High-affinity anti-oestrogen binding site distinct from the oestrogen receptor

Abstract

Non-steroidal anti-oestrogens such as tamoxifen, CI 628, nafoxidine and clomiphene, are structurally related synthetic compounds that antagonize the effects of oestrogen on its target tissues^1,2, and this activity has led to the use of tamoxifen to treat advanced breast cancer³. All these compounds inhibit the binding of tritiated oestradiol to cytosol from oestrogen target tissues^2,4–7, suggesting that anti-oestrogens bind to the oestrogen receptor. This is supported by reports that in the rat uterus^7–10 and dimethyl-benz (α)-anthracene (DMBA)-induced rat mammary carcinoma⁹, oestradiol and anti-oestrogens bind directly to the same number of saturable binding sites. Furthermore, oestrogens and anti-oestrogens are mutually competitive for binding to these sites^8,10. It has thus been generally accepted that the anti-oestrogens exert most of their effects through the specific oestrogen receptor. We now report a further high-affinity, anti-oestrogen binding site which may have a role in regulating the effects of non-steroidal anti-oestrogens.