Role of vascular endothelial growth factor (VEGF) in the formation of vascular system for regulating the adenohyphysial function

血管内皮生长因子（VEGF）在血管系统形成中调节腺垂体功能的作用

基本信息

批准号：
12640649
负责人：
TANAKA Shigeyasu
金额：
$ 2.3万
依托单位：
Shizuoka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

Anterior pituitary hormones are regulated by hypothalamic neurohormones, which are produced in the hypothalamic area and transported to the pars distalis via portal vessels. The hypophyseal portal system provides an important line for carrying hormonal information from the central nervous system to the pituitary. Vascular endothelial growth factor (VEGF) is known to have a mitogenic effect on endothelial cells and renders the endothelium more permeable.The present study using immunohistochemistry and FITC-conjugated to gelatin injection method showed a close relationship between hormone-producing cells and microvessels in hypothalamic-pituitary axis. The Northern blot analysis detected VEGF mRNA in the pars distalis, brain, lung and kidney with the lowest levels in the pars distalis. The in situ RT-PCR method clearly demonstrated the presence of VEGF mRNA-expressing cells in the rostral and ventral regions of the pars distalis at fetal 15.5 day. Expression levels decreased at fetal 18.5 day, but the positive cells were observed throughout the entire ventral region. On the other hand, the microvessels penetrated into the pars distalis at fetal 15.5 day and subsequently expanded into the entire lobe to form the secondary plexus. These results suggest that VEGF is involved in the vascularization of the pars distalis, but not in the formation of portal vessels, because the formation of portal vessels begins at fetal 13.5 day, before the appearance of VEGF in the rostral region of the pars distalis. The dual staining of in situ RT-PCR and immunohistochemistry indicates that some ACTH cells have the potential to produce VEGF. Similar finding was obtained in the bullfrog pituitary glands during metamorphosis. I also cloned cDNA fragments encoding VEGF of rainbow trout and bullfrog. Thus, these data provide fundamental clues in evolutionary aspect of the formation of the vasculalization of hypothalamic-pituitary axis.

垂体前激素受下丘脑神经激素的调节，下丘脑区域产生，并通过门户血管运输到PARS远端。下生理门户网站系统提供了一条重要的线路，可以将荷尔蒙信息从中枢神经系统携带到垂体。已知血管内皮生长因子（VEGF）对内皮细胞具有有丝分裂的作用，并使内皮更渗透。目前使用免疫组织化学和与明胶注射方法结合的FITC偶联的研究显示，激素产生细胞之间的荷尔蒙生成细胞与微生物症之间的亲密关系是在假体象征诊断中的密切关系。北印迹分析检测到pars远端，脑，肺和肾脏中的VEGF mRNA，远端水平最低。原位RT-PCR方法清楚地表明，在胎儿15.5天的pars远端的to骨和腹侧区域中存在表达VEGF mRNA的细胞。胎儿的表达水平降低了18.5天，但在整个腹侧区域都观察到阳性细胞。另一方面，微血管在胎儿15.5天渗透到pars远端，随后扩展到整个叶片中形成次生丛。这些结果表明，VEGF参与了pars远端的血管化，但不参与门户血管的形成，因为门户血管的形成开始于胎儿13.5天，然后在PARS远处的the the ostral区域出现VEGF之前。原位RT-PCR和免疫组织化学的双重染色表明一些ACTH细胞具有产生VEGF的潜力。在变形过程中，在牛蛙垂体中获得了类似的发现。我还克隆了编码彩虹鳟鱼和牛蛙的VEGF的cDNA碎片。因此，这些数据提供了下丘脑垂体轴血管化的进化方面的基本线索。