Effect of Cu 2+ ions on the binding of estrogen to the human myometrial estrogen binding protein

Abstract

The binding of estrogens to the estrogen binding protein in human myometrial cytosol and the effect of Cu 2+ ions on the binding characteristics have been investigated. The dissociation constants at 20 °C for the estrogen receptor complex were 0.081, 0.21 and 0.24 nM for estradiol, estriol and estrone, respectively. Both the affinity and the number of binding sites were affected in the presence of Cu 2+ ions which indicated a mixed type inhibition of the binding of steroid to the receptor. The second order association rate constants decreased in the presence of Cu 2+ ions and the effect seemed to be reinforced by an increase in temperature. No change in the sedimentation coefficient of the estrogen receptor complex occurred in the presence of Cu 2+ ions although less steroid was bound. Cu 2+ ion concentrations above 10 μM were required before remarkable alterations in the binding characteristics were established. As the copper level in human uterine fluid of women using a Cu-IUD have been shown to be in the range of 20 μM, the interaction of Cu 2+ ions with the binding of estrogens to their specific receptors has to be considered as one factor responsible for the changes in the uterus in the presence of the device.