{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:28:31Z","timestamp":1785853711969,"version":"3.56.0"},"reference-count":71,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:p> Androgens appear to enhance, whereas estrogens mitigate, cardiac hypertrophy. However, signaling pathways in cells for short (3 min) and longer term (48 h) treatment with 17\u03b2-estradiol (E2) or 5\u03b1-dihydrotestosterone (DHT) are understudied. We compared the effect of adrenergic stimulation by norepinephrine (NE; 1 \u03bcM) alone or in combination with DHT (10 nM) or E2 (10 nM) treatment in neonatal rat ventricular myocytes (NRVMs) by cell area, protein synthesis, sarcomeric structure, gene expression, phosphorylation of extracellular signal-regulated (ERK), and focal adhesion kinases (FAK), and phospho-FAK nuclear localization. NE alone elicited the expected hypertrophy and strong sarcomeric organization, and DHT alone gave a similar but more modest response, whereas E2 did not alter cell size. Effects of NE dominated when used with either E2 or DHT with all combinations. Both sex hormones alone rapidly activated FAK but not ERK. Long-term or brief exposure to E2 attenuated NE-induced FAK phosphorylation, whereas DHT had no effect. Neither hormone altered NE-elicited ERK activation. Longer term exposure to E2 alone reduced FAK phosphorylation and reduced nuclear phospho-FAK, whereas its elevation was seen in the presence of NE with both sex hormones. The mitigating effects of E2 on the NE-elicited increase in cell size and the hypertrophic effect of DHT in NRVMs are in accordance with results observed in whole animal models. This is the first report of rapid, nongenomic sex hormone signaling via FAK activation and altered FAK trafficking to the nucleus in heart cells. <\/jats:p>","DOI":"10.1152\/japplphysiol.00994.2009","type":"journal-article","created":{"date-parts":[[2010,1,1]],"date-time":"2010-01-01T01:15:12Z","timestamp":1262308512000},"page":"686-696","source":"Crossref","is-referenced-by-count":11,"title":["Signaling responses after exposure to 5\u03b1-dihydrotestosterone or 17\u03b2-estradiol in norepinephrine-induced hypertrophy of neonatal rat ventricular myocytes"],"prefix":"10.1152","volume":"108","author":[{"given":"Yevgeniya E.","family":"Koshman","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics and"},{"name":"The Cardiovascular Institute, Loyola University Chicago Stritch School of Medicine, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariann R.","family":"Piano","sequence":"additional","affiliation":[{"name":"Department of Biobehavioral Health Science, University of Illinois at Chicago, Chicago; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Russell","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorie W.","family":"Schwertz","sequence":"additional","affiliation":[{"name":"Department of Biobehavioral Health Science, University of Illinois at Chicago, Chicago; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","first-page":"S34","volume":"20","author":"Agabiti-Rosei E","year":"2002","journal-title":"J Hypertens Suppl"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2003-0138"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-09-0044"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000105682.85732.BD"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.03.011"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.02.020"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.6.2132"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00766.2006"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00199.2004"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-006-9248-x"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.12.015"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025438000942"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000038488.38975.1A"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(99)00066-2"},{"key":"B15","first-page":"633","volume":"21","author":"Cabral AM","year":"1988","journal-title":"Braz J Med Biol Res"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.86.4.1099"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2741\/2681"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01087.2002"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2006.03.037"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2004.12.013"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0489"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00772-1"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.26.6.979"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00761.2002"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(98)00347-7"},{"key":"B26","first-page":"345","volume":"15","author":"Drolet MC","year":"2006","journal-title":"J Heart Valve Dis"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707353"},{"key":"B28","first-page":"717","volume":"58","author":"Frantz S","year":"2007","journal-title":"J Physiol Pharmacol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-0214"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.91.6.1739"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1054\/jcaf.2002.32195"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1055\/s-2004-814445"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(02)02193-8"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9307"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1159\/000110458"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.058339"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.11.018"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199005313222203"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1159\/000176053"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.90.2.928"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.3.256"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200347200"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2007.04585.x"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1291\/hypres.25.153"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.34.5.1041"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00701-0"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.3.H1136"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1042\/cs0610265"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M414409200"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.12.164"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1023\/A:1024119224033"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00076-6"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(12)61058-1"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.56.6.884"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00723.2004"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1258\/mi.2009.009018"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.33.2.676"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/3.suppl_A.103"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(02)02473-6"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06722"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000081595.25297.1B"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1067\/mhj.2001.113218"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1161\/hc3601.095577"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(03)00423-6"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-1139"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2002.282.1.H256"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2004.10.050"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.679589"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(98)00036-9"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00659.2005"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2008.042788"}],"container-title":["Journal of Applied Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/japplphysiol.00994.2009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T21:50:50Z","timestamp":1567979450000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/japplphysiol.00994.2009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3]]},"references-count":71,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2010,3]]}},"alternative-id":["10.1152\/japplphysiol.00994.2009"],"URL":"https:\/\/doi.org\/10.1152\/japplphysiol.00994.2009","relation":{},"ISSN":["8750-7587","1522-1601"],"issn-type":[{"value":"8750-7587","type":"print"},{"value":"1522-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3]]}}}