{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:58:23Z","timestamp":1791295103450,"version":"4.1.0"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"16","license":[{"start":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T00:00:00Z","timestamp":1505865600000},"content-version":"vor","delay-in-days":184,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/501100000925","name":"Department of Health, Australian Government | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1022648"],"award-info":[{"award-number":["APP1022648"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2017,4,18]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>The cause of polycystic ovary syndrome (PCOS) is unknown, but androgen excess is a key feature. We combined a hyperandrogenized PCOS mouse model with global and tissue- and cell-specific androgen-resistant mouse lines to uncover the sites of androgen action that initiate PCOS. We demonstrate that direct androgen actions, particularly in neurons but less so in granulosa cells, are required for the development of key reproductive and metabolic PCOS features. These data highlight the previously overlooked importance of extraovarian neuroendocrine androgen action in the origins of PCOS. Targeting androgen-driven mechanisms may represent new options for developing a mechanism-based treatment of PCOS.<\/jats:p>","DOI":"10.1073\/pnas.1616467114","type":"journal-article","created":{"date-parts":[[2017,3,20]],"date-time":"2017-03-20T20:55:39Z","timestamp":1490043339000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":197,"title":["Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome"],"prefix":"10.1073","volume":"114","author":[{"given":"Aimee S. L.","family":"Caldwell","sequence":"first","affiliation":[{"name":"Andrology Laboratory, ANZAC Research Institute, University of Sydney, Sydney, NSW 2139, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa C.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Andrology Laboratory, ANZAC Research Institute, University of Sydney, Sydney, NSW 2139, Australia;"},{"name":"Discipline of Obstetrics and Gynaecology, School of Women\u2019s and Children\u2019s Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Desai","sequence":"additional","affiliation":[{"name":"Andrology Laboratory, ANZAC Research Institute, University of Sydney, Sydney, NSW 2139, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Andrology Laboratory, ANZAC Research Institute, University of Sydney, Sydney, NSW 2139, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Gilchrist","sequence":"additional","affiliation":[{"name":"Discipline of Obstetrics and Gynaecology, School of Women\u2019s and Children\u2019s Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4200-7476","authenticated-orcid":false,"given":"David J.","family":"Handelsman","sequence":"additional","affiliation":[{"name":"Andrology Laboratory, ANZAC Research Institute, University of Sydney, Sydney, NSW 2139, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsty A.","family":"Walters","sequence":"additional","affiliation":[{"name":"Andrology Laboratory, ANZAC Research Institute, University of Sydney, Sydney, NSW 2139, Australia;"},{"name":"Discipline of Obstetrics and Gynaecology, School of Women\u2019s and Children\u2019s Health, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2017,3,20]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2011.09.024"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1385\/ENDO:30:1:27"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2015-1018"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/imj.12495"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0b013e32832afd4d"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1159\/000342179"},{"key":"e_1_3_3_7_2","first-page":"702","article-title":"Polycystic ovaries in female-to-male transsexuals","volume":"39","author":"Pache TD","year":"1993","unstructured":"TD Pache, BC Fauser, Polycystic ovaries in female-to-male transsexuals. Clin Endocrinol (Oxf) 39, 702\u2013703 (1993).","journal-title":"Clin Endocrinol (Oxf)"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.111.097808"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2012.10.005"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.01.013"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.05.011"},{"key":"e_1_3_3_12_2","first-page":"18","article-title":"The role of androgen receptor activity mediated by the CAG repeat polymorphism in the pathogenesis of PCOS","volume":"6","author":"Baculescu N","year":"2013","unstructured":"N Baculescu, The role of androgen receptor activity mediated by the CAG repeat polymorphism in the pathogenesis of PCOS. J Med Life 6, 18\u201325 (2013).","journal-title":"J Med Life"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1418216112"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.4103\/1008-682X.161600"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8529(05)70077-3"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308058101"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1507514112"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1887"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1530\/REP-14-0517"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1754"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1196"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0248"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.112.102012"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-3776"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9464"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8502"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/jez.1401650316"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0168"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.3109\/09513590.2012.754876"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.4103\/0974-1208.106338"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-984741"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1415038112"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2012.02.002"},{"key":"e_1_3_3_34_2","first-page":"2248","article-title":"Determinants of abnormal gonadotropin secretion in clinically defined women with polycystic ovary syndrome","volume":"82","author":"Taylor AE","year":"1997","unstructured":"AE Taylor, , Determinants of abnormal gonadotropin secretion in clinically defined women with polycystic ovary syndrome. J Clin Endocrinol Metab 82, 2248\u20132256 (1997).","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2014.12.003"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03347020"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2004.01973.x"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2012.10.010"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1530\/JME-12-0247"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v6.i15.1296"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1290"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1523236113"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2586"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1050"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-259234"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1677\/jme.1.01884"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(03)00099-6"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00263.2013"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10100"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/gene.1078"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-1750"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63377"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.02.009"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1616467114","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1616467114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T03:07:56Z","timestamp":1649819276000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1616467114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,20]]},"references-count":53,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2017,4,18]]}},"alternative-id":["10.1073\/pnas.1616467114"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1616467114","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727449229.793530333","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,20]]},"assertion":[{"value":"2017-03-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}