雌激素相关受体在肾脏疾病中的作用

雌激素相关受体（estrogen-related receptors,ERRs）是核受体超家族的重要成员,是一类无需与配体结合即可产生生物学功能的受体。ERRs主要有3种亚型：ERRα、ERRβ及ERRγ。虽然ERRs的序列与雌激素受体同源,但它们的活化并不需要雌激素参与,在细胞呼吸、细胞发育、细胞增殖、能量代谢及线粒...     

雌激素相关受体在肾脏疾病中的作用

雌激素相关受体(estrogen-related receptors, ERRs)是核受体超家族的重要成员, 是一类无需与配体结合即可产生生物学功能的受体。ERRs主要有3种亚型:ERRα、ERRβ及ERRγ。虽然ERRs的序列与雌激素受体同源, 但它们的活化并不需要雌激素参与, 在细胞呼吸、细胞发育、细胞增殖、能量代谢及线粒体生物合成等方面发挥重要作用。近年来研究发现, ERRs与肾脏疾病的发生与发展也密切相关。本文就ERRs的生物学功能及其在肾脏疾病中的研究进展进行综述。     

17β-雌二醇调控骨外膜来源成骨样细胞雌激素受体及相关受体α基因表达

目的 探讨雌激素受体（estrogen receptors，ER）及雌激素相关受体α（estrogen related—receptord，ERRα）基因在骨外膜来源成骨样细胞的表达及其与雌激素调控的关系。方法6周龄、雌性Wistar大鼠颅骨骨外膜来源的成骨样细胞分别在含有0．01、0．05、0．1、0125、0．5、0．75、1.5、10nmol／L9种浓度17β-雌二醇（17β—E2）或对照的成骨诱导培养液中培养7d，提取细胞总RNA，采用RT—PCR法分析ER及ERRα基因的表达情况。结果 ERα基因表达阴性，ERβ基因呈弱表达。从0-0．25nmol／L范围内可以看剑ERβ的表达水平有上升趋势。5nmol／L和10nmol／L雌激素组ERβ的表达水平显著低于其他雌激素组（P〈0．01）ERRα表达阳性，各雌激素组的表达水平均显著高于对照组（P〈0．01）。0．25nmol／L组的ERRα表达水平最高、0．5nmol／L组次之，两组的表达水平显著高于其他雌激素组（R0．05）；10nmol／L组表达水平昆若低于其他雌激素组（P〈0．05）。结论 雌激素上调了骨外膜来源成骨样细胞ERRα的表达水平，低水平的雌激素有可能上调ERβ的表达水平。血清17β—E2水平维持在早、晚卯泡期的生理浓度有可能扶得最佳的骨保护疗效。     

雌激素及其受体对骨质疏松症影响的研究进展

骨质疏松症(osteoporosis)是一种全身性骨量减少及骨组织微结构改变,从而导致骨脆性增加及易发生骨折的一种常见的、全身性的骨代谢疾病。其致病因素很多,现在认为雌激素水平是影响女性骨密度的重要因素,雌激素缺乏是公认的骨质疏松症的重要诱因之一。雌激素的效应主要通过雌激素受体来发挥。本文就雌激素及其受体对骨质疏松症的影响做一阐述。     

雌激素受体相关受体α在乳房肥大中的表达

目的探讨雌激素受体相关受体α（ERRα）在乳房肥大中的表达和作用。方法选择28例乳房肥大患者的乳腺组织（单侧总体积在600ml以上）作为标本，未婚育者15例，已育哺乳者13例；与12例乳房发育正常者的乳腺组织标本做比较，采用免疫组化法检测两组乳腺组织中ERRa的表达情况。结果ERRa蛋白主要分布于乳腺上皮细胞和脂肪细胞的细胞核内。乳房肥大组ERRα的总阳性率为53．6％，乳房正常发育组阳性率为8．3％，两组比较差异有统计学意义（P〈0．05）。已育哺乳组和未婚育组ERRα的表达分别为46．2％与60％，两者比较差异无统计学意义（P〉O．05）。结论ERRα与乳房肥大的形成存在一定的相关性。     

雌激素受体与特发性脊柱侧凸及骨质疏松症的关系

雌激素属类固醇激素,通过与细胞内受体结合发挥基因转录的作用。雌激素受体(EstrogenReceptor ,ER )分为ERα和ERβ两种亚型。随着分子生物学技术的发展和应用及ER的研究日益深入,对雌激素在骨代谢调节中的作用机制有了进一步的理解,目前特发性脊柱侧凸(AdolescentIdiopathicScoliosis ,AIS)的发病机制不明,且AIS存在着骨量降低、骨质疏松症已被证实,故本文就雌激素受体与AIS及骨质疏松症的分子学机制做一综述。1　ER的结构和功能ER是核受体超家族成员之一[1] ,位于胞浆和胞核内,具有转录因子的作用。1986年Green等从人乳腺癌细…     

雌激素与雌激素受体骨代谢调节作用

雌激素缺乏是绝经后骨质疏松症发生的主要原因,雌激素或雌激素受体调节剂与雌激素受体结合后通过多种分子生物学机制,抑制破骨细胞骨吸收,促进成骨细胞骨形成、提高骨密度,达到治疗绝经后骨质疏松症的目的。本文综述了雌激素、选择性雌激素受体调节剂与雌激素受体相互作用对骨代谢的调节机制、雌激素治疗骨质疏松症的动物实验研究以及雌激素治疗骨质疏松症的临床研究进展,旨在为临床骨质疏松治疗策略提供科学依据。     

雌激素受体在前列腺癌中的研究现状

前列腺癌是一种男性高发疾病,长期以来阻断雄激素被用作治疗前列腺癌的主要方法,但是越来越多的研究表明雌激素在正常或异常的前列腺生长中扮演了重要角色。本文将就雌激素受体（estrogen receptors,ERs）及其与前列腺癌发生、发展的关系,以及选择性ERs调节剂（selective estrogen receptor modulators,SERMs）在前列腺癌治疗中的应用予以综述。     

雌激素受体β水平预测乳腺癌预后的研究进展

乳腺癌是一种激素依赖性肿瘤,雌激素在其发生、发展中起重要作用,而雌激素须通过雌激素受体（ER）介导发挥生物学作用。ER是由其基因编码的一种核转录因子,包括α和β两个亚型。相关研究表明ERα表达缺失或突变与乳腺癌预后不良有关,而ERβ表达与乳腺癌预后的相关性,体外实验与临床研究的结果不尽相同。本文就ERβ及其亚型在乳腺癌发生、发展和内分泌治疗中的作用以及对乳腺癌预后的预测价值做一综述。     

雌激素和孕激素及其受体在肝门部胆管癌中的水平及意义

肝门部胆管癌(hilar cholangiocarcinoma,HCCA)发病率近年来有增加趋势,目前其致癌因子尚不明确。我们对42例HCCA组织进行雌激素(estrogen,E)、孕激素(progesterone,P)、雌激素受体(estrogen receptor,ER)及孕激素受体(progesterone receptor,PR)联合检测,旨在探讨它们在HCCA发     

Bone endothelial cells as estrogen targets

Summary In the present study, we investigated the effects of estrogens on bone endothelial cell metabolism and the presence of estrogen binding sites in the same cells. For these studies, we have used a continuous cell line of clonal bovine bone endothelial cells for evidence of a direct response to estrogensin vitro. Receptor analysis to intact viable cells was steroid specific and saturable, with an apparent dissociation constant of 17.2 nM and a B_max of 3.2 × 10⁴ sites/cell. Northern blot analysis revealed a 6.5-kilobase mRNA that hybridized with a cDNA to human estrogen receptor. The 6.5-kilobase size is in close agreement with the reported size of the human estrogen receptor mRNA.In vitro estrogen responses of bone endothelial cells included a stimulation of cell proliferation as well as an inhibition of parathyroid hormone responsiveness. These findings clearly demonstrate the presence of functional estrogen receptors in bone endothelial cellsin vitro, suggesting a role of estrogens in bone angiogenesis and in the entire process of bone remodeling.     

Association of aromatase and estrogen receptor gene polymorphisms with hip fractures

Summary Two polymorphisms of the aromatase and estrogen receptor genes appeared to interact to influence the risk of hip fractures in women. Introduction Allelic variants of the aromatase gene have been associated with bone mineral density and vertebral fractures. Our objective was to analyze the relationship between two polymorphisms of the aromatase and estrogen receptor genes and hip fractures. Methods We studied 498 women with hip fractures and 356 controls. A C/G polymorphism of the aromatase gene and a T/C polymorphism of the estrogen receptor α gene were analyzed using Taqman assays. Aromatase gene expression was determined in 43 femoral neck samples by real-time RT-PCR. Results There were no significant differences in the overall distribution of genotypes between the fracture and control groups. However, among women with a TT genotype of the estrogen receptor, the CC aromatase genotype was more frequent in women with fractures than in controls (39 vs. 23%, p = 0.009). Thus, women homozygous for T alleles of estrogen receptor and C alleles of aromatase were at increased risk of fracture (odds ratio 2.0; 95% confidence interval 1.2–3.4). The aromatase polymorphism was associated with RNA levels in bone tissue, which were three times lower in samples with a CC genotype (p = 0.009). Conclusions These common polymorphisms of the aromatase and estrogen receptor genes appear to interact, influencing the risk of hip fractures in women. Supported by grants from Fondo de Investigaciones Sanitarias (FIS 04/28 and 06/34).     

Persistent bone-sparing effect of interleukin-1 receptor antagonist: A hypothesis on the role of IL-1 in ovariectomy-induced bone loss

The recent finding that treatment with the interleukin-1 (IL-1) inhibitor, interleukin-1 receptor antagonist (IL-1ra) decreases bone loss and bone resorption in ovariectomized rats, strongly suggested that IL-1 mediates, at least in part, the effects of estrogen deficiency on bone resorption. Although in vitro studies have shown that IL-1 activates mature osteoclasts and stimulates osteoclastogenesis, the two main mechanisms by which estrogen deficiency stimulates bone resorption, it is still unclear whether IL-1 mediates both effects of estrogen deficiency in vivo. To investigate this matter, we have examined the changes in bone mineral density (BMD) which occur in ovariectomized rats after completion of 1 month of estrogen or IL-1ra treatment begun at the time of ovariectomy. Ovariectomy caused a marked decreased in BMD which was blocked by 17 estradiol and decreased by IL-1ra. Cessation of estrogen therapy was followed by a rapid induction of bone loss, indicating that estrogen blocks the activation and utilization of mature osteoclasts without depleting the bone microenvironment of osteoclast precursors and mature, inactive osteoclasts. In contrast, ovariectomized rats treated with IL-1ra maintained a stable bone density for the first 4 weeks after completion of the treatment. In these rats, bone loss resumed not earlier than 6 weeks after discontinuation of the IL-1ra treatment. Estrogen deficiency was necessary to unveil the bone-sparing effect of IL-1ra because in a control experiment in which rats were treated with IL-1ra for the 4 weeks before ovariectomy, BMD began to decrease immediately after ovariectomy. Based on these results we propose the hypothesis that in conditions of estrogen deficiency, the main effect of IL-1ra is to block the proliferation and differentiation of osteoclast precursors, an event that results in the depletion of mature, rapidly responsive osteoclasts. We also suggest that estrogen may have important direct effects on the regulation of osteoclast activity.     

镁与女性绝经后骨质疏松的关系研究进展

女性绝经后体内雌激素水平下降可导致骨质疏松。近年来有学者发现,除了雌激素通过调节钙离子水平在骨代谢过程中发挥重要作用外,镁离子也有可能会影响骨质的形成与吸收。血清镁及雌激素相互作用改变了骨质的钙含量,即二者与女性绝经后骨质疏松存在一定关联,但两者之间的具体关系却并不十分明确。众多试验结果表明,相对于单独一种镁离子或钙离子含量对骨质疏松发生率的影响,在女性绝经后体内雌激素水平低下的情况下,镁/钙离子的含量比显得更为重要。研究显示,血清镁离子含量过高或者过低都可能会引起钙离子代谢异常,可能导致两种离子的浓度比失衡,进而对骨代谢产生不利影响,增加女性绝经后患骨质疏松的风险。因此维持绝经后体内镁/钙平衡有利于维持骨组织代谢的稳定,同时为治疗骨质疏松提供线索。即不能单纯的强调补充镁离子或者钙离子,而是应该根据患者血清中钙镁离子的具体浓度和比例来制定治疗方案。     

核受体在胆结石形成中的作用机制

胆石症是临床常见病,特别是在女性和某些特殊种族群体.非水溶性胆固醇晶体的形成是由于胆汁中的胆固醇、胆盐、磷脂三个主要脂质之间的失衡造成的.而许多参与肝脏内胆汁脂质分泌的蛋白质是受几个转录因子所调控的,包括核受体肝脏X受体和胆汁酸受体.有证据证实,在人类以及小鼠的基因和病理生理中,胆结石的形成和这些核受体具有相关性.此外,最新的资料还表明,雌激素受体在异常胆固醇代谢中的作用会导致胆结石疾病的发生.因此,更好的研究核受体在胆结石形成中的作用机制,将有助于医师在临床工作中制订对胆结石疾病更有效的治疗策略.     

雌激素-雌激素受体信号通路对趋化因子的调控作用研究进展

雌激素参与机体多项生理、病理调节机制,在机体稳态中发挥不可或缺的作用。趋化因子作为低分子量趋化性细胞因子超家族的一员,活跃于机体各个系统的调节,并且其自身的表达也受到了全身各系统的调控,如内分泌系统的性甾体类固醇激素等。本文对雌激素-雌激素受体信号通路对趋化因子的调控及其机制作一综述。     

雄激素对骨的作用

雄激素是由19个碳原子组成的同化激素,除参与生殖作用外,还影响机体的其他代谢过程,如骨代谢。雄激素在骨的生长发育和维持内环境的稳定中有重要作用。经研究证明骨细胞表面有雄激素受体,表明雄激素对骨细胞的作用是直接的;同时,雄激素经芳香化酶转化为雌激素也是一条重要的调节途径。雄激素在获得骨峰值和维持骨量中起重要作用,并且与年龄相关性骨量丢失的关系相当密切。