Estrogen regulation of neurokinin B gene expression in the mouse arcuate nucleus is mediated by estrogen receptor α
Estrogen regulation of neurokinin B gene expression in the mouse arcuate nucleus is mediated by estrogen receptor α
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DOI：
10.1210/en.2003-0894
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发表时间：
2004-02-01
期刊：
影响因子：
4.8
通讯作者：
Merchenthaler, I
中科院分区：
文献类型：
--
作者：
Dellovade, TL;Merchenthaler, I
神经激肽B（NKB）基因表达在绝经后妇女下丘脑漏斗（弓状）核中升高。雌激素替代减少了表达NKB mRNA的神经元的数量和单个细胞内的表达水平。类似地，NKB基因表达在卵巢切除大鼠中升高，并且在雌激素治疗后降低。雌激素在大脑中的作用可以通过雌激素受体α（ER α）或雌激素受体β（ER β）介导。在啮齿动物弓状核（ARC）中，ER α细胞比ER β细胞多，提示ER α可能直接负责雌激素对NKB基因表达的调节。然而，不能排除通过ER β的间接影响。在这里，我们使用ER α和ER β基因敲除小鼠，以确定类型的ER负责介导的雌激素作用对NKB基因表达的ARC。使用原位杂交组织化学，我们已经发现，雌激素治疗显着减少NKB基因表达的ARC卵巢切除ER β基因敲除小鼠，但没有影响NKB mRNA水平ER α基因敲除小鼠。这些数据表明，ER α介导与啮齿动物卵巢切除术相关的NKB基因表达增加，也可能是绝经后妇女NKB增加的原因。
Neurokinin B ( NKB) gene expression is elevated in the infundibular ( arcuate) nucleus of the hypothalamus in postmenopausal women. Estrogen replacement decreases both the number of NKB mRNA- expressing neurons and the level of expression within individual cells. Similarly, NKB gene expression is elevated in ovariectomized rats and reduced after estrogen treatment. The actions of estrogen in the brain can be mediated via either estrogen receptor alpha( ERalpha) or estrogen receptor beta( ERbeta). In the rodent arcuate nucleus ( ARC), more ERalpha- than ERbeta- containing cells are present, suggesting that ERalpha might be directly responsible for estrogen regulation of NKB gene expression. However, an indirect effect via ER beta could not be ruled out. Here we used ERalpha knockout and ERbeta knockout mice to identify the type of ER responsible for mediating estrogen action on NKB gene expression in the ARC. Using in situ hybridization histochemistry, we have found that estrogen treatment significantly reduced NKB gene expression in the ARC of ovariectomized ERbeta knockout mice, but had no effect on NKB mRNA levels in ERalpha knockout mice. These data indicate that ER alpha mediates the increase in NKB gene expression associated with ovariectomy in rodents and might also be responsible for the increase in NKB in postmenopausal women.