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Figure 2. Estrogen-Receptor Action.
Each class of SERMs (orange symbols) has a slightly different shape, although all will bind to the estrogen receptor. When it binds to an estrogen, antiestrogen, or SERM, the estrogen receptor undergoes a conformational change that permits its spontaneous dimerization and facilitates the subsequent interaction of the dimer with estrogen response elements (EREs) located within target genes. The estrogen-receptor–ligand complex also leads to binding of various coregulator proteins that vary with its conformational structure. Some estrogen-receptor–SERM complexes favor corepressor recruitment (red) that, in a given target cell, increases its antagonist activity, and others favor coactivator recruitment (blue) that increases its agonist activity. Some SERMs may also facilitate the interaction of the estrogen receptor with yet-to-be-identified coactivators (green) with which estrogens or antiestrogens would not normally couple. It has now been determined that estrogen facilitates the interaction of the estrogen receptor with coactivators. The antagonist-activated estrogen receptor, on the other hand, interacts preferentially with corepressors. The binding of different SERMs to the receptor permits the receptor to adopt conformational states that are different from each other and also distinct from that induced by classic estrogen agonists or antagonists.The implication of this model is that SERM activity will be influenced by the relative levels of expression of the coregulator proteins (corepressors and coactivators) that are expressed in different target cells.
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Correction
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Riggs and Hartmann, 
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