Modulation of the oestrogen receptor: a process with distinct susceptible steps

The selective oestrogen receptor modulators (SERMs) constitute a group of substances which are capable of regulating the agonistic/antagonistic profile of the oestrogen receptor in distinct tissues. Their potential utility is considerable since, among the pleiotropic range of effects that oestrogens exert on their target tissues, they may provide a selective profile that better suits each clinical necessity. This review summarizes the principal steps of oestrogen action where modifications have resulted in changes of the effect profile. Three different steps of oestrogen action have been highlighted as being susceptible to modulation: type of ligand, particular species of oestrogen receptor, and particulars at the target tissue. Two main families of SERMs, the triphenylethylene derivatives, with tamoxifen as the main actor, and the benzothiophene derivatives, mainly represented by raloxifene, provide much of the basic and clinical knowledge on the influence of the type of ligand. Two types of oestrogen receptor, and , add the second variable susceptible to modulating the response to receptor activation. Finally, the ligand–receptor complex may define particular events in its interaction with DNA, such as binding to promoters other than the oestrogen response element, recruitment of concrete sets of local transcription factors, or other options.