Role of ligand in oestrogen-receptor function.

Introduction Oestrogens are able to regulate gene expression by binding to specific receptors that function as transcription factors [ 1-31. Hormone binding is required initially for the dissociation of an inactive, oligomeric, receptor complex to allow receptor dimerization and high-affinity DNA binding [4, 51 and, secondly, to produce the full transcriptional activity of the receptor [6-91. In view of the role of oestrogens as mitogens in certain types of cells and the observation that approximately 30% of breast cancer can be treated with endocrine therapy, a large number of anti-oestrogens have been developed as potential drugs. T o date these antioestrogens appear to fall into two groups. One group, which includes the non-steroidal antioestrogen tamoxifen, also act as partial agonists while another group, which includes ICI 164384, appear to act predominantly as ‘pure’ anti-oestrogens [ 10, 1 11. The molecular basis for the action of different ligands is now beginning to emerge and is the subject of this review.