Cross-talk between IGF-I and estradiol in the brain: Focus on neuroprotection
Cross-talk between IGF-I and estradiol in the brain: Focus on neuroprotection
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DOI：
10.1159/000097485
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发表时间：
2006-01-01
影响因子：
4.1
通讯作者：
Mendez, Pablo
中科院分区：
文献类型：
--
作者：
Garcia-Segura, Luis M.;Sanz, Amaya;Mendez, Pablo
雌激素在大脑中的作用涉及与生长因子的相互作用，如胰岛素样生长因子-I(IGF-I)。大脑中的许多细胞共表达雌激素受体(ER)和胰岛素样生长因子-I受体(IGF-IR)，这两种因素相互作用调节神经功能。多项研究表明，IGF-IR和内质网在神经保护中存在相互作用。雌激素的神经保护作用可通过抑制IGF-IR信号来阻断，而IGF-I的神经保护作用可通过抑制ER信号来阻断。这些结果提示，脑损伤后雌激素和IGF-I的神经保护作用依赖于神经细胞中ER和IGF-IR的共同激活。ERα通过PI3K/Akt/GSK3β信号通路与IGF-IR的关系可能代表了雌激素和IGF-I协同促进神经保护作用的汇合点。去卵巢大鼠注射雌二醇后，ERα与IGF-IR和PI3K/Akt/GSK3信号通路的组成成分相关，并调节脑内Akt和GSK3的活性。相反，IGF-I调节神经母细胞瘤细胞中ERα的转录活性，PI3K/Akt/GSK3信号通路参与了这一作用。版权所有(C)2006 S.Karger AG，巴塞尔。
The actions of estradiol in the brain involve the interaction with growth factors, such as insulin-like growth factor-I (IGF-I). Many cells in the brain coexpress receptors for estradiol (ERs) and IGF-I (IGF-IR) and both factors interact to regulate neural function. Several studies have shown that there is an interaction of IGF-IR and ERs in neuroprotection. Neuroprotective effects of estradiol are blocked by the inhibition of IGF-IR signaling, while the neuroprotective effects of IGF-I are blocked by the inhibition of ER signaling. These findings suggest that the neuroprotective actions of estradiol and IGF-I after brain injury depend on the coactivation of both ERs and IGF-IR in neural cells. The relationship of ER alpha with IGF-IR through the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 beta (PI3K/Akt/GSK3) signaling pathway may represent the point of convergence used by estradiol and IGF-I to cooperatively promote neuroprotection. Administration of estradiol to ovariectomized rats results in the association of ER alpha with IGF-IR and with components of the PI3K/Akt/GSK3 signaling pathway and in the regulation of the activity of Akt and GSK3 in the brain. Conversely, IGF-I regulates ER alpha transcriptional activity in neuroblastoma cells and the PI3K/Akt/GSK3 signaling pathway is involved in this effect. Copyright (c) 2006 S. Karger AG, Basel.