Bidirectional transcription regulation of glial fibrillary acidic protein by estradiol in vivo and in vitro.
Bidirectional transcription regulation of glial fibrillary acidic protein by estradiol in vivo and in vitro.
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DOI：
10.1210/endo.139.7.6084
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发表时间：
1998-07
期刊：
影响因子：
4.8
通讯作者：
D. Stone;Yubei Song;Christopher P. Anderson;K. Krohn;C. Finch;I. Rozovsky
中科院分区：
文献类型：
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作者：
D. Stone;Yubei Song;Christopher P. Anderson;K. Krohn;C. Finch;I. Rozovsky
胶质纤维酸性蛋白（GFAP）表达显示正常动情周期期间大鼠下丘脑和海马的周期性变化。为了阐明转录在 GFAP 调节中的作用，我们通过原位杂交检测了正常循环大鼠下丘脑和海马中 GFAP 内含子 1 的水平。发情前期下午，血浆雌二醇水平最高，下丘脑弓状核中的 GFAP 转录和信使 RNA 均增加，齿状回外分子层中的 GFAP 转录和信使 RNA 均减少。在海马门中，GFAP 转录和信使 RNA 在动情周期中均未发生变化。在体外，星形胶质细胞表现出双向反应，例如雌二醇处理增加了单型星形胶质细胞培养物中的 GFAP 转录，但降低了与神经元共培养的星形胶质细胞中的 GFAP 转录。 GFAP 启动子 5' 上游区域雌激素反应元件的功能是通过定点诱变和凝胶迁移测定中人重组雌激素受体的结合来确定的。我们得出的结论是，雌激素可能通过雌激素受体结合直接作用于星形胶质细胞，并且转录反应的方向受到星形胶质细胞-神经元相互作用的影响。
Glial fibrillary acidic protein (GFAP) expression shows cyclic variation in the rat hypothalamus and hippocampus during the normal estrous cycle. To elucidate the role of transcription in the regulation of GFAP, we examined levels of GFAP intron 1 by in situ hybridization in the hypothalamus and hippocampus of normal, cycling rats. On the afternoon of proestrus, when plasma estradiol levels are highest, GFAP transcription and messenger RNA were both increased in the arcuate nucleus of the hypothalamus and decreased in the outer molecular layer of the dentate gyrus. In the hilus of the hippocampus, neither GFAP transcription nor messenger RNA changed during the estrous cycle. In vitro, astrocytes showed bidirectional responses, such that estradiol treatment increased GFAP transcription in monotypic astrocytic cultures but decreased GFAP transcription in astrocytes cocultured with neurons. The functionality of an estrogen response element in the 5'-upstream region of the GFAP promoter was established by site-directed mutagenesis and binding of human recombinant estrogen receptor in gel shift assays. We conclude that estrogen may act directly upon astrocytes by estrogen receptor binding, and that the direction of the transcriptional response is influenced by astrocyte-neuron interactions.