One of the target genes is FKBP5, and its transcriptional activation by the GR dimer creates a negative feedback loop, whereby hypercortisolemia and glucocorticoid resistance can be attributed to the excess FKBP5 protein that has enhanced affinity for the glucocorticoid receptor (Scammell et al., 2001). This evidence concerns the gene NR3C1 and adrenal gland hyperfunction.