Lipton A, Vinijsanun A, Martin L
J Endocrinol. 1984 Dec;103(3):383-8. doi: 10.1677/joe.0.1030383.
The non-steroidal antioestrogen tamoxifen (trans-1-(4-beta-dimethylaminoethoxyphenyl)-1,2-diphenylbut- 1-ene), widely used in the treatment of breast cancer, and its oestrogenic cis-isomer rapidly inhibited contractile responses of isolated rat myometrium to supramaximal concentrations of oxytocin (1.28 X 10(-6) mol/l). Both compounds were effective at concentrations comparable with the plasma concentrations of tamoxifen reached in therapy (i.e. 5 X 10(-7) to 5 X 10(-6) mol/l). Inhibition was too rapid in onset (less than 3 min) to involve changes in RNA transcription and protein synthesis, and was not prevented or reversed by the addition of oestradiol to the bath. We conclude that the inhibition did not involve the classical oestrogen receptor pathway. Oestradiol-17 beta at concentrations above 10(-6) mol/l also inhibited the myometrium and potentiated the effects of the anti-oestrogens. Our experiments suggest that the anti-oestrogens and oestradiol act via a similar route with tamoxifen having an equilibrium affinity approximately tenfold greater than that of oestradiol.
非甾体类抗雌激素他莫昔芬（反式-1-(4-β-二甲基氨基乙氧基苯基)-1,2-二苯基丁-1-烯）被广泛用于治疗乳腺癌，其雌激素顺式异构体可迅速抑制离体大鼠子宫肌层对超最大浓度催产素（1.28×10⁻⁶摩尔/升）的收缩反应。这两种化合物在与治疗中他莫昔芬所达到的血浆浓度相当的浓度下（即5×10⁻⁷至5×10⁻⁶摩尔/升）均有效。抑制作用起效太快（不到3分钟），不可能涉及RNA转录和蛋白质合成的变化，且向浴槽中添加雌二醇并不能阻止或逆转这种抑制作用。我们得出结论，这种抑制作用不涉及经典的雌激素受体途径。浓度高于10⁻⁶摩尔/升的17β-雌二醇也能抑制子宫肌层，并增强抗雌激素的作用。我们的实验表明，抗雌激素和雌二醇通过相似途径起作用，他莫昔芬的平衡亲和力约为雌二醇的十倍。
