Estrogen augments glucose transporter and IGF1 expression in primate cerebral cortex
Estrogen augments glucose transporter and IGF1 expression in primate cerebral cortex
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DOI：
10.1096/fj.00-0398com
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发表时间：
2001-04-01
期刊：
影响因子：
4.8
通讯作者：
Bondy, CA
中科院分区：
文献类型：
--
作者：
Cheng, CM;Cohen, M;Bondy, CA
在实验模型系统中，雌激素对神经组织有许多积极的作用，包括刺激轴突生长和神经递质合成，以及保护不同类型的神经损伤。在人类中，雌激素治疗被认为可以预防阿尔茨海默氏症。为了研究雌激素作用的潜在介质，并确定选择性雌激素受体调节剂(SERM)如他莫昔芬在灵长类动物大脑中是否具有雌激素样作用，我们观察了去卵巢恒河猴额叶皮质中葡萄糖转运体和胰岛素样生长因子1(IGF1)及其受体的表达。我们用赋形剂治疗一组3天，用17β雌二醇(E_2)治疗另一组，用他莫昔芬治疗第三组。用原位杂交、免疫组织化学和免疫印迹分析方法研究促葡萄糖转运体(GLUT)1、3和4的表达。Glut3和Glut4集中在皮质神经元，Glut1集中在毛细血管和神经胶质细胞。E2处理诱导GLUT3和GLUT4mRNA水平增加2-4倍，GLUT3和GLUT4蛋白水平增加较少但显著。E2处理诱导实质组织Glut1基因表达水平增加了70%，但对血管Glut1基因表达没有明显影响。IGF1和IGF1受体mRNAs主要集中在皮质神经元中，其分布与GLUT3和GUT4相似。雌激素组IGF1基因表达水平显著升高，但激素处理不影响IGF1受体基因表达水平。他莫昔芬可增加大脑皮层GLUT3和4mRNA水平，但不影响Glut1、IGF1或IGF1受体的表达。这项研究提供了新的数据，表明GLUT 3和4和IGF1在灵长类大脑皮质神经元中共同表达，而它们的表达被雌激素增强。这些发现表明，上调葡萄糖转运蛋白和IGF1的表达可能有助于雌激素对神经组织的有益作用。他莫昔芬是一种乳房抗雌激素药物，被证明对猴子的高级大脑中枢具有雌激素样的作用，这表明一些SERM可能与更年期女性分享雌激素的神经保护潜力。
Estrogen has many positive effects on neural tissue in experimental model systems, including stimulation of neurite growth and neurotransmitter synthesis and protection against diverse types of neural injury. In humans, estrogen treatment is reputed to protect against Alzheimer's disease. To investigate potential mediators of estrogen's action and determine whether selective estrogen receptor modulators (SERMs) such as tamoxifen have estrogen-like effects in the primate brain, we evaluated the expression of glucose transporters and insulin-like growth factor 1 (IGF1) and its receptor in the frontal cortex of ovariectomized rhesus monkeys. We treated one group for 3 days with vehicle, another with 17 beta estradiol (E2), and a third with tamoxifen. The expression of facilitative glucose transporters (Gluts) 1, 3, and 4 was investigated using in situ hybridization, immunohistochemistry, and immunoblot analysis. Gluts 3 and 4 were concentrated in cortical neurons and Glut1 in capillaries and glial cells. E2 treatment induced two- to fourfold increases in Glut3 and Glut4 mRNA levels and lesser but significant increases in Glut3 and 4 protein levels. E2 treatment induced an similar to 70% increase in parenchymal Glut1 mRNA levels, but did not appreciably affect vascular Glut1 gene expression. IGF1 and IGF1 receptor mRNAs were concentrated in cortical neurons in a distribution similar to Gluts 3 and 4. IGF1 mRNA levels were significantly increased in E2-treated animals but IGF1 receptor mRNA levels were not altered by hormone treatment. Tamoxifen increased cerebral cortical Glut3 and 4 mRNA levels, but did not affect Glut1, IGF1, or IGF1 receptor expression. This study provides novel data showing that Gluts 3 and 4 and IGF1 are coexpressed by primate cerebral cortical neurons, where their expression is enhanced by estrogen. These findings suggest that up-regulation of glucose transporter and IGF1 expression may contribute to estrogen's salutary effects on neural tissue. Tamoxifen, an antiestrogen at the breast, is shown to have estrogen-like effects on higher brain centers in the monkey, suggesting that some SERMs may share estrogen's neuroprotective potential for menopausal women.