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• W2037115668 endingPage "1831" @default.
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• W2037115668 abstract "The insulin-like growth factor (IGF) binding proteins (IGFBPs) are a family of proteins that bind IGF-I and IGF-II and modulate their biological activities. IGFBP-1 is distinctive among the IGFBPs in its rapid regulation in response to metabolic and hormonal changes. The synthetic glucocorticoid, dexamethasone, increases IGFBP-1 mRNA abundance and gene transcription in rat liver and in H4-II-E rat hepatoma cells. A glucocorticoid response element (GRE) located at nucleotide (nt) −91/−77 is required for dexamethasone to stimulate rat IGFBP-1 promoter activity in transient transfection assays in H4-II-E cells. In addition to the GRE, three accessory regulatory sites [a putative hepatocyte nuclear factor-1 (HNF-1) site (nt −62/−50), an insulin-response element (nt− 108/−99), and an upstream site (nt −252/−236)] are involved in dexamethasone stimulation under some, but not all, circumstances. The present study begins to address the mechanism by which transcription factors bound to the putative HNF-1 site act synergistically with the glucocorticoid receptor (GR) bound to the GRE. In gel shift assays, HNF-1α and HNF-1β in H4-II-E extracts bind to the palindromic HNF-1 site. Both half-sites are required. Overexpression of HNF-1β enhances dexamethasone-stimulated promoter activity. Both the HNF-1 site and the GRE must be intact for stimulation to occur. By contrast, overexpression of HNF-1α does not enhance dexamethasone-stimulated promoter activity, although, as also observed with overexpression of HNF-1β, it inhibits basal promoter activity. Thus, the synergistic effects of HNF-1β and the GR on dexamethasone-stimulated promoter activity require that they are bound to the HNF-1 site and the GRE, respectively, and may involve protein-protein interactions between the transcription factors, or between them and the basal transcription machinery or a steroid receptor coactivator. Synergy between the ubiquitously expressed GR and HNF-1, which is developmentally regulated and expressed in a limited number of tissues, provides a possible mechanism for tissue- and development-specific regulation of glucocorticoid action." @default.
• W2037115668 created "2016-06-24" @default.
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• W2037115668 date "1997-11-01" @default.
• W2037115668 modified "2023-09-23" @default.
• W2037115668 title "Hepatocyte Nuclear Factor 1 and the Glucocorticoid Receptor Synergistically Activate Transcription of the Rat Insulin-like Growth Factor Binding Protein-1 Gene" @default.
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• W2037115668 doi "https://doi.org/10.1210/mend.11.12.0021" @default.
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