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Human follicle-stimulating hormone ß subunit expression depends on FOXL2 and SMAD4
Ongaro,Luisina1; Schang,Gauthier1; Zhou,Ziyue1; Kumar,T. Rajendra2; Treier,Mathias3; Deng,Chu Xia4; Boehm,Ulrich5; Bernard,Daniel J.1
2020-05-12
Source PublicationEndocrinology (United States)
ISSN0013-7227
Volume161Issue:5
Other Abstract

Follicle-stimulating hormone (FSH), an essential regulator of mammalian fertility, is synthesized by pituitary gonadotrope cells in response to activins. In mice, activins signal via SMAD3, SMAD4, and FOXL2 to regulate transcription of the FSHβ subunit (Fshb) gene. Gonadotrope-specific deletion of Foxl2, alone or in combination with Smad4, renders mice FSH-deficient. Whether human FSHB expression is similarly regulated is not known. Here, we used a combination of transgenic and conditional knockout mouse strains to assess the roles of activins, FOXL2, and SMAD4 in regulation of the human FSHB gene. First, we cultured pituitaries from mice harboring a human FSHB transgene (hFSHB mice) and measured both murine Fshb and human FSHB messenger ribonucleic acid (mRNA) expression in response to exogenous activins or two antagonists of endogenous activin-like signaling (follistatin-288 and SB431542). Both murine Fshb and human FSHB expression were stimulated by activins and reduced by the inhibitors. Next, we analyzed human FSHB expression in hFSHB mice carrying floxed Foxl2 and Smad4 alleles. Cre-mediated ablation of FOXL2 and SMAD4 strongly reduced basal and activin-stimulated murine Fshb and human FSHB expression in cultured pituitaries. Finally, the hFSHB transgene was previously shown to rescue FSH production and fertility in Fshb knockout mice. However, gonadotrope-specific Foxl2/Smad4 knockout females carrying the hFSHB transgene have significantly reduced murine Fshb and human FSHB pituitary mRNA levels and are hypogonadal. Collectively, these data suggest that similar to Fshb regulation in mice, FOXL2 and SMAD4 play essential roles in human FSHB expression.

KeywordFsh Transgene Gonadotrope Activin Pituitary Foxl2 Smad4
DOI10.1210/endocr/bqaa045
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaEndocrinology & Metabolism
WOS SubjectEndocrinology & Metabolism
WOS IDWOS:000532825800005
PublisherENDOCRINE SOC, 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036
Scopus ID2-s2.0-85086935273
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Cited Times [WOS]:6   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorBernard,Daniel J.
Affiliation1.Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada
2.Department of Obstetrics and Gynecology, University of Colorado Denver-Anschutz Medical Campus, Aurora, CO, US
3.Max-Delbrück Center for Molecular Medicine (MDC), Genetics of Metabolic and Reproductive Disorders, Berlin, Germany
4.Faculty of Health Sciences, University of Macau, China
5.Experimental Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germanyermany
Recommended Citation
GB/T 7714
Ongaro,Luisina,Schang,Gauthier,Zhou,Ziyue,et al. Human follicle-stimulating hormone ß subunit expression depends on FOXL2 and SMAD4[J]. Endocrinology (United States),2020,161(5).
APA Ongaro,Luisina,Schang,Gauthier,Zhou,Ziyue,Kumar,T. Rajendra,Treier,Mathias,Deng,Chu Xia,Boehm,Ulrich,&Bernard,Daniel J..(2020).Human follicle-stimulating hormone ß subunit expression depends on FOXL2 and SMAD4.Endocrinology (United States),161(5).
MLA Ongaro,Luisina,et al."Human follicle-stimulating hormone ß subunit expression depends on FOXL2 and SMAD4".Endocrinology (United States) 161.5(2020).
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