Davies P, Syne J S, Nicholson R I
Endocrinology. 1979 Dec;105(6):1336-42. doi: 10.1210/endo-105-6-1336.
The antiestrogen tamoxifen has been used successfully in the treatment of breast cancer. In an attempt to elucidate its mode of action, its effects on steroid hormone receptor concentration and RNA polymerase activities in the uteri of ovariectomized rats have been compared with those of estradiol. A single dose of estradiol and tamoxifen, separately or in combination, produced slight increases in uterine wet weight 12 h after injection. Whereas both estradiol and tamoxifen could promote translocation of the estrogen receptor, only estradiol caused cytoplasmic replenishment of the receptor. Both compounds, separately and in combination, stimulated the production of cytoplasmic progesterone receptor 12 h after treatment. Estradiol produced and maintained significant elevations in RNA polymerase I activity, whereas the effects on this enzyme brought about by taxoxifen were less and transitory. However, estrogen and antiestrogen caused equal increases in RNA polymerase II activity, but, again, the effects of taxoxifen were shortlived when compared to those brought about by estradiol. Stimulation of RNA polymerase II activity was due to the availability of increased numbers of apparent initiation sites. These results point to a basic inefficacy in the antiestrogen-receptor complex; although it is able to promote early tissue responses characteristic of an estrogen, these cannot be sufficiently maintained.
抗雌激素他莫昔芬已成功用于乳腺癌治疗。为阐明其作用方式，已将其对去卵巢大鼠子宫中甾体激素受体浓度及RNA聚合酶活性的影响与雌二醇的影响进行了比较。单独或联合给予单剂量的雌二醇和他莫昔芬，注射12小时后子宫湿重略有增加。虽然雌二醇和他莫昔芬均可促进雌激素受体的转位，但只有雌二醇能使受体在细胞质中得到补充。两种化合物单独及联合使用时，在处理12小时后均能刺激细胞质孕酮受体的产生。雌二醇可使RNA聚合酶I活性显著升高并维持这一水平，而他莫昔芬对该酶的作用较小且短暂。然而，雌激素和抗雌激素均可使RNA聚合酶II活性等量增加，但同样，与雌二醇相比，他莫昔芬的作用持续时间较短。RNA聚合酶II活性的刺激是由于明显起始位点数量增加所致。这些结果表明抗雌激素 - 受体复合物基本无效；尽管它能够促进雌激素特有的早期组织反应，但这些反应无法充分维持。
