The human brain has distinct regional expression patterns of estrogen receptor ar mRNA isoforms derived from alternative promoters
The human brain has distinct regional expression patterns of estrogen receptor ar mRNA isoforms derived from alternative promoters
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DOI：
10.1046/j.1471-4159.2000.0751390.x
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发表时间：
2000-10-01
影响因子：
4.7
通讯作者：
Hurd, YL
中科院分区：
文献类型：
--
作者：
Österlund, MK;Grandien, K;Hurd, YL
人类雌激素受体(ER) α基因由多个启动子转录而成，在非翻译区产生具有独特5'端的mRNA亚型。在本研究中，替代启动子被证明可以调节人脑不同神经元群中的内质网α基因表达。采用原位杂交组织化学方法，发现ER α基因的A和B启动子在人前脑中具有活性，而C启动子不具有活性。A启动子转录的mRNA异构体在ER α mRNA存在的大部分脑区表达水平较低。相比之下，B启动子mRNA亚型更受限制，主要定位于高表达的ER α mRNA区域。RT-PCR分析的不同mRNA同种异构体的大体解剖分布与原位杂交的结果基本一致。众所周知，雌激素可以调节许多不同的脑功能，如与生殖、情绪和认知相关的神经内分泌事件，可能由不同的神经元群介导。因此，目前不同神经元群体中ER α启动子表达的研究结果表明，多种启动子的使用是实现ER α表达分化调控的可能机制，这取决于细胞表型，从而取决于特定神经元介导的功能。
The human estrogen receptor (ER) alpha gene is transcribed from multiple promoters, generating mRNA isoforms with unique 5' ends in the untranslated region. In the present study, alternative promoters were shown to regulate the ER alpha gene expression in different neuronal populations of the human brain. By using in situ hybridization histochemistry, the A and B promoters, but not the C promoter, in the ER alpha gene were found to be active in the human forebrain. The mRNA isoform transcribed from the A promoter was expressed in low levels in most of the brain areas where ER alpha mRNA was present. In contrast, the B promoter mRNA isoform was more restricted, localized predominantly in high-expressing ER alpha mRNA regions. The gross anatomical distribution of the different mRNA isoforms analyzed with RT-PCR generally supported the results obtained by the in situ hybridization. Estrogen is known to modulate many different brain functions, such as neuroendocrine events associated with reproduction, mood, and cognition, likely to be mediated by different neuronal populations. Thus, the current findings of alternative ER alpha promoter expression in distinct neuronal populations suggest that multiple promoter usage is a possible mechanism to achieve differentiated regulation of the ER alpha expression, dependent on the cell phenotype and consequently the functions mediated by the specific neuron.