Glucocorticoids are a family of steroids necessary for the regulation of energy metabolism, and the immune and inflammatory responses. These compounds exert their effect through their interaction with the glucocorticoid receptor (GR) and that complex's subsequent association with DNA. All normal mammalian tissues examined to date have been shown to contain GR. The human GR exists in two forms, alpha and beta, which are thought to be the result of alternative splicing of a single gene. Sequence analysis indicates that the a and b forms of human GR are 777 and 742 amino acids long, respectively. They are identical up to residue 727, after which they diverge. After ligand binding, the 94kD GRalpha isoform has been observed to translocate from the cytoplasm to the nucleus where it regulates gene expression. In contrast, the 90kD GRbeta isoform does not appear to bind either glucocorticoid agonists or antagonists, and has been localized predominantly in the nucleus independent of hormone treatment in some human cell lines. Studies suggest that human GRα has a greater affinity for GREs than GRbeta only when in the ligand bound state.