Title: Follicle‐stimulating hormone synthesis and fertility depend on SMAD4 and FOXL2
Abstract: The FASEB JournalVolume 28, Issue 8 p. 3396-3410 Research CommunicationFree to Read Follicle-stimulating hormone synthesis and fertility depend on SMAD4 and FOXL2 Jérôme Fortin, Corresponding Author Jérôme Fortin [email protected] Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, CanadaCorrespondence: Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Rm. 1315, Montréal, QC, H3G 1Y6, Canada. E-mail: J.F., [email protected]; D.J.B., [email protected] for more papers by this authorUlrich Boehm, Ulrich Boehm Department of Pharmacology and Toxicology, University of Saarland School of Medicine, Homburg, GermanySearch for more papers by this authorChu-Xia Deng, Chu-Xia Deng National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USASearch for more papers by this authorMathias Treier, Mathias Treier Max Delbrück Center for Molecular Medicine, Berlin, GermanySearch for more papers by this authorDaniel J. Bernard, Corresponding Author Daniel J. Bernard [email protected] Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, CanadaCorrespondence: Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Rm. 1315, Montréal, QC, H3G 1Y6, Canada. E-mail: J.F., [email protected]; D.J.B., [email protected] for more papers by this author Jérôme Fortin, Corresponding Author Jérôme Fortin [email protected] Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, CanadaCorrespondence: Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Rm. 1315, Montréal, QC, H3G 1Y6, Canada. E-mail: J.F., [email protected]; D.J.B., [email protected] for more papers by this authorUlrich Boehm, Ulrich Boehm Department of Pharmacology and Toxicology, University of Saarland School of Medicine, Homburg, GermanySearch for more papers by this authorChu-Xia Deng, Chu-Xia Deng National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USASearch for more papers by this authorMathias Treier, Mathias Treier Max Delbrück Center for Molecular Medicine, Berlin, GermanySearch for more papers by this authorDaniel J. Bernard, Corresponding Author Daniel J. Bernard [email protected] Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, CanadaCorrespondence: Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Rm. 1315, Montréal, QC, H3G 1Y6, Canada. E-mail: J.F., [email protected]; D.J.B., [email protected] for more papers by this author First published: 16 April 2014 https://doi.org/10.1096/fj.14-249532Citations: 1 This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Follicle-stimulating hormone (FSH) is an essential regulator of gonadal function and fertility. Loss-of-function mutations in the FSHB/Fshb gene cause hypogonadotropic hypogonadism in humans and mice. Both gonadotropin-releasing hormone (GnRH) and activins, members of the transforming growth factor β (TGFβ) superfamily, stimulate FSH synthesis; yet, their relative roles and mechanisms of action in vivo are unknown. Here, using conditional gene-targeting, we show that the canonical mediator of TGFβ superfamily signaling, SMAD4, is absolutely required for normal FSH synthesis in both male and female mice. Moreover, when the Smad4 gene is ablated in combination with its DNA binding cofactor Foxl2 in gonadotrope cells, mice make essentially no FSH and females are sterile. Indeed, the phenotype of these animals is remarkably similar to that of Fshb -knockout mice. Not only do these results establish SMAD4 and FOXL2 as essential master regulators of Fshb transcription in vivo, they also suggest that activins, or related ligands, could play more important roles in FSH synthesis than GnRH.—Fortin, J., Boehm, U., Deng, C.-X., Treier, M., Bernard, D. J. Follicle-stimulating hormone synthesis and fertility depend on SMAD4 and FOXL2. FASEB J. 28, 3396–3410 (2014). www.fasebj.org Citing Literature Supporting Information Filename Description fsb2028008012-sup-0001.zipZip archive, 1.1 MB Supplementary material Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume28, Issue8August 2014Pages 3396-3410 RelatedInformation