The many faces of estrogen signaling.
The many faces of estrogen signaling.
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DOI：
10.11613/bm.2014.035
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发表时间：
2014
期刊：
影响因子：
3.3
通讯作者：
Marc J
中科院分区：
文献类型：
--
作者：
Vrtačnik P;Ostanek B;Mencej-Bedrač S;Marc J
雌激素长期以来被认为是女性生殖功能的重要调节因子；然而，在过去几年中，我们对雌激素在人体中所起作用的理解发生了重大变化。现在人们普遍认为，雌激素和雄激素在女性和男性的生理和病理方面都具有重要功能。这在一定程度上是由于雌激素的局部合成和作用，这使得雌激素信号传导的作用超出了内分泌系统的范畴。此外，三种雌激素受体（ER），即ERα、ERβ和G蛋白偶联雌激素受体1（GPER1）能够通过几种不同的机制调节靶基因转录。ERα和ERβ主要与导致靶基因表达的直接和间接基因组信号通路相关。另一方面，膜结合的GPER1负责雌激素的快速非基因组作用，激活各种蛋白激酶级联反应。雌激素信号传导还与另一个重要的调节实体，即表观遗传机制紧密相连。翻译后组蛋白修饰、微小RNA（miRNA）和DNA甲基化已被证明会影响ER的基因表达，同时也受雌激素信号传导的调节。此外，雌激素信号传导的一些辅调节因子也表现出染色质修饰活性，进一步强调了表观遗传机制在雌激素信号传导中的重要性。本综述希望强调雌激素信号传导超出其经典内分泌调节作用的新方面，尤其强调它与表观遗传机制的紧密交织。
Estrogens have long been known as important regulators of the female reproductive functions; however, our understanding of the role estrogens play in the human body has changed significantly over the past years. It is now commonly accepted that estrogens and androgens have important functions in both female and male physiology and pathology. This is in part due to the local synthesis and action of estrogens that broadens the role of estrogen signaling beyond that of the endocrine system. Furthermore, there are several different mechanisms through which the three estrogen receptors (ERs), ERα, ERβ and G protein-coupled estrogen receptor 1 (GPER1) are able to regulate target gene transcription. ERα and ERβ are mostly associated with the direct and indirect genomic signaling pathways that result in target gene expression. Membrane-bound GPER1 is on the other hand responsible for the rapid non-genomic actions of estrogens that activate various protein-kinase cascades. Estrogen signaling is also tightly connected with another important regulatory entity, i.e. epigenetic mechanisms. Posttranslational histone modifications, microRNAs (miRNAs) and DNA methylation have been shown to influence gene expression of ERs as well as being regulated by estrogen signaling. Moreover, several coregulators of estrogen signaling also exhibit chromatin-modifying activities further underlining the importance of epigenetic mechanisms in estrogen signaling. This review wishes to highlight the newer aspects of estrogen signaling that exceed its classical endocrine regulatory role, especially emphasizing its tight intertwinement with epigenetic mechanisms.