{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:36:12Z","timestamp":1792024572040,"version":"4.4.0"},"reference-count":35,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T00:00:00Z","timestamp":1707782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100011611","name":"Shinshu Public Utility Foundation for Promotion of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011611","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Research","award":["21K15400"],"award-info":[{"award-number":["21K15400"]}]},{"name":"Scientific Research","award":["15H02536"],"award-info":[{"award-number":["15H02536"]}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sirt3 is a mitochondrial protein deacetylase functioning in energy metabolism, regulation of intracellular reactive oxygen species (ROS) levels, and aging. Although Sirt3 loss has negative effects on fertility of oocytes during in vitro fertilization and on progesterone production in granulosa cells, Sirt3's function in Leydig cells remains unclear. Therefore, we investigated Sirt3 activity in Leydig cells, focusing on androgen production. To do so, we performed immunohistochemistry to confirm Sirt3 localization in gonads and observed strong Sirt3 immunostaining in Leydig cells of human testes and of Sirt3+\/+ and Sirt3+\/\u2212 mouse testes, while Sirt3\u2212\/\u2212 mouse testis tissue was negative. In human ovary, hilus cells were strongly Sirt3-positive, theca cells showed weak positivity, and granulosa cells showed very weak or almost no immunostaining. Next, we used the murine Leydig tumor cell line MA-10 as a model. We overexpressed Sirt3 but observed no changes in proliferation, expression of Star, Cyp11a1 (p450scc gene), and Hsd3b, or progesterone production in MA-10 cells. Sirt3 knockdown significantly reduced proliferation, suppressed expressions of steroidogenic enzymes and of transcription factors Ad4bp (Sf-1 gene) and Gata4, and decreased progesterone production. Sirt3 knockdown in MA-10 cells also increased intracellular ROS levels based on CM-H2DCFDA fluorescence dye analysis and increased the proportion of both early and late apoptotic (necrotic) cells based on Annexin V\/7AAD assays. These results indicate that Sirt3 has a potential function in androgen production in Leydig cells by regulating intracellular ROS levels.<\/jats:p>","DOI":"10.1210\/endocr\/bqae017","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T19:31:42Z","timestamp":1707939102000},"source":"Crossref","is-referenced-by-count":11,"title":["Sirt3 Regulates Proliferation and Progesterone Production in Leydig Cells via Suppression of Reactive Oxygen Species"],"prefix":"10.1210","volume":"165","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9045-0835","authenticated-orcid":false,"given":"Hisanori","family":"Matoba","sequence":"first","affiliation":[{"name":"Department of Infection and Host Defense, Shinshu University School of Medicine , Matsumoto 390-8621 , Japan"},{"name":"Department of Molecular Pathology, Shinshu University School of Medicine , Matsumoto 390-8621 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8735-5274","authenticated-orcid":false,"given":"Chifumi","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Shinshu University School of Medicine , Matsumoto 390-8621 , Japan"},{"name":"Department of Biotechnology, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University , Matsumoto 390-8621 , Japan"},{"name":"Center for Medical Education and Clinical Training, Shinshu University School of Medicine , Matsumoto 390-8621 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuaki","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo , Bunkyo-ku 113-8654, Tokyo , Japan"},{"name":"Department of Pathology and Matrix Biology, Graduate School of Medicine, Mie University , Tsu 514-0001 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatomo","family":"Kawakubo","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Shinshu University School of Medicine , Matsumoto 390-8621 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanobu","family":"Momose","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Shinshu University Hospital , Matsumoto 390-8621 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Sano","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Shinshu University Hospital , Matsumoto 390-8621 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Imamura","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Shinshu University School of Medicine , Matsumoto 390-8621 , Japan"},{"name":"Department of Laboratory Medicine and Pathology, Shinshu University Hospital , Matsumoto 390-8621 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo , Bunkyo-ku 113-8654, Tokyo , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Shinshu University School of Medicine , Matsumoto 390-8621 , Japan"},{"name":"Department of Pathology, North Alps Medical Center Azumi Hospital , Ikeda-machi, Kitaazumi-gun 399-8695 , 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