Nicholson R I, Davies P, Griffiths K
J Endocrinol. 1977 Apr;73(1):135-42. doi: 10.1677/joe.0.0730135.
Studies on the mode of action of tamoxifen have shown that this compound ultimately causes regression of mammary tumours induced in female rats by 7,12-dimethylbenz(a)-anthracene, but induces preliminary effects similar to those produced by oestradiol-17beta. Following a single intravenous injection of either substance, a sequence of events was observed which included depletion of cytoplasmic receptor, a concomitant increase in nuclear receptor and a subsequent replenishment of cytoplasmic receptor. Tamoxifen and oestradiol-17beta induced a transient increase in RNA polymerase B activity, followed by increases in RNA polymerase A and, again, RNA polymerase B activity. Tamoxifen, unlike oestradiol-17beta, could not maintain replenishment of cytoplasmic receptor, the increase in RNA polymerase A activity or the secondary rise in RNA polymerase B activity. The basic anti-oestrogenic properties of tamoxifen may be implicit in its inability to maintain oestrogen stimulation, and may be linked to its retention time within the nuclei.
对他莫昔芬作用模式的研究表明，该化合物最终会使雌性大鼠由7,12-二甲基苯并(a)蒽诱导产生的乳腺肿瘤消退，但会引发与17β-雌二醇产生的类似初步效应。单次静脉注射这两种物质中的任何一种后，观察到一系列事件，包括细胞质受体耗竭、核受体随之增加以及随后细胞质受体的补充。他莫昔芬和17β-雌二醇诱导RNA聚合酶B活性短暂增加，随后RNA聚合酶A增加，接着RNA聚合酶B活性再次增加。与17β-雌二醇不同，他莫昔芬无法维持细胞质受体的补充、RNA聚合酶A活性的增加或RNA聚合酶B活性的二次升高。他莫昔芬的基本抗雌激素特性可能隐含在其无法维持雌激素刺激中，并且可能与其在细胞核内的保留时间有关。
