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• W2028293843 endingPage "3509" @default.
• W2028293843 startingPage "3505" @default.
• W2028293843 abstract "The beta-isoform of human glucocorticoid receptor beta (hGRbeta) acts as a natural dominant negative inhibitor of hGRalpha-induced transactivation of glucocorticoid-responsive genes. We determined hGRbeta ability to suppress hGRalpha transactivation that was induced by commonly used synthetic glucocorticoids. HepG2/C3A cells were transiently cotransfected with GR cDNA and a glucocorticoid-responsive promoter, luciferase (MMTV-luc). Transfected cells were incubated for 16 h with glucocorticoid and luciferase. For each compound, a dose-response curve was constructed, and half-maximal effective concentrations and maximal transcriptional activities were compared. hGRbeta, at a 1:1 ratio to hGRalpha, differentially suppressed hGRalpha-induced maximal transcriptional activity stimulated by triamcinolone, dexamethasone, hydrocortisone, and betamethasone (by 96, 68, 62, and 49%, respectively) but not by methylprednisolone. The suppressive effect of hGRbeta on hGRalpha-induced transactivation was stronger at lower concentrations of all tested glucocorticoids, whereas it was blunted at higher concentrations. We conclude that the potency of the dominant negative effect of hGRbeta on hGRalpha-induced transactivation depends on both the type and the dose of the synthetic glucocorticoids in use. These results may provide helpful information concerning the selection of synthetic glucocorticoids for treatment of pathological conditions in which hGRbeta modulates the sensitivity of tissues to glucocorticoids." @default.
• W2028293843 created "2016-06-24" @default.
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• W2028293843 date "2005-06-01" @default.
• W2028293843 modified "2023-10-17" @default.
• W2028293843 title "The Human Glucocorticoid Receptor (GR) Isoform β Differentially Suppresses GRα-Induced Transactivation Stimulated by Synthetic Glucocorticoids" @default.
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• W2028293843 doi "https://doi.org/10.1210/jc.2004-1646" @default.
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