雌激素作用简介

雌激素主要成分为雌二醇 (Ｅ2 ) ,是Ｇ18类固醇激素 ,外周雌激素主要由睾丸、卵巢产生 ,脑内主要由下丘脑、边缘系统的神经元产生。近年的研究表明 ,雌激素除对生殖系统、代谢具有重要作用外 ,还对中枢神经系统、心血管系统、消化系统等具有广泛的重要作用。1　雌激素的作用机制[2 ]　　雌激素的生物学作用是通过基因组机制和非基因组机制实现的。雌激素通过与细胞核受体结合 ,启动转录和蛋白合成过程而发挥其基因组效应。雌激素的非基因组效应与细胞膜受体有关 ,雌激素的核受体分为α和 β两个亚型。其膜受体的来源、作用和结构仍不甚清楚…     

染色质免疫沉淀技术及其在结核病免疫调控研究中的进展

人类许多疾病都伴有基因表达调控的改变.基因表达的调控是细胞对外部或内部刺激发生应答的方式,涉及基因组DNA和一系列结合蛋白的相互作用.     

HIV-1 Tat蛋白免疫抑制作用的研究进展

Tat蛋白是HIV-1编码的重要调控蛋白,其最主要的功能就是在病毒感染的细胞内反式激活病毒基因组转录的起始和延伸,启动病毒复制.近年来发现,Tat蛋白还具有其它多种胞内外活性,在HIV-1感染所引起的免疫抑制、神经系统损伤及Kaposi肉瘤形成等过程中发挥重要作用.本文主要研究Tat蛋白免疫抑制的结构基础及其作用机制.     

脂筏与感染性疾病

脂筏是生物膜中含有特殊脂质和蛋白质的微区,不仅是跨膜信号转导等多种生命活动的重要参与者,而且在感染性疾病的发生和发展中扮演了重要的角色。脂筏是多种病原体进入宿主细胞的位点,支持病毒粒子的组装和出芽,其信号转导功能一方面可以启动宿主细胞的保护性免疫应答,另一方面也被病原体利用,以利于病原体的传播和疾病发生。此外,脂筏在朊蛋白感染、HCV基因组复制、多种细菌毒素作用以及维持疟原虫的胞内寄生生活等方面也都有重要作用。脂筏在感染性疾病中的重要作用提示,它很有可能成为扭转这些疾病发生和进程以及治疗这些疾病的重要入手点。     

NOD1、NOD2:两个重要的天然免疫胞内识别受体

机体对微生物入侵的免疫炎症应答过程中模式识别受体(patternrecognitionreceptors,PRRs)是启动机体天然免疫应答机制的关键,主要在获得性免疫系统被活化之前发挥抗感染作用。NOD1和NOD2这两个蛋白分子作为一种新的胞内识别受体参与了细胞凋亡和核因子NF-κB的活化,并与一些炎症性疾病密切相关,在天然免疫中发挥了重要的作用。     

淋巴结内树突状细胞研究进展

ＤＣ是具有最强的抗原提呈和启动机体免疫应答能力的一类抗原提呈细胞，居留于淋巴结内的ＤＣ主要为并指状ＤＣ和滤泡状ＤＣ，在功能和特征上均有各自的特性，在外周ＤＣ向淋巴结的迁移中，多种细胞因子发挥着重要的调控作用，有关ＤＣ在肿瘤等疾病中的作用是当前研究的热点之一。     

选择性雌激素受体调节剂及其心血管保护作用

选择性雌激素受体调节剂 (SERMs)是一类在不同靶组织中可表现为雌激素激动剂或拮抗剂作用的化合物。雷洛昔芬是新一代SERMs代表药物。SERMs作用机制涉及雌激素受体、配体、应答元件、雌激素受体相关蛋白等方面。SERMs对于心血管疾病保护作用主要表现在对血脂的调节和对血管壁的直接作用。与激素替代疗法比较 ,SERMs对不同脂蛋白调节作用各异 ;SERMs具有调节血管壁增殖作用 ,其机制可能与eNOS(内皮一氧化氮合酶 )激活、Akt和ERK信号转导途径有关     

免疫细胞TLRs信号转导机制研究进展

Toll蛋白最早发现在果蝇胚胎发育过程中，对背腹侧体轴细胞的形成起重要调控作用。在成虫，Toll蛋白诱导抗真菌多肽Drosomycin的合成，参与抗真菌天然免疫应答；Toll同源分子18-wheel分子则在抗细菌感染中发挥作用。     

雌性大鼠心内神经节中雌激素受体及其mRNA的表达

目的 在雌激素受体蛋白及ERmRNA水平提供雌激素对心内神经节中神经元作用的形态学依据。方法 采用免疫组织化学及原位杂交技术。结果 在心内神经节部分神经元中，雌激素受体免疫反应及其mRNA原位杂交反应阳性。雌激素受体免疫反应沉淀物呈棕黄色，定位于胞核，雌激素受体mRNA免疫反应沉淀物呈棕黄色，定位于胞浆。结论 大鼠心内神经节中，部分神经元能合成雌激素受体蛋白，说明ER阳性神经元可以为雌激素提供结合位点，因此，这些神经元可能受到雌激素的影响。     

雌激素受体与系统性红斑狼疮的关系

系统性红斑狼疮（SLE）发病机理涉及免疫系统自身识别的丧失,较易发生于生育期女性。雌激素对SLE的发病及病情发展有重要影响。雌激素通过与T、B细胞核内表达的雌激素受体ER-α和ER-β结合进而刺激或调节特异性免疫相关基因的转录。受体结构以及与靶基因相互作用的差异造成了雌激素的异常活动,使得对自身抗原耐受起重要作用的一系列调节通路紊乱,从而导致自身免疫病如SLE的发生。多种经典和非经典雌激素信号的传导通路在转录和转录后水平均调控T细胞活化基因的表达,造成SLE患者的T细胞对雌激素应答的敏感性差异。     

Estrogen receptor alpha is expressed on the cell-surface of embryonic hypothalamic neurons

Although the biological activity of estrogen is generally mediated through nuclear estrogen receptors, a large body of evidence indicates that estrogen may also affect target cells upon binding to putative membrane estrogen receptors (mER) coupled to intracellular signaling cascades; however, no agreement has been reached on the nature and precise location of the putative estrogen receptor (ER) responsible for these rapid effects. In the present report we show that the expression of ERalpha is associated with the plasma membrane fraction of rat hypothalamic tissue at embryonic day 16. Moreover, our experiments extend these results to rat hypothalamic neurons in vitro showing that ERalpha can be detected from the cell exterior as a biotinylated cell-surface protein. We have also shown that the mERalpha is under regulation of estradiol, and the ERalpha agonist, 4,4',4'-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol, induced extracellular-signal-regulated kinase signaling in a dose-dependent manner and in a time-course not compatible with genomic actions, supporting the notion of a membrane-initiated phenomenon.     

Membrane estrogen receptors activate the metabotropic glutamate receptors mGluR5 and mGluR3 to bidirectionally regulate CREB phosphorylation in female rat striatal neurons

Along with its ability to directly regulate gene expression, estradiol influences cell signaling and brain functions via rapid, membrane-initiated events. In the female rat striatum, estradiol activates membrane-localized estrogen receptors to influence synaptic neurotransmission, calcium channel activity, and behaviors related to motor control. Yet, the mechanism by which estradiol acts to rapidly affect striatal physiology has remained elusive. Here we find that membrane estrogen receptors (ERs) couple to the metabotropic glutamate receptors mGluR5 and mGluR3, providing the framework to understand how membrane estrogen receptors affect striatal function. Using CREB phosphorylation as a downstream measure of ER/mGluR activation, membrane-localized estrogen receptor α (ERα) activates mGluR5 signaling to mediate mitogen-activated protein kinase (MAPK)-dependent CREB phosphorylation. Further, ERα and estrogen receptor β (ERβ) activate mGluR3 to attenuate L-type calcium channel-dependent CREB signaling. Interestingly, while this fundamental mechanism of ER/mGluR signaling was initially characterized in hippocampal neurons, estrogen receptors in striatal neurons are paired with a different set of mGluRs, resulting in the potential to functionally isolate membrane-initiated estrogen signaling across brain regions via use of specific mGluR modulators. These results provide both a mechanism for the rapid actions of estrogens within the female striatum, as well as demonstrate that estrogen receptors can interact with a more diverse set of surface membrane receptors than previously recognized.     

人类蜕膜细胞的核体

利用电镜我们发现在人底蜕膜的蜕膜细胞有单纯及复合核体存在。因为雌激素能促使单纯核体的形成和转化为复合核体,我们认为蜕膜细胞里的核体与雌激素的作用有关。由于黄体酮能阻止核体形成,蜕膜细胞核体数量的多少可能与母体血液中雌激素和黄体酮的浓度比例及蜕膜细胞所含此二激素的受体数有关。复合核体合成的rRNA将可促进蜕膜细胞合成生乳素等蛋白激素。     

Membrane oestrogen receptors on rat pituitary tumour cells: immuno-identification and responses to oestradiol and xenoestrogens

Our laboratory has identified plasma membrane oestrogen receptors on a GH3/B6 rat pituitary tumour cell line and several sublines which produce rapid (within minutes), non-genomic responses to oestrogens. Oestrogen receptors have been identified by their binding to nine different antibodies (Abs) which together recognize at least seven epitopes on the oestrogen receptor-alpha. GH3/B6/F10 cells, a membrane oestrogen receptor-enriched subline, elevate intracellular calcium levels in response to 10 nM oestradiol. Prolactin release in these cells is triggered by both 1 pM and 1 nM oestradiol and diethylstilbestrol (DES). A membrane oestrogen receptor-alpha immunocytochemical signal rapidly disappears (at 3 min) and reappears (at 12-15 min) when 1 nM oestradiol, 10 nM diethylstilbestrol, or 10 nM nonylphenol is applied to the cells. This suggests that both oestrogens and xenoestrogens can utilize this alternative pathway for oestrogenic action. Xenoestrogens, which have so far shown weak effects in genomic assay systems, should now be retested for activity in eliciting membrane-initiated oestrogenic responses.     

Estrogen restores cellular immunity in injured male mice via suppression of interleukin-6 production.

This study examined whether estrogen treatment can improve immunity in male mice after combined ethanol and burn injuries. 17beta-Estradiol [estrogen, given subcutaneously (s.c.)] or oil (control) was administered at 30 min and 24 h postinjury. At 48 h postinjury, ethanol/burn-injured mice demonstrated significant suppression of cellular immunity. Estrogen treatment restored the delayed-type hypersensitivity (P<0.01) and splenocyte-proliferative (P<0.05) responses, reduced macrophage interleukin-6 (IL-6) (P<0.05), and increased survival after bacterial challenge (P<0.01). In vitro neutralization of IL-6, combined with macrophage supernatant experiments, confirmed that the beneficial effects of estrogen treatment were mediated through modulation of macrophage IL-6 production. Moreover, estrogen treatment resulted in a decrease in splenic nuclear factor-kappaB (NF-kappaB) activation in injured mice. There were no changes in cellular NF-kappaB or IkappaBalpha protein expression or IkappaBalpha phosphorylation at serine 32. Taken together, these studies suggest that estrogen treatment of injured male mice improves cellular immunity through direct modulation of NF-kappaB activation.     

人类胎儿子宫内膜的核体

在研究人类胎儿子宫内膜的超微结构时,我们发现子宫内膜的上皮细胞有单纯及复合核体的存在。由于雌激素能促进单纯核体的形成和转化,及母体的雌激素和黄体酮能通过胎盘进入胎儿血液循环,我们认为人类胎儿子宫内膜的复合核体的形成与母体雌激素的作用有关。复合核体所合成的rRNA将可增加蛋白质的合成,以应内膜上皮增生之需要。因为黄体酮能阻止核体的形成,胎儿子宫内膜能否出现核体,可能与胎儿血液里雌激素和黄体酮的浓度比例及子宫内膜上皮细胞所含此二激素的受体数有关。     

Immunocytochemical characterization of afferents to estrogen receptor-containing neurons in the medial preoptic area of the rat.

Double-label immunocytochemistry has been employed to elucidate the chemical nature of the afferent neuronal projections to the estrogen receptor-containing neurons located in the medial preoptic area of the rat brain. To ensure a clear separation of the immunolabelled afferent profiles from the estrogen receptors, the former were visualized first and the diaminobenzidine reaction product was silver-gold intensified. Using a monoclonal antibody raised against purified human estrogen receptors, we observed an intense nuclear immunoreactivity in Vibratome, semithin and ultrathin sections. Neuropeptide-Y, serotonin-, phenylethanolamine N-methyltransferase- and adrenocorticotrophin-immunoreactive axons and varicosities were observed in close apposition to the estrogen receptor-positive cells. At the ultrastructural level, neuropeptide-Y-immunoreactive boutons were seen in synaptic contact with cells showing estrogen receptor immunoreactivity in their nucleus. These results indicate that neurons located in the medial preoptic area, one of the principal sites for the control of female reproductive function, may be influenced by both estrogen and neurotransmitters/neuropeptides via, respectively, nuclear receptors and synaptic contacts.     

Immunocytochemical identification of estrogen receptor in ovarian carcinomas. Localization with monoclonal estrophilin antibodies compared with biochemical assays

Estrogen receptor (estrophilin) has been identified in ovarian carcinomas by a variety of physicochemical methods. Since these methods require disruption of the tissue, they do not provide any anatomic information about the cellular distribution and location of receptor. The authors have used monoclonal estrophilin antibodies and an indirect immunoperoxidase technique to study the immunocytochemical localization of estrogen receptor in 43 tissue samples of ovarian carcinoma from 27 patients. The immunocytochemical findings were compared with the results of conventional estrogen receptor assays of cytosolic and nuclear extracts prepared from adjacent pieces of ovarian carcinoma. Exclusively nuclear localization of estrogen receptor was observed with the immunocytochemical technique in all of the 25 tumor samples which had a cytosolic estrogen receptor content, determined by either the dextran-coated charcoal or hydroxylapatite techniques, greater than 700 fmoles/gm wet weight of tissue. Only 3 of 16 tumor samples with cytosolic estrophilin concentrations of less than 700 fmoles/gm wet weight displayed nuclear staining for estrogen receptor; two of these three were metastases from receptor-rich primaries. Specific cytoplasmic staining for estrogen receptor was not observed. These results indicate that many ovarian carcinomas have estrogen receptor, predominantly localized in the nucleus, which is similar to tissues of the female genital tract (vagina, cervix, endometrium, fallopian tube) and breast carcinoma.