{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:50:01Z","timestamp":1787237401592,"version":"build-2736575974"},"reference-count":51,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,12,1]]},"abstract":"<jats:p>In this study we aimed to elucidate a possible role of T in the regulation of sclerostin, a glycoprotein secreted by osteocytes known to regulate bone mass. To this end, we evaluated the effect of T stimulation on sclerostin production and gene expression in human cultured osteocytes. In addition, we evaluated serum sclerostin levels in a cohort of 20 hypogonadal male patients, compared with 20 age-matched eugonadal controls. Stimulation with DHT decreased sclerostin expression in cultured osteocytes in a time- and dose-dependent manner. Confirming a direct androgen receptor-mediated effect on sclerostin production, flutamide coincubation and silencing of androgen receptor gene in osteocytes abolished the DHT effects. In addition, hypogonadal patients showed higher serum sclerostin levels with respect to controls (145.87 \u00b1 50.83 pg\/mL vs 84.02 \u00b1 32.15 pg\/mL; P &amp;lt; .001) and in both probands and controls, serum T levels were negatively correlated with sclerostin (R = \u22120.664, P = 0.007, and R = \u22120.447, P = .045, respectively). Finally, multiple stepwise regression analysis showed that T represented the only independent predictor of sclerostin levels. In conclusion, by showing a direct correlation between T and sclerostin, both in vivo and in vitro, this study adds further support to the emerging clinical and experimental studies focusing on sclerostin as a therapeutic target for osteoporosis treatment.<\/jats:p>","DOI":"10.1210\/en.2015-1244","type":"journal-article","created":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T13:00:39Z","timestamp":1442926839000},"page":"4534-4544","source":"Crossref","is-referenced-by-count":23,"title":["Regulation of Sclerostin Production in Human Male Osteocytes by Androgens: Experimental and Clinical Evidence"],"prefix":"10.1210","volume":"156","author":[{"given":"Andrea","family":"Di Nisio","sequence":"first","affiliation":[{"name":"Department of Medicine (A.D.N., L.D.T., E.S., M.S.R., A.F., C.F.), University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"De Toni","sequence":"first","affiliation":[{"name":"Department of Medicine (A.D.N., L.D.T., E.S., M.S.R., A.F., C.F.), University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Speltra","sequence":"first","affiliation":[{"name":"Department of Medicine (A.D.N., L.D.T., E.S., M.S.R., A.F., C.F.), University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Santa","family":"Rocca","sequence":"first","affiliation":[{"name":"Department of Medicine (A.D.N., L.D.T., E.S., M.S.R., A.F., C.F.), University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Taglialavoro","sequence":"first","affiliation":[{"name":"Operative Unit of Andrology and Medicine of Human Reproduction, and Department of Surgical, Oncological, and Gastroenterological Sciences (G.T.), University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Ferlin","sequence":"first","affiliation":[{"name":"Department of Medicine (A.D.N., L.D.T., E.S., M.S.R., A.F., C.F.), University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Foresta","sequence":"first","affiliation":[{"name":"Department of Medicine (A.D.N., L.D.T., E.S., M.S.R., A.F., C.F.), University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2015,9,22]]},"reference":[{"key":"2020071611595730000_B1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1210\/edrv.23.3.0465","article-title":"Sex steroids and the construction and conservation of the adult skeleton","volume":"23","author":"Riggs","year":"2002","journal-title":"Endocr Rev"},{"key":"2020071611595730000_B2","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1210\/jcem-69-3-523","article-title":"Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodeling","volume":"69","author":"Stepan","year":"1989","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071611595730000_B3","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1002\/jbmr.5650101009","article-title":"Short-term effects of testosterone treatment on reduced bone density in boys with constitutional delay of puberty","volume":"10","author":"Bertelloni","year":"1995","journal-title":"J Bone Miner Res"},{"key":"2020071611595730000_B4","first-page":"1152","article-title":"A longitudinal evaluation of bone mineral density in adult men with histories of delayed puberty","volume":"81","author":"Finkelstein","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071611595730000_B5","doi-asserted-by":"crossref","first-page":"4576","DOI":"10.1210\/jcem.86.10.7960","article-title":"Sexual dimorphism in skeletal size, density, and strength","volume":"86","author":"Seeman","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071611595730000_B6","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1359\/jbmr.060103","article-title":"Relative impact of androgen and estrogen receptor activation in the effects of androgens on trabecular and cortical bone in growing male mice: a study in the androgen receptor knockout mouse model","volume":"21","author":"Venken","year":"2006","journal-title":"J Bone Miner Res"},{"key":"2020071611595730000_B7","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/jor.1100080418","article-title":"Differential effects of androgens on cortical bone histomorphometry in gonadectomized male and female rats","volume":"8","author":"Turner","year":"1990","journal-title":"J Orthop Res"},{"key":"2020071611595730000_B8","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1359\/JBMR.050404","article-title":"Free testosterone is a positive, whereas free estradiol is a negative, predictor of cortical bone size in young Swedish men: the GOOD study","volume":"20","author":"Lorentzon","year":"2005","journal-title":"J Bone Miner Res"},{"key":"2020071611595730000_B9","doi-asserted-by":"crossref","first-page":"e008","DOI":"10.1621\/nrs.06008","article-title":"Diverse roles of androgen receptor (AR) domains in AR-mediated signaling","volume":"6","author":"Claessens","year":"2008","journal-title":"Nucl Recept Signal"},{"issue":"3","key":"2020071611595730000_B10","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1677\/jme.1.01884","article-title":"Genomic actions of the androgen receptor are required for normal male sexual differentiation in a mouse model","volume":"35","author":"Notini","year":"2005","journal-title":"J Mol Endocrinol"},{"issue":"3","key":"2020071611595730000_B11","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1073\/pnas.86.3.854","article-title":"Identification of androgen receptors in normal human osteoblast-like cells","volume":"86","author":"Colvard","year":"1989","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"2020071611595730000_B12","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/BF00295958","article-title":"Immunocytochemical identification of androgen receptor in mouse osteoclast-like multinucleated cells","volume":"54","author":"Mizuno","year":"1994","journal-title":"Calcif Tissue Int"},{"issue":"1","key":"2020071611595730000_B13","first-page":"31","article-title":"Androgen receptors in bone-forming tissue","volume":"51","author":"Noble","year":"1999","journal-title":"Horm Res"},{"issue":"3","key":"2020071611595730000_B14","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1359\/jbmr.061117","article-title":"Osteoblast deletion of exon 3 of the androgen receptor gene results in trabecular bone loss in adult male mice","volume":"22","author":"Notini","year":"2007","journal-title":"J Bone Miner Res"},{"issue":"3","key":"2020071611595730000_B15","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1677\/joe.0.1750683","article-title":"Osteoblast differentiation influences androgen and estrogen receptor-\u03b1 and -\u03b2 expression","volume":"175","author":"Wiren","year":"2002","journal-title":"J Endocrinol"},{"issue":"5","key":"2020071611595730000_B16","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1210\/er.2012-1026","article-title":"The osteocyte: an endocrine cell. and more","volume":"34","author":"Dallas","year":"2013","journal-title":"Endocr Rev"},{"issue":"1","key":"2020071611595730000_B17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1357-2725(03)00241-3","article-title":"The osteocyte","volume":"36","author":"Knothe Tate","year":"2004","journal-title":"Int J Biochem Cell Biol"},{"issue":"23","key":"2020071611595730000_B18","doi-asserted-by":"crossref","first-page":"6267","DOI":"10.1093\/emboj\/cdg599","article-title":"Osteocyte control of bone formation via sclerostin, a novel BMP antagonist","volume":"22","author":"Winkler","year":"2003","journal-title":"EMBO J"},{"key":"2020071611595730000_B19","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1096\/fj.05-4221fje","article-title":"Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation","volume":"19","author":"Poole","year":"2005","journal-title":"FASEB J"},{"issue":"19","key":"2020071611595730000_B20","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.2106\/JBJS.M.01096","article-title":"A review of osteocyte function and the emerging importance of sclerostin","volume":"96","author":"Compton","year":"2014","journal-title":"J Bone Joint Surg Am"},{"issue":"12","key":"2020071611595730000_B21","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1002\/jbmr.1713","article-title":"Androgen receptor (AR) in osteocytes is important for the maintenance of male skeletal integrity: evidence from targeted AR disruption in mouse osteocytes","volume":"27","author":"Sinnesael","year":"2012","journal-title":"J Bone Miner Res"},{"key":"2020071611595730000_B22","doi-asserted-by":"crossref","first-page":"361","DOI":"10.2144\/0000113876","article-title":"Isolation and culture of primary osteocytes from the long bones of skeletally mature and aged mice","volume":"52","author":"Stern","year":"2012","journal-title":"Biotechniques"},{"issue":"4","key":"2020071611595730000_B23","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1210\/en.2009-1048","article-title":"Androgen receptor-dependent activation of endothelial nitric oxide synthase in vascular endothelial cells: role of phosphatidylinositol 3-kinase\/akt pathway","volume":"151","author":"Yu","year":"2010","journal-title":"Endocrinology"},{"issue":"2","key":"2020071611595730000_B24","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.bone.2009.10.007","article-title":"Relaxin stimulates osteoclast differentiation and activation","volume":"46","author":"Ferlin","year":"2010","journal-title":"Bone"},{"issue":"11","key":"2020071611595730000_B25","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1002\/art.24888","article-title":"Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis","volume":"60","author":"Appel","year":"2009","journal-title":"Arthritis Rheum"},{"issue":"10","key":"2020071611595730000_B26","doi-asserted-by":"crossref","first-page":"4616","DOI":"10.1210\/en.2012-1525","article-title":"The organizational and aromatization hypotheses apply to rapid, nonclassical hormone action: neonatal masculinization eliminates rapid estradiol action in female hippocampal neurons","volume":"153","author":"Meitzen","year":"2012","journal-title":"Endocrinology"},{"issue":"41","key":"2020071611595730000_B27","doi-asserted-by":"crossref","first-page":"29809","DOI":"10.1074\/jbc.M113.485938","article-title":"Resorption controls bone anabolism driven by parathyroid hormone (PTH) receptor signaling in osteocytes","volume":"288","author":"Rhee","year":"2013","journal-title":"J Biol Chem"},{"issue":"8","key":"2020071611595730000_B28","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1210\/en.2014-1046","article-title":"Parathyroid hormone receptor signaling induces bone resorption in the adult skeleton by directly regulating the RANKL gene in osteocytes","volume":"155","author":"Ben-Awadh","year":"2014","journal-title":"Endocrinology"},{"key":"2020071611595730000_B29","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s12672-013-0152-z","article-title":"On the origins of the androgen receptor low molecular weight species","volume":"4","author":"Mudryj","year":"2013","journal-title":"Horm Cancer"},{"issue":"4","key":"2020071611595730000_B30","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1359\/jbmr.081217","article-title":"Mineralization and bone resorption are regulated by the androgen receptor in male mice","volume":"24","author":"Chiang","year":"2009","journal-title":"J Bone Miner Res"},{"key":"2020071611595730000_B31","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1210\/en.2007-0270","article-title":"Targeting the Wnt\/\u03b2-catenin pathway to regulate bone formation in the adult skeleton","volume":"148","author":"Baron","year":"2007","journal-title":"Endocrinology"},{"key":"2020071611595730000_B32","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1172\/JCI28551","article-title":"Regulation of bone mass by Wnt signaling","volume":"116","author":"Krishnan","year":"2006","journal-title":"J Clin Invest"},{"issue":"12","key":"2020071611595730000_B33","doi-asserted-by":"crossref","first-page":"6741","DOI":"10.1210\/jc.2005-2370","article-title":"Sclerostin and Wnt signaling\u2014the pathway to bone strength","volume":"90","author":"Ott","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071611595730000_B34","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1084\/jem.20031454","article-title":"Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist","volume":"199","author":"van Bezooijen","year":"2004","journal-title":"J Exp Med"},{"key":"2020071611595730000_B35","doi-asserted-by":"crossref","first-page":"26770","DOI":"10.1074\/jbc.M504308200","article-title":"SOST is a ligand for LRP5\/LRP6 and a Wnt signaling inhibitor","volume":"280","author":"Semenov","year":"2005","journal-title":"J Biol Chem"},{"key":"2020071611595730000_B36","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.cytogfr.2005.02.005","article-title":"SOST\/sclerostin, an osteocyte-derived negative regulator of bone formation","volume":"16","author":"van Bezooijen","year":"2005","journal-title":"Cytokine Growth Factor Rev"},{"issue":"2","key":"2020071611595730000_B37","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S8756-3282(97)00234-2","article-title":"In vivo tracer transport through the lacunocanalicular system of rat bone in an environment devoid of mechanical loading","volume":"22","author":"Knothe Tate","year":"1998","journal-title":"Bone"},{"issue":"11","key":"2020071611595730000_B38","doi-asserted-by":"crossref","first-page":"5056","DOI":"10.1210\/jc.2010-0720","article-title":"Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women","volume":"95","author":"Drake","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"issue":"19","key":"2020071611595730000_B39","doi-asserted-by":"crossref","first-page":"3962","DOI":"10.1038\/emboj.2011.328","article-title":"Dual role of FoxA1 in androgen receptor binding to chromatin, androgen signalling and prostate cancer","volume":"30","author":"Sahu","year":"2011","journal-title":"EMBO J"},{"issue":"2","key":"2020071611595730000_B40","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.bone.2009.03.676","article-title":"The \u22129247 T\/C polymorphism in the SOST upstream regulatory region that potentially affects C\/EBP\u03b1 and FOXA1 binding is associated with osteoporosis","volume":"45","author":"Huang","year":"2009","journal-title":"Bone"},{"key":"2020071611595730000_B41","first-page":"F142","article-title":"A large scale candidate gene screen identifies an association between the Sclerostin (SOST) locus and femoral neck areal BMD in older men","volume":"21","author":"Moffett","year":"2006","journal-title":"J Bone Miner Res"},{"issue":"10","key":"2020071611595730000_B42","doi-asserted-by":"crossref","first-page":"e13637","DOI":"10.1371\/journal.pone.0013637","article-title":"MicroRNAs are mediators of androgen action in prostate and muscle","volume":"5","author":"Narayanan","year":"2010","journal-title":"PLoS One"},{"issue":"6","key":"2020071611595730000_B43","first-page":"379","article-title":"Altered bone status in unilateral testicular cancer survivors: role of CYP2R1 and its luteinizing hormone-dependency","volume":"36","author":"Foresta","year":"2013","journal-title":"J Endocrinol Invest"},{"issue":"11","key":"2020071611595730000_B44","doi-asserted-by":"crossref","first-page":"4266","DOI":"10.1210\/en.2014-1283","article-title":"Uncarboxylated osteocalcin stimulates 25-hydroxy vitamin D production in Leydig cell line through a GPRC6a-dependent pathway","volume":"155","author":"De Toni","year":"2014","journal-title":"Endocrinology"},{"issue":"2","key":"2020071611595730000_B45","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s00198-013-2462-y","article-title":"Sclerostin serum levels in prostate cancer patients and their relationship with sex steroids","volume":"25","author":"Garc\u00eda-Fontana","year":"2014","journal-title":"Osteoporos Int"},{"issue":"4","key":"2020071611595730000_B46","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1530\/EJE-12-1074","article-title":"Serum sclerostin levels in men with idiopathic osteoporosis","volume":"168","author":"Lapauw","year":"2013","journal-title":"Eur J Endocrinol"},{"issue":"1","key":"2020071611595730000_B47","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/jbmr.128","article-title":"Regulation of circulating sclerostin levels by sex steroids in women and in men","volume":"26","author":"M\u00f6dder","year":"2011","journal-title":"J Bone Miner Res"},{"key":"2020071611595730000_B48","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/bonekey.2013.174","article-title":"Inactivation of the androgen receptor in bone-forming cells leads to trabecular bone loss in adult female mice","volume":"2","author":"M\u00e4\u00e4tt\u00e4","year":"2013","journal-title":"Bonekey Rep"},{"issue":"7","key":"2020071611595730000_B49","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1002\/jbmr.2485","article-title":"The effects of androgens on murine cortical bone do not require AR or ER\u03b1 signaling in osteoblasts and osteoclasts","volume":"30","author":"Ucer","year":"2015","journal-title":"J Bone Miner Res"},{"issue":"14","key":"2020071611595730000_B50","doi-asserted-by":"crossref","first-page":"4461","DOI":"10.1523\/JNEUROSCI.0296-09.2009","article-title":"Conditional inactivation of androgen receptor gene in the nervous system: effects on male behavioral and neuroendocrine responses","volume":"29","author":"Raskin","year":"2009","journal-title":"J Neurosci"},{"issue":"6","key":"2020071611595730000_B51","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1210\/er.2014-1024","article-title":"Sex steroid actions in male bone","volume":"35","author":"Vanderschueren","year":"2014","journal-title":"Endocr Rev"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/156\/12\/4534\/8987558\/endo4534.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/156\/12\/4534\/8987558\/endo4534.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,21]],"date-time":"2022-05-21T23:46:11Z","timestamp":1653176771000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/156\/12\/4534\/2422764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,22]]},"references-count":51,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2015,12,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2015-1244","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,22]]}}}