.0835895100","article-title":"Stabilization of beta-catenin by a Wnt-independent mechanism regulates cardiomyocyte growth","volume":"100","author":"S Haq","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"ref59","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1161\/HYPERTENSIONAHA.106.079426","article-title":"The fuzzy logic of physiological cardiac hypertrophy","volume":"49","author":"GW Dorn 2nd","year":"2007","journal-title":"Hypertension"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0168255","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:48:50Z","timestamp":1601254130000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0168255"}},"subtitle":[],"editor":[{"given":"Paula A.","family":"da Costa Martins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,12,15]]},"references-count":59,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2016,12,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0168255","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,15]]}}}