BINDING OF TAMOXIFEN TO ESTROGEN-RECEPTOR PROTEINS UNDER EQUILIBRIUM AND NONEQUILIBRIUM CONDITIONS

Data have been presented from sucrose density gradient analysis, protamine sulphate precipitation and specificity studies to show that oestradiol-17β and tamoxifen share a common binding protein. In addition, the binding of [3H]-tamoxifen to cytosol preparations from human and rat mammary adenocarcinomas and rat uteri was measured under equilibrium conditions using Scatchard analysis. The relative affinity values obtained were, however, greater than those calculated from competitive binding studies. In addition the competition between tamoxifen and oestradiol-17β for oestrogen binding sites at 4°C decreased with increasing incubation time. Based on competitive binding experiments, the principal metabolite of tamoxifen, metabolite B, associated with oestrogen receptor proteins with a higher affinity than tamoxifen. Kinetic studies indicate that these variations probably result from the relative dissociation rates of metabolite B and tamoxifen from the oestrogen receptor, tamoxifen dissociating much more rapidly than metabolite B. It is also proposed that kinetic studies may have important implications with respect to the mechanism of action of tamoxifen. © 1979.