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

The selective oestrogen receptor modulators (SERMs) constitute a group of s ubstances which are capable of regulating the agonistic/antagonistic profil e 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 b etter suits each clinical necessity. This review summarizes the principal s teps of oestrogen action where modifications have resulted in changes of th e effect profile. Three different steps of oestrogen action have been highl ighted as being susceptible to modulation: type of ligand, particular speci es of oestrogen receptor, and particulars at the target tissue. Two main fa milies of SERMs, the triphenylethylene derivatives, with tamoxifen as the m ain actor, and the benzothiophene derivatives, mainly represented by raloxi fene, provide much of the basic and clinical knowledge on the influence of the type of ligand, Two types of oestrogen receptor, alpha and beta, add th e second variable susceptible to modulating the response to receptor activa tion, Finally, the ligand-receptor complex mag define particular events in its interaction with DNA, such as binding to promoters other than the oestr ogen response element, recruitment of concrete sets of local transcription factors, or other options.