Expression of hypothalamic peptides in mice lacking neuronal nitric oxide synthase:: Reduced β-END immunoreactivity in the arcuate nucleus
Expression of hypothalamic peptides in mice lacking neuronal nitric oxide synthase:: Reduced β-END immunoreactivity in the arcuate nucleus
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DOI：
10.1159/000054390
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发表时间：
1998-12-01
影响因子：
4.1
通讯作者：
Wolf, G
中科院分区：
文献类型：
--
作者：
Bernstein, HG;Keilhoff, G;Wolf, G
气体一氧化氮（NO）是脑信号传导中的重要信使。沿着许多其他功能，NO被认为影响各种下丘脑激素（促肾上腺皮质激素释放激素（CRH）、促性腺激素释放激素（GnRH）和加压素）的表达和/或释放。为了进一步了解NO在神经内分泌机制中的作用，我们在缺乏神经元型NO合酶（nNOS）的突变小鼠中研究了CRH、neurophysin（加压素/催产素的载体蛋白）和阿黑皮素原（POMC），以及POMC衍生的肽β-内啡肽（β-END）、α-促黑素细胞激素（α-MSH）和促肾上腺皮质激素（ACTH）的表达。此外，通过NADPH-黄递酶组织化学和瓜氨酸免疫组织化学以及内皮NOS（eNOS）和nNOS亚型的免疫组织化学定位和Western印迹分析，研究了nNOS阴性小鼠的剩余NO生成能力。在所有研究中的下丘脑肽中，只有β-END在突变小鼠中被发现改变。弓状核的β-END产生神经元的形态测定分析显示，突变小鼠中免疫反应性细胞显著减少，而前体POMC以及其他POMC衍生肽的表达被发现是不变的。除此之外，与野生型动物相比，在nNOS阴性小鼠的室旁核中发现较少的β-END免疫反应性纤维。因此，下丘脑β-END的减少可能是一个翻译后事件，可能反映了正常表达nNOS的下丘脑神经元的内啡肽能神经支配受到干扰。
The gas nitric oxide (NO) is an important messenger in brain signaling. Along with many other functions, NO is thought to influence the expression and/or release of various hypothalamic hormones (corticotropin-releasing hormone (CRH), gonadotropin-releasing hormone (GnRH) and vasopressin). To learn more about the role of NO in neuroendocrine mechanisms, we studied in mutant mice lacking neuronal isoform of NO synthase (nNOS) the cellular expression of CRH, neurophysin (the carrier protein of vasopressin/oxytocin) and proopiomelanocortin (POMC), as well as of the POMC-derived peptides beta-endorphin (beta-END), alpha-melanocyte-stimulating hormone (alpha-MSH) and corticotropin (ACTH) by use of immunohistochemistry and in situ hybridization. Additionally, the remaining NO-generating capacities of the nNOS minus mice were investigated by NADPH-diaphorase histochemistry and citrulline immunohistochemistry as well as by immunohistochemical localization and Western blot analysis of endothelial NOS (eNOS) and nNOS isoforms. Amongst all hypothalamic peptides under investigation, only beta-END was found to be altered in mutant mice. A morphometric analysis of beta-END producing neurons of the arcuate nucleus revealed that significantly less cells were immunoreactive in mutant mice, whereas the expression of the precursor POMC as well as of other POMC-derived peptides was found to be unchanged. In addition to that, fewer beta-END-immunoreactive fibers were found in the paraventricular nucleus of nNOS minus mice in comparison to wild-type animals. Hence, the reduction of hypothalamic beta-END is probably a posttranslational event that might reflect a disturbed endorphinergic innervation of those hypothalamic neurons which normally express nNOS.