{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T22:11:00Z","timestamp":1767910260366,"version":"3.49.0"},"reference-count":83,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-81387"],"award-info":[{"award-number":["MOP-81387"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The peptide hormone insulin-like 3 (INSL3) is produced almost exclusively by Leydig cells of the male gonad. INSL3 has several functions such as fetal testis descent and bone metabolism in adults. Insl3 gene expression in Leydig cells is not hormonally regulated but rather is constitutively expressed. The regulatory region of the Insl3 gene has been described in various species; moreover, functional studies have revealed that the Insl3 promoter is regulated by various transcription factors that include the nuclear receptors AR, NUR77, COUP-TFII, LRH1, and SF1, as well as the Kr\u00fcppel-like factor KLF6. However, these transcription factors are also found in several tissues that do not express Insl3, indicating that other, yet unidentified factors, must be involved to drive Insl3 expression specifically in Leydig cells. Through a fine functional promoter analysis, we have identified a 35-bp region that is responsible for conferring 70% of the activity of the mouse Insl3 promoter in Leydig cells. All tri- and dinucleotide mutations introduced dramatically reduced Insl3 promoter activity, indicating that the entire 35-bp sequence is required. Nuclear proteins from MA-10 Leydig cells bound specifically to the 35-bp region. The 35-bp sequence contains GC- and GA-rich motifs as well as potential binding elements for members of the CREB, C\/EBP, AP1, AP2, and NF-\u03baB families. The Insl3 promoter was indeed activated 2-fold by NF-\u03baB p50 but not by other transcription factors tested. These results help to further define the regulation of Insl3 gene transcription in Leydig cells.<\/jats:p>","DOI":"10.3390\/ijms232315060","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T01:54:31Z","timestamp":1669859671000},"page":"15060","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A 35-bp Conserved Region Is Crucial for Insl3 Promoter Activity in Mouse MA-10 Leydig Cells"],"prefix":"10.3390","volume":"23","author":[{"given":"Xavier C.","family":"Giner","sequence":"first","affiliation":[{"name":"Reproduction, Mother and Child Health, Room T3-67, CHU de Qu\u00e9bec\u2014Universit\u00e9 Laval Research Centre, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenley Joule","family":"Pierre","sequence":"additional","affiliation":[{"name":"Reproduction, Mother and Child Health, Room T3-67, CHU de Qu\u00e9bec\u2014Universit\u00e9 Laval Research Centre, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas M.","family":"Robert","sequence":"additional","affiliation":[{"name":"Reproduction, Mother and Child Health, Room T3-67, CHU de Qu\u00e9bec\u2014Universit\u00e9 Laval Research Centre, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4738-6284","authenticated-orcid":false,"given":"Jacques J.","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Reproduction, Mother and Child Health, Room T3-67, CHU de Qu\u00e9bec\u2014Universit\u00e9 Laval Research Centre, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"Centre for Research in Reproduction, Development and Intergenerational Health, Department of Obstetrics, Gynecology and Reproduction, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1159\/000179780","article-title":"Role of androgens in fetal and pubertal development","volume":"18","author":"Forest","year":"1983","journal-title":"Horm. 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