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We investigate serum hormone levels, Leydig cell number, gene and protein expression in vivo. We also explore the effects of FGF16 treatment on stem Leydig cell proliferation in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>FGF16 lowers serum testosterone levels (21.6% of the control at a dose of 100\u00a0ng\/testis) without affecting the levels of luteinizing hormone (LH) and follicle\u2010stimulating hormone (FSH) on post\u2010EDS day 28 in vivo. FGF16 increases Leydig cell number at doses of 10 and 100\u00a0ng\/mg without affecting Sertoli cell number, increases the percentage of PCNA\u2010positive Leydig cells, and down\u2010regulates the expression of Leydig cell genes (<jats:italic>Lhcgr<\/jats:italic>, <jats:italic>Scarb1<\/jats:italic>, <jats:italic>Star<\/jats:italic>, <jats:italic>Cyp11a1<\/jats:italic>, <jats:italic>Cyp17a1<\/jats:italic> and <jats:italic>Hsd17b3<\/jats:italic>) and Sertoli cell genes (<jats:italic>Fshr<\/jats:italic>, <jats:italic>Dhh<\/jats:italic> and <jats:italic>Sox9<\/jats:italic>) and their proteins in vivo. FGF16 increases phosphorylation of AKT1 and AKT2 as well as EKR1\/2 in vivo, indicating that it possibly acts via AKT1\/ATK2 and ERK1\/2 pathways. FGF16 also lowers medium testosterone levels and down\u2010regulates the expression of Leydig cell genes (<jats:italic>Lhcgr<\/jats:italic>, <jats:italic>Scarb1<\/jats:italic>, <jats:italic>Star<\/jats:italic>, <jats:italic>Cyp11a1<\/jats:italic>, <jats:italic>Cyp17a1<\/jats:italic> and <jats:italic>Hsd17b3<\/jats:italic>) but increases EdU incorporation into stem Leydig cells in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that FGF16 stimulates stem and progenitor Leydig cell proliferation but blocks their differentiation, thus lowering testosterone biosynthesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jcmm.14157","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T08:25:29Z","timestamp":1548318329000},"page":"2632-2644","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Fibroblast growth factor 16 stimulates proliferation but blocks differentiation of rat stem Leydig cells during regeneration"],"prefix":"10.1111","volume":"23","author":[{"given":"Yue","family":"Duan","sequence":"first","affiliation":[{"name":"Department of Neonatology, The Second Affiliated Hospital and Yuying Children\u2019s Hospital Wenzhou Medical University Wenzhou Zhejiang China"},{"name":"Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children\u2019s Hospital Wenzhou Medical University Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children\u2019s Hospital Wenzhou Medical University Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children\u2019s Hospital Wenzhou Medical University Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children\u2019s Hospital Wenzhou Medical University Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0188-400X","authenticated-orcid":false,"given":"Xiaoling","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children\u2019s Hospital Wenzhou Medical University Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children\u2019s Hospital Wenzhou Medical University Wenzhou Zhejiang 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