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, and this activity has led to the use of tamoxifen to treat advanced breast cancer. All these compounds inhibit the binding of tritiated oestradiol to cytosol from oestrogen target tissues, suggesting that anti-oestrogens bind to the oestrogen receptor. This is supported by reports that in the rat uterus and dimethyl-benz (alpha)-anthracene (DMBA)-induced rat mammary carcinoma, 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. 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.