Oestrogen receptors and antagonism of steroid hormone action

Abstract

NON-STEROIDAL anti-oestrogens antagonise the effects of oestrogen on uterine growth, vaginal cornification and ovulation¹, and their mechanism of action has been suggested to reside in their ability to compete for cytoplasmic oestrogen binding sites, or receptors, thereby reducing the formation of receptor oestrogen complexes^2–4. Since the formation of these complexes in oestrogen target tissues, with subsequent translocation to nuclear sites, is considered the primary event in oestrogen action^5,6, the reduction in their number would lead to decreased physiological responses to oestrogen. This implies that the receptor antagonist complex should have a lower intrinsic biological activity than that of the receptor oestradiol complex; that is, the ability of the receptor antagonist complex to stimulate oestrogenic responses would be less than that of the receptor oestradiol complex. Based on these assumptions, oestrogen antagonism should be observed after a single injection of oestrogen and antagonists; we have now found that this is not the case. Thus, non-steroidal anti-oestrogens could not be acting as antagonists by competing initially for oestrogen receptors.