Gustafsson J A
Climacteric. 2006 Jun;9(3):156-60. doi: 10.1080/14689360600734328.
Estrogen receptor beta (ERbeta) was discovered in 1995 and reported on in 1996. During the 10 years following this event, our understanding of estrogen signaling has changed remarkably. We now know that estradiol, the major endogenous activator of ER, is non-selective for the two receptors, and that ERalpha and ERbeta are, in many contexts, antagonistic against one another, an example of a yin/yang relationship, perhaps nature's way to accomplish subtle regulatory changes of estrogen signaling as a response to ever-shifting physiological requirements. Needless to say, this knowledge is of paramount significance pharmaceutically, and several ERbeta-selective agonists, intended for use against a multitude of diseases, have already been synthesized and patented by drug companies. Clearly, the next 5-10 years will be extremely exciting in view of results from clinical trials testing the clinical utility of ERbeta targeted drugs.
雌激素受体β(ERβ)于1995年被发现,并于1996年被报道。在这一事件后的10年里,我们对雌激素信号传导的理解发生了显著变化。我们现在知道,雌二醇作为ER的主要内源性激活剂,对这两种受体没有选择性,而且在许多情况下,ERα和ERβ相互拮抗,这是一种阴阳关系的例子,也许是大自然实现雌激素信号传导微妙调节变化以应对不断变化的生理需求的方式。不用说,这些知识在药学上具有至关重要的意义,几家制药公司已经合成并申请了几种用于治疗多种疾病的ERβ选择性激动剂的专利。显然,鉴于测试ERβ靶向药物临床效用的临床试验结果,未来5到10年将非常令人兴奋。