{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:13Z","timestamp":1787028493883,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001081","name":"Hunter Medical Research Institute","doi-asserted-by":"publisher","award":["G2101102"],"award-info":[{"award-number":["G2101102"]}],"id":[{"id":"10.13039\/501100001081","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Newcastle","award":["G2101102"],"award-info":[{"award-number":["G2101102"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucocorticoids are steroids involved in key physiological processes such as development, metabolism, inflammatory and stress responses and are mostly used exogenously as medications to treat various inflammation-based conditions. They act via the glucocorticoid receptor (GR) expressed in most cells. Exogenous glucocorticoids can negatively impact the function of the Leydig cells in the testis, leading to decreased androgen production. However, endogenous glucocorticoids are produced by the adrenal and within the testis, but whether their action on GR in Leydig cells regulates steroidogenesis is unknown. This study aimed to define the role of endogenous GR signalling in adult Leydig cells. We developed and compared two models; an inducible Cre transgene driven by expression of the Cyp17a1 steroidogenic gene (Cyp17-iCre) that depletes GR during development and a viral vector-driven Cre (AAV9-Cre) to deplete GR in adulthood. The delivery of AAV9-Cre ablated GR in adult mouse Leydig cells depleted Leydig cell GR more efficiently than the Cyp17-iCre model. Importantly, adult depletion of GR in Leydig cells caused reduced expression of luteinising hormone receptor (Lhcgr) and of steroidogenic enzymes required for normal androgen production. These findings reveal that Leydig cell GR signalling plays a physiological role in the testis and highlight that a normal balance of glucocorticoid activity in the testis is important for steroidogenesis.<\/jats:p>","DOI":"10.3390\/ijms232315015","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T04:32:53Z","timestamp":1669782773000},"page":"15015","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Novel Model Using AAV9-Cre to Knockout Adult Leydig Cell Gene Expression Reveals a Physiological Role of Glucocorticoid Receptor Signalling in Leydig Cell Function"],"prefix":"10.3390","volume":"23","author":[{"given":"Anne-Louise","family":"Gannon","sequence":"first","affiliation":[{"name":"College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalucia L.","family":"Darbey","sequence":"additional","affiliation":[{"name":"College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Chensee","sequence":"additional","affiliation":[{"name":"College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7803-1611","authenticated-orcid":false,"given":"Ben M.","family":"Lawrence","sequence":"additional","affiliation":[{"name":"College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liza","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Kelso","sequence":"additional","affiliation":[{"name":"College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Reed","sequence":"additional","affiliation":[{"name":"College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1497-2321","authenticated-orcid":false,"given":"Shanmathi","family":"Parameswaran","sequence":"additional","affiliation":[{"name":"College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Smith","sequence":"additional","affiliation":[{"name":"College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee B.","family":"Smith","sequence":"additional","affiliation":[{"name":"College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"MRC Centre for Reproductive Health, The Queen\u2019s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK"},{"name":"Office for Research, Griffith University, Southport, QLD 4222, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Rebourcet","sequence":"additional","affiliation":[{"name":"College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"ref_1","first-page":"109","article-title":"Disorders of Adrenal Steroidogenesis: Impact on Gonadal Function and Sex Development","volume":"14","author":"Mooij","year":"2016","journal-title":"Pediatr. 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