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Notably, the IGF system has been reported to mediate the proliferation of steroidogenic cells. However, the precise role and contribution of the membrane receptors mediating those effects, namely, ins\u00fclin receptor (INSR) and type\u2010I ins\u00fclin\u2010like growth factor receptor (IGF1R), have not, to o\u00fcr knowledge, been investigated. We show here that specific deletion of both\n                    <jats:italic>Insr<\/jats:italic>\n                    and\n                    <jats:italic>Igf1r<\/jats:italic>\n                    in steroidogenic cells in mice leads to severe alterations of adrenocortical and testicular development. Double\u2010mutant mice display drastic size reduction of both adrenocortex and testes, with impaired corticosterone, testosterone, and sperm production. Detailed developmental analysis of the testes revealed that fetal Leydig cell (LC) function is normal, but there is a failure of adult LC maturation and steroidogenic function associated with accumulation of progenitor LCs (PLCs). Cell\u2010lineage tracing revealed PLC enrichment is secondary to\n                    <jats:italic>Insr<\/jats:italic>\n                    and\n                    <jats:italic>Igf1r<\/jats:italic>\n                    deletion in differentiated adult LCs, suggesting a feedback mechanism between cells at different steps of differentiation. Taken together, these data reveal the cell\u2010autonomous and nonautonomous roles of the IGF system for proper development and maintenance of steroidogenic lineages.\u2014Neirijnck, Y., Calvel, P., Kilcoyne, K. R., K\u00fchne, F., Stevant, I., Griffeth, R. J., Pitetti, J.\u2010L., Andric, S. A., H\u00fc, M.\u2010C., Pralong, F., Smith, L. B., Nef, S. Insulin and IGF1 receptors are essential for the development and steroidogenic function of ad\u00fclt Leydig cells. FASEB J. 32, 3321\u20133335 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700769rr","type":"journal-article","created":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T09:54:12Z","timestamp":1516787652000},"page":"3321-3335","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Insulin and IGF1 receptors are essential for the development and steroidogenic function of adult Leydig cells"],"prefix":"10.1096","volume":"32","author":[{"given":"Yasmine","family":"Neirijnck","sequence":"first","affiliation":[{"name":"Department of Genetic Medicine and Development University of Geneva Medical School  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Calvel","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development University of Geneva Medical School  Geneva Switzerland"},{"name":"G\u00e9n\u00e9tique Animale et Biologie Int\u00e9grative (GABI) Institut National de la Recherche Agronomique (INRA) AgroParisTech Universit\u00e9 Paris-Saclay  Jouy-en-Josas France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen R.","family":"Kilcoyne","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Centre for Reproductive Health University of Edinburgh  Edinburgh Scotland United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"K\u00fchne","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development University of Geneva Medical School  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"St\u00e9vant","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development University of Geneva Medical School  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Griffeth","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development University of Geneva Medical School  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-L\u00fcc","family":"Pitetti","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development University of Geneva Medical School  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana A.","family":"Andric","sequence":"additional","affiliation":[{"name":"Laboratory for Reproductive Endocrinology and Signaling Faculty of Sciences University of Novi Sad  Novi Sad Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Chun","family":"Hu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Physiology National Taiwan University College of Medicine  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Pralong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University Hospital  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee B.","family":"Smith","sequence":"additional","affiliation":[{"name":"Medical Research Council (MRC) Centre for Reproductive Health University of Edinburgh  Edinburgh Scotland United Kingdom"},{"name":"School of Environmental and Life Sciences, University of Newcastle  Callaghan New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Nef","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development University of Geneva Medical School  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2015.01.009"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2014.02.012"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-416021-7.00007-9"},{"key":"e_1_2_8_5_1","first-page":"101","volume":"58","author":"Potter S. 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