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We report that an alternatively spliced form of\n                    <jats:italic>DENND1A<\/jats:italic>\n                    (DENND1A.V2) is increased in PCOS theca cells, the source of the excess androgens that characterizes PCOS. Forced expression of DENND1A.V2 in normal theca cells increased expression of genes encoding steroidogenic enzymes, leading to augmented androgen biosynthesis, whereas silencing of DENND1A.V2 in PCOS theca cells reverts them to a normal phenotype. Our findings establish that increased DENND1A.V2 expression is sufficient to promote a PCOS phenotype in human theca cells, information that can inform development of diagnostic tests as well as novel therapeutic interventions.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1400574111","type":"journal-article","created":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T02:13:03Z","timestamp":1396318383000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":208,"title":["Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype"],"prefix":"10.1073","volume":"111","author":[{"given":"Jan M.","family":"McAllister","sequence":"first","affiliation":[{"name":"Departments of aPathology and"},{"name":"Obstetrics and Gynecology, Pennsylvania State College of Medicine, Hershey, PA 17033; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavi","family":"Modi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Miller","sequence":"additional","affiliation":[{"name":"Departments of aPathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Biegler","sequence":"additional","affiliation":[{"name":"Departments of aPathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Bruggeman","sequence":"additional","affiliation":[{"name":"Departments of aPathology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Legro","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology, Pennsylvania State College of Medicine, Hershey, PA 17033; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Jerome F.","family":"Strauss","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2014,3,31]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/nrendo.2011.227","article-title":"Polycystic ovary syndrome in 2011: Genes, aging and sleep apnea in polycystic ovary syndrome","volume":"8","author":"Dunaif A","year":"2012","unstructured":"A Dunaif, Polycystic ovary syndrome in 2011: Genes, aging and sleep apnea in polycystic ovary syndrome. 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