title: The mechanism of action of the copper intrauterine device.
abstract: 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.
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D003300:Copper / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000032:analysis / Q000473:pathology; D004967:Estrogens / Q000378:metabolism; D005260:Female; D007434:Intrauterine Devices; D011374:Progesterone / Q000378:metabolism; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000473:pathology
chemical_list: D004967:Estrogens; D011956:Receptors, Cell Surface; D011374:Progesterone; D003300:Copper