Martin L, Pollard J W, Fagg B
J Endocrinol. 1976 Apr;69(1):103-15. doi: 10.1677/joe.0.0690103.
It has been suggested that oestriol protects against breast cancer, because in some experiments on uterine growth it is only weakly active, and partially inhibits the effects of oestradiol-17beta. When its effects are measured 24 h after a single injection, oestriol behaves as a typical impeded oestrogen with low potency and a flat dose-response line. This does not result from failure to stimulate certain critical stages of growth but from failure to sustain the products of growth. We found that oestriol induced all phases of uterine growth including DNA synthesis and cell division. It was as effective as oestradiol in stimulating early increases in protein synthesis and uterine weight, and half as effective in stimulating epithelial cells to replicate DNA and divide. However, epithelial cell numbers did not increase after a single injection of oestriol because cell death rate increased at the same time as mitotic rate, apparently as a result of the more rapid loss of oestriol from the uterus. Repeated injections of oestriol prevented premature cell death and produced as much uterine hypertrophy and hyperplasia as oestradiol-17beta. These results support the thesis that the oestrogenic potency of a substance is largely determined by the duration of its occupation of receptors. Thus in situations of continuous production, (e.g. pregnancy) oestriol would be as active as oestradiol and unlikely to exert any significant 'buffering' or protective action. The findings are also discussed in relation to a new model for the regulation of cell proliferation.
有人提出，雌三醇可预防乳腺癌，因为在一些关于子宫生长的实验中，它的活性较弱，且部分抑制了17β-雌二醇的作用。单次注射后24小时测量其效果时，雌三醇表现为典型的低效雌激素，效价低且剂量反应曲线平缓。这并非由于未能刺激生长的某些关键阶段，而是由于未能维持生长产物。我们发现，雌三醇可诱导子宫生长的各个阶段，包括DNA合成和细胞分裂。在刺激蛋白质合成和子宫重量的早期增加方面，它与雌二醇一样有效，而在刺激上皮细胞复制DNA和分裂方面，其效果是雌二醇的一半。然而，单次注射雌三醇后上皮细胞数量并未增加，因为细胞死亡率与有丝分裂率同时增加，这显然是由于雌三醇从子宫中更快流失所致。重复注射雌三醇可防止细胞过早死亡，并产生与17β-雌二醇一样多的子宫肥大和增生。这些结果支持了这样一种观点，即一种物质的雌激素效价在很大程度上取决于其占据受体的持续时间。因此，在持续产生（如怀孕）的情况下，雌三醇的活性将与雌二醇相同，不太可能发挥任何显著的“缓冲”或保护作用。还结合细胞增殖调控的新模型对这些发现进行了讨论。
