Department of Pharmacology, Pharmacy College, Nanjing Medical University, Nanjing, People's Republic of China.
Neurol Sci. 2013 Jul;34(7):1167-72. doi: 10.1007/s10072-012-1213-8. Epub 2012 Oct 14.
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.
海马体富含糖皮质激素受体 (GR) 和神经元型一氧化氮合酶 (nNOS)。但是，在生理状态下，这两种分子之间的关系尚未被揭示。在这里，我们报告说，nNOS 敲除小鼠的海马体中 GR 表达增加。全身给予 7-硝基吲唑 (7-NI)，一种选择性 nNOS 活性抑制剂，以及选择性将 7-NI 输注到海马体中，均可导致海马体中 GR 表达增加。此外，KCl 暴露可诱导 nNOS 的过度表达，导致培养的海马神经元中 GR 蛋白水平降低。此外，阻断海马体中的 nNOS 活性会导致血浆中皮质酮 (CORT，啮齿动物中的糖皮质激素) 浓度降低，并降低下丘脑促肾上腺皮质释放因子的表达。结果表明，nNOS 是海马体中 GR 的内源性抑制剂，而海马体中的 nNOS 可能通过 GR 参与调节下丘脑-垂体-肾上腺轴的活性。
