Figure 2: Molecular mechanism of GR signaling pathways. Glucocorticoids diffuse across the cell membrane to the cytosol, where they bind GR. Glucocorticoid binding promotes dissociation of GR from chaperone proteins (HSPs) and subsequent nuclear translocation. Once in the nucleus, GR forms hetero- or homodimers and interacts with DNA to control gene transcription. Ligand-bound GR can lead to either activation or repression of gene transcription. TF: transcription factor; GRE, glucocorticoid response element; nGRE, negative glucocorticoid response element; TFRE: transcription factor response element.