雌激素及雌激素受体对高血压心肌肥厚的影响

雌激素通过雌激素受体（estrogen receptor，ER）的介导对心血管系统发挥保护作用。雌激素被动扩散进入细胞后与雌激素受体结合，通过影响肾素血管紧张素系统（RAS）、NO合成、钙离子通道，改善脂质代谢等方面导致高血压心肌肥厚。雌激素受体调节剂（SERMs）如雷洛昔芬等也可以与ER结合，发挥抗心肌肥厚的作用。     

Estrogen decreases expression of chemokine receptors, and suppresses chemokine bioactivity in murine monocytes

Problem:  We propose that the ability of estrogen exposure to increase the probability of a woman developing breast cancer may be related to decreased chemokine activity and suppression of immune surveillance in mammary tissue. The present study was conducted to determine whether estrogen could decrease monocyte bioactivity through alteration of chemokine receptor expression.
Method of study:  We examined the effect of estrogen and tamoxifen on the expression of the chemokine receptors CCR2 and CXCR3 on murine monocytes treated in culture and in vivo . Effects of estrogen on chemokine activation of monocytes were also evaluated.
Results:  Estrogen and tamoxifen significantly decreased expression of CCR2 and, to a lesser extent, CXCR3 on murine monocytes. Estrogen decreased chemotaxis of monocytes towards MCP-1/JE. The chemokines MCP-1/JE and MIP-1 α were unable to evoke increases in intracellular calcium in murine monocytes treated with estrogen, alone or in combination with tamoxifen.
Conclusions:  Our results show that estrogen suppresses the ability of monocytes to respond to certain chemokines, suggesting that estrogen exposure might decrease immune surveillance in tissues where the action of specific chemokines is involved.     

雌激素与甲状腺癌的关系

 雌激素主要通过其特异受体作用于甲状腺癌细胞。雌激素可以通过其特异受体即雌激素受体（ER）结合雌激素反应因子,激活多种基因影响甲状腺癌细胞生长。以及雌激素通过丝裂原活化蛋白激酶(MAPK)信号转导途径刺激甲状腺癌细胞生长。     

雌激素及其受体在克罗恩病发生和发展中作用的研究进展

克罗恩病(CD)的发生与内分泌系统的调节紊乱相关,其中雌激素及其受体的失调在CD的发病机制中扮演着重要的作用。研究发现雌激素可以下调相关炎性因子的表达,适当地补充雌激素有助于减轻炎性反应程度。而其受体(GPER、ERα和ERβ)表达也在局部免疫反应方面起作用,三者表达水平的失调介导肠道炎性反应的发生。结合目前的研究来看,雌激素及其受体有望成为研究CD发生发展的新方向。     

外阴营养不良患者病变组织中性激素受体的检测

目的：研究外阴营养不良与性激素受体的关系。方法：采用直接荧光法，测定了１１例患者病变组织的性激素受体（ＳＨＲ）。其中增生型４例，硬化苔藓型４例，混合型３例。并对其中８例进行了外阴未发病组织ＳＨＲ对照。结果：（１）患者病变组织及未发病组织表皮各层及真皮层内均有不同程度的雌激素受体（ＥＲ）、孕激素受体（ＰＲ）、雄激素受体（ＡＲ）阳性率；（２）患者病变组织及未发病组织基底层ＥＲ、ＡＲ无或少于表皮其它各层     

选择性雌激素受体调节剂

雌激素替代疗法(estrogen replacement therapy,ERT)是治疗绝经后综合征的首选治疗方案,但是长期应用导致子宫内膜增生、乳腺癌等.选择性雌激素受体调节剂主要通过ER 亚型、共调节子、靶启动子、雌激素受体相关受体等机制实现其组织选择性,在发挥骨骼、心血管保护作用的同时,减少了对乳腺及生殖系统的副作用.目前,选择性雌激素受体调节剂的种类、作用的组织特异性及其临床应用在医学界引起广泛关注,具有广阔的发展前景.     

Endogenous pain modulation during the formalin test in estrogen receptor beta knockout mice

The involvement of estrogen in pain has been investigated in many ways. However the specific role played by estrogen receptors remains elusive. Estrogen receptors alpha and beta mediate different physiological functions. For example, estrogen receptor beta is more closely related to non-reproductive effects than the alpha subtype is. To verify the involvement of estrogen receptor beta on acute and persistent pain as well as on endogenous pain inhibitory mechanisms, hotplate and formalin tests were carried out in wild type (WT) and estrogen receptor beta knockout (ERbeta KO) mice of both sexes. Ovariectomies followed by estrogen and progesterone replacement were performed in female groups to insure comparable sex hormone levels. We found that nociceptive responses are lower in ERbeta KO female than in WT female mice during the interphase and early tonic phase II of the formalin test but not during acute and late tonic phases. Moreover, behavioral and spinal (c-Fos) differences were only observed in females. ERbeta KO females had lower c-Fos expression in laminae I-II and IV-V of the spinal cord than WT females. These results suggest that estrogen, through its actions on ERbeta, dampens the efficacy of endogenous pain modulation mechanisms during the interphase and/or inflammation process in the early phase II, triggering an increase in spinal nociceptive neuronal activity. This confirms our previous observations that estrogen specifically influences nociceptive responses during the interphase of the formalin test and demonstrates a role for ERbeta on endogenous pain modulation systems.     

Histological and immunohistochemical study of estrogen and progesterone receptors in normal human breast tissue in adult age groups vulnerable to malignancy

Analysis of receptor status has become standard procedure for assessing breast cancer patients. Estrogen causes epithelial proliferation in breast tissue via the estrogen receptor (ER). The progesterone receptor (PR) is also regulated by the estrogen gene. Analyzing ER and PR together gives information regarding the likely response of carcinoma patients to hormonal therapy. The aim of the present study was to record the expression patterns of ER and PR in normal mammary tissue in different age groups to provide reference data to facilitate histological diagnosis. Breast tissues from the upper outer quadrant of each side of 27 adult female cadavers were examined after H & E staining. ER and PR were identified and examined by immunohistochemistry. The percentage area occupied by parenchyma relative to stromal tissue was calculated in different age groups and was about 4:6, 3.5:6.5, 3:7, 2:8, and 1.5:8.5 in the 3rd, 4th and 5th, 6th, 7th, 8th and 9th, and 10th decades of life, respectively. Both ER and PR were present in all age groups and the numbers of both receptors were maximal during the 4th decade. The distribution and staining patterns for both ER and PR were recorded in different age groups. The contiguous pattern of ER, which is considered pathognomonic of breast carcinoma, was not seen except in one case in the 6th decade. Moderately stained ER and PR receptor sites predominated throughout. The study of normal breast tissue of similar age might provide comparisons that will help histopathologists to make clinical diagnoses from breast biopsies. Clin. Anat. 29:729–737, 2016. © 2016 Wiley Periodicals, Inc.     

巨乳症的临床与病理学观察

目的 研究巨乳症的临床与病理学特点。方法 采用免疫组化S-P法测定10例巨乳症组织中雌激素受体(ER)、孕激素受体(PR)的表达。结果 巨乳症乳腺组织光镜下以l司质纤维组织、脂肪组织及血管增生为主，ER( )或ER和PR( )为75％。结论 巨乳症的发生与乳腺对雌激素的敏感性增强有关。     

Estrogen receptor variants are present in many normal human tissues

Estrogen receptors (ER) are present in various reproductive tissues as well as in other tissues not considered classical targets for estrogen. A variety of alternatively spliced ER variants which co-exist with the wild-type receptor has also been described in many tissues. We analyzed the presence of both wild-type and variant receptors from normal human tissues of various origin using semi-nested PCR and direct automated sequence of the amplified products. We demonstrate that many normal human tissues of various origin contain a number of spliced variants of the estrogen receptor that co-exist with the wild-type receptor. Variants lacking exons 2, 4, 5, and 7 are detected in a variety of normal human tissues.     

雌激素诱导干细胞成骨研究新进展

背景：雌激素与人体正常骨代谢有紧密联系,并可以为干细胞诱导成骨提供有利条件。 目的：文章就雌激素在多种干细胞诱导成骨中的应用情况及其作用机制、安全性、效果、优缺点、突出特性等进行综述。 方法：由第一作者应用计算机检索PubMed数据库,以“estrogen,bone  marrow  mesenchymal stem cells,adipose derived stem cells,embryonic stem cells,osteogenesis”为检索词;应用计算机检索CNKI数据库、万方数据库以“雌激素,骨髓间充质干细胞,脂肪干细胞,胚胎干细胞,诱导成骨”为检索词。 结果与结论：最终纳入50篇文献进行分析。雌激素在人体中是最重要的内分泌激素,在干细胞诱导成骨的研究中是一种安全有效的诱导剂,促进干细胞增殖与成骨分化,并在不同干细胞上表现出来的作用特点不同。其主要作用机制为：直接作用于位于干细胞上的雌激素受体发挥作用,也可以诱导产生各种细胞因子间接影响细胞增殖与分化。雌激素的浓度等级、干细胞上雌激素受体基因的编码调控表达转录、构建细胞支架等尚存在一定的争议,需进一步研究。     

The Normal Genital Tract of the Female California Sea Lion (Zalophus californianus): Cyclic Changes in Histomorphology and Hormone Receptor Distribution

Changes in reproductive tract histomorphology, and estrogen (ERα) and progesterone receptor (PR) expression throughout the breeding cycle were evaluated in free‐ranging stranded female California sea lions (Zalophus californianus). Hormone receptor expression in the ovaries, uterus, cervix, and vagina was evaluated using an immunohistochemical technique with monoclonal antibodies. During a large portion of the cycle, ovaries contained both a corpora lutea (CL) and follicles in varying stages of development. In the periods of pupping and estrus during June and July, and in the spring morphologic features of the endometrium suggested estrogen influence. There were areas of squamous differentiation in the pseudostratified columnar epithelium of the cervix and vagina in some animals during estrus and in the spring. Estrogen receptor immunohistochemical scores were highest during pupping and estrus and in the spring and lowest during embryonic diapause. Cyclic changes in uterine PR expression throughout the cycle were minimal. Both ERα and PR were expressed in epithelial and stromal cells throughout the cervix and vagina, however, receptor expression was typically higher in the stroma. Stromal cell hormone receptors may play an important role in epithelial responses to circulating sex hormones. The results of this investigation add to the general knowledge of California sea lion reproduction and establish baseline information on reproductive tract hormone receptors that will aid in determining the factors involved in urogenital cancer development in sea lions. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.     

Estrogen receptors alpha and beta (ERalpha and ERbeta) and androgen receptor (AR) in human sperm: localization of ERbeta and AR in mitochondria of the midpiece

BACKGROUND: The central role of estrogens and androgens in the male reproductive system has focused attention on the presence and distribution of their cognate receptors [estrogen receptor (ER) alpha, ERbeta and androgen receptor (AR)] in male reproductive tissues and cells. Since the presence of steroid hormone receptors in mitochondria of mammalian cells has been well documented, we investigated the possibility of mitochondrial localization of sex steroid hormone receptors in sperm. METHODS AND RESULTS: Applying immunofluorescence labelling and confocal laser scanning microscopy we show that the estrogen receptor beta and the AR of human sperm are specifically enriched in the midpiece, at the site of the mitochondria, which were visualized by labelling with the vital dye CMX. Nuclear and mitochondrial localization of AR was also detected in LnCap human prostate cancer cells. Differentially, most of the ERalpha immunostaining is in the form of a compact zone at a region corresponding to the equatorial segment of the upper post-acrosomal region of the sperm head. Immunoblotting experiments using sperm extracts revealed the presence of a 66 and a 45 kDa protein reacting with the ERalpha antibody, one 64 kDa protein reacting with the ERbeta antibody and a 110 and a 90 kDa protein reacting with the antibody against AR. CONCLUSIONS: Our findings suggest that the differential localization of AR and ER isoforms in human sperm reveals distinct roles of these receptors in the physiology of sperm cells and, perhaps, also in the process of fertilization.     

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.     

17β-雌二醇对未成熟雌性大鼠体液免疫及胸腺内雌激素受体的影响

本研究以生理浓度范围的 17β 雌二醇处理未成熟的SD雌性大鼠 ,探讨 17β 雌二醇对其性激素分泌、体液免疫功能和胸腺内雌激素受体的影响。实验分三组 ,分别为高剂量组 (0 1mg )、低剂量组 (0 0 5mg )和对照组 ,给药 4周后用放射免疫法检测了血清雌二醇和睾酮水平 ;用酶联免疫吸附法测定白细胞介素 6 (IL 6 )、肿瘤坏死因子α (TNF α )和免疫球蛋白G(IgG )的水平 ;用免疫组化法测定胸腺内雌激素受体水平。结果表明 17β 雌二醇一方面可以下调IL 6、TNF α,另一方面可以提高IgG水平 ,并且可以提高胸腺内雌激素受体水平。由于本实验结果和睾酮并无关系 ,我们认为雌二醇在生理浓度下对免疫系统有一定的调节作用 ,该作用有可能是通过雌激素受体来实现。提示随着生殖周期的变化 ,E2 水平可能影响某些疾病的发生和发展     

左旋18-甲基炔诺酮对大鼠雌激素水平及下丘脑雌激素受体阳性细胞的影响

目的:观察左旋18-甲基炔诺酮(LNG)对大鼠雌激素(E)水平及下丘脑内雌激素受体(ER)阳性细胞的影响。方法:正常雌性SD大鼠分为给药对照组、给药组、停药对照组、停药组,应用免疫组织化学方法显示下丘脑ER阳性细胞并检测血清E浓度。结果:给药组较给药对照组E浓度下降,弓状核(Arc)、下丘脑腹内侧核(VMH)内ER阳性细胞的数量减少、光密度下降。停药后基本恢复正常。结论:长期LNG作用导致给药大鼠血清E水平下降;长期LNG作用引起大鼠下丘脑ER数量减少、活性减低,推测ER可能参与影响促性腺激素释放激素的分泌;停药后ER的形态学变化恢复正常,所以LNG的作用基本上是可逆的。     

Normal Morphology and Hormone Receptor Expression in the Male California Sea Lion (Zalophus californianus) Genital Tract

Histomorphology and estrogen α (ER α), and progesterone receptor (PR) expression were evaluated in free‐ranging stranded male California sea lions (Zalophus californianus). Hormone receptor expression was evaluated using an immunohistochemical technique with monoclonal antibodies. Estrogen and PRs were identified in the efferent ductules, prostate gland, corpus cavernosa, corpus spongiosium, penile urethra, and in the epithelium and stroma of both the penis and prepuce. In some tissues, ER α expression was more intense in the stroma, emphasizing the importance of the stroma in hormone‐mediated growth and differentiation of reproductive organs. To our knowledge, this is the first study to localize ER α and PR to the epithelium of the glans penis. The results of this investigation add to the general knowledge of male California sea lion reproduction and suggest that estrogens could have a role in the function of the male reproductive tract. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.