Figure 5.

Simplified schematic of the results. (1) I.p. injection of dexamethasone transiently decreases corticosterone levels. (2) Fkbp5 protein acts as an inhibitory chaperone preventing GR translocation to the nucleus. With increased corticosterone binding, Fkbp5 is displaced by Fkbp4, allowing for translocation and exertion of its action as a transcription factor. (3) GR translocation to the nucleus acts on Fkbp5 via its glucocorticoid response elements (GREs) regulating processes such as methylation. Fkbp5 methylation alters Fkbp5 mRNA levels (4) that, in turn, affect the Fkbp5 protein levels (5). (6) The Fkbp5 protein levels negatively correlate with the GR sensitivity.