Specifically, ACTH-induced phosphorylation of CREB require the activation of several nuclear receptors and co-regulators, including members of the CRTC family (CRTC1-3) (Smith et al., 2019), Nur77 (Martin et al., 2008) and steroidogenic factor 1 (SF-1) (Sugawara et al., 1996), and the repression of a number of negative regulators, including salt inducible kinase 1 (SIK1) (Takemori and Okamoto, 2008) and dosage sensitive sex-reversal, adrenal hypoplasia (Zazopoulos et al., 1997). This evidence concerns the gene CALR and chronic primary adrenal insufficiency.