{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:23:12Z","timestamp":1790839392803,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS (Japan Society for the Promotion of Science) KAKENHI","doi-asserted-by":"publisher","award":["21H00235"],"award-info":[{"award-number":["21H00235"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS (Japan Society for the Promotion of Science) KAKENHI","doi-asserted-by":"publisher","award":["R02B-025"],"award-info":[{"award-number":["R02B-025"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Kawasaki Medical School","award":["21H00235"],"award-info":[{"award-number":["21H00235"]}]},{"name":"Kawasaki Medical School","award":["R02B-025"],"award-info":[{"award-number":["R02B-025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nuclear receptor subfamily 5 group A member 1 (NR5A1) is expressed in the pituitary gonadotrope and regulates their differentiation. Although several regulatory regions were implicated in Nr5a1 gene expression in the pituitary gland, none of these regions have been verified using mouse models. Furthermore, the molecular functions of NR5A1 in the pituitary gonadotrope have not been fully elucidated. In the present study, we generated mice lacking the pituitary enhancer located in the 6th intron of the Nr5a1 gene. These mice showed pituitary gland-specific disappearance of NR5A1, confirming the functional importance of the enhancer. Enhancer-deleted male mice demonstrated no defects at fetal stages. Meanwhile, androgen production decreased markedly in adult, and postnatal development of reproductive organs, such as the seminal vesicle, prostate, and penis was severely impaired. We further performed transcriptomic analyses of the whole pituitary gland of the enhancer-deleted mice and controls, as well as gonadotropes isolated from Ad4BP-BAC-EGFP mice. These analyses identified several genes showing gonadotrope-specific, NR5A1-dependent expressions, such as Spp1, Tgfbr3l, Grem1, and Nr0b2. These factors are thought to function downstream of NR5A1 and play important roles in reproductive organ development through regulation of pituitary gonadotrope functions.<\/jats:p>","DOI":"10.3390\/ijms24010192","type":"journal-article","created":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T02:09:03Z","timestamp":1671761343000},"page":"192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Intronic Enhancer Is Essential for Nr5a1 Expression in the Pituitary Gonadotrope and for Postnatal Development of Male Reproductive Organs in a Mouse Model"],"prefix":"10.3390","volume":"24","author":[{"given":"Yuichi","family":"Shima","sequence":"first","affiliation":[{"name":"Division of Microscopic and Developmental Anatomy, Department of Anatomy, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Fukuoka, Japan"},{"name":"Department of Anatomy, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Miyabayashi","sequence":"additional","affiliation":[{"name":"Division of Microscopic and Developmental Anatomy, Department of Anatomy, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takami","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Medical Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare, 288 Matsushima, Kurashiki 701-0193, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5627-026X","authenticated-orcid":false,"given":"Koji","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Okayama, Japan"},{"name":"School of Medical Technology, Faculty of Health and Medical Care, Saitama Medical University, 1397-1 Yamane, Hidaka 350-1241, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuki","family":"Kajimoto","sequence":"additional","affiliation":[{"name":"Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd. (SNBL), 16-1 Minamiakasaka, Kainan-shi 642-0017, Wakayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Lim","family":"Cho","sequence":"additional","affiliation":[{"name":"Center for Advanced Biomolecular Recognition, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seoul 02792, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Tsuchida","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8272-2781","authenticated-orcid":false,"given":"Yoshihisa","family":"Uenoyama","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Tsukamura","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Faculty of Life and Environmental Sciences, University of Yamanashi, 4-4-37, Takeda, Kofu 400-8510, Yamanashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Center for Advanced Biomolecular Recognition, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seoul 02792, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Toida","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Okayama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17294","DOI":"10.1073\/pnas.0404743101","article-title":"Targeted disruption of luteinizing hormone beta-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and infertility","volume":"101","author":"Ma","year":"2004","journal-title":"Proc. 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