Clark J H, Paszko Z, Peck E J
Endocrinology. 1977 Jan;100(1):91-6. doi: 10.1210/endo-100-1-91.
The relationship between nuclear retention or residency or receptor estrogen complexes and the agonistic and antagonistic properties of estriol was examined. Cytoplasmic estrogen receptor (Rc) and uterine weight were measured 24 and 48 h after treatment with estradiol (E2), estriol (E3), or or both hormones (E2 and E3). Levels of Rc were elevated in all groups at either time. Since levels of Rc were above control in each case, Rc does not appear to be the limiting factor in the antagonistic effect of estriol. Therefore, the effect of these steroids on translocation and retention of nuclear receptor estrogen complexes (RnE) was examined. Rats were injectd as above and RnE measured by 3[H] estradiol exchange 1, 3, and 6 h after injection. All treatments cause equal translocation of receptor of the nuclear compartment. However, by 6 h the quantity of Rn present in E2 treated animals was significantly above controls while that in E2 + E3 animals was intermediate. E3 alone failed to cause significant nuclear retention of Rn. These patterns of retention correlate with the weight and cytoplasmic receptor responses above and suggest that the short nuclear residency time of RnE3 complexes relates to the antagonism of E3. To test this, these estrogens were administered via paraffin pellets to maintain blood levels of each hormone. Levels of Rn were elevated 24 and 48 h after implant with no significant differences between treatment groups. Likewise, there were no differences in the growth response. Uterine weights were highly stimulated in all three cases (300% above control). These results indicate that E3 acts as an estrogen antagonist when injected as a bolus because of the short nuclear retention time of RnE3 complexes. However, when E3 is present continuously and RnE3 is elevated and maintained, E3 is a potent estrogen without antagonistic properties.
研究了核保留或驻留或受体雌激素复合物与雌三醇的激动和拮抗特性之间的关系。在用雌二醇（E2）、雌三醇（E3）或两种激素（E2和E3）处理24小时和48小时后，测量细胞质雌激素受体（Rc）和子宫重量。在任一时刻，所有组中的Rc水平均升高。由于每种情况下Rc水平均高于对照，因此Rc似乎不是雌三醇拮抗作用的限制因素。因此，研究了这些类固醇对核受体雌激素复合物（RnE）易位和保留的影响。大鼠按上述方法注射，并在注射后1、3和6小时通过3[H]雌二醇交换测量RnE。所有处理均导致受体向核区室的等量易位。然而，到6小时时，E2处理动物中Rn的含量明显高于对照，而E2 + E3动物中的Rn含量处于中间水平。单独使用E3未能导致Rn的显著核保留。这些保留模式与上述子宫重量和细胞质受体反应相关，表明RnE3复合物的短核驻留时间与E3的拮抗作用有关。为了验证这一点，通过石蜡丸剂给予这些雌激素以维持每种激素的血液水平。植入后24小时和48小时，Rn水平升高，各治疗组之间无显著差异。同样，生长反应也没有差异。在所有三种情况下，子宫重量均受到高度刺激（比对照高300%）。这些结果表明，当作为推注注射时，E3作为雌激素拮抗剂起作用，因为RnE3复合物的核保留时间短。然而，当E3持续存在且RnE3升高并维持时，E3是一种有效的雌激素，没有拮抗特性。
