Human neurons express type I GnRH receptor and respond to GnRH I by increasing luteinizing hormone expression.
Human neurons express type I GnRH receptor and respond to GnRH I by increasing luteinizing hormone expression.
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DOI：
10.1677/joe.1.07047
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发表时间：
2006-12
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影响因子：
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通讯作者：
Andrea C. Wilson;M. S. Salamat;Ryan J. Haasl;K. Roche;A. Karande;S. V. Meethal;E. Terasawa;R. Bowen;C. Atwood;C. Atwood
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文献类型：
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作者：
Andrea C. Wilson;M. S. Salamat;Ryan J. Haasl;K. Roche;A. Karande;S. V. Meethal;E. Terasawa;R. Bowen;C. Atwood;C. Atwood
促性腺激素释放激素受体I（GnRHR I）已被定位到大鼠大脑的边缘系统，不过通过这些受体进行的促性腺激素释放激素（GnRH）信号传导的功能效应尚不清楚。在本文中，我们对GnRHR I在人类海马体和大脑皮层中的表达情况，以及GnRHR I在人类神经母细胞瘤细胞中的功能特性进行了研究。在CA2区、CA1区和终板的锥体细胞的细胞体以及顶树突上，均检测到强烈的GnRHR I免疫反应性，但在海马体的下托区明显较弱。在大脑皮层神经元中也观察到免疫标记，包括位于内嗅皮层和枕颞叶回的神经元，但在齿状回颗粒层未观察到。在对照组和阿尔茨海默病患者的大脑之间，未观察到免疫组化染色的差异。在人类神经母细胞瘤细胞（M17、SH-SY5Y）和大鼠胚胎原代神经元中检测到GnRHR I信使核糖核酸（mRNA）和蛋白质（成熟、未成熟及其他变体）的表达，且其表达会随分化和GnRH处理而变化。由于GnRHR I由垂体外细胞表达，且绝经/男性更年期后下丘脑促性腺激素释放激素I（GnRH I）的分泌显著增加，我们用GnRH I对在无血清条件下培养的人类M17神经母细胞瘤细胞处理6小时，并检测促黄体生成素（LH）的表达。M17神经母细胞瘤细胞表达LHβ mRNA，而免疫印迹分析表明存在三种LH变体（约30、47和60千道尔顿），低浓度的GnRH I可使其表达上调，而高浓度的GnRH I则使其表达下调。在分化的大鼠胚胎原代皮层神经元中，也发现LH表达增加。我们的研究结果表明，表达GnRHR I的神经元具有功能，能够通过上调LH的生成对GnRH I作出反应。生殖期过后GnRH I分泌的激增，可能解释了LH在老年人类和大鼠锥体细胞中的积累现象。
Gonadotropin-releasing hormone receptor I (GnRHR I) has been localized to the limbic system of the rat brain, although the functional consequences of GnRH signaling through these receptors is unknown. In this paper, we characterize the expression of GnRHR I in the human hippocampus and cortex, and the functionality of GnRHR I in human neuroblastoma cells. Robust GnRHR I immunoreactivity was detected in the cell body as well as along the apical dendrites of pyramidal neurons in the CA2, CA1, and end plate, but was clearly lower in the subiculum of the hippocampus. Immunolabeling was also evident in cortical neurons, including those located in the entorhinal cortex and occipitotemporal gyrus but was not observed within the granular layer of the dentate gyrus. No differences in immunohistochemical staining were observed between control and Alzheimer's disease brain. GnRHR I mRNA and protein (mature, immature, and other variant) expression was detected in human neuroblastoma cells (M17, SH-SY5Y) and rat embryonic primary neurons and varied with differentiation and GnRH treatment. Since GnRHR I was expressed by extrapituitary cells, and hypothalamic GnRH I secretion markedly increases post-menopause/andropause, we treated human M17 neuroblastoma cells cultured in serum-free conditions with GnRH I for 6 h and measured LH expression. M17 neuroblastoma cells express LHbeta mRNA, while immunoblot analysis indicated the presence of three LH variants (approximately 30, 47, and 60 kDa) that were upregulated by low concentrations of GnRH I, but down-regulated at higher GnRH I concentrations. LH expression was also found to increase in differentiating embryonic rat primary cortical neurons. Our results demonstrate that neurons expressing GnRHR I are functional, responding to GnRH I by upregulating LH production. Post-reproductive surges in GnRH I secretion may explain the accumulation of LH in pyramidal neurons of the aged human and rat.