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脑雌激素研究新进展 总被引:1,自引:0,他引:1
脑内雌激素的来源包括透过血脑屏障的循环雌激素以及脑局部合成的雌激素。雌激素可以调节脑发育、突触可塑性,以及学习和记忆等脑的高级功能,也能调节胆碱能系统、多巴胺能系统和5-羟色胺能系统等的生理功能。雌激素具有两类受体:一是经典的核受体ER-α和ER-β;二是近年新发现的膜性受体ER-X和G蛋白偶联受体GPR30(G protein-coupled receptor)以及Gαq-ER。核受体介导雌激素的基因型效应即调节特异性靶基因的转录,而膜性受体(包括核受体的膜性成分)介导快速的非基因型效应,但也可通过第二信使系统发挥间接的转录调控功能。由于脑源性雌激素具备神经递质/神经调质的部分功能性特征,因此雌激素仅仅是一种激素还是可以作为神经递质/神经调质的假说引起了研究者的极大兴趣。 相似文献
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Caveolin-1(窖蛋白-1)单倍不足可以促进正常乳腺细胞的早期转化, 与新型雌激素受体亚型ERα36介导的膜始动雌激素信号通路的激活有关, 但是关于其机制并未被研究清楚. 本文利用siRNA技术建立了Caveolin-1低表达而ERα36高表达的稳定传代细胞模型MCF10ACE, 采用基因芯片技术检测了ERα36高表达时雌激素信号通路基因表达谱, 研究了ERα36在雌激素激活的PI3K/AKT信号通路中的作用及其与乳腺细胞转化的关系. 结果表明: (1) Caveolin-1表达降低时可以以雌激素依赖性方式促进ERα36表达增加; (2) ERα36高表达可介导MCF10ACE细胞雌激素抗凋亡信号通路(PI3K/AKT)的激活, 促进其与增殖信号通路MEK/ERK之间的交叉对话, 从而使人乳腺细胞增殖加快, 逐渐转化. 结果提示, Caveolin-1与ERα36相互作用调节膜起始的雌激素信号通路是控制乳腺细胞转化的重要机制. 相似文献
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由膜受体介导的信号转导过程在淋巴细胞发育、分化和活化过程中起着重要的作用,转接蛋白是淋巴细胞信号转导中发挥承上启下作用的分子。它们被相应的蛋白酶磷酸化后,可以通过招募具有特定氨基酸基序的蛋白质,将信号转导通路中不同阶段的分子募集在一起,从而实现信号的整合和分流。NTAL/LAB是新发现的跨膜转接蛋白,体外B细胞受体、FcγRI和FcεRI受体的交联可以引起该分子的迅速磷酸化,提示NTAL/LAB可能参与了这些受体介导的信号转导途径,从而影响淋巴细胞的发育和功能。本文将对NTAL/LAB在主要淋巴细胞发育和分化中的作用作一介绍。 相似文献
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除了经典的基因组效应以外,雌激素还可以通过细胞内信号转导途径在几分钟甚至是几秒钟内产生快速生物学效应,被称为雌激素的非基因组效应.这种雌激素的非基因组效应与基因组效应一样,也存在着组织、细胞的特异性.本文将对雌激素膜受体存在的依据、以膜ER为核心的多分子复合物的特性及其介导的信号通路以及雌激素快速生物学效应的组织/细胞特异性作一综述. 相似文献
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李安毅郭晓汐刘莹杨洋徐天瑞安输 《生理学报》2016,(1):57-64
Gab家族蛋白(Grb2-associated binder family proteins)是生长因子受体结合蛋白2的结合蛋白。在哺乳动物中,Gab家族蛋白包括Gab1、Gab2和Gab3。该家族蛋白可通过介导膜受体与信号转导蛋白间的耦联及各信号分子间的相互作用参与信号转导,其主要是通过激活SHP2/RAS/ERK和PI3K/AKT两条经典的信号通路,进而参与一系列的生物应答。研究显示,Gab蛋白的表达或功能异常与肿瘤、炎症和心血管疾病的发生、发展密切相关。本文就Gab蛋白结构、参与信号转导的调节机制及其在肿瘤、炎症和心血管疾病发生、发展中的作用进行综述。 相似文献
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Estrogen receptor alpha-mediated silencing of caveolin gene expression in neuronal cells 总被引:8,自引:0,他引:8
Zschocke J Manthey D Bayatti N van der Burg B Goodenough S Behl C 《The Journal of biological chemistry》2002,277(41):38772-38780
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脑内雌激素水平下降被认为与女性阿尔茨海默病(AD)相关,女性阿尔茨海默病患者脑中胞浆、细胞核、线粒体中的雌激素受体?茁(estrogen receptor β,ERβ)水平也较正常老年女性低.老年大鼠脑内ERβ水平发生显著下降.敲除ERβ影响小鼠的学习和记忆功能,雌激素或ERβ选择性激动剂能够改善神经元突触相关蛋白表达.在神经元中,ERβ与线粒体共定位,提示定位于线粒体上的ERβ,可能参与线粒体功能的调节,从而影响神经元功能. 相似文献
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目的:观察雌激素受体(ERα和ERβ)在非繁殖期成年无蹼壁虎(Gekko swinhonis)心脏的表达并比较性别差异。方法:应用显示雌激素受体的免疫组织化学方法。结果:ERα和ERβ阳性反应均见于无蹼壁虎心肌细胞和成纤维细胞,且受体的表达无性别差异;ERα表达存在明显的心房(11.56±1.67)心室(6.68±1.88)差异(P〈0.01)。结论:雌激素可能是通过ERα主要作用于心房,通过ERβ调节整个心脏的机能;雌激素受体含量与性别无关,可能与生理条件下受体的活性及功能状态有关。 相似文献
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Caveolin cycles between plasma membrane caveolae and the Golgi complex by microtubule-dependent and microtubule-independent steps 总被引:12,自引:5,他引:7 下载免费PDF全文
《The Journal of cell biology》1995,131(6):1421-1433
Caveolin is a protein associated with the characteristic coats that decorate the cytoplasmic face of plasma membrane caveolae. Recently it was found that exposure of human fibroblasts to cholesterol oxidase (CO) rapidly induces caveolin to redistribute to the ER and then to the Golgi complex, and that subsequent removal of CO allows caveolin to return to the plasma membrane (Smart, E. J., Y.-S. Ying, P. A. Conrad, R. G. W. Anderson, J. Cell Biol. 1994, 127:1185-1197). We now present evidence that caveolin normally undergoes microtubule-dependent cycling between the plasma membrane and the Golgi. In cells that were treated briefly with nocodazole and then with a mixture of nocodazole plus CO, caveolin relocated from the plasma membrane to the ER and then to the ER/Golgi intermediate compartment (ERGIC), but subsequent movement to the Golgi was not observed. Even in the absence of CO, nocodazole caused caveolin to accumulate in the ERGIC. Nocodazole did not retard the movement of caveolin from the Golgi to the plasma membrane after removal of CO. Incubation of cells at 15 degrees followed by elevation of the temperature to 37 degrees caused caveolin to accumulate first in the ERGIC and then in the Golgi, before finally reestablishing its normal steady state distribution predominantly in plasma membrane caveolae. In cells released from a 15 degrees block, movement of caveolin from the Golgi to the plasma membrane was not inhibited by nocodazole. Taken together, these results imply that caveolin cycles constitutively between the plasma membrane and the Golgi by a multi- step process, one of which, ERGIC-to-Golgi transport, requires microtubules. This novel, bidirectional pathway may indicate roles for microtubules in the maintenance of caveolae, and for caveolin in shuttling fatty acids and cholesterol between the plasma membrane and the ER/Golgi system. 相似文献
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雌激素受体亚型及其配体调节基因转录机制的研究 总被引:9,自引:0,他引:9
本文综述雌激素受体亚型(ERα和ERβ)的结构,功能,组织分布,生理作用及雌激素受体配体调节基因转录的机制,目的是深入系统地了解植物雌激素和选择性雌激素受体调节剂的作用路径及其组织特异性的发生机制,最终为提高雌激素类药物的选择性,优化以临床为基础的药物设计提供一条较为系统的思路。结果表明,ERα和ERβ对不同雌激素类化合物产生不同应答,配体的结构不同,调节基因转录的路径不同和募集的辅调节蛋白的不同是雌激素受体两种亚型组织特异性激活或抑制的主要原因。 相似文献
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Takuya Imamura 《Hormones and behavior》2011,59(3):345-34799
Epigenetic regulation of the nuclear estrogen and androgen receptors, ER and AR, constitutes the molecular basis for the long-lasting effects of sex steroids on gene expression in cells. The effects prevail at hundreds of gene loci in the proximity of estrogen- and androgen-responsive elements and many more such loci through intra- and even inter-chromosomal level regulation. Such a memory system should be active in a flexible manner during the early development of vertebrates, and later replaced to establish more stable marks on genomic DNA. In mammals, DNA methylation is utilized as a very stable mark for silencing of the ERα and AR isoform expression during cancer cell and normal brain development. The factors affecting the DNA methylation of the ERα and AR genes in cells include estrogen and androgen. Since testosterone induces brain masculinization through its aromatization to estradiol in a narrow time window of the perinatal stage in rodents, the autoregulation of estrogen receptors, especially the predominant form of ERα, at the level of DNA methylation to set up the “cell memory” affecting the sexually differentiated status of brain function has been attracting increasing attention. The alternative usage of the androgen-AR system for brain masculinization and estrogenic regulation of AR expression in some species imply that the DNA methylation pattern of the AR gene can be established by closely related but different systems for sex steroid-induced phenomena, including brain masculinization. 相似文献
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Jakacka M Ito M Martinson F Ishikawa T Lee EJ Jameson JL 《Molecular endocrinology (Baltimore, Md.)》2002,16(10):2188-2201
We created a nonclassical estrogen receptor (ER) knock-in mouse model by introducing a mutation that selectively eliminates classical ER signaling through estrogen response elements, while preserving the nonclassical ER pathway. Heterozygous nonclassical ER knock-in (NERKI) females are infertile. Their ovaries contain no corpora lutea, reflecting a defect in ovulation, and the stromal cells contain lipid droplets, suggesting altered steroidogenesis. The uteri are enlarged with evidence of cystic endometrial hyperplasia, and the mammary glands are hypoplastic. These phenotypic features indicate differential ER effects on growth and development in various estrogen-responsive tissues. These findings suggest that nonclassical ER signaling pathways play an important physiological role in the development and function of the reproductive system. 相似文献
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