Marr W, Elder M G, Lim L
Biochem J. 1980 Sep 15;190(3):563-70. doi: 10.1042/bj1900563.
The administration of oestradiol-17 beta or ethynyloestradiol as well as the synthetic progestogen norethisterone acetate resulted in translocation of the oestrogen receptor. Progesterone and the synthetic progestogen (+)-norgestrel were ineffective. The increases in nuclear oestrogen receptor content 1 h after injection of each steroid were similar but different subsequently. The increase with oestradiol-17 beta extended for 3--6 h and for at least 9 h with ethynyloestradiol. With norethisterone acetate, nuclear content was still increased after 24 h. Oestrogen injection resulted in cytosol receptor depletion and a 'deficit' in receptor content extending for 6 h, whereas norethisterone acetate-induced translocation was quantitative. With injections of norethisterone acetate + ethynyloestradiol the increase at 1 h and retention of the nuclear receptors were similar to that with norethisterone acetate alone. In contrast, the depletion of cytosol receptor and its restoration were similar to that seen with ethynyloestradiol alone, suggesting that norethisterone acetate did not interfere with the oestrogen receptor replenishment. Specific binding in vitro of [3H]oestradiol-17 beta in liver cytosols was inhibited by (+)-norgestrel and norethisterone acetate, but not progesterone, at concentrations of 10--100 microM. Nuclear receptors present after norethisterone acetate injection bound oestrogen with high affinity (Kd = 1.52 nM), similar to receptors of oestrogen-injected animals. In the uterus, differential retention of nuclear receptors in response to oestrogens is associated with different cellular responses. The differences in the response of the receptor system in liver to the various steroids suggests that the corresponding tissue responses may also be dissimilar. These results are discussed in relation to the problems of liver dysfunction in oral-contraceptive users.
注射17β - 雌二醇或炔雌醇以及合成孕激素醋酸炔诺酮会导致雌激素受体易位。孕酮和合成孕激素（+） - 炔诺孕酮则无此作用。注射每种甾体激素1小时后，细胞核内雌激素受体含量的增加相似，但随后有所不同。注射17β - 雌二醇后，细胞核内雌激素受体含量的增加持续3 - 6小时，注射炔雌醇后至少持续9小时。注射醋酸炔诺酮后，24小时后细胞核内受体含量仍会增加。注射雌激素会导致胞质溶胶受体耗竭，且受体含量的“亏缺”持续6小时，而醋酸炔诺酮诱导的易位是定量的。注射醋酸炔诺酮 + 炔雌醇后，1小时时细胞核受体的增加及保留情况与单独注射醋酸炔诺酮相似。相比之下，胞质溶胶受体的耗竭及其恢复情况与单独注射炔雌醇时相似，这表明醋酸炔诺酮不会干扰雌激素受体的补充。在10 - 100微摩尔浓度下，（+） - 炔诺孕酮和醋酸炔诺酮可抑制肝胞质溶胶中[3H]17β - 雌二醇的体外特异性结合，但孕酮无此作用。注射醋酸炔诺酮后细胞核内存在的受体与雌激素结合的亲和力较高（解离常数Kd = 1.52纳摩尔），与注射雌激素的动物的受体相似。在子宫中，对雌激素的细胞核受体的不同保留与不同的细胞反应相关。肝脏中受体系统对各种甾体激素反应的差异表明相应的组织反应也可能不同。结合口服避孕药使用者肝功能障碍的问题对这些结果进行了讨论。
