Interactions of estrogen and insulin-like growth factor-I in the brain:: molecular mechanisms and functional implications
Interactions of estrogen and insulin-like growth factor-I in the brain:: molecular mechanisms and functional implications
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DOI：
10.1016/s0960-0760(02)00261-3
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发表时间：
2002-12-01
影响因子：
4.1
通讯作者：
Garcia-Segura, LM
中科院分区：
文献类型：
--
作者：
Cardona-Gómez, GP;Mendez, P;Garcia-Segura, LM
在大脑中，就像在其他组织中一样，雌二醇与生长因子相互作用。参与雌二醇神经作用的生长因子之一是胰岛素样生长因子-I（IGF-I）。在中枢神经系统中，雌二醇和IGF-I协同作用，调节神经元发育、神经可塑性、神经内分泌事件和神经组织对损伤的反应。参与这些相互作用的精确分子机制仍然没有很好地理解。在中枢神经系统中，雌激素受体（ER）和IGF-I受体（IGF-IR）在相同细胞中大量共表达。此外，脑中雌激素受体和IGF-I受体的表达是交叉调节的。此外，使用针对细胞外信号调节激酶（ERK）1和ERK 2以及Akt/蛋白激酶B（Akt/PK B）的磷酸化形式的特异性抗体，已经表明雌二醇影响脑中的IGF-I信号传导途径。雌激素治疗导致成年卵巢切除大鼠脑中ERK和Akt/PKB磷酸化的剂量依赖性增加。此外，雌二醇和IGF-I对成年大鼠脑内Akt/PKB的激活有协同作用。这些发现表明，雌激素在大脑中的作用可能部分通过激活IGF-I受体的信号通路来介导。(C)2003爱思唯尔科技有限公司版权所有。
In the brain, as in other tissues, estradiol interacts with growth factors. One of the growth factors that is involved in the neural actions of estradiol is insulin-like growth factor-I (IGF-I). Estradiol and IGF-I cooperate in the central nervous system to regulate neuronal development, neural plasticity, neuroendocrine events and the response of neural tissue to injury. The precise molecular mechanisms involved in these interactions are still not well understood. In the central nervous system there is abundant co-expression of estrogen receptors (ERs) and IGF-I receptors (IGF-IRs) in the same cells. Furthermore, the expression of estrogen receptors and IGF-I receptors in the brain is cross-regulated. In addition, using specific antibodies for the phosphorylated forms of extracellular-signal regulated kinase (ERK) 1 and ERK2 and Akt/protein kinase B (Akt/PKB) it has been shown that estradiol affects IGF-I signaling pathways in the brain. Estradiol treatment results in a dose-dependent increase in the phosphorylation of ERK and Akt/PKB in the brain of adult ovariectomized rats. In addition, estradiol and IGF-I have a synergistic effects on the activation of Akt/PKB in the adult rat brain. These findings suggest that estrogen effects in the brain may be mediated in part by the activation of the signaling pathways of the IGF-I receptor. (C) 2003 Elsevier Science Ltd. All rights reserved.