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1 Introduction Glucocorticoids are essential hormones for vertebrate life that act via the glucocorticoid receptor (GR), a nearly ubiquitously expressed molecule with diverse functions throughout the body ( 2 Glucocorticoid physiology The synthesis and secretion of endogenous glucocorticoids are under the control of the hypothalamic-pituitary-adrenal (HPA) axis, which in turn is regulated by the diurnal circadian rhythm ( 2.1 Glucocorticoid receptor physiology: structure GR is encoded by the ~ 126-kb NR3C1 gene and is composed of nine exons ( Figure 1 ) ( Figure 1 In addition to the splice variants, GR has eight alternative translation initiation sites in exon 2, arising from leaky ribosomal shunting of the mRNA ( Figure 1 )