BACKGROUND Visceral obesity is increasingly prevalent among adolescents and young adults and is commonly recognized as a risk factor for type 2 diabetes.Estrogen[17β-estradiol(E2)]is known to offer protection against...BACKGROUND Visceral obesity is increasingly prevalent among adolescents and young adults and is commonly recognized as a risk factor for type 2 diabetes.Estrogen[17β-estradiol(E2)]is known to offer protection against obesity via diverse me-chanisms,while its specific effects on visceral adipose tissue(VAT)remain to be fully elucidated.AIM To investigate the impact of E2 on the gene expression profile within VAT of a mouse model of prediabetes.METHODS Metabolic parameters were collected,encompassing body weight,weights of visceral and subcutaneous adipose tissues(VAT and SAT),random blood glucose levels,glucose tolerance,insulin tolerance,and overall body composition.The gene expression profiles of VAT were quantified utilizing the Whole Mouse Genome Oligo Microarray and subsequently analyzed through Agilent Feature Extraction software.Functional and pathway analyses were conducted employing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses,respectively.RESULTS Feeding a high-fat diet(HFD)moderately increased the weights of both VAT and SAT,but this increase was mitigated by the protective effect of endogenous E2.Conversely,ovariectomy(OVX)led to a significant increase in VAT weight and the VAT/SAT weight ratio,and this increase was also reversed with E2 treatment.Notably,OVX diminished the expression of genes involved in lipid metabolism compared to HFD feeding alone,signaling a widespread reduction in lipid metabolic activity,which was completely counteracted by E2 adminis-tration.This study provides a comprehensive insight into E2's local and direct protective effects against visceral adiposity in VAT at the gene level.CONCLUSION In conclusion,the present study demonstrated that the HFD-induced over-nutritional challenge disrupted the gene expression profile of visceral fat,leading to a universally decreased lipid metabolic status in E2 deficient mice.E2 treatment effectively reversed this condition,shedding light on the mechanistic role and therapeutic potential of E2 in combating visceral obesity.展开更多
Objective:To evaluate the effect of estrogen pre-treatment in patients with different ovarian response in antagonist protocol.Methods:Randomized controlled trials(RCTs)and retrospective studies about the effect of est...Objective:To evaluate the effect of estrogen pre-treatment in patients with different ovarian response in antagonist protocol.Methods:Randomized controlled trials(RCTs)and retrospective studies about the effect of estrogen pre-treatment in antagonist prorocol were searched in PubMed,Web of Science,China National Knowledge Infrastructure,Wanfang Database.R software was used for meta-analysis.Results:Seven RCTs and two retrospective studies were included.In order to explore the source of heterogeneity,subgroup analysis was used,which was mainly conducted according to the ovarian response of the included population,which were divided into low responders,non-low responders and mixed responders.In the study about gonadotropin hormone(Gn)days,patients were divided into wash-out subgroup and non-wash-out subgroup according to drug use-pattern.Meta-results showed that the number of Gn days increased significantly in the non-wash-out subgroup(WMD=1.07,95%CI[0.83;1.31],I2=66%).The number of Gn days in the wash-out subgroup were not affected(WMD=-0.12,95%CI[-0.45;0.21],I2=0%).In the low-response subgroup,the number of oocytes retrieved(WMD=0.46,95%CI[-0.23;1.16],I2=81%),the fresh cycle clinical pregnancy rate(RR=0.77,95%CI[0.55;1.06],I2=73%)and the cycle cancellation rate(RR=0.80,95%CI[0.40;1.61],I2=83%)were not significantly changed with estrogen pre-treatment.In the non-low-response subgroup,the number of oocytes obtained(WMD=0.21,95%CI[-0.69;1.11],I2=2%),fresh cycle clinical pregnancy rate(RR=0.94,95%CI[0.77;1.14],I2=41%),live birth rate(RR=0.82,95%CI[0.62;1.08],I2=0%)and cycle cancellation rate(RR=0.89,95%CI[0.54;1.47],I2=2%)were not significantly changed with estrogen pre-treatment.Conclusions:Estrogen pre-treatment(with non-wash-out period)in antagonist protocol increases Gn days,dose not improve IVF outcomes in non-low responders and low responders.展开更多
Objective:Using data mining tools,study the potential pathways of estrogen’s cardiovascular effects.Methods:The GeneExpression Omnibus database was used to download the relevant high-throughput microarray dataset GSE...Objective:Using data mining tools,study the potential pathways of estrogen’s cardiovascular effects.Methods:The GeneExpression Omnibus database was used to download the relevant high-throughput microarray dataset GSE72180,which was then analyzed for differential genes using the GEO2R online analysis tool,gene function and pathway enrichment analysis using DAVID 6.8,protein interaction network analysis using the STRING database,and core network extraction using the MCODE algorithm.Results:A total of 131 differential genes were identified and enriched for gene function and signaling pathway analysis,which indicated that these genes were related with focal adhesion and the HIF-1 signaling pathway.MCODE algorithm analysis extracted 1 core sub-network of these genes to be related to ubiquitin protein transferase activity,protein polyubiquitination,protein ubiquitination involved in ubiquitin-dependent proteolytic metabolic processes,ligase activity,and clustering on ubiquitin-mediated protein hydrolysis signaling pathway.Conclusion:By using data mining tools,it is possible to identify how estrogen may influence the cardiovascular system by controlling the ubiquitination process.This information may be used as a reference for etiology and preventive studies of cardiovascular illnesses.展开更多
OBJECTIVE To investigate the effect of quercetin on primary cultured newborn rat cortex neuron cell which is estrogen depletion,and discuss the possible mechanism,to provide new ideas and strategies for developing a d...OBJECTIVE To investigate the effect of quercetin on primary cultured newborn rat cortex neuron cell which is estrogen depletion,and discuss the possible mechanism,to provide new ideas and strategies for developing a drug of neurodegenerative disease.METHODS Rat cortex neurons were isolated from one day old Sprague Dawley rats and treated with estrogen,quercetin and estrogen receptor antagonists(ICI182,780).Cell viability was determined by MTT assay,neurite outgrowth was measured by fluorescent microsope and estrogen receptors were determine by Western blot.RESULTS Quercetin functions like estrogen to increase cortex neuronal cell viability,the Que(50,100μmol·L^(-1))group compared with the control group could significantly improve the activity of the cortical neurons(P<0.05).It can also increase neurite out growth,the Que(50,100μmol·L^(-1))group significantly promoted the formation of synapse,most of the neurons were full,and the synapses of neurons became thick,growth,and connect to a dense neural network.And in the Western blot experiments,Que(50,100μmol·L^(-1))group could obviously increase the expression of estrogen receptor alpha protein,in addition,the neural protective effect of quercetin can be inhibited by ICI182,780.CONCLUSION Quercetin like estrogen can protected cortex neuronal and the effect of quercetin on cortex neuronal cells was mediated by estrogen receptor alpha.展开更多
Endocrine therapy using estrogen receptor-α(ER-α) antagonists for attenuating horm2one-driven cell proliferation is a major treatment modality for breast cancers.To exploit any DNA repair deficiencies associated wit...Endocrine therapy using estrogen receptor-α(ER-α) antagonists for attenuating horm2one-driven cell proliferation is a major treatment modality for breast cancers.To exploit any DNA repair deficiencies associated with endocrine therapy,we investigated the functional and physical interactions of ER-α with O^6-methylguanine DNA methyltransferase(MGMT),a unique DNA repair protein that confers tumor resistance to various anticancer alkylating agents.The ER-α-positive breast cancer cell lines(MCF-7,T47D) and ER- negative cell lines(MDAMB-468,MDAMB-231),and established inhibitors of ER-α and MGMT,namely,ICI-182,780(Faslodex) and O^6-benzylguanine,respectively,were used to study MGMT- ER interactions.The MGMT gene promoter was found to harbor one full and two half estrogen-responsive elements(EREs) and two antioxidant-responsive elements(AREs).MGMT expression was upregulated by estrogen,downregulated by tamoxifen in Western blot and promoter-linked reporter assays.Similarly,both transient and stable transfections of Nrf-2(nuclear factor-erythroid 2-related factor-2)increased the levels of MGMT protein and activity 3 to 4-fold reflecting novel regulatory nodes for this drugresistance determinant.Of the different ER-α antagonists tested,the pure anti-estrogen fulvestrant was most potent in inhibiting the MGMT activity in a dose,time and ER-α dependent manner,similar to O^6-benzylguanine.Interestingly,fulvestrant exposure led to a degradation of both ER-α and MGMT proteins and O^6-benzylguanine also induced a specific loss of ER-α and MGMT proteins in MCF-7 and T47 D breast cancer cells with similar kinetics.Immunoprecipitation revealed a specific association of ER-α and MGMT proteins in breast cancer cells.Furthermore,silencing of MGMT gene expression triggered a decrease in the levels of both MGMT and ER-α proteins.The involvement of proteasome in the drug-induced degradation of both proteins was also demonstrated.Fulvestrant enhanced the cytotoxicity of MGMT-targeted alkylating agents,namely,temozolomide and BCNU by 3 to 4-fold in ER-α positive cells,but not in ER-negative cells.We conclude that MGMT and ER-α proteins exist as a complex and are co-targeted for ubiquitin-conjugation and subsequent proteasomal degradation.The findings offer a clear rationale for combining alkylating agents with endocrine therapy.展开更多
AIM:To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHOD...AIM:To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHODS:A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples. RESULTS:No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69vs 37.708 ± 5.31,P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13,P = 0.04), mRNA (2.278 ± 1.19vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67,P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06vs 0.532 ± 0.11,P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07). CONCLUSION:The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study.展开更多
Postmenopausal women with Alzheimer’s disease exhibit dramatically reduced sensitivity to estrogen replacement therapy,which is though to be related to an estrogen receptor(ER)α/ERβratio imbalance arising from a si...Postmenopausal women with Alzheimer’s disease exhibit dramatically reduced sensitivity to estrogen replacement therapy,which is though to be related to an estrogen receptor(ER)α/ERβratio imbalance arising from a significantly decreased level of ERs of the brain.The aim of our study was to investigate whether valproic acid(VPA)can enhance the beneficial effects of estrogen on cognitive function through restoration of ERαand ERβexpression in the brain.We removed the ovaries of female APP/PS1 mice to simulate the low estrogen levels present in postmenopausal women and then administered VPA(30 mg/kg,intraperitoneal injection,once daily),17β-estradiol(E2)(2.4μg,intraperitoneal injection,once daily),liquiritigenin(LG)(50μg/kg,intragastric infusion,once daily),VPA+E2,or VPA+LG for 4 successive weeks.Compared with treatment with a single drug,treatment with VPA+E2 or VPA+LG significantly increased the level of glycogen synthase kinase 3β,increased the expression of estrogen receptorα,reduced the expression of small ubiquitin-like modifiers,and increased the level of estrogen receptorβ.This resulted in enhanced sensitivity to estrogen therapy,reduced amyloidβaggregation,reduced abnormal phosphorylation of the tau protein,reduced neuronal loss,increased dendritic spine and postsynaptic density,and significantly alleviated memory loss and learning impairment in Alzheimer’s disease.This study was approved by the Chongqing Medical University Animal Protection and Ethics Committee,China on March 6,2013.展开更多
Several epidemiological,cellular,and molecular studies demonstrate the role of environmental chemicals with endocrine disrupting activities,typical of Westernized societies,in the pathogenesis of numerous diseases inc...Several epidemiological,cellular,and molecular studies demonstrate the role of environmental chemicals with endocrine disrupting activities,typical of Westernized societies,in the pathogenesis of numerous diseases including cancer.Nonetheless this information,the design and execution of studies on endocrine disruptors are not yet cognizant that the specific actions of individual hormones often change with development and ageing,they may be different in males and females and may be mediated by different receptors isoforms expressed in different tissues or at different life stages.These statements are particularly true when assessing the hazard of endocrine disruptors against 17β-estradiol(E2)actions in that this hormone is crucial determinant of sexrelated differences in anatomical,physiological,and behavioral traits which characterize male and female physiology.Moreover,E2 is also involved in carcinogenesis.The oncogenic effects of E2 have been investigated extensively in breast and ovarian cancers where hormone-receptor modulators are now an integral part of targeted treatment.Little is known about the E2preventive signalling in colorectal cancer,although this disease is more common in men than women,the difference being more striking amongst pre-menopausal women and age-matched men.This review aims to dissect the role and action mechanisms of E2 in colorectal cancer evaluating the ability of estrogen disruptors(i.e.,xenoestrogens)in impair these E2 actions.Data discussed here lead to define the possible role of xenoestrogens in the impairment and/or activation of E2signals important for colorectal cancer prevention.展开更多
Objective To investigate the expressions of estrogen receptor(ER)subtypes and c-met proto-oncogene in human endometrial carcinomas and to assess the clinical significance of ER and c-met in this carcinoma.Methods Reve...Objective To investigate the expressions of estrogen receptor(ER)subtypes and c-met proto-oncogene in human endometrial carcinomas and to assess the clinical significance of ER and c-met in this carcinoma.Methods Reverse transcription PCR(RT-PCR)was used to detect the expressions of ERα,ERβ and c-met proto-oncogene mRNA in 30 samples of endometrial carcinoma and 11 samples of normal endometrium.Results The expression of ERα in endometrial carcinoma(0.70±0.40)was significantly reduced in comparison to that in normal endometrium(1.14±0.56,P<0.05).A similar finding was made for the expression of ERβ in carcinoma(0.24±0.18)versus normal tissues(0.48±0.20,P<0.05).In contrast,c-met mRNA expression was increased in endometrial carcinoma(1.45±0.72)compared to that in normal endometrium(0.42±0.31,P<0.01).A decrease tendency of the expression of ERα was also found from Stage Ⅰ(0.82±0.41)to a more severe Stag Ⅱ-Ⅲ of endometrial carcinoma(0.42±0.17,P<0.05).The analysis of ERα and ERβ mRNA revealed a decrease tendency from shallow to deep invasion of the uterine muscles(P<0.05).We found that the expressions of ERα and ERβ were negatively correlated with c-met proto-oncogene with a coefficient correlation of-0.63(P<0.01)and-0.32(P<0.05),respectively.Conclusion ERα and ERβ are both involved in mutagenic action of carcinogen.C-met proto-oncogene plays an important role in the carcinogenesis and development of endometrial carcinoma.C-met and ER expressions show a negative correlation in the development of endometrial carcinoma.展开更多
The main estrogens:estradiol,estrone,and their acyl-esters have been studied essentially related to their classical estrogenic and pharmacologic functions.However,their main effect in the body is probably the sustaine...The main estrogens:estradiol,estrone,and their acyl-esters have been studied essentially related to their classical estrogenic and pharmacologic functions.However,their main effect in the body is probably the sustained control of core energy metabolism.Estrogen nuclear and membrane receptors show an extraordinary flexibility in the modulation of metabolic responses,and largely explain gender and age differences in energy metabolism:part of these mechanisms is already sufficiently known to justify both.With regard to energy,the estrogen molecular species act essentially through four key functions:(1)Facilitation of insulin secretion and control of glucose availability;(2)Modulation of energy partition,favoring the use of lipid as the main energy substrate when more available than carbohydrates;(3)Functional protection through antioxidant mechanisms;and(4)Central effects(largely through neural modulation)on whole body energy management.Analyzing the different actions of estrone,estradiol and their acyl esters,a tentative classification based on structure/effects has been postulated.Either separately or as a group,estrogens provide a comprehensive explanation that not all their quite diverse actions are related solely to specific molecules.As a group,they constitute a powerful synergic action complex.In consequence,estrogens may be considered wardens of energy homeostasis.展开更多
Objective Previous study suggested that estradiol(E2)plays an important role in otolith shedding by regulating the expression of otoconin 90(OC90).The purpose of this article is to provide further data on the effect a...Objective Previous study suggested that estradiol(E2)plays an important role in otolith shedding by regulating the expression of otoconin 90(OC90).The purpose of this article is to provide further data on the effect and mechanism of E2 on the morphology of otolith.Methods The rats receiving bilateral ovariectomy(OVX)were used as animal models.Co-immunoprecipitation was used to observe the relationship between estrogen receptor(ER)and estrogen-related receptorα(ERRα).The morphology of otolith was observed under the scanning electron microscopy.Western blotting and qPCR were used for quantitative analysis of the roles of ER and ERRαin regulating OC90 expression.Results The looser otoliths were observed in rats receiving bilateral OVX,which could be reversed by supplementation with E2.The level of ERRαwas decreased in bilateral OVX rats.ER and ERRαinteracted with each other on the regulation of the expression of OC90.Conclusion Our results suggest ER and ERRαare both important downstream receptors involved in regulating OC90 expression in utricles of rats,and ERRαprobably functions by interacting with ER.This provides evidence for the mechanism of otolith shedding.And it may be significant for future studies of targeted prevention and therapies for benign paroxysmal positional vertigo.展开更多
Objective The aim of this study was to determine if isoflavone genistien has protective effects against high glucose-induced cell apoptosis in human aortic endlthelial cells, and investigate the possible mechanism for...Objective The aim of this study was to determine if isoflavone genistien has protective effects against high glucose-induced cell apoptosis in human aortic endlthelial cells, and investigate the possible mechanism for this protection. Methods Human aortic endothelial cells subjected to normal (5mmol/L) or high glucose (25mmol/L) were treated with genistein at 0, 50, 100nmol/L. Parallel experiments were performed with 100nM 17b-estradiol, and also in the presence and absence of the pure anti-estrogen ICI-182,780 (100nmol/L). The effects on cell apoptotic DNA fragmentation were determined using cell death ELISA, and the effects on cellular proliferation were determined using tritiated thymidine incorporation assay. Estrogen receptor expression was detected by Taqman quantitative PCR. Results Genistein at 100nmol/L significantly reduced high glucose-induced DNA fragmentation, and reversed cell DNA synthesis inhibition (P <0.001) after 24 hours' incubation. The effect of genistein was completely blocked by ICI-182,780 administration. Estrogen receptor beta, but not alpha was found to be expressed in these cells. Conclusion Isoflavone genistein shows protection against high glucose-induced cell damage through estrogen receptor beta, reducing apoptotic DNA damage and protecting from the inhibition of cell proliferation.展开更多
Objective:To investigate the estrogenic effect of(8,9)-furanyl-pterocarpan-3-ol(FPC)on growth of human breast cancer T47D cells and the interactions between the FPC and tamoxifen(TAM),on the growth of estrogen recepto...Objective:To investigate the estrogenic effect of(8,9)-furanyl-pterocarpan-3-ol(FPC)on growth of human breast cancer T47D cells and the interactions between the FPC and tamoxifen(TAM),on the growth of estrogen receptor-dependent breast cancer T47D cells.Methods:The proliferation effect of FPC were conducted on T47D cells in vitro by MTT test.T47D cells were treated with FPC alone(0.01-200μmol/L)or in combination with TAM 20 nmol/L.Furthermore,the expression of ERαor c-Myc were also determined by immunohistochemistry.Results:The results indicated that administration of an anti-estrogen TAM showed growth inhibitory effect on T47D cells,wheraes co-administered with low concentration(less than 1μmol/L)of FPC attenuated to promote cell proliferation.In contrast,the combination of TAM with higher doses(more than 20μmol/L)of FPC showed growth inhibitory.This result was supported by immunocytochemistry studies that the administration of 20 nmol/L TAM down-regulated ER-αand c-Myc,but the combination of 20 nmol/L TAM and 1μmol/L FPC robustly up-regulated expression of ER-α.Thus,the reduced growth inhibition of TAM 20 nmol/L by FPC 1μmol/L on T47D cells may act via the modulation of ER-α.Conclusions:The findings indicate and suggest that FPC had estrogenic activity at low concentrations and anti-estrogenic effect that are likely to be regulated by c-Myc and estrogen receptors.We also confirm that low concentration of FPC attenuated the growth-inhibitory effects of TAM on mammary tumor prevention.Therefore,the present study suggests that caution is warranted regarding the consumption of dietary FPC by breast cancer patients while on TMA therapy.展开更多
Relatively little is known about the effects of estrogen on postischemic cerebral vasomotor dynamics after ischemic injury. Emerging hypotheses suggest that the timing after menopause at which hormone replacement is i...Relatively little is known about the effects of estrogen on postischemic cerebral vasomotor dynamics after ischemic injury. Emerging hypotheses suggest that the timing after menopause at which hormone replacement is initiated might be important and might modulate the potential benefits of estrogen on brain rescue once a cerebral ischemic event occurs. Therefore, we sought to determine if protracted hypoestrogenicity modifies estrogen’s protective effects on postischemic pial artery dilatory dysfunction and if the arachidonic acid metabolite 20-hydroxyeicosatetraeonic (20-HETE) contributes to the dysfunction. Pial artery dilation to acetylcholine was examined before and 1 hour after 15 minutes forebrain ischemia. The rat study groups included: sexually mature males (M), naive (N), OVX (OV), estrogen-treated OVX females (E1;estrogen started 1 week post ovariectomy) and delayed estrogen-treated (E10;started 10 weeks post ovariectomy) females. Postischemic responses were assessed before and after superfusion of the 20-HETE synthesis inhibitor N-hydroxy-N’-(4-butyl-2-methylphenyl)-formamidine (HET0016). Postischemic acetylcholine dilation was depressed in M, OV and E10 compared to N and E1 rats. Compared to E1, delayed estrogen replacement worsened acetylcholine-induced dilation. Postischemic microvascular estrogen receptor alpha (ERα) density was similar in the OV, E1 and E10 rats. Postischemic application of HET0016 failed to improve acetylcholine dilation. Continuous infusion of HET0016 during and after ischemia did not reverse postischemic pial vasodilatory dysfunction. Timing of estrogen replacement may be critical for vascular health after cerebral ischemic injury. Postischemic loss of acetylcholine reactivity does not appear to involve mechanisms related to 20-HETE synthesis or microvascular ERα expression.展开更多
The aim of the present study have been reported to review the estrogen level in the patients with the breast cancer and healthy individuals.Breast cancer is one of the most common diseases in women worldwide that is c...The aim of the present study have been reported to review the estrogen level in the patients with the breast cancer and healthy individuals.Breast cancer is one of the most common diseases in women worldwide that is characterized by uncontrolled growth of malignant cells in the mammary epithelial tissue.The estrogen was found at normal level in most patients with ER-positive breast cancer and in healthy individuals,while its high level was higher among patients with ER-negative breast cancer.Many studies show evidences about the role of estrogen at a high level on the development of breast cancer.The association between the estrogen levels and the presence of Candida spp.in vagina of patients with breast cancer was reviewed.展开更多
MRI provides a highly sensitive technique for early detection of abnormal breast tissue. It is useful for identifying a status of proliferation, angiogenesis, and microvascular permeability, which may indicate early b...MRI provides a highly sensitive technique for early detection of abnormal breast tissue. It is useful for identifying a status of proliferation, angiogenesis, and microvascular permeability, which may indicate early breast neoplasm formation. We retrospectively studied 2005 breast MRI images from Taiwan Residents women and classified them as either healthy or unhealthy according to BI-RADS categories. A subgroup of our study patients had received estrogen supplements, containing estrogen components or phytoestrogen, for at least 3 months. These patients’ images were also classified into the healthy and unhealthy groups. These two groups were compared and a significant difference was found between them (P < 0.002). Comparison of the MRI images also identified certain cases that demonstrated a typical estrogen/phytoestrogen effect or a withdrawal effect. The overuse of estrogen or phytoestrogen supplements can increase breast glandular tissue proliferation, as reflected on MRI images. Such proliferation may increase the patient’s risk of future breast cancer.展开更多
Phytoestrogens are natural compounds found in some vegetables, and they replicate many of the physiochemical and physiological properties of estrogens, including the regulation of mood. The phytoestrogen genistein exe...Phytoestrogens are natural compounds found in some vegetables, and they replicate many of the physiochemical and physiological properties of estrogens, including the regulation of mood. The phytoestrogen genistein exerts anxiolytic-like effects in rats with a chronic absence of ovarian hormones, but the mechanism involved in this effect remains to be explored. The present study explored the participation of estrogen receptor-β in the anxiolytic-like effect of genistein (1.0 mg/kg, i.p., for 4 days) in Wistar rats with 12-weeks postovariectomy, considered as experimental model of post-surgical menopause. In the light/dark test, a useful tool for anxiety study and for the screening of anxiolytic drugs, genistein reduced the latency to enter and increased the time spent in the light compartment and significantly increased the frequency and time spent exploring the light compartment compared with the control group, which is considered as an anxiolytic-like effect at experimental level. All behavioral effects produced by genistein in the light/dark test were blocked by previous tamoxifen administration (5.0 mg/kg, s.c., for 6 days), a non selective antagonist for estrogen receptor-β. The effects produced by genistein or tamoxifen in this test were not related to significant changes in general motor activity evaluated in the open field test. In conclusion, the specific contribution of present investigation was identify that estrogen receptor-β is involved in the anxiolytic-like effect produced by phytoestrogen genistein in rats with a long-term absence of ovarian hormones;supporting the hypothesis that estrogen receptor-β participates in the regulation of anxiety associated with low concentration of ovarian hormones and in the anxiolytic-like effects produced by natural estrogenic compounds such as phytoestrogens.展开更多
Objective:To study the effect of estrogen on anovulatory dysfunctional uterine bleeding(ADUB).Methods:Primary endometrial epithelial cells of Hainan Lizu female was cultured and hydrolylic activity of gelalinase was d...Objective:To study the effect of estrogen on anovulatory dysfunctional uterine bleeding(ADUB).Methods:Primary endometrial epithelial cells of Hainan Lizu female was cultured and hydrolylic activity of gelalinase was determined by gelatin zymography analysis.Cellular mRNA and protein synthesis was blocked respectively to determine whether the increased expression of MMP-2/9 was induced by estrogen.The expression of VEGF was blocked by siRNA.After treatment with various factors.MMP-9,VEGF,total Erk and phosphorylated Erk expression in primary uterine epithelial cells was detected by Western blotting analysis.Cell MMP-2/9mRNA levels was measured by real-time RT-PCR.Results:The activity and expression of MMP2/9 was inereased in the endometrium of patients with ADUB.Estrogen could up-regulate the expression of VEGF and activate Erk 1/2-Elk1 signal path.After interference by siRNA,ERK1/2 pathway was blocked in cells,and the expression of MMP-2/9 was down-regulated.ERK1/2 specific blocker U0126 blocked ERK phosphorylation,and it could down-regulate the expression of MMP-2/9.Conclusions:The results showed that the estrogen can increase the expression of VEGF,and thus activate ERK1/2 pathway to induce MMP-2/9 expression.展开更多
Worldwide, gastric cancer is one of the most common malignancies with high mortality. Various aspects of thedevelopment and progression of gastric cancer continue to be extensively investigated in order to further our...Worldwide, gastric cancer is one of the most common malignancies with high mortality. Various aspects of thedevelopment and progression of gastric cancer continue to be extensively investigated in order to further our understanding and provide more effective means for the prevention, diagnosis, and treatment of the disease. Estrogen receptors(ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. There are two distinct forms of ERs, namely ERα and ERβ, with several alternative-splicing isoforms for each. They show distinct tissue distribution patterns and exert different biological functions. Dysregulation of ERs has been found to be associated closely with many diseases, including cancer. A number of studies have been conducted to investigate the role of ERs in gastric cancer, the possible mechanisms underlying these roles, and the clinical relevance of deregulated ERs in gastric cancer patients. To date, inconsistent associations of different ERs with gastric cancer have been reported. These inconsistencies may be caused by variations in in vitro cell models and clinical samples, including assay conditions and protocols with regard to different forms of ERs. Given the potential of the deregulated ERs as diagnostic/prognostic markers or therapeutic targets for gastric cancer, it will be important to identify/confirm the association of each ER isoform with gastric cancer, to determine the specific roles and interactions that these individual ER isoforms play under specific conditions in the development and/or progression of gastric cancer, and to elucidate precisely these mechanisms. In this review, we summarize the achievements from early ER studies in gastric cancer to the most up-to-date discoveries, with an effort to provide a comprehensive understanding of the role of ERs roles in gastric cancer and its possible mechanisms. Furthermore, we propose directions for future investigations.展开更多
The role of CyclinD1 and estrogen receptor (ER) in the process of proliferation and metastasis of breast neoplasm and their relationship were studied. The expression levels of CyclinD1 and ER in the tissue samples wer...The role of CyclinD1 and estrogen receptor (ER) in the process of proliferation and metastasis of breast neoplasm and their relationship were studied. The expression levels of CyclinD1 and ER in the tissue samples were detected by using flow cytometry and L SAB immunohistochemistry staining, respectively. The results showed that CyclinD1 and ER expression levels in breast cancer were significantly higher than in benign breast neoplasm (P<0.05). The CyclinD1 expression levels in stage I was much lower than in stages Ⅱ, Ⅲ, Ⅳ (P<0.05). The positive rate of ER was not related with tumor size, lymph node metastasis and TNM stage (P>0.05), but the CyclinD1 expression level in ER (+) group was significantly higher than in ER (-) group (P<0.05). It was concluded that CyclinD1 expression level might be obviously related with the proliferation and metastasis of breast neoplasm and ER.展开更多
基金Supported by National Natural Science Foundation of China,No.81270901 and No.81970672.
文摘BACKGROUND Visceral obesity is increasingly prevalent among adolescents and young adults and is commonly recognized as a risk factor for type 2 diabetes.Estrogen[17β-estradiol(E2)]is known to offer protection against obesity via diverse me-chanisms,while its specific effects on visceral adipose tissue(VAT)remain to be fully elucidated.AIM To investigate the impact of E2 on the gene expression profile within VAT of a mouse model of prediabetes.METHODS Metabolic parameters were collected,encompassing body weight,weights of visceral and subcutaneous adipose tissues(VAT and SAT),random blood glucose levels,glucose tolerance,insulin tolerance,and overall body composition.The gene expression profiles of VAT were quantified utilizing the Whole Mouse Genome Oligo Microarray and subsequently analyzed through Agilent Feature Extraction software.Functional and pathway analyses were conducted employing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses,respectively.RESULTS Feeding a high-fat diet(HFD)moderately increased the weights of both VAT and SAT,but this increase was mitigated by the protective effect of endogenous E2.Conversely,ovariectomy(OVX)led to a significant increase in VAT weight and the VAT/SAT weight ratio,and this increase was also reversed with E2 treatment.Notably,OVX diminished the expression of genes involved in lipid metabolism compared to HFD feeding alone,signaling a widespread reduction in lipid metabolic activity,which was completely counteracted by E2 adminis-tration.This study provides a comprehensive insight into E2's local and direct protective effects against visceral adiposity in VAT at the gene level.CONCLUSION In conclusion,the present study demonstrated that the HFD-induced over-nutritional challenge disrupted the gene expression profile of visceral fat,leading to a universally decreased lipid metabolic status in E2 deficient mice.E2 treatment effectively reversed this condition,shedding light on the mechanistic role and therapeutic potential of E2 in combating visceral obesity.
基金Hainan Clinical Medical CenterMajor Science and Technology Project of Hainan Province(No.ZDKJ2021037)+3 种基金National Natural Science Foundation of China(No.81960283,82072880)Funded by the Innovation Center of Academician Team of Hainan ProvinceKey R&D Project of Hainan Province(No.ZDYF2022SHFZ311)Hainan Science and Technology Program(Clinical Medical Research Center:LCYX202203,LCYX202102)。
文摘Objective:To evaluate the effect of estrogen pre-treatment in patients with different ovarian response in antagonist protocol.Methods:Randomized controlled trials(RCTs)and retrospective studies about the effect of estrogen pre-treatment in antagonist prorocol were searched in PubMed,Web of Science,China National Knowledge Infrastructure,Wanfang Database.R software was used for meta-analysis.Results:Seven RCTs and two retrospective studies were included.In order to explore the source of heterogeneity,subgroup analysis was used,which was mainly conducted according to the ovarian response of the included population,which were divided into low responders,non-low responders and mixed responders.In the study about gonadotropin hormone(Gn)days,patients were divided into wash-out subgroup and non-wash-out subgroup according to drug use-pattern.Meta-results showed that the number of Gn days increased significantly in the non-wash-out subgroup(WMD=1.07,95%CI[0.83;1.31],I2=66%).The number of Gn days in the wash-out subgroup were not affected(WMD=-0.12,95%CI[-0.45;0.21],I2=0%).In the low-response subgroup,the number of oocytes retrieved(WMD=0.46,95%CI[-0.23;1.16],I2=81%),the fresh cycle clinical pregnancy rate(RR=0.77,95%CI[0.55;1.06],I2=73%)and the cycle cancellation rate(RR=0.80,95%CI[0.40;1.61],I2=83%)were not significantly changed with estrogen pre-treatment.In the non-low-response subgroup,the number of oocytes obtained(WMD=0.21,95%CI[-0.69;1.11],I2=2%),fresh cycle clinical pregnancy rate(RR=0.94,95%CI[0.77;1.14],I2=41%),live birth rate(RR=0.82,95%CI[0.62;1.08],I2=0%)and cycle cancellation rate(RR=0.89,95%CI[0.54;1.47],I2=2%)were not significantly changed with estrogen pre-treatment.Conclusions:Estrogen pre-treatment(with non-wash-out period)in antagonist protocol increases Gn days,dose not improve IVF outcomes in non-low responders and low responders.
基金supported by Jilin Provincial Department of Education Project(20200201515 JC).
文摘Objective:Using data mining tools,study the potential pathways of estrogen’s cardiovascular effects.Methods:The GeneExpression Omnibus database was used to download the relevant high-throughput microarray dataset GSE72180,which was then analyzed for differential genes using the GEO2R online analysis tool,gene function and pathway enrichment analysis using DAVID 6.8,protein interaction network analysis using the STRING database,and core network extraction using the MCODE algorithm.Results:A total of 131 differential genes were identified and enriched for gene function and signaling pathway analysis,which indicated that these genes were related with focal adhesion and the HIF-1 signaling pathway.MCODE algorithm analysis extracted 1 core sub-network of these genes to be related to ubiquitin protein transferase activity,protein polyubiquitination,protein ubiquitination involved in ubiquitin-dependent proteolytic metabolic processes,ligase activity,and clustering on ubiquitin-mediated protein hydrolysis signaling pathway.Conclusion:By using data mining tools,it is possible to identify how estrogen may influence the cardiovascular system by controlling the ubiquitination process.This information may be used as a reference for etiology and preventive studies of cardiovascular illnesses.
基金supported by Science and Technology Research Project of Hebei Higher School,Hebei Education Department(ZD2015131)Natural Science Foundation of Hebei Province(H2012405016)
文摘OBJECTIVE To investigate the effect of quercetin on primary cultured newborn rat cortex neuron cell which is estrogen depletion,and discuss the possible mechanism,to provide new ideas and strategies for developing a drug of neurodegenerative disease.METHODS Rat cortex neurons were isolated from one day old Sprague Dawley rats and treated with estrogen,quercetin and estrogen receptor antagonists(ICI182,780).Cell viability was determined by MTT assay,neurite outgrowth was measured by fluorescent microsope and estrogen receptors were determine by Western blot.RESULTS Quercetin functions like estrogen to increase cortex neuronal cell viability,the Que(50,100μmol·L^(-1))group compared with the control group could significantly improve the activity of the cortical neurons(P<0.05).It can also increase neurite out growth,the Que(50,100μmol·L^(-1))group significantly promoted the formation of synapse,most of the neurons were full,and the synapses of neurons became thick,growth,and connect to a dense neural network.And in the Western blot experiments,Que(50,100μmol·L^(-1))group could obviously increase the expression of estrogen receptor alpha protein,in addition,the neural protective effect of quercetin can be inhibited by ICI182,780.CONCLUSION Quercetin like estrogen can protected cortex neuronal and the effect of quercetin on cortex neuronal cells was mediated by estrogen receptor alpha.
基金supported by grants from the Cancer Prevention Research Institute of Texas(RP130266)the Carson-Leslie Foundation and the Association for Research of Childhood Cancer
文摘Endocrine therapy using estrogen receptor-α(ER-α) antagonists for attenuating horm2one-driven cell proliferation is a major treatment modality for breast cancers.To exploit any DNA repair deficiencies associated with endocrine therapy,we investigated the functional and physical interactions of ER-α with O^6-methylguanine DNA methyltransferase(MGMT),a unique DNA repair protein that confers tumor resistance to various anticancer alkylating agents.The ER-α-positive breast cancer cell lines(MCF-7,T47D) and ER- negative cell lines(MDAMB-468,MDAMB-231),and established inhibitors of ER-α and MGMT,namely,ICI-182,780(Faslodex) and O^6-benzylguanine,respectively,were used to study MGMT- ER interactions.The MGMT gene promoter was found to harbor one full and two half estrogen-responsive elements(EREs) and two antioxidant-responsive elements(AREs).MGMT expression was upregulated by estrogen,downregulated by tamoxifen in Western blot and promoter-linked reporter assays.Similarly,both transient and stable transfections of Nrf-2(nuclear factor-erythroid 2-related factor-2)increased the levels of MGMT protein and activity 3 to 4-fold reflecting novel regulatory nodes for this drugresistance determinant.Of the different ER-α antagonists tested,the pure anti-estrogen fulvestrant was most potent in inhibiting the MGMT activity in a dose,time and ER-α dependent manner,similar to O^6-benzylguanine.Interestingly,fulvestrant exposure led to a degradation of both ER-α and MGMT proteins and O^6-benzylguanine also induced a specific loss of ER-α and MGMT proteins in MCF-7 and T47 D breast cancer cells with similar kinetics.Immunoprecipitation revealed a specific association of ER-α and MGMT proteins in breast cancer cells.Furthermore,silencing of MGMT gene expression triggered a decrease in the levels of both MGMT and ER-α proteins.The involvement of proteasome in the drug-induced degradation of both proteins was also demonstrated.Fulvestrant enhanced the cytotoxicity of MGMT-targeted alkylating agents,namely,temozolomide and BCNU by 3 to 4-fold in ER-α positive cells,but not in ER-negative cells.We conclude that MGMT and ER-α proteins exist as a complex and are co-targeted for ubiquitin-conjugation and subsequent proteasomal degradation.The findings offer a clear rationale for combining alkylating agents with endocrine therapy.
基金Supported by Wholly granted from R and D, CMD Pharma Limited, United Kingdom
文摘AIM:To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHODS:A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples. RESULTS:No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69vs 37.708 ± 5.31,P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13,P = 0.04), mRNA (2.278 ± 1.19vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67,P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06vs 0.532 ± 0.11,P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07). CONCLUSION:The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study.
基金This study was supported by the National Natural Science Foundation of China,Nos.81671257,81371221,31600825(all to GQH).
文摘Postmenopausal women with Alzheimer’s disease exhibit dramatically reduced sensitivity to estrogen replacement therapy,which is though to be related to an estrogen receptor(ER)α/ERβratio imbalance arising from a significantly decreased level of ERs of the brain.The aim of our study was to investigate whether valproic acid(VPA)can enhance the beneficial effects of estrogen on cognitive function through restoration of ERαand ERβexpression in the brain.We removed the ovaries of female APP/PS1 mice to simulate the low estrogen levels present in postmenopausal women and then administered VPA(30 mg/kg,intraperitoneal injection,once daily),17β-estradiol(E2)(2.4μg,intraperitoneal injection,once daily),liquiritigenin(LG)(50μg/kg,intragastric infusion,once daily),VPA+E2,or VPA+LG for 4 successive weeks.Compared with treatment with a single drug,treatment with VPA+E2 or VPA+LG significantly increased the level of glycogen synthase kinase 3β,increased the expression of estrogen receptorα,reduced the expression of small ubiquitin-like modifiers,and increased the level of estrogen receptorβ.This resulted in enhanced sensitivity to estrogen therapy,reduced amyloidβaggregation,reduced abnormal phosphorylation of the tau protein,reduced neuronal loss,increased dendritic spine and postsynaptic density,and significantly alleviated memory loss and learning impairment in Alzheimer’s disease.This study was approved by the Chongqing Medical University Animal Protection and Ethics Committee,China on March 6,2013.
文摘Several epidemiological,cellular,and molecular studies demonstrate the role of environmental chemicals with endocrine disrupting activities,typical of Westernized societies,in the pathogenesis of numerous diseases including cancer.Nonetheless this information,the design and execution of studies on endocrine disruptors are not yet cognizant that the specific actions of individual hormones often change with development and ageing,they may be different in males and females and may be mediated by different receptors isoforms expressed in different tissues or at different life stages.These statements are particularly true when assessing the hazard of endocrine disruptors against 17β-estradiol(E2)actions in that this hormone is crucial determinant of sexrelated differences in anatomical,physiological,and behavioral traits which characterize male and female physiology.Moreover,E2 is also involved in carcinogenesis.The oncogenic effects of E2 have been investigated extensively in breast and ovarian cancers where hormone-receptor modulators are now an integral part of targeted treatment.Little is known about the E2preventive signalling in colorectal cancer,although this disease is more common in men than women,the difference being more striking amongst pre-menopausal women and age-matched men.This review aims to dissect the role and action mechanisms of E2 in colorectal cancer evaluating the ability of estrogen disruptors(i.e.,xenoestrogens)in impair these E2 actions.Data discussed here lead to define the possible role of xenoestrogens in the impairment and/or activation of E2signals important for colorectal cancer prevention.
文摘Objective To investigate the expressions of estrogen receptor(ER)subtypes and c-met proto-oncogene in human endometrial carcinomas and to assess the clinical significance of ER and c-met in this carcinoma.Methods Reverse transcription PCR(RT-PCR)was used to detect the expressions of ERα,ERβ and c-met proto-oncogene mRNA in 30 samples of endometrial carcinoma and 11 samples of normal endometrium.Results The expression of ERα in endometrial carcinoma(0.70±0.40)was significantly reduced in comparison to that in normal endometrium(1.14±0.56,P<0.05).A similar finding was made for the expression of ERβ in carcinoma(0.24±0.18)versus normal tissues(0.48±0.20,P<0.05).In contrast,c-met mRNA expression was increased in endometrial carcinoma(1.45±0.72)compared to that in normal endometrium(0.42±0.31,P<0.01).A decrease tendency of the expression of ERα was also found from Stage Ⅰ(0.82±0.41)to a more severe Stag Ⅱ-Ⅲ of endometrial carcinoma(0.42±0.17,P<0.05).The analysis of ERα and ERβ mRNA revealed a decrease tendency from shallow to deep invasion of the uterine muscles(P<0.05).We found that the expressions of ERα and ERβ were negatively correlated with c-met proto-oncogene with a coefficient correlation of-0.63(P<0.01)and-0.32(P<0.05),respectively.Conclusion ERα and ERβ are both involved in mutagenic action of carcinogen.C-met proto-oncogene plays an important role in the carcinogenesis and development of endometrial carcinoma.C-met and ER expressions show a negative correlation in the development of endometrial carcinoma.
文摘The main estrogens:estradiol,estrone,and their acyl-esters have been studied essentially related to their classical estrogenic and pharmacologic functions.However,their main effect in the body is probably the sustained control of core energy metabolism.Estrogen nuclear and membrane receptors show an extraordinary flexibility in the modulation of metabolic responses,and largely explain gender and age differences in energy metabolism:part of these mechanisms is already sufficiently known to justify both.With regard to energy,the estrogen molecular species act essentially through four key functions:(1)Facilitation of insulin secretion and control of glucose availability;(2)Modulation of energy partition,favoring the use of lipid as the main energy substrate when more available than carbohydrates;(3)Functional protection through antioxidant mechanisms;and(4)Central effects(largely through neural modulation)on whole body energy management.Analyzing the different actions of estrone,estradiol and their acyl esters,a tentative classification based on structure/effects has been postulated.Either separately or as a group,estrogens provide a comprehensive explanation that not all their quite diverse actions are related solely to specific molecules.As a group,they constitute a powerful synergic action complex.In consequence,estrogens may be considered wardens of energy homeostasis.
基金supported by grants from Scientific Research Plan Project of Science and Technology Commission of Shanghai Municipality(No.18ZR1439200)Talents Training Program of Pudong Hospital affiliated to Fudan University(No.PX201705).
文摘Objective Previous study suggested that estradiol(E2)plays an important role in otolith shedding by regulating the expression of otoconin 90(OC90).The purpose of this article is to provide further data on the effect and mechanism of E2 on the morphology of otolith.Methods The rats receiving bilateral ovariectomy(OVX)were used as animal models.Co-immunoprecipitation was used to observe the relationship between estrogen receptor(ER)and estrogen-related receptorα(ERRα).The morphology of otolith was observed under the scanning electron microscopy.Western blotting and qPCR were used for quantitative analysis of the roles of ER and ERRαin regulating OC90 expression.Results The looser otoliths were observed in rats receiving bilateral OVX,which could be reversed by supplementation with E2.The level of ERRαwas decreased in bilateral OVX rats.ER and ERRαinteracted with each other on the regulation of the expression of OC90.Conclusion Our results suggest ER and ERRαare both important downstream receptors involved in regulating OC90 expression in utricles of rats,and ERRαprobably functions by interacting with ER.This provides evidence for the mechanism of otolith shedding.And it may be significant for future studies of targeted prevention and therapies for benign paroxysmal positional vertigo.
文摘Objective The aim of this study was to determine if isoflavone genistien has protective effects against high glucose-induced cell apoptosis in human aortic endlthelial cells, and investigate the possible mechanism for this protection. Methods Human aortic endothelial cells subjected to normal (5mmol/L) or high glucose (25mmol/L) were treated with genistein at 0, 50, 100nmol/L. Parallel experiments were performed with 100nM 17b-estradiol, and also in the presence and absence of the pure anti-estrogen ICI-182,780 (100nmol/L). The effects on cell apoptotic DNA fragmentation were determined using cell death ELISA, and the effects on cellular proliferation were determined using tritiated thymidine incorporation assay. Estrogen receptor expression was detected by Taqman quantitative PCR. Results Genistein at 100nmol/L significantly reduced high glucose-induced DNA fragmentation, and reversed cell DNA synthesis inhibition (P <0.001) after 24 hours' incubation. The effect of genistein was completely blocked by ICI-182,780 administration. Estrogen receptor beta, but not alpha was found to be expressed in these cells. Conclusion Isoflavone genistein shows protection against high glucose-induced cell damage through estrogen receptor beta, reducing apoptotic DNA damage and protecting from the inhibition of cell proliferation.
基金Supported in part by Hibah Competition Grant Research of Faculty of PharmacyGadjah Mada University(Grant No.UGM/FA/851.d/M/05/01)
文摘Objective:To investigate the estrogenic effect of(8,9)-furanyl-pterocarpan-3-ol(FPC)on growth of human breast cancer T47D cells and the interactions between the FPC and tamoxifen(TAM),on the growth of estrogen receptor-dependent breast cancer T47D cells.Methods:The proliferation effect of FPC were conducted on T47D cells in vitro by MTT test.T47D cells were treated with FPC alone(0.01-200μmol/L)or in combination with TAM 20 nmol/L.Furthermore,the expression of ERαor c-Myc were also determined by immunohistochemistry.Results:The results indicated that administration of an anti-estrogen TAM showed growth inhibitory effect on T47D cells,wheraes co-administered with low concentration(less than 1μmol/L)of FPC attenuated to promote cell proliferation.In contrast,the combination of TAM with higher doses(more than 20μmol/L)of FPC showed growth inhibitory.This result was supported by immunocytochemistry studies that the administration of 20 nmol/L TAM down-regulated ER-αand c-Myc,but the combination of 20 nmol/L TAM and 1μmol/L FPC robustly up-regulated expression of ER-α.Thus,the reduced growth inhibition of TAM 20 nmol/L by FPC 1μmol/L on T47D cells may act via the modulation of ER-α.Conclusions:The findings indicate and suggest that FPC had estrogenic activity at low concentrations and anti-estrogenic effect that are likely to be regulated by c-Myc and estrogen receptors.We also confirm that low concentration of FPC attenuated the growth-inhibitory effects of TAM on mammary tumor prevention.Therefore,the present study suggests that caution is warranted regarding the consumption of dietary FPC by breast cancer patients while on TMA therapy.
文摘Relatively little is known about the effects of estrogen on postischemic cerebral vasomotor dynamics after ischemic injury. Emerging hypotheses suggest that the timing after menopause at which hormone replacement is initiated might be important and might modulate the potential benefits of estrogen on brain rescue once a cerebral ischemic event occurs. Therefore, we sought to determine if protracted hypoestrogenicity modifies estrogen’s protective effects on postischemic pial artery dilatory dysfunction and if the arachidonic acid metabolite 20-hydroxyeicosatetraeonic (20-HETE) contributes to the dysfunction. Pial artery dilation to acetylcholine was examined before and 1 hour after 15 minutes forebrain ischemia. The rat study groups included: sexually mature males (M), naive (N), OVX (OV), estrogen-treated OVX females (E1;estrogen started 1 week post ovariectomy) and delayed estrogen-treated (E10;started 10 weeks post ovariectomy) females. Postischemic responses were assessed before and after superfusion of the 20-HETE synthesis inhibitor N-hydroxy-N’-(4-butyl-2-methylphenyl)-formamidine (HET0016). Postischemic acetylcholine dilation was depressed in M, OV and E10 compared to N and E1 rats. Compared to E1, delayed estrogen replacement worsened acetylcholine-induced dilation. Postischemic microvascular estrogen receptor alpha (ERα) density was similar in the OV, E1 and E10 rats. Postischemic application of HET0016 failed to improve acetylcholine dilation. Continuous infusion of HET0016 during and after ischemia did not reverse postischemic pial vasodilatory dysfunction. Timing of estrogen replacement may be critical for vascular health after cerebral ischemic injury. Postischemic loss of acetylcholine reactivity does not appear to involve mechanisms related to 20-HETE synthesis or microvascular ERα expression.
文摘The aim of the present study have been reported to review the estrogen level in the patients with the breast cancer and healthy individuals.Breast cancer is one of the most common diseases in women worldwide that is characterized by uncontrolled growth of malignant cells in the mammary epithelial tissue.The estrogen was found at normal level in most patients with ER-positive breast cancer and in healthy individuals,while its high level was higher among patients with ER-negative breast cancer.Many studies show evidences about the role of estrogen at a high level on the development of breast cancer.The association between the estrogen levels and the presence of Candida spp.in vagina of patients with breast cancer was reviewed.
文摘MRI provides a highly sensitive technique for early detection of abnormal breast tissue. It is useful for identifying a status of proliferation, angiogenesis, and microvascular permeability, which may indicate early breast neoplasm formation. We retrospectively studied 2005 breast MRI images from Taiwan Residents women and classified them as either healthy or unhealthy according to BI-RADS categories. A subgroup of our study patients had received estrogen supplements, containing estrogen components or phytoestrogen, for at least 3 months. These patients’ images were also classified into the healthy and unhealthy groups. These two groups were compared and a significant difference was found between them (P < 0.002). Comparison of the MRI images also identified certain cases that demonstrated a typical estrogen/phytoestrogen effect or a withdrawal effect. The overuse of estrogen or phytoestrogen supplements can increase breast glandular tissue proliferation, as reflected on MRI images. Such proliferation may increase the patient’s risk of future breast cancer.
基金partially supported by a grant from PROMEP(103.5/05/1955,UVER-PTC-155)Sistema Nacional de Investigadores(SNI,Exp.32753 and 19190)+1 种基金Cuerpo Académico UVE-CA-202The second author received a fellowship from CONACyT Reg.223529.
文摘Phytoestrogens are natural compounds found in some vegetables, and they replicate many of the physiochemical and physiological properties of estrogens, including the regulation of mood. The phytoestrogen genistein exerts anxiolytic-like effects in rats with a chronic absence of ovarian hormones, but the mechanism involved in this effect remains to be explored. The present study explored the participation of estrogen receptor-β in the anxiolytic-like effect of genistein (1.0 mg/kg, i.p., for 4 days) in Wistar rats with 12-weeks postovariectomy, considered as experimental model of post-surgical menopause. In the light/dark test, a useful tool for anxiety study and for the screening of anxiolytic drugs, genistein reduced the latency to enter and increased the time spent in the light compartment and significantly increased the frequency and time spent exploring the light compartment compared with the control group, which is considered as an anxiolytic-like effect at experimental level. All behavioral effects produced by genistein in the light/dark test were blocked by previous tamoxifen administration (5.0 mg/kg, s.c., for 6 days), a non selective antagonist for estrogen receptor-β. The effects produced by genistein or tamoxifen in this test were not related to significant changes in general motor activity evaluated in the open field test. In conclusion, the specific contribution of present investigation was identify that estrogen receptor-β is involved in the anxiolytic-like effect produced by phytoestrogen genistein in rats with a long-term absence of ovarian hormones;supporting the hypothesis that estrogen receptor-β participates in the regulation of anxiety associated with low concentration of ovarian hormones and in the anxiolytic-like effects produced by natural estrogenic compounds such as phytoestrogens.
基金supported by Natural Science Foundation of Hainan Province(No.812148)
文摘Objective:To study the effect of estrogen on anovulatory dysfunctional uterine bleeding(ADUB).Methods:Primary endometrial epithelial cells of Hainan Lizu female was cultured and hydrolylic activity of gelalinase was determined by gelatin zymography analysis.Cellular mRNA and protein synthesis was blocked respectively to determine whether the increased expression of MMP-2/9 was induced by estrogen.The expression of VEGF was blocked by siRNA.After treatment with various factors.MMP-9,VEGF,total Erk and phosphorylated Erk expression in primary uterine epithelial cells was detected by Western blotting analysis.Cell MMP-2/9mRNA levels was measured by real-time RT-PCR.Results:The activity and expression of MMP2/9 was inereased in the endometrium of patients with ADUB.Estrogen could up-regulate the expression of VEGF and activate Erk 1/2-Elk1 signal path.After interference by siRNA,ERK1/2 pathway was blocked in cells,and the expression of MMP-2/9 was down-regulated.ERK1/2 specific blocker U0126 blocked ERK phosphorylation,and it could down-regulate the expression of MMP-2/9.Conclusions:The results showed that the estrogen can increase the expression of VEGF,and thus activate ERK1/2 pathway to induce MMP-2/9 expression.
基金Supported by The National Natural Science Foundation of ChinaNo.30271450+1 种基金No.30471955No.30672365 and No.81172516
文摘Worldwide, gastric cancer is one of the most common malignancies with high mortality. Various aspects of thedevelopment and progression of gastric cancer continue to be extensively investigated in order to further our understanding and provide more effective means for the prevention, diagnosis, and treatment of the disease. Estrogen receptors(ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. There are two distinct forms of ERs, namely ERα and ERβ, with several alternative-splicing isoforms for each. They show distinct tissue distribution patterns and exert different biological functions. Dysregulation of ERs has been found to be associated closely with many diseases, including cancer. A number of studies have been conducted to investigate the role of ERs in gastric cancer, the possible mechanisms underlying these roles, and the clinical relevance of deregulated ERs in gastric cancer patients. To date, inconsistent associations of different ERs with gastric cancer have been reported. These inconsistencies may be caused by variations in in vitro cell models and clinical samples, including assay conditions and protocols with regard to different forms of ERs. Given the potential of the deregulated ERs as diagnostic/prognostic markers or therapeutic targets for gastric cancer, it will be important to identify/confirm the association of each ER isoform with gastric cancer, to determine the specific roles and interactions that these individual ER isoforms play under specific conditions in the development and/or progression of gastric cancer, and to elucidate precisely these mechanisms. In this review, we summarize the achievements from early ER studies in gastric cancer to the most up-to-date discoveries, with an effort to provide a comprehensive understanding of the role of ERs roles in gastric cancer and its possible mechanisms. Furthermore, we propose directions for future investigations.
文摘The role of CyclinD1 and estrogen receptor (ER) in the process of proliferation and metastasis of breast neoplasm and their relationship were studied. The expression levels of CyclinD1 and ER in the tissue samples were detected by using flow cytometry and L SAB immunohistochemistry staining, respectively. The results showed that CyclinD1 and ER expression levels in breast cancer were significantly higher than in benign breast neoplasm (P<0.05). The CyclinD1 expression levels in stage I was much lower than in stages Ⅱ, Ⅲ, Ⅳ (P<0.05). The positive rate of ER was not related with tumor size, lymph node metastasis and TNM stage (P>0.05), but the CyclinD1 expression level in ER (+) group was significantly higher than in ER (-) group (P<0.05). It was concluded that CyclinD1 expression level might be obviously related with the proliferation and metastasis of breast neoplasm and ER.
