17β-Estradiol Increases Astrocytic Vascular Endothelial Growth Factor (VEGF) in Adult Female Rat Hippocampus
17β-Estradiol Increases Astrocytic Vascular Endothelial Growth Factor (VEGF) in Adult Female Rat Hippocampus
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DOI：
10.1210/en.2010-1290
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发表时间：
2011-05-01
期刊：
影响因子：
4.8
通讯作者：
Scharfman, Helen E.
中科院分区：
文献类型：
--
作者：
Barouk, Sharon;Hintz, Tana;Scharfman, Helen E.
血管内皮生长因子（VEGF）对于血管生成和血管通透性至关重要。它在内分泌系统中也很重要，其中 VEGF 介导雌激素在子宫等靶组织中的血管效应，这种反应归因于 VEGF 基因上的雌激素反应元件。在这里，我们询问 17β-雌二醇是否会增加大脑中的 VEGF 水平。我们以17β-雌二醇和VEGF均具有重要作用的海马为研究对象，采用免疫细胞化学方法评价VEGF蛋白。比较成年雌性大鼠在发情周期期间 17β-雌二醇血清水平达到峰值（发情前期早晨）和低水平（发情后期早晨）时取样的 VEGF 免疫反应性。此外，成年大鼠被切除卵巢，并在用 17 β-雌二醇或媒介物治疗后进行比较。结果表明，当血清 17β-雌二醇水平升高时，VEGF 免疫反应性增加。共聚焦显微镜显示 VEGF 免疫荧光主要是非神经元的，通常与星形胶质细胞相关。神经胶质 VEGF 标记主要是点状的，而不是弥漫性和不稳定的，因为如果组织切片在水介质中过夜，神经胶质 VEGF 免疫反应性会大大降低。我们得出的结论是，正常女性海马中的 VEGF 蛋白主要是非神经元而不是神经元，并且表明过去使用其他方法的研究低估了神经胶质 VEGF 免疫反应性，因为存在不稳定的细胞外池。我们认为雌激素可能通过增加海马VEGF而对女性海马结构和功能产生作用。 （内分泌学152：1745-1751，2011）
Vascular endothelial growth factor ( VEGF) is critical to angiogenesis and vascular permeability. It is also important in the endocrine system, in which VEGF mediates the vascular effects of estrogens in target tissues such as the uterus, a response attributed to an estrogen response element on the VEGF gene. Here we asked whether 17 beta-estradiol increases VEGF levels in the brain. We focused on the hippocampus, in which 17 beta-estradiol and VEGF both have important actions, and used immunocytochemistry to evaluate VEGF protein. VEGF immunoreactivity was compared in adult female rats sampled during the estrous cycle when serum levels of 17 beta-estradiol peak (proestrous morning) as well as when they are low (metestrous morning). In addition, adult rats were ovariectomized and compared after treatment with 17 beta-estradiol or vehicle. The results demonstrated that VEGF immunoreactivity was increased when serum levels of 17 beta-estradiol were elevated. Confocal microscopy showed that VEGF immunofluorescence was predominantly nonneuronal, often associated with astrocytes. Glial VEGF labeling was primarily punctate rather than diffuse and labile because glial VEGF immunoreactivity was greatly reduced if tissue sections were left in an aqueous medium overnight. We conclude that VEGF protein in normal female hippocampus is primarily nonneuronal rather than neuronal and suggest that glial VEGF immunoreactivity has been underestimated by past studies with other methods because there is a labile extracellular pool. We suggest that estrogens may exert actions on female hippocampal structure and function by increasing hippocampal VEGF. (Endocrinology 152: 1745-1751, 2011)