NR3C1 and Cushing syndrome due to macronodular adrenal hyperplasia: Experimental studies have revealed that sufficient activation of MR is crucial for the normal functions of many structures in the brain, including the hippocampus and hypothalamus and that excessive or prolonged activation of GR caused by long-term synthetic GR agonist treatment or excessive endogenous GCs secretion (for example, due to chronic stress or Cushing syndrome) causes severe cognitive, stress, and mood disorders (Krugers et al., 2010; Fardet et al., 2012; de Kloet et al., 2014, 2018; Burkhardt et al., 2015).