Intracellular GR (and MR) signaling is subject to modulation by other proteins, which may affect function in the context of stress. For example, the GR-binding factor FK506 binding protein 51 (also known as FKBP5) reduces glucocorticoid binding affinity and GR nuclear translocation (Binder, 2009). In PFC, chronic stress enhances expression of FKBP5, which is correlated with impaired GR nuclear trafficking and reduced expression of GR-regulated genes (Guidotti et al., 2012). Stress-related changes in expression of FKBP5 (as well as other GR binding proteins) may represent a mechanism for reduced feedback efficacy and prolonged HPA axis responses (Mizoguchi et al., 2003).
