{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:31:19Z","timestamp":1789662679898,"version":"4.0.1"},"reference-count":66,"publisher":"The Endocrine Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,7,1]]},"abstract":"<jats:p>The transcription factor sex-determining region of the Y chromosome (SRY) plays a key role in human sex determination, because mutations in SRY cause disorders of sex development in XY individuals. During gonadal development, Sry in pre-Sertoli cells activates Sox9 gene transcription, committing the fate of the bipotential gonad to become a testis rather than an ovary. The high-mobility group domain of human SRY contains two independent nuclear localization signals, one bound by calmodulin (CaM) and the other by importin-\u03b2. Although XY females carry SRY mutations in these nuclear localization signals that affect SRY nuclear import in transfected cells, it is not known whether these transport mechanisms are essential for gonadal development and sex determination. Here, we show that mouse Sry protein binds CaM and that a CaM antagonist reduces CaM binding, nuclear accumulation, and transcriptional activity of Sry in transfected cells. CaM antagonist treatment of cultured, sexually indifferent XY mouse fetal gonads led to reduced expression of the Sry target gene Sox9, defects in testicular cord formation, and ectopic expression of the ovarian markers Rspondin1 and forkhead box L2. These results indicate the importance of CaM for SRY nuclear import, transcriptional activity, testis differentiation, and sex determination.<\/jats:p>","DOI":"10.1210\/en.2010-1475","type":"journal-article","created":{"date-parts":[[2011,5,10]],"date-time":"2011-05-10T21:14:00Z","timestamp":1305062040000},"page":"2883-2893","source":"Crossref","is-referenced-by-count":15,"title":["Inhibition of SRY-Calmodulin Complex Formation Induces Ectopic Expression of Ovarian Cell Markers in Developing XY Gonads"],"prefix":"10.1210","volume":"152","author":[{"given":"Helena","family":"Sim","sequence":"first","affiliation":[{"name":"Molecular Genetics and Development Division (H.S., A.A., D.P.C., S.B.-F., V.R.H.), Prince Henry's Institute of Medical Research, Monash Medical Centre, and Department of Biochemistry and Molecular Biology, Melbourne, Victoria 3168, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Argentaro","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Development Division (H.S., A.A., D.P.C., S.B.-F., V.R.H.), Prince Henry's Institute of Medical Research, Monash Medical Centre, and Department of Biochemistry and Molecular Biology, Melbourne, Victoria 3168, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Czech","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Development Division (H.S., A.A., D.P.C., S.B.-F., V.R.H.), Prince Henry's Institute of Medical Research, Monash Medical Centre, and Department of Biochemistry and Molecular Biology, Melbourne, Victoria 3168, Australia;"},{"name":"Monash University (V.R.H., D.P.C.), Melbourne, Victoria 3168, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Bagheri-Fam","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Development Division (H.S., A.A., D.P.C., S.B.-F., V.R.H.), Prince Henry's Institute of Medical Research, Monash Medical Centre, and Department of Biochemistry and Molecular Biology, Melbourne, Victoria 3168, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.","family":"Sinclair","sequence":"additional","affiliation":[{"name":"Murdoch Children's Research Institute and Department of Paediatrics (A.H.S.), The University of Melbourne, Royal Children's Hospital, Parkville, Victoria 3052, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Koopman","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (P.K.), The University of Queensland, Brisbane, Queensland 4072, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Boizet-Bonhoure","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique Humaine Centre National de la Recherche Scientifique Unit\u00e9 Propre de Recherche 1142 (B.B.-B., F.P.), 34396 Montpellier Cedex 5, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Poulat","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique Humaine Centre National de la Recherche Scientifique Unit\u00e9 Propre de Recherche 1142 (B.B.-B., F.P.), 34396 Montpellier Cedex 5, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent R.","family":"Harley","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Development Division (H.S., A.A., D.P.C., S.B.-F., V.R.H.), Prince Henry's Institute of Medical Research, Monash Medical Centre, and Department of Biochemistry and Molecular Biology, 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