Anorexigenic hormones leptin, insulin, and α-melanocyte-stimulating hormone directly induce neurotensin (NT) gene expression in novel NT-expressing cell models
Anorexigenic hormones leptin, insulin, and α-melanocyte-stimulating hormone directly induce neurotensin (NT) gene expression in novel NT-expressing cell models
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DOI：
10.1523/jneurosci.2269-05.2005
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发表时间：
2005-10-12
影响因子：
5.3
通讯作者：
Belsham, DD
中科院分区：
文献类型：
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作者：
Cui, H;Cai, F;Belsham, DD
神经降压素 (NT) 除了具有许多已描述的生理功能外，还参与能量稳态的调节。 NT 被认为在一定程度上介导下丘脑中瘦素的作用。我们生成了克隆、永生化下丘脑细胞系 N-39 和 N-36/1，它们是第一个可用于研究 NT 基因调控机制的代表性 NT 表达细胞模型。该细胞系表达 Ob-R-b 瘦素受体神经肽 Y (NPY)-Y1、Y2、Y4、Y5 受体、黑皮质素 4 受体、胰岛素受体和 NT 受体。瘦素、胰岛素和α-黑素细胞刺激激素治疗可将 NT mRNA 水平诱导约 1.5 倍至两倍，但 NPY 则不会。瘦素介导的NT基因表达诱导在10(-11)和10(-7)M时是双相的。瘦素反应区位于NT基因5'调节区的-381至-250bp内。此外，我们在染色质沉淀测定中证明了瘦素介导的信号转导器和转录激活剂（STAT）在10（-11）M处直接与该区域结合，但不是10（-7）M瘦素。瘦素诱导的 NT 调节因显性失活 STAT3 蛋白表达而减弱。这些数据支持这样的假设：NT 可能在摄食和能量稳态的神经内分泌控制中具有直接作用。
Neurotensin (NT) is implicated in the regulation of energy homeostasis, in addition to its many described physiological functions. NT is postulated to mediate, in part, the effects of leptin in the hypothalamus. We generated clonal, immortalized hypothalamic cell lines, N-39 and N-36/1, which are the first representative NT-expressing cell models available for the investigation of NT gene regulation and control mechanisms. The cell lines express the Ob-R-b leptin receptor neuropeptide Y (NPY)-Y1, Y2, Y4, Y5 receptors, melanocortin 4 receptor, insulin receptor, and the NT receptor. NT mRNA levels are induced by similar to 1.5-fold to twofold with leptin, insulin, and alpha-melanocyte stimulating hormone treatments but not by NPY. Leptin-mediated induction of NT gene expression was biphasic at 10(-11) and 10(-7) M. The leptin responsive region was localized to within -381 to -250 bp of the 5' regulatory region of the NT gene. Furthermore, we demonstrated direct leptin-mediated signal transducers and activators of transcription ( STAT) binding to this region at 10(-11) M, but not 10(-7) M leptin, in chromatin precipitation assays. Leptin-induced NT regulation was attenuated by dominant-negative STAT3 protein expression. These data support the hypothesis that NT may have a direct role in the neuroendocrine control of feeding and energy homeostasis.