This schematic depicts the role of GR translocation in glucocorticoid negative feedback. Glucocorticoids readily cross the plasma membrane to bind nuclear GRs. GRs then are shuttled into the nucleus by multiple co-chaperones (in green), such as PPID and FKBP52. Once inside, GRs bind to glucocorticoid response elements (GREs) on genes to repress transcription of CRF and precursors for ACTH. Other co-chaperones (in red), including Bag1 and Fkbp5, inhibit GR translocation, an effect which can attenuate negative feedback.