Estrogen-Receptor Binding

Estrogen receptor refers to a group of receptors which are activated by the hormone 17β-estradiol (estrogen). Two types of estrogen receptor exist: ER which is a member of the nuclear hormone family of intracellular receptors and the estrogen G protein coupled receptor GPR30 (GPER), which is a G-protein coupled receptor.


The ER's helix 12 domain plays a crucial role in determining interactions with coactivators and corepressors and thereby the respective agonist or antagonist effect of the ligand.
Different ligands may differ in their affinity for alpha and beta isoforms of the estrogen receptor:
17-beta-estradiol binds equally well to both receptors
estrone and raloxifene bind preferentially to the alpha receptor
estriol and genistein to the beta receptor
Subtype selective estrogen receptor modulators preferentially bind to either the α- or β-subtype of the receptor. Additionally, the different estrogen receptor combinations may respond differently to various ligands which may translate into tissue selective agonistic and antagonistic effects.The ratio of α- to β- subtype concentration has been proposed to play a role in certain diseases.
The concept of selective estrogen receptor modulators is based on the ability to promote ER interactions with different proteins such as transcriptional coactivator or corepressors. Furthermore the ratio of coactivator to corepressor protein varies in different tissues. As a consequence, the same ligand may be an agonist in some tissue (where coactivators predominate) while antagonistic in other tissues (where corepressors dominate). Tamoxifen, for example, is an antagonist in breast and is therefore used as a breast cancer treatment[16] but an ER agonist in bone (thereby preventing osteoporosis) and a partial agonist in the endometrium (increasing the risk of uterine cancer) .

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