Objective To investigate the protective effects of estrogen on rabbit retinal damages induced by chronic ocular hypertension.Methods A total of 18 white New Zealand female rabbits were randomly divided into ovariectomized (OV) group and sham OV (SOV) group. Bilateral ovaries were remove in OV group while only the adipose tissue around ovarian were remove in SOV group. Chronic ocular hypertension was induced by anterior chamber injection of carbomer. Retinal cell apoptosis was measured by terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL), the expression of bcl-2, bax were detected by immunohistochemistry. The images were captured under microscope and analyzed with computer-image-analysis system. Results Four, six and eight weeks after ocular hypertension modeling, the OV retinas have less retinal ganglion cells, thinner optic nerve fiber layer and inner nuclear layer and more TUNEL positive cells (t=3.285，4.012，3.624；P＜0.01). The OV retinas also have less bcl-2 expression (t=4.256，3.867，3.459；P＜0.01), more bax positive cells (t=3.211，3.625，3.253；P＜0.01). Bcl-2 expression was negatively correlated with TUNEL positive cells indicating bcl-2 can inhibit apoptosis. Bax expression was positively correlated with TUNEL positive cells indicating bax induce apoptosis.ConclusionEstrogen has a neuroprotection role to rabbit retina under chronic ocular hypertension by reducing apoptosis.
Objective To investigate the express of ERβ protein in female slow transit constipation (STC) patients. Methods Immunohistochemistry and Western blot technique were used to detect the distribution and expression of estrogen receptor β (ERβ) protein of 20 patients with STC and 20 aged-matched controls. Results ERβ expressions were detected in mucous layer, myenteric nerve plexus and submucous nerve plexus in two groups. In comparison with the control group, the expression of ERβ protein of STC group was much lower (Plt;0.01). The expression of ERβ protein of sigmoid colon in STC group was significantly lower than that in control group (Plt;0.05). Conclusion The expression of ERβ protein decreased in myenteric and submucous nerve plexus of sigmoid colon tissues may involve in the pathogenesis of STC.
ObjectiveTo evaluate the protective effect of estrogen on survival of retinal ganglion cells (RGCs) after transient retinal ischemia-reperfusion (RIR) in rats.MethodsRIR was induced in 60 ovariectomized adult rats (OVX) by increasing intraocular pressure via an intracameral catheter. All of the rats were divided into two groups randomly: in experimental group, the rats underwent a subcutaneous injection with 17β-estrodiol（100 μg/kg） 2 hours before retinal ischemia; and in the control group, saline water was injected correspondingly. The number of RGCs and the thickness of the inner retinal layers were mesured by HE staining method before and 12, 24, 48, and 72 hours after reperfusion. TdT-mediated biotin-dUTP nick end labelling (TUNEL) staining technique was used to examine the apoptosis of RGCs.ResultsTwenty-four and 48 hours after reperfusion, the number of apoptotic cells in experimental group was obvious lower than that in the control group(Plt;0.05), and the number of RGCs in experimental group was higher than that in the control group(Plt;0.05).ConclusionEstrogen can protect retinal neurons from transient RIR in ovariectomized rats.(Chin J Ocul Fundus Dis, 2005,21:177-179)
Objective To explore the effect of toremifene on estrogen receptor （ER） expression and tumor micro-angiogenesis in rat Lewis lung carcinoma. Methods Cell suspension of rat Lewis lung carcinoma was implanted into 40 female Wistar rats subcutaneously. The rats were randomly divided into a control group，a estradiol group （0.006 mg/mL），a low dose toremifene group （0.25 mg/mL） and a high dose toremifene group （5 mg/mL）. Tumor size was measured every 3 days and the tumor growth curve was charted. On 15th day，the tumor weight and the growth inhibition rate were measured. Immunohistochemical method was used to detect the expressions of estrogen receptor α （ERα），estrogen receptor β （ERβ），vascular endothelial growth factor （VEGF），and platelet endothelial cell adhesion molecule-1 （PECAM-1）. Integral optical density （IOD） of ERα，ERβ and VEGF was calculated by image analysis software. Quantitative method of Weidner with PECAM-1 was employed for microvessel density （MVD） count. Results Tumor size of the four groups all presented a quadratic function growth trend with time （Plt;0.05）. Tumor growth speed was slower in toremifene groups of low and high doses than that in the control group and the estradiol group. The growth inhibition rate of the estradiol group，the low dose toremifene group and the high dose toremifene group was －15.1%，22.6%，and 45.1%，respectively. The expressions of ERα，VEGF，and MVD in the estradiol group were significantly higher than those in the control group，the low dose toremifene group and the high dose toremifene group （all Plt;0.05）. The expressions of ERα，VEGF，and MVD in the low dose toremifene group were significantly lower than those in control group，but higher than those in high dose toremifene group （all Plt;0.05）.The expression of ERα was positively related to VEGF （r=0.664，Plt;0.05） and MVD（r=0.593，Plt;0.05）. Conclusion Toremifene can inhibit tumor growth，which maybe involved in inhibiting ERα mediated VEGF expression.
Objective： To observe the effect of estrogen on the expr ession of pigment epithelium derived factor (PEDF) in cultured retinal Muuml;ller cells under the anoxic condition． Methods：After the anoxic retinal Muuml;ll er cells were tre ated with estrogen (E2) with the concentration of 10-6、10-5 and 10-7 mmol/L, t he level of expression of PEDF mRNA and the protein was detected by reverse tran scriptionpolymerase chain reaction and Western blotting analysis. Results：Th e expression of PEDF mRNA and protein decreased 24 hours after anoxia. E2 with t he concentration of 10-5 and 10-6 mmol/L inhibited the decrease of expression of PEDF mRNA and protein induced by anoxia, which related to the concentration of E2． Conclusion：strogen can regulate the expression of PEDF, which ma y play an important role in the regulation of retinal neovascularization．
Objective To explore the role of estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in estrogen-induced proliferation of endometrial cancer, and explore whether metformin inhibits the proliferation of endometrial cancer cells through ERα and ERβ. Methods Stable transfected Ishikawa cells were constructed by lentivirus. The effects of down-regulated ERα and ERβ on estrogen-induced Ishikawa cell proliferation were detected by methyl thiazolyl tetrazolium assay. The effects of down-regulated ERα and ERβ on estrogen-induced Ishikawa cell cycle were detected by flow cytometry. In addition, quantitative real-time polymerase chain reaction and Western blotting assays were used to detect changes in the expression of cyclinD1 and P21 involved in cell cycle regulation. The effects of down-regulated ERα and ERβ on estrogen-induced Ishikawa cell proliferation were observed by adding metformin to estrogen treatment. Results Down-regulation of ERα inhibited the proliferation and cell cycle of Ishikawa cells (P<0.05). Down-regulation of ERα also inhibited the expression of cyclinD1 and promoted the expression of P21 (P<0.05). Down-regulation of ERα counteracted the effect of estrogen-induced cell proliferation, cell cycle, and the expression changes of cyclinD1 and P21 (P<0.05). Down-regulation of ERβ promoted the proliferation and cell cycle of Ishikawa cells (P<0.05). Down-regulation of ERβ also promoted the expression of cyclinD1 and inhibited the expression of P21 (P<0.05). Down-regulation of ERβ enhanced the effect of estrogen-induced cell proliferation, cell cycle, and the expression changes of cyclinD1 and P21 (P<0.05). Metformin inhibited the proliferation of estrogen-induced Ishikawa cells (P<0.05), while in the down-regulated ERα Ishikawa cells or down-regulated ERβ Ishikawa cells, the inhibition of metformin on Ishikawa cells disappeared (P<0.05). Conclusions ERα may promote estrogen-induced proliferation of endometrial cancer cells, while ERβ may inhibit estrogen-induced proliferation of endometrial cancer cells. In addition, ERα and ERβ may also mediate the inhibitory effect of metformin on endometrial cancer cells.
Objective In vivo, the microenvironment of epidermal stem cells (ESCs) is complex, and estrogen might be involved in the micro environment. To investigate the biological effects of estrogen on the prol iferation and migration of ESCs in vitro. Methods hESCs were isolated from normal human foreskin and cultured. The second generation of hESCs were identified with flow cytometry after being marked with integrin β1, cytokeratin 19 (CK19), CK14, and CK10 antigens.hESCs of 2 × 106 cell density were cultured with ESCs special medium supplemented with 0.1 nmol/L Diethylstilbestrol in group A (estrogen group), with ESCs special medium supplemented with 10 nmol/L Raloxifene hydrochloride in group B (ER blocking agent group), and with ESCs special medium in group C (control group), respectively. The 100 μm “scratch” wounds were created by scraping confluent hESCs plated on Petri dishes with a sterile pipette tip in vitro. The migrating cells from the wound edge were quantified at 24, 48, and 72 hours after incubation. The rates of wound heal ing were calculated by SigmaScan Pro 5.0 software at 72 hours. The prol iferating effect of estrogen on hESCs was determined with MTT method at 24, 48, 72, 96, and 120 hours. Results Cultured primary hESCs could adhere to the wall showing ovoid in shape and grew into colonies. Flow cytometry showed the positive results for integrin β1, CK19, and CK14 (with positive rate of 96.63%, 95.47%, and 94.27%, respectively) and the negative result for CK10 (with positive rate of 1.32%). In group A, the number of cells crossing the wound edge was more than those of group B and group C at 24, 48, and 72 hours. The rates of wound heal ing were 69.00% ± 0.05% in group A, 35.00% ± 0.05% in group B, and 48.00% ± 0.06% in group C at 72 hours, showing significant differences among groups (P lt; 0.05). The prol iferating speed of hESCs was significantly higher in group A than in groups B and C (P lt; 0.01), and significantly higher in group C than in group B (P lt; 0.01) at 24, 48, 72, 96, and 120 hours. Conclusion The estrogen can promote the prol iferation and migration of hESCs in vitro. It may be involved in many biological activity of skin.
Objective To investigate the relationship between the level of testosterone and estradiol in serum and central serous chorioretinopathy (CSC).Methods The clinical data of 200 patients with active phase CSC who diagnosed by clinical manifestation, examination of fundus and fluorescence fundus angiography (FFA), were retrospectively analyzed. Two hundreds healthy people were collected as a control group. The blood of ulnar vein was collected and the method of magnetic homogeneous enzyme immunoassay was used to detect the level of testosterone and estradiol in serum of two groups. The results were analyzed statistically by t test.Results The values of testosterone and estradiol of male were all higher in CSC group than that in control group，the differences were statistical significance（t=2.804，2.913；P=0.010，0.008）；it was also higher in female（t=2.078，2.807；P=0.049，0.010）. The value of testosterone/estradiol of male was higher than that of female in CSC group，the difference was statistical significance(t=2.231，P=0.046).Conclusions The level of testosterone and estradiol in serum of CSC group increased obviously, especially the value of testosterone/estradiol. The increase of estradiol and testosterone/estradiol may be an etiological factor of CSC.
Objective To systematically evaluate the correlation between endometriosis (EM) in Chinese women and Xba I polymorphism in intron-1 of estrogen receptor α (ER-α) gene. Methods Such databases as PubMed, MEDLINE, The Cochrane Library (Issue 3, 2012), VIP, CBM, WanFang Data and CNKI were searched to collect case-control studies about the correlation between EM and Xba I polymorphism in intron-1 of ER-α gene. The retrieval time was from 1980 to 2012. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data and assessed the quality, and then the meta-analysis was conducted by using RevMan 5.0 and Stata 12.0 software. Results A total of 7 studies involving 676 EM patients and 688 healthy volunteers were included. The results of meta-analyses showed that Chinese women with X/X genotype had similar risk of EM compared to those with x/x genotype (OR=0.95, 95%CI 0.58 to 1.54, P=0.82) or X/x genotype (OR=0.73, 95%CI 0.44 to 1.20, P=0.22). The allele X also showed similar risk of EM compared to the allele x (OR=1.11, 95%CI 0.93 to 1.33, P=0.25). Conclusion At present, it has not yet been found that the incidence of EM in Chinese women is related to the Xba I polymorphism in intron-1 of ER-α gene as well as the allele X. For the quantity and quality limitation of the included studies, this conclusion has to be proved by more studies.
Biodistribution of125I-labeled 17α-vinyestradiol-3-acetate (125I-VE2A)in nude mice bearing human breast cancer containing different estrogen receptor (ER) content was studied to understand the relation between this compound and ER and, consequently, to develop the ER imaging. Each mouse was injected with 92.5 kBq tracer from tail vein and then killed after two hours. The radioactivity uptake rate in one gram of tumor tissue and tissues from other vital organs were measured, and the radioactivity uptake ratio of tumor to nontumor tissue was also measured. Results: The radioactivity uptake rate and the radioactivity uptake ratio of tumor to nontumor tissue in ER positive tumor (MCF-7) were much higher than those in ER negative tumor (MDA-MB-231). Conclusions: This compound, IVE2A has affinity to ER positive target organ or tumor and promise the probability to define the content and site of ER in vivo or in tumor.