TWO MODES OF INTERACTION BETWEEN OESTROGEN AND ANTI-OESTROGEN

ABSTRACT A comparative investigation was carried out on the modes of action of anti-oestrogenic substances of different chemical structures and of different biological profiles. Most extensively investigated were mesobutoestrol and U-11100A. While meso-butoestrol is only antagonistic when applied locally to a target tissue, U-11100A is a systemic antagonist. The interactions of these compounds with tritium-labelled 17β-oestradiol were tested in vivo and in vitro on mouse uteri and vaginae and in vitro on an experimental rat mammary carcinoma. It was found that meso-butoestrol had a very high competitive affinity for the oestrogen binding sites but that its action was easily reversible and particularly so on the vagina. Since it is not retained its antagonistic activity is only manifested biologically under special circumstances. U-11100A had a lower affinity for the binding sites but its blocking action was much less reversible. By combination with the binding sites to a stable complex of low intrinsic biological activity it prevents the full action of a »true« oestrogen. The results illustrate the complexity in the interactions between oestrogens, anti-oestrogens and the target tissues. To characterize the actions of an anti-oestrogen, both affinity for the binding sites and ease of reversibility should be considered. Furthermore, binding characteristics of different target tissues are not necessarily similar.