Figure 6. GR isoforms produced through alternative splicing or use of different translational initiation sites. The human GR (NR3C1) gene contains two terminal exons 9 (9alpha and 9beta) alternatively spliced to produce the classic GR (GRalpha-A) and GRbeta-A. C-terminal dark yellow-colored domains in GRalpha-A and GRbeta-A show their specific portions. Using at least 8 different translation initiation sites located in NTD, the human GR (NR3C1) gene produces multiple GR isoforms termed A through D (A, B, C1-C3 and D1-D3) with distinct transcriptional activities on glucocorticoid-responsive genes. Since GRalpha and GRbeta share a common mRNA domain that contains the same translation initiation sites, the GRbeta variant mRNA appears to be also translated through the same initiation sites and to produce 8 isoforms with different lengths of NTD. Modified from (20,37). AF-1 and -2: activation function-1 and -2; DBD; DNA-binding domain; HD: hinge region; LBD: Ligand-binding domain