Cano A, Hermenegildo C
Department of Pediatrics, Obstetrics and Gynecology, Facultad de Medicina, Valencia, Spain.
Hum Reprod Update. 2000 May-Jun;6(3):207-11. doi: 10.1093/humupd/6.3.207.
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, alpha and beta, 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.
选择性雌激素受体调节剂（SERM）是一类能够调节不同组织中雌激素受体激动/拮抗特性的物质。其潜在用途相当广泛，因为在雌激素对其靶组织产生的多效性作用范围内，它们可能提供更符合每种临床需求的选择性作用模式。本综述总结了雌激素作用的主要步骤，这些步骤中的修饰导致了作用模式的改变。已强调雌激素作用的三个不同步骤易于调节：配体类型、特定种类的雌激素受体以及靶组织的特性。SERM的两个主要家族，以他莫昔芬为主的三苯乙烯衍生物和主要以雷洛昔芬为代表的苯并噻吩衍生物，提供了许多关于配体类型影响的基础和临床知识。两种类型的雌激素受体，α和β，增加了第二个易于调节受体激活反应的变量。最后，配体-受体复合物在其与DNA的相互作用中可能定义特定事件，例如与雌激素反应元件以外的启动子结合、募集具体的局部转录因子组或其他选择。
