In vivo imaging of transcriptionally active estrogen receptors
In vivo imaging of transcriptionally active estrogen receptors
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DOI：
10.1038/nm809
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发表时间：
2003-01-01
期刊：
影响因子：
82.9
通讯作者：
Maggi, A
中科院分区：
文献类型：
--
作者：
Ciana, P;Raviscioni, M;Maggi, A
通过细胞内受体，雌激素不仅控制生殖组织，而且还控制其他系统的生长、分化和功能(1-3)。雌激素受体是配体依赖性转录因子，其活性受雌激素或生长因子和神经递质下游的替代细胞内信号传导途径调节(4-6)。为了确定体内雌激素受体活性的动态以及雌激素受体对17β-雌二醇的依赖性，我们培育了一只转基因小鼠，该小鼠在激活的雌激素受体的控制下表达荧光素酶报告基因。正如预期的那样，用冷却的电荷耦合装置相机监测的荧光素酶活性与生殖组织和肝脏中的循环雌激素水平平行，表明雌激素受体的峰值转录活性发生在发情前期。相比之下，在骨骼和大脑等组织中，雌激素受体的活性在动情间期达到峰值。当小鼠接受传统的激素治疗时，这些组织特异性反应被掩盖。我们还证明，在性激素产生之前的未成熟小鼠以及卵巢切除的成年小鼠中，雌激素受体是活跃的。这些发现强调了雌激素受体的激素非依赖性激活的重要性，并对雌激素的治疗用途（例如激素替代疗法）具有影响。
Through intracellular receptors, estrogens control growth, differentiation and function of not only reproductive tissues, but also other systems(1-3). Estrogen receptors are ligand-dependent transcription factors whose activity is modulated either by estrogens, or by alternative intracellular signaling pathways downstream of growth factors and neurotransmitters(4-6). To determine the dynamics of estrogen receptor activity and the dependence of estrogen receptor on 17beta-estradiol in vivo, we generated a transgenic mouse that expresses a luciferase reporter gene under the control of activated estrogen receptors. As expected, luciferase activity, monitored with a cooled charged coupled device camera, paralleled circulating estrogen levels in reproductive tissues and in liver, indicating that the peak transcriptional activity of the estrogen receptor occurred at proestrus. In contrast, in tissues such as bone and brain, the peak activity of estrogen receptors was observed at diestrus. These tissue-specific responses are masked when mice undergo conventional hormone treatment. We also demonstrate that estrogen receptors are active in immature mice before gonadal production of sex hormones as well as in ovariectomized adult mice. These findings emphasize the importance of hormone-independent activation of the estrogen receptor, and have implications for the therapeutic use of estrogens, such as hormone replacement therapy.