Jordan V C, Rowsby L, Dix C J, Prestwich G
J Endocrinol. 1978 Jul;78(1):71-81. doi: 10.1677/joe.0.0780071.
The dose-related effects of non-steroidal antioestrogens and oestrogens on the measurement of cytoplasmic oestrogen receptors in the rat uterus have been determined. The simultaneous administration of tamoxifen or monohydroxytamoxifen and oestradiol on three consecutive days resulted in dose-dependent decreases in both the wet weight of the uterus and the number of available cytoplasmic oestrogen receptors. The oestrogenic triphenylethylenes ICI 47 699 and ICI 3188 both produced dose-dependent decreases in the number of available cytoplasmic oestrogen receptors. Increasing doses of ICI 47 699 resulted in increasing concentrations of oestrogen receptors within the nucleus. The effects of tamoxifen and oestradiol-17 beta were compared in the ovariectomized mouse; replenishment of uterine oestrogen receptors was less evident in tamoxifen-treated animals than in animals receiving oestradiol, although increases in uterine weight were similar. A single large dose of tamoxifen (50 microgram) produced a prolonged depletion of cytoplasmic oestrogen receptors whilst stimulating rises in uterine weight and DNA and protein content. The results demonstrate that the depletion of the uterine cytoplasmic oestrogen receptor pool is a function of the dose administered for any compound with the ability to translocate oestrogen receptors to the nucleus and as such is not an exclusive characteristic of non-steroidal antioestrogens.
已确定非甾体类抗雌激素和雌激素对大鼠子宫细胞质雌激素受体测量的剂量相关效应。连续三天同时给予他莫昔芬或单羟基他莫昔芬与雌二醇，导致子宫湿重和可用细胞质雌激素受体数量呈剂量依赖性下降。雌激素性三苯乙烯类化合物ICI 47699和ICI 3188均使可用细胞质雌激素受体数量呈剂量依赖性减少。ICI 47699剂量增加导致细胞核内雌激素受体浓度升高。在去卵巢小鼠中比较了他莫昔芬和17β-雌二醇的作用；尽管子宫重量增加相似，但在他莫昔芬处理的动物中，子宫雌激素受体的补充不如接受雌二醇的动物明显。单次大剂量他莫昔芬（50微克）导致细胞质雌激素受体长期耗竭，同时刺激子宫重量、DNA和蛋白质含量增加。结果表明，子宫细胞质雌激素受体池的耗竭是任何具有将雌激素受体转运至细胞核能力的化合物给药剂量的函数，因此不是非甾体类抗雌激素的独有特征。
