Lieberman M E, Gorski J, Jordan V C
J Biol Chem. 1983 Apr 25;258(8):4741-5.
A hypothetical model of the ligand interaction with the estrogen receptor binding site has been developed to describe the structural features necessary to initiate or to inhibit prolactin synthesis in vitro. The biological potency of the binding ligands is directly related to their relative binding affinity (RBA) for the estrogen receptor. The relative potencies of antiestrogens to inhibit estradiol-stimulated prolactin synthesis was trans-monohydroxytamoxifen identical to cis-monohydroxytamoxifen identical to tamoxifen, consistent with their RBAs for uterine estrogen receptor. Similarly the relative potency of estrogens to stimulate prolactin synthesis was diethylstilbestrol identical to estradiol greater than ICI 77,949 greater than ICI 47,699 identical to zuclomiphene, consistent with their RBAs. The compound LY126412 (trioxifene without the aminoethoxy side chain) did not interact with the estrogen receptor at the concentrations tested (10(-8)--10(-6) M) or exhibit estrogenic or antiestrogenic properties using the prolactin synthesis assay. Overall, the ligand-receptor model stresses the structural requirement for high affinity binding and the critical positioning of the alkylamino-ethoxy side chain in space (in relation to the ligand-binding site on the estrogen receptor) to prevent prolactin synthesis.
已建立一个配体与雌激素受体结合位点相互作用的假设模型，以描述在体外启动或抑制催乳素合成所需的结构特征。结合配体的生物学活性与其对雌激素受体的相对结合亲和力（RBA）直接相关。抗雌激素抑制雌二醇刺激的催乳素合成的相对效力，反式单羟基他莫昔芬与顺式单羟基他莫昔芬相同，且与他莫昔芬相同，这与其对子宫雌激素受体的RBA一致。同样，雌激素刺激催乳素合成的相对效力，己烯雌酚与雌二醇相同，大于ICI 77,949，大于ICI 47,699且与氯米芬相同，与其RBA一致。化合物LY126412（没有氨基乙氧基侧链的三苯氧胺）在测试浓度（10^(-8) - 10^(-6) M）下不与雌激素受体相互作用，并且在使用催乳素合成测定法时不表现出雌激素或抗雌激素特性。总体而言，配体-受体模型强调了高亲和力结合的结构要求以及烷基氨基乙氧基侧链在空间中的关键定位（相对于雌激素受体上的配体结合位点）以防止催乳素合成。
