雌激素受体信号转导途径和功能

雌激素及其受体对绝经后女性心血管系统生理和病理多方面有重要的影响,具有潜在的临床治疗意义。研究发现,雌激素对机体的作用主要通过与雌激素受体(ER)的结合实现。雌激素受体分为两大类,即经典的雌激素受体ERα、ERβ以及膜雌激素受体以GPER为代表。雌激素与其受体结合引起效应的作用途径分为基因型和非基因型两种。该文主要对雌激素受体信号转导途径和功能进行综述,尤其将膜雌激素受体GPER对心血管系统的作用作为重点,便于进一步研究雌激素及其受体的作用机制,为临床更年期动脉粥样硬化的治疗提供参考。     

雌激素及其受体信号转导途径的研究进展

雌激素因具有广泛的生物学效应，日益成为研究的热点。雌激素的作用是由雌激素受体（ER）介导的，ER具有广泛的组织分布，包括生殖系统、骨骼、心血管系统等，为雌激素发挥生物学效应提供了保证。本文就雌激素及其受体信号转导途径的相关国内外研究进展作一综述。     

G蛋白偶联雌激素受体在雌激素相关肿瘤发生中的作用

在经典的雌激素核受体α和β之外,雌激素或雌激素样物质也可以经过膜受体,即G蛋白偶联雌激素受体(GPER)发挥功能。G蛋白偶联雌激素受体是雌激素非基因通路信号转导过程的重要介导因子,在雌激素相关肿瘤细胞的发生和治疗中具有重要的意义。现针对G蛋白偶联雌激素受体在雌激素相关肿瘤细胞中介导的效应及有关机制的研究进展进行综述。     

雌激素受体α和雌激素受体β的表达及其对乳腺癌预后的影响

雌激素是乳腺癌重要的有丝分裂刺激剂,这种促分裂作用是通过乳腺组织中的雌激素受体（estrogenreceptor,ER）介导的。ER是雌激素信号通路中的一个关键蛋白,属于核受体超家族成员,是一类重要的核转录因子,因其在生殖系统、骨组织、心血管和中枢神经系统中发挥着重要的生理作用,故成为治疗乳腺癌药物的作用靶标。     

G蛋白偶联雌激素受体30与激素依赖性肿瘤发生发展的相关性研究进展

<正>雌激素是生物体内一种重要的类固醇激素,不仅在生殖系统,而且在神经内分泌系统、心血管系统、泌尿系统及骨骼系统等多个系统中都发挥着广泛且重要的生理和病理作用。雌激素通过与相应的雌激素受体结合发挥相应的效能,经典的雌激素受体即雌激素核受体(estrogen receptor,ER)位于细胞核,包括ERα和ERβ两种亚型。传统观点认为雌激素主要通过其经典的核受体途径发挥慢速基因效应,此途径发挥作     

线粒体雌激素受体的新功能

雌激素对控制多种组织细胞的增殖和凋亡十分关键，通过与雌激素受体结合，二聚化，激活细胞核内雌激素反应元件（ERE）发挥雌激素效应。雌激素可以快速活化多种蛋白激酶通路，包括丝裂原活化蛋白激酶（MAPK），磷脂酰肌醇3激酶（P13K），同时提高第二信使（如cAMP）水平。这些反应均由膜ER（mER）介导，并促进了细胞增殖。     

槲皮素、补骨脂素对人乳腺癌T47D细胞两种受体亚型表达的影响

目的探讨槲皮素和补骨脂素的雌激素作用以及调控雌激素受体亚型表达的作用机制。方法10μmol.L-1槲皮素和10μmol.L-1补骨脂素分别处理T47D细胞48 h,采用RT-PCR和Western blot方法测定对雌激素依赖性乳腺癌细胞T47D雌激素受体亚型ERα和ERβ表达的影响,并以雌激素受体拮抗剂ICI182,780为工具药来评价槲皮素和补骨脂素发挥雌激素样作用与雌激素受体的关系。结果槲皮素、补骨脂素在10μmol.L-1可明显诱导T47D细胞ERαmRNA和蛋白表达,而对ERβ表达没有影响。当与ICI182,780共孵育T47D细胞ERα表达被拮抗。结论槲皮素、补骨脂素产生的促进ER阳性细胞增殖的雌激素样作用是通过增加ERα表达实现的。     

泌尿系统肿瘤中雌激素受体作用的研究进展

雌激素受体（ER）是类固醇激素受体超家族成员,可调节生殖系统的增殖和分化,进而影响各种生理功能,对肝、肾、脑、骨骼及心血管等系统亦有不同程度的作用。本文综述泌尿系统肿瘤中雌激素受体作用的研究进展。     

雌激素受体、孕激素受体与子宫肌瘤生长的关系

子宫肌瘤是妇科常见的良性肿瘤,肌瘤生长速度和体积与临床症状密切相关,月经过多、并发贫血、腹痛及压迫症状是选择手术最常见的原因。雌激素、孕激素是肌瘤发生、发展中的主要原因。近年来随着深入研究,认识到一些激素与生长因子如雌、孕激素受体（ER、PR）、血管内皮生长因子（WEGF）、胰岛素生长因子受体（IGFIRα）在子宫肌瘤生长中也发挥着重要作用。本文就通过ER、PR在子宫肌瘤中的含量探讨其在子宫肌瘤生长中的影响。     

雌激素受体的生物学功能及其在骨骼肌发育和前列腺癌中作用的研究进展

雌激素受体(ER)是核受体家族中重要的一员,在多种组织中广泛表达,包括肌肉、乳腺、前列腺等.ER主要包括ERα 和ERβ,当雌激素与ER结合后,通过形成同源或异源二聚体进入细胞核中促进多种转录因子的激活,从而调节复杂、动态的基因网络.ER在调节细胞的增殖、凋亡和自噬等过程中发挥重要作用,且与多种疾病的发生与发展密切相关...     

选择性雌激素受体调节剂的作用机制研究近况

选择性雌激素受体调节剂(SERM)在不同的靶组织可以表现为雌激素激动剂和(或)拮抗剂，本文综述了近年来关于SERM结构、ER亚型、共调节子、靶启动子、细胞亚型、细胞内信号通路、雌激素受体相关受体等对SERM组织选择性的影响的研究状况。     

脂肪细胞雌激素受体的测定及表达水平的研究

目的　研究不同部位的脂肪细胞雌激素受体 (estrogenreceptor ,ER)的表达水平 ,探讨脂肪细胞与雌激素之间的关系。方法　对 64例成人腹部皮下脂肪组织及内脏大网膜脂肪组织 ,应用免疫组织化学法染色并进行图象分析。结果　成人脂肪细胞核内雌激素受体呈阳性反应 ;男性腹部皮下脂肪细胞的ER阳性细胞的光密度高于大网膜脂肪ER阳性细胞的光密度 (P <0 .0 5 ) ;女性的腹部皮下脂肪细胞的ER阳性细胞的光密度与大网膜脂肪组织ER阳性细胞的光密度相比差异无显著性 (P >0 .0 5 )。结论　 ( 1)脂肪细胞的ER免疫阳性反应表达于脂肪细胞的细胞核。 ( 2 )男性的不同部位脂肪细胞的ER表达不同 ,而女性不同部位脂肪细胞ER的表达一致     

睾酮诱导小鼠形成条件性位置偏爱和雌激素受体相关

目的:研究雌激素受体与睾酮诱导小鼠条件性位置偏爱的关系。方法:通过皮下注射睾酮训练小鼠形成条件性位置偏爱;在注射睾酮前注射雌激素受体拮抗剂ICI182780和他莫西芬,通过观察睾酮条件性位置偏爱的变化来判断雌激素受体是否在其中起作用。结果:0.5、1、2 mg.kg-1睾酮训练12 d,可以诱导小鼠产生条件性位置偏爱。雌激素受体拮抗剂ICI182780(2 mg.kg-1)或他莫西芬(1 mg.kg-1)可以抑制睾酮诱导的小鼠条件性位置偏爱。结论:睾酮具有奖赏效应,雌激素受体可能参与睾酮的奖赏效应。     

Quantitative analysis of expression level of estrogen and progesterone receptors and VEGF genes in human endometrial stromal cells after treatment with nicotine

Cigarette smoke is a complex mixture of toxic chemicals, including nicotine, carbon monoxide, and several recognized carcinogens and mutagens. Nicotine has a direct disturbing influence on steroid hormones (estrogen and progesterone), which are essential components of the female reproductive system, but the effect of nicotine on the hormone receptors is not yet clear. The aim of this study was to elucidate the effect of nicotine on the expression of estrogen receptor (ER), progesterone receptor (PR), and vascular endothelial growth factor (VEGF) in endometrial stromal cells. Expression levels of PR, ER, and VEGF in human endometrial stromal primary cells treated with nicotine (0, 10^?11, 10^?8, and 10^?6?μM) for 24?h were measured by quantitative real-time PCR. MTT assay demonstrated that nicotine decreased cell viability in a dose-dependent manner. Real-time PCR data showed that despite decrease in ER expression in the nicotine-treated groups compared with the control, nicotine exerted an increased inhibitory effect on PR expression compared to that on ER expression. VEGF mRNA expression in nicotine-treated endometrial stromal cells was increased. The results from this study provide novel evidence for inhibitory effects of nicotine on steroid hormones receptor expression in human primary endometrial cells. Also, our data suggest that nicotine might have angiogenesis effects on these cells.     

Hydrophobic Interactions Improve Selectivity to ERα for Ben-zothiophene SERMs

The discovery, pharmacology, and biophysical characterization of an ERα selective benzothiophene (BTPα) is described. BTPα (4) is a high affinity ligand with 140-fold greater selectivity for ERα (K(i)=0.25 nM) over ERbeta (K(i)=35 nM). In rodent models of estrogen action, BTPα blocks the effects of estrogen in the uterus but mimics the effects estrogen on bone. The basis of ERα selectivity for BTPα was evaluated by using protein crystallography and hydrogen/deuterium exchange (HDX) mass spectrometry. HDX data supports that the n-butyl chain of BTPα stabilizes helix 7 in ERα relative to that of ERβ which we propose leads to an enhancement of affinity to the alpha receptor sub-type.     

Novel estrogen receptor ligands and their structure–activity relationship evaluated by scintillation proximity assay for high‐throughput screening

The estrogen receptor (ER) is an important drug target with allosteric characteristics that binds orthotopic hormones and other ligands. A recently developed scintillation proximity (SPA)‐based assay for high‐throughput screening (HTS) of compound libraries was used to identify novel estrogen receptor ligands that might have ER subtype selective binding activity. Radioligand binding was determined in a multi‐detector scintillation counter designed for microtitration plates. Equilibrium binding experiments and kinetic competition tests were performed with [³H]‐estradiol and human ERα and ERβ receptors. A library of 6,000 structurally diverse compounds was screened. From this, several novel ligands were identified that showed pronounced subtype‐selective differences in ligand binding for ERα and ERβ. The observed equilibrium dissociation constant (K_d) for the binding of [³H]estradiol to ERα and ERβ receptors were approximately 0.25 and 0.64 nM, respectively. When 17β‐estradiol, raloxifene and daidzein were tested for binding affinity to ERα in a competition assay, the IC₅₀ values were 0.34, 1.31, and 75.6 nM, respectively. When tested for binding affinity to ERβ, the IC₅₀ values were 1.05, 11.4, and 10.6 nM, respectively. The results obtained show that the methodology is valid in comparison to previously published data regarding estradiol and other standard compounds (raloxifene and daidzein) binding characteristics of estrogen receptors. The assay is also well suited to applied research as a tool in HTS of compound libraries in the search of ER ligands. Several novel active compounds were identified and selected as potent ER subtype ligands. Drug Dev Res 64:203–212, 2005. © 2005 Wiley‐Liss, Inc.     

The role of estrogen receptor in melanoma

The estrogen receptor (ER) belongs to the group of sex hormone receptors and binds the biologically active form of estrogen, 17β-estradiol. Expression of ER in tumor tissue is a well-established prognostic marker in breast cancer. The role of ER has been extensively studied in several other types of human cancers. This report investigates the potential role of ER as a surrogate marker for predicting melanoma progression, response to therapy, and patient survival. In addition, the authors review what is known, so far, about ER signaling pathways and their potential role in carcinogenesis and progression of cutaneous melanoma. Possibilities and limitations of using ER as a therapeutic target in the treatment of melanoma is also discussed.