adrenal161

Figure 1: Genomic and nongenomic glucocorticoid actions. Upon binding to the ligand, the activated hGR dissociates from heat shock proteins (HSPs) and translocates into the nucleus, where it homodimerizes and binds to glucocorticoid response elements (GREs) in the promoter region of target genes or interacts with other transcription factors (TFs), such as activator protein-1 (AP-1), nuclear factor-B (NF-B) and signal transducer and activator of transcription-5 (STAT5), ultimately modulating the transcriptional activity of respectively GRE- or TFRE-containing genes. In addition to the well-known genomic actions, most of the nongenomic glucocorticoid actions are mediated by membrane-bound GRs, which trigger the activation of kinase signaling pathways. GR: glucocorticoid receptor; HSP: heat shock proteins; FKBP: immunophilins; p160: nuclear receptor coactivators p160; SWI/SNF: switching/sucrose non-fermenting complex; DRIP/TRAP: vitamin D receptor-interacting protein/thyroid hormone receptor-associated protein complex; MAPK: mitogen-activated protein kinases; cPLA2α: cytosolic phospholipase A2 alpha; PI3K: phosphatidylinositol 3-kinase; eNOS: endothelial nitric oxide synthetase; NO: nitric oxide.