Di Carlo F, Reboani C, Conti G, Genazzani E
J Endocrinol. 1978 Nov;79(2):201-8. doi: 10.1677/joe.0.0790201.
The effects of doxorubicin and methotrexate on the oestradiol-induced depletion, replenishment and subsequent increase beyond the normal value (overshoot) in the number of uterine cytoplasmic oestrogen receptors were investigated in intact rats. Injection of doxorubicin (0.5 mg/kg, i.v.) or methotrexate (1mg/kg, i.m.) 5 min after a single i.p. injection of 10 ng oestradiol-17beta (which is able to induce a 50% depletion in the number of oestrogen receptors) caused a significant increase in the oestradiol-induced depletion. Both drugs inhibited the replenishment and the overshoot phases until 48 h after treatment, although the effect was more marked with doxorubicin. Experiments in vitro showed that both methotrexate and doxorubicin affected the capacity of oestradiol-17beta to bind to specific cytoplasmic receptors, inducing an increase in binding when used at low concentrations and a decrease at higher concentrations. The effects of doxorubicin and methotrexate on the depletion, replenishment and overshoot of oestrogen receptors seemed to be partly dependent on the inhibition of protein synthesis and partly due to direct action on the binding of oestradiol-17beta to its receptors.
在完整大鼠中研究了阿霉素和甲氨蝶呤对子宫细胞质雌激素受体数量的影响，这些影响包括雌二醇诱导的受体数量减少、补充以及随后超过正常值（过冲）的增加。在单次腹腔注射10 ng 17β-雌二醇（能够使雌激素受体数量减少50%）5分钟后，静脉注射阿霉素（0.5 mg/kg）或肌肉注射甲氨蝶呤（1mg/kg），会导致雌二醇诱导的受体数量减少显著增加。两种药物均抑制受体数量的补充和过冲阶段，直至治疗后48小时，不过阿霉素的作用更为明显。体外实验表明，甲氨蝶呤和阿霉素均影响17β-雌二醇与特定细胞质受体结合的能力，低浓度使用时会导致结合增加，高浓度使用时则导致结合减少。阿霉素和甲氨蝶呤对雌激素受体数量减少、补充和过冲的影响似乎部分取决于对蛋白质合成的抑制，部分归因于对17β-雌二醇与其受体结合的直接作用。
