Neuronal nitric oxide synthase is an endogenous negative regulator of glucocorticoid receptor in the hippocampus
Neuronal nitric oxide synthase is an endogenous negative regulator of glucocorticoid receptor in the hippocampus
复制标题
神经元一氧化氮合酶是海马糖皮质激素受体的内源性负调节因子
DOI：
10.1007/s10072-012-1213-8
复制
发表时间：
2013-07-01
影响因子：
3.3
通讯作者：
Zhou, Qi-Gang
中科院分区：
文献类型：
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作者：
Liu, Meng-ying;Zhu, Li-Juan;Zhou, Qi-Gang
海马富含糖皮质激素受体（GR）和神经元型一氧化氮合酶（nNOS）。但在生理状态下，这两种分子之间的关系尚未得到揭示。在这里，我们报告nNOS敲除小鼠海马中GR表达增加。全身给予选择性nNOS活性抑制剂7-硝基吲唑（7-NI）和选择性海马内输注7-NI均导致海马GR表达增加。此外，KCl暴露可诱导nNOS过度表达，导致培养海马神经元GR蛋白水平下降。此外，海马中nNOS活性的阻断导致血浆中皮质酮（CORT，啮齿动物中的糖皮质激素）浓度降低和下丘脑中促肾上腺皮质激素释放因子表达降低。结果提示，nNOS是海马GR的内源性抑制剂，可能通过GR参与调节下丘脑-垂体-肾上腺轴的活动。
The hippocampus is rich in both glucocorticoid receptor (GR) and neuronal nitric oxide synthase (nNOS). But the relationship between the two molecules under physiological states remains unrevealed. Here, we report that nNOS knockout mice display increased GR expression in the hippocampus. Both systemic administration of 7-Nitroindazole (7-NI), a selective nNOS activity inhibitor, and selective infusion of 7-NI into the hippocampus resulted in an increase in GR expression in the hippocampus. Moreover, KCl exposure, which can induce overexpression of nNOS, resulted in a decrease in GR protein level in cultured hippocampal neurons. Moreover, blockade of nNOS activity in the hippocampus leads to decreased corticosterone (CORT, glucocorticoids in rodents) concentration in the plasma and reduced corticotrophin-releasing factor expression in the hypothalamus. The results indicate that nNOS is an endogenous inhibitor of GR in the hippocampus and that nNOS in the hippocampus may participate in the modulation of Hypothalamic–Pituitary–Adrenal axis activity via GR.