{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:27:29Z","timestamp":1792805249029,"version":"4.5.0"},"reference-count":71,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Health, National Health and Medical Research Council (NHMRC)","award":["APP1158344"],"award-info":[{"award-number":["APP1158344"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Newcastle HDR Research Training Program","award":["APP1158344"],"award-info":[{"award-number":["APP1158344"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Androgens such as testosterone and dihydrotestosterone (DHT) are essential for male sexual development, masculinisation, and fertility. Testosterone is produced via the canonical androgen production pathway and is essential for normal masculinisation and testis function. Disruption to androgen production can result in disorders of sexual development (DSD). In the canonical pathway, 17\u03b2-hydroxysteroid dehydrogenase type 3 (HSD17B3) is viewed as a critical enzyme in the production of testosterone, performing the final conversion required. HSD17B3 deficiency in humans is associated with DSD due to low testosterone concentration during development. Individuals with HSD17B3 mutations have poorly masculinised external genitalia that can appear as ambiguous or female, whilst having internal Wolffian structures and testes. Recent studies in mice deficient in HSD17B3 have made the surprising finding that testosterone production is maintained, male mice are masculinised and remain fertile, suggesting differences between mice and human testosterone production exist. We discuss the phenotypic differences observed and the possible other pathways and enzymes that could be contributing to testosterone production and male development. The identification of alternative testosterone synthesising enzymes could inform the development of novel therapies to endogenously regulate testosterone production in individuals with testosterone deficiency.<\/jats:p>","DOI":"10.3390\/ijms232415555","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T01:51:26Z","timestamp":1670550686000},"page":"15555","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["New Insights into Testosterone Biosynthesis: Novel Observations from HSD17B3 Deficient Mice"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7803-1611","authenticated-orcid":false,"given":"Ben M.","family":"Lawrence","sequence":"first","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":"Lee B.","family":"Smith","sequence":"additional","affiliation":[{"name":"College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Office for Research, Griffith University, Southport, QLD 4222, Australia"},{"name":"MRC Centre for Reproductive Health, The Queen\u2019s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK"}],"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":[[2022,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/nrendo.2013.73","article-title":"Risks and benefits of testosterone therapy in older men","volume":"9","author":"Spitzer","year":"2013","journal-title":"Nat. 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