左旋18甲基炔诺酮增加大鼠血清瘦素及下丘脑瘦素受体表达

口服避孕药因具有高效、安全的特点而在临床广泛应用,但随之带来的副作用日益引起学者的重视,如体重增加、月经异常等,关于其引起体重增加的有关研究少见报道。瘦素(leptin)是近年来发现的衡量体脂水平的重要指标,又是连接能量和生殖的桥梁。因此,本研究选用左旋18-甲基炔诺酮(     

左旋18-甲基炔诺酮对大鼠下丘脑GnRH神经元的影响

目的：观察孕激素类避孕药—左旋18-甲基炔诺酮(LNG)对大鼠下丘脑GnRH神经元的影响。方法：正常雌性大鼠分为长期给药组(灌服LNG90d)和停药组(停药后正常喂养20d)。免疫组织化学方法显示下丘脑GnRH阳性神经元。结果：长期给药组与对照组相比斜角带(db)、视前区(MPA)内GnRH阳性神经元构成比发生改变,棘型神经元减少,阳性神经元光密度减低,阳性纤维膨体密度降低,正中隆起(ME)处阳性纤维密度增加。停药后基本恢复正常。结论：从形态学上证实LNG作用于下丘脑水平;停药后GnRH阳性神经元形态学变化可恢复正常,表明LNG具有高效安全性。     

去卵巢大鼠骨质疏松对下丘脑雌激素α受体的影响

目的 观察去卵巢雌性大鼠骨质疏松对下丘脑雌激素α受体(estrogen receptor alpha,ERa)及基基因表达的影响。方法 将45只SD大鼠随机分为对照组、假手术对照组和去卵巢组,用免疫组织化学方法和原位杂交方法检测下丘脑ERa及其mRNA表达。结果 去卵巢组ERa受体及其mRNA阳性细胞与对照组比较显著减少(P<0.01)。结论 下丘脑ERa受体及其mRNA阳性细胞的减少可能在绝经后骨质疏松发生起重要作用。     

心理应激雌性大鼠海马-下丘脑-垂体雌激素受体的变化

目的：探讨雌性大鼠心理应激状态下，海马-下丘脑-垂体雌激素受体（ER）的改变，进而阐明卵巢内分泌功能失调的机制。 方法: 采用声-光-电复合刺激作为心理应激制造大鼠卵巢内分泌功能失调模型；采用免疫组化方法和图像分析仪定量分析海马-下丘脑-垂体ER的表达。 结果： 采用声-光-电复合刺激雌性大鼠后，大鼠海马-下丘脑-垂体ER的表达下降。 结论： 心理应激雌性大鼠海马-下丘脑-垂体ER下降可能是卵巢内分泌功能失调的机制之一。     

LNG对大鼠下丘脑内NPY神经元的影响

左旋18-甲基炔诺酮(Levonorgestrel LNG)是第二代全合成孕激素类口服避孕药,反馈性调节下丘脑—垂体轴是其作用机制之一。在下丘脑-垂体-性腺轴中,多种神经递质参与了下丘脑促性腺激素释放激素(gonadotrop in-releasing hor-mone,GnRH)的分泌调节,其中神经多肽Y(neuropeptide Y     

大鼠下丘脑内的一氧化氮合酶与雌激素受体双标神经元

目的:探讨一氧化氮合酶(NOS)和雌激素受体(ER)在下丘脑诸核团的分布及共存,为揭示雌激素与一氧化氮之间的内在联系提供形态学依据。方法:采用NADPH-d组织化学法并结合免疫组织化学技术,观察雌性大鼠下丘脑内NOS阳性神经元、ER阳性神经元以及NOS/ER双染神经元的形态及分布。结果:NOS阳性神经元主要分布在下丘脑室旁核、视上核、下丘脑外侧区和室周核;ER阳性神经元在下丘脑诸核团的表达不及NOS阳性神经元广泛;NOS与ER双染神经元主要分布在下丘脑的室旁核、视上核、下丘脑外侧区及室周核;其他区域可见散在分布的双染神经元。结论:NOS与ER双染神经元主要集中分布在视上核的背内侧和背外侧部及室旁核小细胞部腹内侧区,在下丘脑外侧区分布较广但比较分散,室周核呈散在分布。     

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。     

雌激素对去势大鼠髁突软骨雌激素受体基因表达的影响

目的探讨不同浓度的雌二醇(E2)对去势大鼠髁突软骨雌激素受体(ER)基因ERα和ERβ表达的影响。方法将SD大鼠分为对照组(control)、假手术组(sham)、去势组(OVX)、及时和延迟替代治疗组(OVX/17β-E2),每天静脉注射不同浓度雌二醇(5×10、5×10~2和5×10~3μg/kg),阴道上皮脱落细胞涂片监测雌激素水平,用Western blot和real-time PCR法检测大鼠颞下颌关节髁突软骨ERα和ERβ的蛋白及mRNA表达。结果去势大鼠阴道上皮细胞MI指数180/12/8,表明雌激素水平低下(P0.05)。及时补给生理浓度雌二醇(5×10~2μg/kg)能维持髁突软骨ER于正常范围,延迟补给生理浓度雌二醇不能恢复或改善ER表达;及时和延迟补给高浓度(5×10~3μg/kg)及低浓度(50μg/kg)E2均抑制ER蛋白和mRNA合成(P0.05),且高浓度效应显著。结论及时补充合理浓度的雌激素对去势大鼠颞下颌关节的正常生理功能具有重要意义。     

过热对大鼠下丘脑肾上腺素α2受体的影响

本文用ＳＤ大鼠，清醒状态于热环境中引起过热（至直肠温度３９．５±０．５℃和４２．０±０．５℃，并维持３０ｍｉｎ），用放射配基结合分析方法（￣３Ｈ－ｄｏｎｉｄｉｎｅ）发现急性热暴露后，其４２℃组α＿２受体最大结合容量（Ｂｍａｘ）为４５．０±１７．７ｍｏｌ／ｍｇ蛋白，低于对照组（７５．５±２３．９ｆｍｏｌ／ｍｇ蛋白）和３９．５℃组（８１．１±２１，７ｆｍｏｌ／ｍｇ），而亲和力（Ｋｄ）无显著差别．结果表明，在过热状态下，α＿２受体数量明显下降，但其亲和力并不下降。由于α＿２受体密度的下降，可能使儿茶酚胺对体温调节中枢的作用下降。     

ADAM12 expression predicts clinical outcome in estrogen receptor-positive breast cancer

Objectives: Our study was aimed to make sure whether ADAM12 could serve as a prognostic biomarker of estrogen receptor (ER) -positive breast cancer. Methods: 127 patients with ER-positive breast cancer were included in the present study. The level of ADAM12 was assayed through real-time quantitative PCR (RT-qPCR). Levels of ADAM12 in tumor tissues and adjacent normal tissues were compared with paired t-test. The association of ADAM12 expression with clinical characteristics was analyzed via χ² test. Kaplan-Meier survival curve was used to evaluate the role of ADAM12 expression in overall survival (OS) of patients. Cox-regression analysis was performed to judge if ADAM12 could serve as a prognostic marker in breast cancer. Results: The level of ADAM12 was upregulated in tumor tissues of breast cancer compared to that of adjacent normal tissues (P < 0.05). The expression of ADAM12 was closely related to the Ki-67 and HER2 status (P < 0.05 for both). The results of Kaplan-Meier survival curve showed that patients with higher level of ADAM12 exhibited shorter survival time compared to that of low level of ADAM12 (P < 0.001). Cox regression analysis showed that ADAM12 might be a biomarker in predicting prognosis of patients with ER-positive breast cancer (HR = 7.116, 95% CI = 3.329-15.212). Conclusion: ADAM12 appears to be a prognostic marker in ER-positive breast cancer.     

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。     

人胎盘滋养层细胞雌激素α,β受体免疫细胞化学研究

目的:探讨雌激素-α,β型受体（estrogen recoptor α,β）在人胎盘滋养层细胞的表达和定位。方法:采用细胞培养结合免疫细胞化学ABC法。结果:人胎盘及培养的人胎盘绒毛合体、细胞滋养层细胞均呈雌激素α,β受体免疫反应性,雌激素受体免疫反应阳性物质定位于胞核内,细胞质为阴性。结论:人胎盘滋养层细胞存在雌激素α,β受体,这为研究雌激素对人胎盘滋养层细胞的功能调控提供了形态学依据。     

雌激素作用分子机制研究进展

雌激素在体内具有广泛的生物学活性。女性进入绝经期后 ,体内雌激素水平显著下降 ,出现与之相关的绝经期综合症 ,以及心血管疾病如冠心病、动脉粥样硬化和骨质疏松等。使用激素替代疗法能明显减少上述疾病的发生[1 ] 。本文重点在分子机制水平上对雌激素作用研究进展进行综述。     

Expression of G protein-coupled estrogen receptor in irritable bowel syndrome and its clinical significance

Objectives: Estrogen is suggested to participate in pathogenesis of irritable bowel syndrome (IBS), but expression of G protein-coupled estrogen receptor (GPER) in the colon of IBS patients has never been investigated. The aim of this study was to investigate the expression of GPER and classical estrogen receptors in the colon of IBS patients and healthy controls. Methods: Colonic biopsies were obtained by endoscopy from patients with IBS (n = 46) and healthy subjects (n = 13). Expression of GPER, estrogen receptor α (ERα) and estrogen receptor β (ERβ) in mast cells were measured by double-labelling immunofluorescence. Quantification of mRNA expression was performed for GPER, ERα and ERβ by real-time polymerase chain reaction. Results: Differential distribution of GPER, ERα and ERβ were detected in human colonic mucosa. The expression of GPER in the cytoplasm of mast cells and GPER-positive cells was significantly higher in diarrhea-predominant IBS (D-IBS) patients than that in constipation-predominant IBS (C-IBS, P < 0.001) patients and healthy subjects (P = 0.005). ERα and ERβ were not detected in majority of mast cells in colonic mucosa and no difference of immunostaining results for ERα and ERβ was found among these three groups. A positive correlation (r = 0.451, P = 0.011) between GPER-positive cell counts and abdominal pain severity was observed in D-IBS group. Relative mRNA expression of GPER in D-IBS was also higher than that in C-IBS (P = 0.018) and healthy subjects (P = 0.011). Conclusions: The present study, for the first time, demonstrated the expression of GPER in human colonic mucosa and its correlation with abdominal pain severity.     

同型半胱氨酸经甲基化修饰下调去卵巢大鼠主动脉雌激素受体α基因的表达

目的观察同型半胱氨酸(Hcy)对大鼠雌激素受体α(ERα)基因表达和其启动子CpG岛甲基化的影响。方法高效液相色谱仪检测血浆Hcy水平;RT-PCR和甲基化特异性PCR(MSP)分别检测ERαmRNA表达水平及基因启动子CpG岛的甲基化状态。结果去卵巢和给予甲硫氨酸饮食均可升高大鼠血浆Hcy水平。去卵巢和Hcy均可使大鼠ERαmRNA表达减少,但5′-Aza可使细胞ERαmRNA表达增多。假手术组大鼠主动脉ERα基因启动子有2例(20%)存在甲基化,去卵巢组有3例(30%)存在甲基化,而去卵巢 Hcy组有6例(60%)存在甲基化,对照组细胞ERα启动子CpG岛完全去甲基化,Hcy组细胞甲基化增强,5′-Aza使细胞去甲基化。结论Hcy可经甲基化修饰方式下调去卵巢大鼠主动脉ERαmRNA表达。