The general structure of human progesterone receptors. The PR protein consists of four structurally and functionally distinct domains: the N-terminal transactivation domain (NTD), the DNA binding domain (DBD), a small hinge region, and the C-terminal ligand-binding domain (LBD). The LBD shares the greatest degree of homology among the different human PR isoforms. In addition to hPRA and hPRB, hPRC lacks the first of two zinc fingers and be defective in DNA binding, whereas hPRM lacks both NTD and DBD. The structure of both hPRC and hPRM predicts extra-nuclear localization. hPRS contains only LBD and may be involved in the progesterone-induced nuclear translocation. hPR, human progesterone receptor; aa, amino acids; AF, activation function.