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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >RNAi-mediated silencing of estrogen receptor in the ventromedial nucleus of hypothalamus abolishes female sexual behaviors
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RNAi-mediated silencing of estrogen receptor in the ventromedial nucleus of hypothalamus abolishes female sexual behaviors

机译：RNAi介导的下丘脑腹膜内雌激素受体沉默消除了女性的性行为

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Estrogen receptor alpha (ER alpha) plays a major role in the regulation of neuroendocrine functions and behaviors by estrogens. Although the generation of ER alpha knockout mice advanced our knowledge of ER alpha functions, gene deletion using this method is global and potentially confounded by developmental consequences. To achieve a site-specific knockdown of ER alpha in the normally developed adult brain, we have generated an adeno-associated virus vector expressing a small hairpin RNA targeting ER alpha. After bilateral injection of this vector into the hypothalamic ventromedial nucleus in ovariectomized female mice, expression levels of ER alpha as well as the estrogen-inducible progesterone receptor were profoundly reduced despite the continued presence of this receptor elsewhere in the brain. Functionally, silencing of ER alpha in the ventromedial nucleus abolished female proceptive and receptive sexual behaviors while enhancing rejection behavior. These results provide evidence that adeno-associated virus-mediated long-term knockdown of genes can be used to delineate their effects on complex behaviors in discrete brain regions.
机译：雌激素受体α（ER alpha）在雌激素调节神经内分泌功能和行为中起主要作用。尽管ER alpha基因敲除小鼠的产生提高了我们对ER alpha功能的了解，但是使用这种方法进行基因缺失是全球性的，并可能因发育后果而混淆。为了在正常发育的成年大脑中实现ERα的位点特异性敲低，我们产生了腺相关病毒载体，表达了靶向ERα的小发夹RNA。在将这种载体双向注入卵巢切除的雌性小鼠的下丘脑腹膜内侧核中后，尽管该受体在大脑中的其他位置继续存在，但其ERα的表达水平以及雌激素诱导的孕激素受体均被显着降低。在功能上，腹内侧核中ERα的沉默消除了女性的性行为和接受性行为，同时增强了排斥行为。这些结果提供了证据，表明腺相关病毒介导的基因的长期敲低可以用来描述它们对离散脑区域复杂行为的影响。

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