Growth Hormone-Activated STAT5 May Indirectly Stimulate IGF-I Gene Transcription through HNF-3 gamma

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dc.contributor.authorEleswarapu, Satyanarayanaen
dc.contributor.authorGe, Xiaomeien
dc.contributor.authorWang, Yingen
dc.contributor.authorYu, Jieen
dc.contributor.authorJiang, Honglinen
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.date.accessed2014-07-07en
dc.date.accessioned2014-07-08T13:02:19Zen
dc.date.available2014-07-08T13:02:19Zen
dc.date.issued2009-12en
dc.description.abstractIGF-I is abundantly expressed in the liver under the stimulation of GH. We showed previously that expression of hepatocyte nuclear factor (HNF)-3 gamma, a liver-enriched transcription factor, was strongly stimulated by GH in bovine liver. In this study, we determined whether GH-increased HNF-3 gamma might contribute to GH stimulation of IGF-I gene expression in bovine liver and the underlying mechanism. A sequence analysis of the bovine IGF-I promoter revealed three putative HNF-3 binding sites, which all appear to be conserved in mammals. Chromatin immunoprecipitation assays showed that GH injection increased binding of HNF-3 gamma to the IGF-I promoter in bovine liver. Gel-shift assays indicated that one of the three putative HNF-3 binding sites, HNF-3 binding site 1, bound to the HNF-3 gamma protein from bovine liver with high affinity. Cotransfection analyses demonstrated that this HNF-3 binding site was essential for the transcriptional response of the IGF-I promoter to HNF-3 gamma in CHO cells and to GH in primary mouse hepatocytes. Using similar approaches, we found that GH increased binding of the signal transducer and activator of transcription 5 (STAT5) to the HNF-3 gamma promoter in bovine liver, that this binding occurred at a conserved STAT5 binding site, and that this STAT5 binding site was necessary for the HNF-3 gamma promoter to respond to GH. Taken together, these results suggest that in addition to direct action, GH-activated STAT5 may also indirectly stimulate IGF-I gene transcription in the liver by directly enhancing the expression of the HNF-3 gamma gene. (Molecular Endocrinology 23: 2026-2037, 2009)en
dc.description.sponsorshipNational Institutes of Health DK67961en
dc.description.sponsorshipUnited States Department of Agriculture Cooperative State Research, Educationen
dc.description.sponsorshipExtension Service Grant 2009-35205-05221en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationSatyanarayana Eleswarapu, Xiaomei Ge, Ying Wang, Jie Yu, and Honglin Jiang. "Growth Hormone-Activated STAT5 May Indirectly Stimulate IGF-I Gene Transcription through HNF-3γ," Molecular Endocrinology 2009 23:12, 2026-2037. DOI: http://dx.doi.org/10.1210/me.2009-0178en
dc.identifier.doihttps://doi.org/10.1210/me.2009-0178en
dc.identifier.issn0888-8809en
dc.identifier.urihttp://hdl.handle.net/10919/49397en
dc.identifier.urlhttp://press.endocrine.org/doi/abs/10.1210/me.2009-0178en
dc.language.isoenen
dc.publisherEndocrine Societyen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectmessenger-ribonucleic-aciden
dc.subjectbinding-sitesen
dc.subjectdna-bindingen
dc.subjecttissueen
dc.subjectconcentrationsen
dc.subjectglucose-homeostasisen
dc.subjectsignal transduceren
dc.subjectsexual-dimorphismen
dc.subjectliver-functionen
dc.subjectbody growthen
dc.subjectrat-liveren
dc.subjectendocrinology & metabolismen
dc.titleGrowth Hormone-Activated STAT5 May Indirectly Stimulate IGF-I Gene Transcription through HNF-3 gammaen
dc.title.serialMolecular Endocrinologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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