Eleswarapu, SatyanarayanaGe, XiaomeiWang, YingYu, JieJiang, Honglin2014-07-082014-07-082009-12Satyanarayana 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.2009-01780888-8809http://hdl.handle.net/10919/49397IGF-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)application/pdfenIn Copyrightmessenger-ribonucleic-acidbinding-sitesdna-bindingtissueconcentrationsglucose-homeostasissignal transducersexual-dimorphismliver-functionbody growthrat-liverendocrinology & metabolismArticle - Refereedhttp://press.endocrine.org/doi/abs/10.1210/me.2009-0178https://doi.org/10.1210/me.2009-0178