For instance, it has been well-established that genetic and epigenetic variations in the NR3C1 and FKBP5 genes contribute to hypercortisolemia and glucocorticoid resistance, because changes in NR3C1 and FKBP5 gene expression directly affect extracellular glucocorticoid levels and intracellular glucocorticoid signaling.78 This evidence concerns the gene NR3C1 and adrenal gland hyperfunction.