Tamaya T, Nakata Y, Ohno Y, Nioka S, Furuta N
Fertil Steril. 1976 Jul;27(7):767-72.
The effects of copper ions on the binding of steroids to receptors revealed that the inhibitory effect of Cu++ was apparent at 10(-6)M, ANd the binding capacities decreased to 10% at 10(-2)M Cu++. The kinetic study demonstrated that Cu++ was a competitive inhibitor of steroid hormone-receptor binding (Ki divided by 2.7 X 10(-5)M to estrogen receptor; Ki divided by 5.1 X 10(-6)M to progesterone receptor). These results indicate that copper ions interfere at the steroid-binding site of receptor and that progesterone receptor is more affected by copper ions than is estrogen receptor. The sedimentation pattern showed the dissociation and aggregation of receptor macromolecules by copper. These phenomena may indicate the biologic inactivation of receptor. In fact, morphologically, progestational proliferation was severely inhibited and estrogenic action seemed to be inhibited. The Timm stain showed copper uptake by endometrial epithelium and superficial stromata. The copper content apparently increased in the cytoplasm of uteri bearing a copper intrauterine device, compared with controls. In vivo, the concentration of cytoplasmic copper was approximately 1.4 X 10(-6)M, which was obviously inhibitory to steroid hormone-receptor interaction. However, complete morphologic suppression of the progestational effect by copper cannot exclude the coexistence of some other mechanism in these phenomena.
铜离子对类固醇与受体结合的影响表明，Cu++的抑制作用在10^(-6)M时就很明显，在10^(-2)M Cu++时结合能力降至10%。动力学研究表明，Cu++是类固醇激素-受体结合的竞争性抑制剂（对雌激素受体的Ki为2.7×10^(-5)M；对孕激素受体的Ki为5.1×10^(-6)M）。这些结果表明，铜离子在受体的类固醇结合位点产生干扰，且孕激素受体比雌激素受体更易受铜离子影响。沉降模式显示铜会使受体大分子解离和聚集。这些现象可能表明受体的生物失活。事实上，从形态学上看，孕激素增殖受到严重抑制，雌激素作用似乎也受到抑制。Timm染色显示子宫内膜上皮和浅层基质摄取铜。与对照组相比，放置宫内节育器的子宫细胞质中的铜含量明显增加。在体内，细胞质铜的浓度约为1.4×10^(-6)M，这对类固醇激素-受体相互作用具有明显的抑制作用。然而，铜对孕激素作用的完全形态学抑制并不能排除这些现象中存在其他机制。
