{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T03:30:47Z","timestamp":1789702247810,"version":"4.0.1"},"reference-count":39,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:p>\n                    Abdominal aortic aneurysm (AAA), one of the pathological phenotypes of vascular aging, is characterized by aortic dilation with impaired arterial wall integrity. Recent epidemiologic studies have shown that men with AAA have lower serum testosterone compared to men without. However, the underlying mechanisms remain unclear. In this study, we investigated the effects of testosterone on AAA formation using a murine AAA model under the conditions of depletion and administration of testosterone. In wild-type male mice (C57BL\/6J), AAA was induced by CaCl\n                    <jats:sub>2<\/jats:sub>\n                    application and angiotensin II infusion at 5 weeks after castration. Exacerbated AAA formation was seen in castrated mice, compared with sham-operated mice. Histological analysis revealed marked infiltration of macrophages in the destroyed aorta and IL-6\/pSTAT3 expression was significantly elevated, suggesting that AAA development by castration is attributable to pronounced inflammation. Conversely, both 4-week and 9-week administration of testosterone significantly prevented AAA formation, and improvement of histological findings was confirmed. Aortic\n                    <jats:italic>F4\/80<\/jats:italic>\n                    ,\n                    <jats:italic>Il-1b<\/jats:italic>\n                    and\n                    <jats:italic>Il-6<\/jats:italic>\n                    expression were significantly inhibited both by testosterone administration. Indeed, mice with implanted flutamide exhibited exacerbated AAA formation and aortic\n                    <jats:italic>F4\/80<\/jats:italic>\n                    ,\n                    <jats:italic>Il-1b<\/jats:italic>\n                    and\n                    <jats:italic>Il-6<\/jats:italic>\n                    expression were significantly increased. Taken together, these results demonstrate that testosterone depletion and AR blockade precede AAA formation, and conversely, testosterone administration could suppress AAA formation by regulating macrophage-mediated inflammatory responses. This anti-inflammatory action of testosterone\/AR on AAA formation might provide a mechanistic insight into the vascular protective actions of testosterone and suggest that its proper administration or selective AR modulators might be novel therapeutic strategies for this aortic pathology.\n                  <\/jats:p>","DOI":"10.1530\/joe-18-0646","type":"journal-article","created":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T07:56:29Z","timestamp":1556092589000},"page":"307-317","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":25,"title":["Testosterone inhibits aneurysm formation and vascular inflammation in male mice"],"prefix":"10.1530","volume":"241","author":[{"given":"Bo-Kyung","family":"Son","sequence":"first","affiliation":[{"name":"1Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"},{"name":"2Institute of Gerontology, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Kojima","sequence":"additional","affiliation":[{"name":"1Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumito","family":"Ogawa","sequence":"additional","affiliation":[{"name":"1Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Akishita","sequence":"additional","affiliation":[{"name":"1Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref291","first-page":"21","article-title":"LipoSEARCH\u00ae; analytical GP-HPLC method for lipoprotein profiling and its applications","volume":"3","year":"2013","journal-title":"Journal of Biological Macromolecules"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1152\/ajpendo.1998.274.5.E867","article-title":"Mechanisms contributing to angiotensin II regulation of body weight of https org","year":"1998","journal-title":"American Journal Physiology"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"6994","DOI":"10.1038\/ncomms7994","article-title":"Granulocyte macrophage colony-stimulating factor is required for aortic dissection\/intramural haematoma","volume":"6","year":"2015","journal-title":"Nature Communications"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1136\/hrt.2003.021121","article-title":"Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life","volume":"90","year":"2004b","journal-title":"Heart"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.bcp.2017.05.022","article-title":"Testosterone regulates 3T3-L1 pre-adipocyte differentiation and epididymal fat accumulation in mice through modulating macrophage polarization","volume":"140","year":"2017","journal-title":"Biochemical Pharmacology"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1530\/EJE-06-0737","article-title":"The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes","volume":"156","year":"2007","journal-title":"European Journal of Endocrinology"},{"key":"ref331","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1161\/ATVBAHA.118.311252","article-title":"Testosterone protects against atherosclerosis in male mice by targeting thymic epithelial cells \u2013 brief report","volume":"38","year":"2018","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1161\/HYPERTENSIONAHA.115.05654","article-title":"Androgen receptor promotes abdominal aortic aneurysm development via modulating inflammatory interleukin-1\u03b1 and transforming growth factor-\u03b21 expression","volume":"66","year":"2015","journal-title":"Hypertension"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1046\/j.1365-2249.1996.d01-842.x","article-title":"Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells","volume":"106","year":"1996","journal-title":"Clinical and Experimental Immunology"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.abb.2017.03.007","article-title":"Abnormal lipid\/lipoprotein metabolism and high plasma testosterone levels in male but not female aromatase-knockout mice","volume":"622","year":"2017","journal-title":"Archives of Biochemistry and Biophysics"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.jsbmb.2015.08.007","article-title":"ALPK1 affects testosterone mediated regulation of proinflammatory cytokines production","volume":"154","year":"2015","journal-title":"Journal of Steroid Biochemistry and Molecular Biology"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"3632","DOI":"10.1210\/jcem.87.8.8762","article-title":"Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study","volume":"87","year":"2002","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref271","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.atherosclerosis.2012.05.009","article-title":"Low plasma testosterone and elevated carotid intima-media thickness: importance of low-grade inflammation in elderly men","volume":"223","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref361","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.jvs.2013.11.004","article-title":"Castration of male mice prevents the progression of established angiotensin II-induced abdominal aortic aneurysms","volume":"61","year":"2015","journal-title":"Journal of Vascular Surgery"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1161\/ATVBAHA.107.160382","article-title":"Androgen increases AT1a receptor expression in abdominal aortas to promote angiotensin II-induced AAAs in apolipoprotein E-deficient mice","volume":"28","year":"2008","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1359\/jbmr.1999.14.8.1330","article-title":"The anti-androgen hydroxyflutamide and androgens inhibit Interleukin-6 production by an androgen-responsive human osteoblastic cell line","volume":"14","year":"1999","journal-title":"Journal of Bone and Mineral Research"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"5428","DOI":"10.1210\/en.2010-0663","article-title":"Androgen receptor-dependent and independent atheroprotection by testosterone in male mice","volume":"151","year":"2010","journal-title":"Endocrinology"},{"key":"ref341","first-page":"931","article-title":"Study of androgen and atherosclerosis in old-age male","volume":"6","year":"2005","journal-title":"Journal of Zhejiang University: Science B"},{"key":"ref241","first-page":"263","article-title":"Androgen replacement therapy of male hypogonadism.","year":"1999","journal-title":"Contemporary Endocrinology: Hormone Replacement Therapy"},{"key":"ref371","doi-asserted-by":"crossref","first-page":"701","DOI":"10.2131\/jts.39.701","article-title":"Effects of endosulfan on the immune function of erythrocytes, and potential protection by testosterone propionate","volume":"39","year":"2014","journal-title":"Journal of Toxicological Sciences"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1210\/jc.2007-0862","article-title":"Age-related changes in serum testosterone and sex hormone binding globulin in Australian men: longitudinal analyses of two geographically separate regional cohorts","volume":"92","year":"2007","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1677\/JOE-10-0057","article-title":"Sex hormone modulation of proinflammatory cytokine and C-reactive protein expression in macrophage from older men and postmenopausal women","volume":"206","year":"2010","journal-title":"Journal of Endocrinology"},{"key":"ref01","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1161\/01.ATV.0000143386.26399.84","article-title":"Gender differences in experimental aortic aneurysm formation","volume":"24","year":"2004","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"key":"ref311","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1507\/endocrj.EJ12-0060","article-title":"Low serum free testosterone level is associated with carotid intima-media thickness in middle-aged Japanese men","volume":"59","year":"2012","journal-title":"Endocrine Journal"},{"key":"ref321","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1152\/ajpcell.1997.273.4.1335","article-title":"WichmannMWAyalaAChaudryIH Male sex steroids are responsible for depressing macrophage immune function after trauma - hemorrhage of https org","year":"1997","journal-title":"American Journal Physiology"},{"key":"ref251","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1055\/s-2007-976543","article-title":"Inverse relationship between serum levels of interleukin-1b and testosterone in men with stable coronary artery disease","volume":"39","year":"2007","journal-title":"Hormone and Metabolic Research"},{"key":"ref181","first-page":"157","article-title":"Effect of gonadal steroids on the production of IL-1 and IL-6 by blood mononuclear cells in vitro","volume":"11","year":"1993","journal-title":"Clinical and Experimental Rheumatology"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1210\/jc.2003-031069","article-title":"The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men","volume":"89","year":"2004a","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.1038\/srep04051","article-title":"Tenascin C protects aorta from acute dissection in mice","volume":"4","year":"2014","journal-title":"Scientific Reports"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1111\/j.1749-6632.1999.tb07667.x","article-title":"Sex hormones modulate inflammatory mediators produced by macrophages","volume":"876","year":"1999","journal-title":"Annals of the New York Academy of Sciences"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1210\/jcem.87.2.8201","article-title":"Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study","volume":"87","year":"2002","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref381","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1002\/ptr.5838","article-title":"Protective effects of Lepidium meyenii (Maca) aqueous extract and lycopene on testosterone propionate-induced prostatic hyperplasia in mice","volume":"31","year":"2017","journal-title":"Phytotherapy Research"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1161\/CIRCULATIONAHA.106.628875","article-title":"Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis","volume":"115","year":"2007","journal-title":"Circulation"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1210\/jc.2009-1696","article-title":"Associations of total testosterone, sex hormone-binding globulin, calculated free testosterone, and luteinizing hormone with prevalence of abdominal aortic aneurysm in older men","volume":"95","year":"2010","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref151","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1530\/JOE-12-0582","article-title":"Testosterone a vascular hormone in disease of https org","author":"KellyDMJonesTH","year":"2013","journal-title":"health Journal Endocrinology"},{"key":"ref301","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cellimm.2015.02.004","article-title":"Suppressive effects of androgens on the immune system","volume":"294","year":"2015","journal-title":"Cellular Immunology"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"3866","DOI":"10.1210\/en.2003-1615","article-title":"Orchidectomy, but not ovariectomy, regulates angiotensin II-induced vascular diseases in apolipoprotein E-deficient mice","volume":"145","year":"2004","journal-title":"Endocrinology"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1677\/joe.1.06779","article-title":"Androgen-replacement therapy depresses the ex vivo production of inflammatory cytokines by circulating antigen-presenting cells in aging type-2 diabetic men with partial androgen deficiency","volume":"189","year":"2006","journal-title":"Journal of Endocrinology"},{"key":"ref211","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1210\/jc.2005-1097","article-title":"Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor in older men","volume":"91","year":"2006","journal-title":"Journal of Clinical Endocrinology and Metabolism"}],"container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/241\/3\/JOE-18-0646.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/241\/3\/JOE-18-0646.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:56:38Z","timestamp":1784555798000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/241\/3\/307-317\/5249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6]]},"references-count":39,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1530\/joe-18-0646","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6]]}}}