雌激素受体αβ亚型在人足月妊娠胎盘的表达和定位

研究雌激素受体亚型αβ(ERα，ERβ)在人足月胎盘的表达和定位。方法：采用免疫组化SP法染色。结果：人足月胎盘的滋养细胞有雌激素受体亚型的表达，雌激素受体α亚型主要定位于绒毛的细胞滋养细胞胞核，雌激素受体β亚型主要定位于绒毛的合体滋养细胞胞浆和极少数胞核。结论：人胎盘中雌素受体亚型的分布不平衡，这可能与胎盘的分泌功能密切相关。     

正常及异常组织中雌激素α及β受体的表达

背景:随着雌激素β受体亚型的发现,对重新认识雌激素α,β受体的信号转导途径及作用机制提出了新的课题,深入研究雌激素α,β受体的结构、生理功能和相关依赖性疾病具有重要意义.目的:总结雌激素α,β受体在正常组织和异常组织的表达以及病理生理作用.方法:应用电子计算机检索PubMed数据库和CNKI数据库及PubMed数据库2000-01/2010-05雌激素受体相关综述和论文报告,纳入与雌激素α,β受体结构和功能密切相关的文献,和与雌激素α,β受体在正常不同组织器官和病理组织表达的基础研究和临床实验研究文献.排除重复性实验.结果与结论:符合纳入标准的38篇,结果表明雌激素α,β受体广泛分布在不同组织中,其结构和功能存在着差异,雌激素及其受体通过基因调节机制和非基因调节机制对靶组织产生效应.雌激素α,β受体在不同的组织器官和不同疾病的组织中表达比例和水平存在着差异,即使同一器官内不同的组织细胞表达比例也存在差异.     

雌激素受体a与β表达的研究进展及其在疾病预后判断中的作用

目的：研究雌激素受体分布和表达及其在雌激素相关性疾病预后判断中的作用。资料来源：应用计算机检索PubMed 1986-01／2003-12相关雌激素受体d与β的章，检索词“Estrogen，steroid receptor，prostate gland”，并限定章语言种类为英。同时计算机检索《中国临床康复》杂志2002-01／2004-08相关章，限定章语言种类为汉语，检索词“雌激素”。资料选择：资料纳入标准为①雌激素受体a和β在子宫、卵巢、乳腺、前列腺、神经系统及肿瘤中的表达。②有关雌激素受体a和β的结构、功能及转录、调节。资料提炼：共有26篇章符合纳入标准。资料综合：分别对雌激素受体a和β的结构、功能等及其在子宫、卵巢、乳腺、前列腺、神经系统及肿瘤中的表达及研究进展进行综述。结论：雌激素受体的两种亚型，由于基因、结构、功能、作用机制、分布的不同，对雌激素靶器官和组织的生理、病理产生不同的影响。     

乳腺癌雌激素受体亚型研究进展

乳腺癌是妇女中最常见的恶性肿瘤，其发病率正在逐步上升。乳腺癌是激素依赖性肿瘤，受雌激素和孕激素的调控，在多数乳腺癌组织中均发现有两种激素受体^[1]：雌激素受体（estrogen receptors，ER）和孕激素受体（progesterone receptors，PR）的表达，内源性雌激素参与乳腺上皮的生长分化，在乳腺癌的发生、发展中起至关重要的作用，而雌激素的作用又是由受体ER所介导的^[2]。     

雌激素脑保护的基因和非基因机制学说

目的：认识雌激素脑保护作用的分子机制及其研究进展。资料来源：应用计算机检索数据库http：／／www．ncbi．nlm．nih、gov／PubMed，1984-01／2003—12期间的相关文章，检索词“estrogens,brain，Genome”，并限定文章语言种类为英文。同时计算机检索数据库http：／／www．wanfangdata、com．cn2001-01／2004—10期间的相关文章，限定文章语言种类为中文，检索词“雌激素，脑，基因组”。资料选择：对资料进行初审，选取试验研究查找全文。纳入标准：①研究原著。②不排除是否实施对照和盲法。资料提炼：共收集到35篇关于雌激素脑保护作用的分子机制方面的文献。资料综合：其分子机制主要有以下几个方面：直接基因组机制：通过核型受体激活核内转录因子途径，上调下游基因而起作用；间接基因组作用：又称快速的，非基因途径，通过膜型雌激素受体介导的第二信使途径；非基因作用：非受体作用，直接的抗炎症、抗氧化作用。结论：雌激素通过复杂的机制起到神经保护作用，随着研究的深入，雌激素的作用机制将得到更好得解释，从而为临床应用奠定基础。     

雌激素受体α与β表达的研究进展及其在疾病预后判断中的作用

目的:研究雌激素受体分布和表达及其在雌激素相关性疾病预后判断中的作用。资料来源:应用计算机检索PubMed1986-01/2003-12相关雌激素受体α与β的文章,检索词“Estrogen,steroidreceptor,prostategland”,并限定文章语言种类为英文。同时计算机检索《中国临床康复》杂志2002-01/2004-08相关文章,限定文章语言种类为汉语,检索词“雌激素”。资料选择:资料纳入标准为①雌激素受体α和β在子宫、卵巢、乳腺、前列腺、神经系统及肿瘤中的表达。②有关雌激素受体α和β的结构、功能及转录、调节。资料提炼:共有26篇文章符合纳入标准。资料综合:分别对雌激素受体α和β的结构、功能等及其在子宫、卵巢、乳腺、前列腺、神经系统及肿瘤中的表达及研究进展进行综述。结论:雌激素受体的两种亚型,由于基因、结构、功能、作用机制、分布的不同,对雌激素靶器官和组织的生理、病理产生不同的影响。     

雌激素受体β与雌激素相关肿瘤的研究进展

人们对雌激素受体（estrogen receptor,ER）的认识经历了如下几个阶段,1962年Jensen发现了介导雌激素作用的雌激素受体,1986年Green克隆出雌激素受体蛋白质,1996年Kuiper在大鼠前列腺和卵巢cDNA文库中又成功克隆出一种新型雌激素受体,称为雌激素受体β（estrogen receptor beta,ERβ）,     

雌激素受体α在上皮性卵巢癌中的表达

近年来研究表明雌激素受体(estrogen receptor,ER)与乳腺癌、子宫内膜癌等多种肿瘤的发生、发展及预后有关,但雌激素与卵巢癌的关系仍存在争议[1].ER分为α和β两种亚型,本研究检测了ERα在上皮性卵巢癌中的表达,以探讨ERα在上皮性卵巢癌发生发展中的作用.     

雌激素对骨代谢的调节作用

雌激素对于维持骨吸收与骨形成的平衡具有极其重要的作用。雌激素对骨代谢具有直接作用。雌激素通过破骨细胞和成骨细胞受体，限制骨转换，抑制骨吸收，提高骨密度。雌激素通过骨代谢调节因子、甲状旁腺激素等发挥其间接调节作用。植物雌激素及其衍生物分子结构与雌激素类似，可以与雌激素受体结合发挥雌激素作用。植物雌激素已成为当前雌激素替代疗法的研究热点。     

肾脏雌激素受体亚型表达分布及补肾中药防治肾损害的受体机制

目的：观察雌激素受体α和β在大鼠肾脏中的表达、分布情况，分析补肾中药防治肾损害的受体机制。方法：实验于2000-09／2002-07在河北医科大学生化实验室完成。选用健康雌性SD大鼠45只，按随机数字法分为3组，即正常对照组、肾脏损伤模型组及中药防治组，每组15只。肾脏损伤模型组和中药防治组大鼠每天腹腔注射1mL 9g／L的灭菌AlCl3溶液复制肾脏损伤模型，正常对照组注射1mL灭菌生理盐水，每连续注射3d，间隔1d，共计72d。中药防治组大鼠每天灌胃1mL生药含量为2．6g／mL的补肾中药复方煎剂（由淫羊藿、熟地、制首乌、黄芪、当归、郁金、石菖蒲、茯苓和川芎9味中药组成，由石家庄乐仁堂药业有限公司提供，每付生药含量为125g），正常对照组和肾脏损伤模型组灌胃等量自来水。每连续灌胃7d．间隔1d，共计72d。应用免疫组织化学方法检测雌激素受体α和β在各组大鼠肾组织中的表达水平和分布区域，应用放射免疫分析法测定各组大鼠血清雌二醇水平。结果：45只大鼠全部进入结果分析，无脱失。山雌激素受体亚型在各组大鼠肾组织中的表达和分布情况比较：正常对照组大鼠肾脏皮质和髓质的远曲小管和近曲小管上皮细胞胞浆中都有雌激素受体α和β阳性颗粒，两种受体亚型的髓质反应信号均比皮质强。肾脏损伤模型组大鼠肾脏皮质雌激素受体β反应信号减弱；髓质雌激素受体α反应信号增强。中药防治组大鼠肾水肿基本消失，皮质雌激素受体β反应信号增强至近正常水平，髓质雌激素受体α反应信号降低至近正常水平。②各组大鼠的血清雌二醇水平比较：肾脏损伤模型组大鼠血清雌二醇水平显著低于正常对照组[（19．0&;#177;0．6，40．0&;#177;0．1）pmol／L．P〈0．011，中药防治组大鼠血清雌二醇水平与肾脏损伤模型组相近[（18．0&;#177;0．6）pmol／L，P〉0．051。结论：AlCl3导致肾水肿时，肾脏皮质雌激素受体β表达减弱，髓质雌激素受体α表达增强，血清雌二醇水平降低。补肾中药具有雌二醇样作用，通过拮抗皮质雌激素受体β表达减弱和髓质雌激素受体α表达增强而发挥其肾脏保护作用。     

SERM

SERM is the abbreviation of the selective estrogen receptor modulator which is the synthetic ligands of estrogen receptor (ER) acting estrogenically or anti-estrogenically among various tissues through modifying the ER function. Clomifene, tamoxifen, toremifene and raloxifene are generally classified as SERM in the clinical use. The main cause of postmenopausal osteoporosis is estrogen deficiency and it was revealed that the continuous combined use of conjugated estrogen and medroxyprogesterone acetate reduced the relative risk of femoral neck fracture to 0.66, however increased the relative risk of cardiovascular event and breast cancer to 1.29 or 1.26, respectively. From the standpoint of safe and clinical compliance for the breast and uterine tissue, raloxifene is recommendable for middle aged postmenopausal osteoporosis.     

降脂壮骨中药对食饵性高脂血症大鼠骨组织骨形态发生蛋白2、雌激素受体表达的影响

背景:研究表明活性骨形态发生蛋白2水平的降低可导致严重的类骨质疏松症状,并发现成骨细胞、破骨细胞及骨髓基质细胞上有雌激素受体的存在,认识到雌激素对骨组织具有直接作用.目的:观察降脂壮骨中药对食饵性高脂血症诱发骨质疏松大鼠骨组织骨形态发生蛋白2、雌激素受体表达的影响.方法:健康SD大鼠27只,随机分为3组:正常对照组:上午和下午灌胃生理盐水5 mL/kg;高脂血症诱发骨质疏松模型组:上午灌胃高脂饮食5 mL/kg,下午灌胃生理盐水5 mL/kg;降脂壮骨中药组:上午灌胃高脂饮食5 mL/kg,下午灌胃降脂壮骨中药水提液5 mL/kg.持续干预8周后采用免疫组织化学方法,对其骨组织中骨形态发生蛋白2、雌激素受体的表达水平进行检测,应用原位杂交方法对骨组织中雌激素受体的mRNA水平进行检测.结果与结论:与模型组比较,降脂壮骨中药组骨组织中骨形态发生蛋白2、雌激素受体表达显著增强(P＜0.01),雌激素受体的mRNA表达水平增高.证实降脂壮骨中药能够使食饵性高脂血症诱发骨质疏松大鼠成骨细胞骨形态发生蛋白2、雌激素受体的表达水平增高,起到改善骨质疏松的作用.     

Estrogen receptor alpha mediates acute potassium channel stimulation in human coronary artery smooth muscle cells

The pleiotropic effects of estrogen are mediated via stimulation of two estrogen receptor (ER) subtypes, ERalpha and ERbeta. Although a number of studies have identified expression of one or both subtypes in estrogen target tissues, fewer studies have correlated ER expression with a functional role of these proteins in regulating cellular excitability. In the present study, we have combined cellular fluorescence, immunocytochemistry, and molecular expression techniques with single-channel patch-clamp studies to determine which ER mediates estrogen-stimulated potassium channel activity in human coronary artery smooth muscle cells (HCASMC). We had demonstrated previously that estrogen stimulates activity of the large-conductance, calcium- and voltage-activated potassium (BK(Ca)) channel in HCASMC via a nongenomic mechanism. We now demonstrate expression of both ERalpha and ERbeta subtypes in HCASMC. Functionally, however, expression of ERalpha antisense plasmid abolished the acute effect of estrogen on these channels, whereas estrogen retained its ability to stimulate BK(Ca) channels in cells transfected with only green fluorescence protein. In contrast, overexpression of ERalpha enhanced the stimulatory action of estrogen in HCASMC. Transfection with ERalpha antisense/sense plasmid did not alter ERbeta expression. These findings indicate that the ERalpha isoform mediates estrogen-induced stimulation of BK(Ca) channels in HCASMC and thereby provide evidence for a receptor-dependent signaling mechanism that can mediate estrogen-induced inhibition of cellular excitability.     

Estrogen receptor and selective estrogen receptor modulators (SERMs)]

The incidence of osteoporosis and of cardiovascular disease increases in women after menopause. Although theses diseases can be prevented by estrogen replacement therapy, this treatment is associated with an increased risk of endometrial cancer and perhaps also with an increased risk of breast cancer. Thus, a therapy that could prevent postmenopausal bone loss and lower serum cholesterol concentrations without stimulating reproductive tissues would be desirable. Selective estrogen receptor modulators (SERMs), such as raloxifene and tamoxifen, produce beneficial estrogen-like effects on bone and lipid metabolism, while antagonizing estrogen in reproductive tissue. Both agonist and antagonist activities are mediated via high affinity interaction with the estrogen receptor (ER). Both types of ER (alpha and beta) may be involved in the mechanism by which SERMs produce tissue-selective pharmacology. This review will discuss the roles of ER alpha and ER beta in novel signal transduction pathways.     

雌激素对雌鼠下尿路雌激素受体表达的影响

目的 研究雌激素对去势雌性大鼠膀胱和尿道组织中雌激素受体（ER）α和β亚型表达的影响。 方法 30只成年雌性大鼠分别假手术处理、卵巢切除、卵巢切除术后苯甲酸雌二醇替代治疗,应用实时定量逆转录聚合酶链反应（RT-PCR）和Western blot方法分析大鼠膀胱底部、膀胱颈部及尿道组织中ERα和ERβmRNA及蛋白表达。 结果 Sham组中,ERαmRNA及蛋白在尿道组织中的表达高于膀胱底部和膀胱颈部,ERβmRNA及蛋白在膀胱底部和膀胱颈部的表达则远高于尿道组织。去势使大鼠膀胱尿道ERαmRNA及蛋白表达增加,补充雌激素治疗使其减少接近假手术组。大鼠膀胱尿道ERβmRNA及蛋白表达在不同雌激素状态下无明显变化。结论 ERβ是主要分布于膀胱,ERα主要分布于尿道组织中。雌激素对雌性大鼠下尿路的调控作用主要通过ERα介导。     

Breast Cancer Subtypes Based on ER/PR and Her2 Expression: Comparison of Clinicopathologic Features and Survival

Objective: To compare the clinicopathologic features and survival in the four breast cancer subtypes defined by immunohistochemistry (IHC) expression of estrogen receptor (ER) or progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2): ER/PR+, Her2+; ER/PR+, Her2−; ER/PR−, Her2+; and ER/PR−, Her2−.     

Estrogen receptors and human disease

Estrogens influence many physiological processes in mammals, including but not limited to reproduction, cardiovascular health, bone integrity, cognition, and behavior. Given this widespread role for estrogen in human physiology, it is not surprising that estrogen is also implicated in the development or progression of numerous diseases, which include but are not limited to various types of cancer (breast, ovarian, colorectal, prostate, endometrial), osteoporosis, neurodegenerative diseases, cardiovascular disease, insulin resistance, lupus erythematosus, endometriosis, and obesity. In many of these diseases, estrogen mediates its effects through the estrogen receptor (ER), which serves as the basis for many therapeutic interventions. This Review will describe diseases in which estrogen, through the ER, plays a role in the development or severity of disease.     

Epigenetics of estrogen receptor-negative primary breast cancer

Increasingly, breast cancer is being recognized as a heterogeneous disease comprised of molecularly and phenotypically distinct intrinsic tumor subtypes with different clinical outcomes. This biological heterogeneity has significant implications, particularly as it relates to expression profiling of estrogen receptor (ER) status, as classifying breast cancers based on hormone receptor expression impacts not only prognosis but also treatment options and long-term outcomes. Epigenetics has emerged as a promising field for the assessment of hormone receptor status. Epigenetic aberrations have been shown to regulate ER and offer reversible targets for development of new therapies. This review covers ER-negative breast tumor epigenetic aberrations and summarizes the major epigenetic mechanisms governing ER expression and how it impacts treatment of ER-negative breast cancer.     

甲状旁腺素、维生素D受体、雌激素受体基因多态对糖尿病患者骨密度的影响

目的探讨甲状旁腺素(PTH)基因多态与中国北方汉族人糖尿病患者骨密度的关系。分析维生素D受体(VDR)、雌激素受体(ER)基因多态性对PTH基因多态性与骨密度、骨量减少及骨质疏松关系的影响。方法运用PCR-RFLP技术检测1型糖尿病(T1DM)组54例、2型糖尿病(T2DM)组104例、健康对照(CON)组102例的中国北方汉族人PTH基因多态性。结果甲状旁腺素基因型和等位基因分布频率在T1DM组、T2DM组与CON组间差异无统计学意义(P0.05);DM患者Bb/bb基因型者发生骨量减少/骨质疏松的相对危险度增加(OR=2.8684)。联合VDR基因多态分析,Bbaa基因型组糖尿病患者并发骨量减少/骨质疏松的相对危险度增高(OR=4.3125);联合ER基因多态分析,bPxx基因型骨量减少/骨质疏松的相对危险度也增高(OR=4.0);联合分析PTH、VDR、ER基因型,同时存在3个或4个易感基因型者伴有骨量减少或骨质疏松,相对危险度增加(OR=5.5385)。结论糖尿病患者PTH基因多态性(BST B1位点)可能是预测骨量减少、骨质疏松易感性的遗传标志。联合VDR、ER基因多态有助于识别DM患者发生骨质疏松的高危人群。     

Role of raloxifene in breast cancer prevention in postmenopausal women: clinical evidence and potential mechanisms of action

BACKGROUND: Raloxifene is a selective estrogen-receptor modulator (SERM) indicated for the prevention and treatment of osteoporosis in postmenopausal women. In the Multiple Outcomes of Raloxifene Evaluation (MORE) study, an osteoporosis treatment trial, raloxifene therapy was associated with a reduced incidence of invasive, estrogen receptor (ER)-positive breast cancer compared with placebo (relative risk, 0.16; 95% CI, 0.09-0.30). OBJECTIVE: This review summarizes available preclinical and clinical data pertaining to a potential role for raloxifene in the prevention of breast cancer, and examines the mechanisms of action by which raloxifene may exert an effect. METHODS: Relevant articles were identified through a search of MEDLINE for English-language studies published between 1966 and January 2003. Search terms included raloxifene, keoxifene, tamoxifen, SERM, estrogen, estrogen receptor, breast, mammary, growth factors, and apoptosis. The reference lists of identified articles were reviewed for additional publications. RESULTS: Both preclinical and clinical data suggest a role for raloxifene in the prevention of breast cancer. Like tamoxifen, raloxifene acts as an estrogen antagonist in breast tissue through competitive binding to the ER. Raloxifene may also inhibit breast tissue proliferation through mechanisms independent of the ER. CONCLUSIONS: Given raloxifene's mechanism of action and the preclinical evidence for its role in breast cancer prevention, a clinically favorable effect seems feasible. Results of ongoing clinical studies will provide evidence to support or refute the clinical findings of MORE and thus raloxifene's role in the breast cancer prevention.