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.

垂体前叶激素受下丘脑神经激素调节，下丘脑神经激素在下丘脑区域产生并通过门脉血管转运至远端部。垂体门脉系统提供了将激素信息从中枢神经系统传送到垂体的重要线路。已知血管内皮生长因子 (VEGF) 对内皮细胞具有促有丝分裂作用，并使内皮细胞更具渗透性。本研究采用免疫组织化学和 FITC 缀合明胶注射法，显示激素产生细胞与下丘脑微血管之间存在密切关系。 -垂体轴。 Northern印迹分析检测到远侧部、脑、肺和肾中存在VEGF mRNA，其中远侧部水平最低。原位RT-PCR方法清楚地证明了胎儿15.5天时远侧部的头侧和腹侧区域存在VEGF mRNA表达细胞。表达水平在胎儿 18.5 天时下降，但在整个腹侧区域观察到阳性细胞。另一方面，微血管在胎儿15.5天时穿入远端部，随后扩展到整个叶，形成次级神经丛。这些结果表明VEGF参与远端部的血管化，但不参与门脉血管的形成，因为门脉血管的形成开始于胎儿13.5天，在VEGF出现在远端部的喙部区域之前。原位RT-PCR和免疫组化双重染色表明某些ACTH细胞具有产生VEGF的潜力。在牛蛙变态过程中的垂体中也得到了类似的发现。我还克隆了虹鳟和牛蛙编码 VEGF 的 cDNA 片段。因此，这些数据为下丘脑-垂体轴血管化形成的进化方面提供了基本线索。