Different ligands can induce variable receptor conformations that determine biologic activity. For example, a pure agonist such as estrogen binds to a receptor creating an active configuration, whereas a pure antagonist renders the receptor inactive. Figure 1 illustrates this concept by showing that different ligands bind to receptors and force them into different shapes and therefore distinct biologic activities. A number of compounds have been identified that induce conformational changes intermediate between those induced by agonists or antagonists. At least 3 distinct classes of antiestrogens have been identified.
Different compounds induce different structural alterations within the estrogen receptor.
Reprinted with permission. Recognition of the ligand-receptor complex within the cell nucleus represents the second explanation for differences in the activity of estrogen compounds. Once a ligand enters the cell and binds to an ER, this resulting complex undergoes dimerization to produce a unique ligand-receptor configuration. The dimer binds to specific adaptor proteins that allow contact with the target gene control region. Therefore, adaptors that are exclusively expressed in a single type of tissue, such as bone or uterus, can modify a biologic response.