Estrogen signaling: a subtle balance between ER alpha and ER beta.
Estrogen signaling: a subtle balance between ER alpha and ER beta.
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DOI：
10.1124/mi.3.5.281
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发表时间：
2003-08-01
影响因子：
--
通讯作者：
Gustafsson, Jan-Ake
中科院分区：
文献类型：
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作者：
Matthews, Jason;Gustafsson, Jan-Ake
雌激素的生物学作用是通过雌激素与两种特异性雌激素受体（ER）ER α和ER β中的一种结合来介导的，ER α和ER β属于核受体超家族，一个配体调节的转录因子家族。ER α和ER β是不同基因的产物，并表现出组织和细胞类型特异性表达。缺乏ER α或ER β或两者的小鼠的表征揭示了两种受体亚型在体内雌激素依赖性作用中具有重叠但也具有独特的作用。此外，ER α和ER β在某些配体、细胞类型和启动子环境中具有不同的转录活性。然而，这两种受体在许多组织中共表达，并形成功能性异源二聚体。ER α/β异二聚体在各自同源二聚体存在下的生物学作用尚不清楚。当共表达时，ER β对ER α介导的基因表达表现出抑制作用，并且在许多情况下对抗ER α的作用。还描述了许多ER α和ER β亚型，其中许多改变雌激素介导的基因表达。揭示调节两种ER表达的分子机制，以及ER α和ER β如何直接或间接地影响彼此的功能，对于理解正常和患病组织中雌激素介导的基因调节的细胞和生物学事件至关重要。
The biological actions of estrogens are mediated by estrogen binding to one of two specific estrogen receptors (ERs) ERalpha and ERbeta, which belong to the nuclear receptor superfamily, a family of ligand-regulated transcription factors. ERalpha and ERbeta are products of different genes and exhibit tissue- and cell-type specific expression. The characterization of mice lacking ERalpha, or ERbeta, or both has revealed that both receptor subtypes have overlapping but also unique roles in estrogen-dependent action in vivo. Additionally, ERalpha and ERbeta have different transcriptional activities in certain ligand, cell-type, and promoter contexts. Both receptors, however, are coexpressed in a number of tissues and form functional heterodimers. The biological roles of ERalpha /beta heterodimers in the presence of each respective homodimer are unknown. When coexpressed, ERbeta exhibits an inhibitory action on ERalpha -mediated gene expression and in many instances opposes the actions of ERalpha. A number of ERalpha and ERbeta isoforms have also been described, many of which alter estrogen-mediated gene expression. Uncovering the molecular mechanisms regulating the expression of both ERs, and how ERalpha and ERbeta directly or indirectly affect each other's function are paramount to understanding the cellular and biological events of estrogen-mediated gene regulation in normal and diseased tissues.