Use of adenovirus vector expressing the mouse full estrogen receptor alpha gene to infect mouse primary neurons

Estrogen plays important regulatory and protective roles in the central nervous system through estrogen receptor a mediation. Previous studies applied eukaryotic expression and lentiviral vectors carrying estrogen receptor a to cladfy the underlying mechanisms. In the present study, an adenovirus vector expressing the mouse full estrogen receptor a gene was constructed to identify biological characteristics of estrogen receptor a recombinant adenovirus infecting nerve cells. Primary cultured mouse nerve cells were first infected with estrogen receptor a recombinant adenovirus at various multiplicities of infection, followed by 100 multiplicity of infection. Results showed overexpression of estrogen receptor α mRNA and protein in the infected nerve cells. Estrogen receptor a recombinant adenovirus at 100 multiplicity of infection successfully infected neurons and upregulated estrogen receptor a mRNA and protein expression.

Future directions for using estrogen receptor agonists in the treatment of acute and chronic spinal cord injury

All synthetic and natural estrogen receptor agonists, in- cluding the most potent physiological molecule estrogen or estradiol （E2）, work typically via activation of nuclear estrogen receptor alpha （ERα） and estrogen receptor beta （ERβ）. Both ERα and ERβ modulate the expression of a variety of genes in the cells. Neurons and glial cells express ERa and ERβ. Many studies so far from our and other laboratories have firmly established the mode of actions that ERα and ERβ agonists are very promising anti-inflammatory and neuroprotective agents in the treatment of neurodegenera- rive diseases and injuries including spinal cord injury （SCI） （Chakrabarti et al., 2014a）.

Expression of estrogen receptor alpha,nerve growth factor,interleukin-2,and androgen receptor in the cerebellum of ovariectomized rats following soybean isoflavone treatment

BACKGROUND： Studies have shown that estrogen receptor alpha （ERα）, nerve growth factor （NGF）, interleukin-2 （IL-2）, and androgen receptor （AR） expression in the cerebellum decreases when estrogen levels decrease in vivo. Soybean isoflavone, a type of non-steroid estrogen with similar molecular structure and function to estradiol, exhibits estrogen-like characteristics. OBJECTIVE： To investigate the effects of various doses of soybean isoflavone on expression of ERa, NGF, IL-2, and AR in the cerebellum of ovariectomized rat, and to determine whether there is a dose-dependent effect.DESIGN, TIME AND SETTING： Controlled trial at the cellular and molecular level. The study was performed at the Experimental Animal Engineering Center, College of Veterinary Medicine, Sichuan Agricultural University from July 2006 to May 2008. MATERIALS： Soybean isoflavone, comprised of daidzin, genistein and isoflavone, was provided by Taiyuan Yuantai Biochemical Industry, China. The ERα, NGF, IL-2, and AR in situ hybridization kit, rabbit anti-rat ERa, NGF, IL-2, and AR monoclonal antibodies, and SABC kit were purchased from Wuhan Boster Biological Technology, China. METHODS： A total of 50 female, Sprague Dawley rats, aged 3 months, were randomly assigned to 5 groups, with 10 animals in each group. With the exception of the sham-operation group （abdominal cavity opening alone）, all rats underwent bilateral ovariectomy. At 14 days after surgery, rats in the high-, middle-, and low-dose soybean isoflavone groups were subcutaneously injected with 1.5, 1.0, and 0.5 mg/kg soybean isoflavone, respectively, every 2 days for 6 consecutive weeks. Rats in the sham-operation and ovariectomized groups were subcutaneously injected with absolute alcohol （0.5 mL/kg）. MAIN OUTCOME MEASURES： Expression levels and distribution of ERα, NGF, IL-2, and AR in the cerebellum were detected by immunohistochemistry and in situ hybridization. RESULTS： Compared with the sham-operation group, immunoreactive products and hybridization signals of ERa, NGF, IL-2, and AR were significantly decreased in the cerebellar cortex and nuclei of ovariectomized rats （P 〈 0.05 or P 〈 0.01）, but increased following soybean isoflavone treatment. In particular, levels of the high-dose soybean isoflavone group were almost restored to levels of the sham-operation group （P 〉 0.05）. The immunoreactive products were primarily located in the cytoplasm and neurites, and rarely in the cell membrane and nuclei. However, the hybridization signals were predominantly located in the nuclei, but rarely in the cytoplasm, cell membrane, or neurites. CONCLUSION： Soybean isoflavone upregulated ERα, NGF, IL-2, and AR protein and gene expression in a dose-dependent manner, and played an important role in sustaining and protecting structure and function of cerebellar neurons. Moreover, the similarity of expression patterns of these molecules indicated that they were mutually interactive during the regulation of soybean isoflavone to the cerebellum.

T29C genotype polymorphism of estrogen receptor alpha is associated with initial response to interferon-alpha therapy in chronic hepatitis B patients

BACKGROUND: Virological clearance, delayed progression to cirrhosis or liver cancer, and increased survival are the long-term goals of antiviral therapy in chronic hepatitis B patients. Identification of host factors correlated with therapeutic response may contribute greatly to individual treatment. This study aimed at investigating whether T29C genotype polymorphism of estrogen receptor alpha (ESR1) is associated with the initial response to interferon-alpha (IFN-alpha) therapy in chronic hepatitis B patients. METHODS: The initial responses of 100 patients to IFN-alpha therapy were evaluated and compared by classifying them into three groups according to T29C genotype polymorphism of ESR1: T/T, TIC, and C/C genotype groups. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze the genotype polymorphism in T29C. RESULTS: The frequency of initially combined response was markedly higher in both the T/T and TIC groups than in the C/C group (Z=10.326, P=0.006 and Z=26.247, P=0.000, respectively). In addition, the initial virological response was higher in the T/T and T/C groups than the C/C group (chi(2)=5.674, P=0.017 and chi(2)=4.980, P=0.026, respectively). In 78 initially HBeAg-positive patients, however, the frequency of initial e-antigen disappearance or seroconversion among the T/T, T/C, and C/C genotype groups was 34.15%, 27.78% and 15.79%, respectively, which were not significantly different. CONCLUSION. The T29C genotype polymorphism of ESR1 is associated with the initial response to IFN-alpha in patients with chronic hepatitis B, and might be a significant marker for predicting the initial response to IFN-alpha, at least in this study population. (Hepatobiliary Pancreat Dis Int 2010; 9: 275-279)

G-protein-coupled estrogen receptor as a new therapeutic target for treating coronary artery disease

Coronary heart disease(CHD) continues to be the greatest mortality risk factor in the developed world. Estrogens are recognized to have great therapeutic potential to treat CHD and other cardiovascular diseases; however,a significant array of potentially debilitating side effects continues to limit their use. Moreover,recent clinical trials have indicated that long-term postmenopausal estrogen therapy may actually be detrimental to cardiovascular health. An exciting new development is the finding that the more recently discovered G-protein-coupled estrogen receptor(GPER) is expressed in coronary arteries-both in coronary endothelium and in smooth muscle within the vascular wall. Accumulating evidence indicates that GPER activation dilates coronary arteries and can also inhibit the prolif-eration and migration of coronary smooth muscle cells. Thus,selective GPER activation has the potential to increase coronary blood flow and possibly limit the debilitating consequences of coronary atherosclerotic disease. This review will highlight what is currently known regarding the impact of GPER activation on coronary arteries and the potential signaling mechanisms stimulated by GPER agonists in these vessels. A thorough understanding of GPER function in coronary arteries may promote the development of new therapies that would help alleviate CHD,while limiting the potentially dangerous side effects of estrogen therapy.

Reduced prostate branching morphogenes,s in stromal fibroblast, but not in epithelial, estrogen receptor a knockout mice

Early studies suggested that estrogen receptor alpha （ERa） is involved in estrogen-mediated imprinting effects in prostate development. We recently reported a more complete ERa knockout （KO） mouse model via mating β-actin Cre transgenic mice with floxed ERa mice. These ACTB-ERaKO male mice showed defects in prostatic branching morphogenesis, which demonstrates that ERa is necessary to maintain proliferative events in the prostate. However, within which prostate cell type ERa exerts those important functions remains to be elucidated. To address this, we have bred floxed ERa mice with either fibroblast-specific protein （FSP）-Cre or probasin-Cre transgenic mice to generate a mouse model that has deleted ERa gene in either stromal fibroblast （FSP-ERaKO） or epithelial （pes-ERaKO） prostate cells. We found that circulating testosterone and fertility were not altered in FSP.ERaKO and pes-ERaKO male mice. Prostates of FSP-ERaKO mice have less branching morphogenesis compared to that of wild-type littermates. Further analyses indicated that loss of stromal ERa leads to increased stromal apoptosis, reduced expression of insulin-likegrowth factor-1 （IGF-1） and FGFIO, and increased expression of BMP4. Collectively, we have established the first in vivo prostate stromal and epithelial selective ERaKO mouse models and the results from these mice indicated that stromal fibroblast ERa plays important roles in prostatic branching morphogenesis via a paracrine fashion. Selective deletion of the ERa gene in mouse prostate epithelial cells by probasin-Cre does not affect the regular prostate development and homeostasis.

Co-expression of estrogen receptor and nerve growth factor in rat intrinsic cardiac ganglia

BACKGROUND： Previous studies have shown that neurons expressing estrogen receptor and nerve growth factor exist in the intrinsic cardiac ganglia in rats. However, it remains to be shown whether estrogen receptor and nerve growth factor are co-expressed within these cells. OBJECTIVE： To determine whether estrogen receptor and nerve growth factor are co-expressed in intrinsic cardiac ganglia. DESIGN, TIME AND SETTING： This cellular morphology observational study was performed at the immunohistochemistry Department, Medicine School, Wuhan University of Science and Technology, between March and July in 2007. MATERIALS： Mouse anti-estrogen receptor and rabbit anti-nerve growth factor polyclonal antibody, biotinylated goat anti-mouse IgG, and biotinylated goat anti-rabbit IgG were provided by Wuhan Boster, China. METHODS： Ten healthy, Wistar rats were included in the present study. Ten sections of intrinsic cardiac ganglia from the atrial posterior wall were randomly selected from each rat to perform estrogen receptor and nerve growth factor double-labeling immunohistochemical staining. MAIN OUTCOME MEASURES： Expression of estrogen receptor and nerve growth factor in intrinsic cardiac ganglia of rats. RESULTS： Immunohistochemistry results demonstrated expression of estrogen receptor and nerve growth factor in rat intrinsic cardiac ganglia, and double-labeling revealed co-expression of estrogen receptor and nerve growth factor in intrinsic cardiac ganglial cells. CONCLUSION： Estrogen receptor and nerve growth factor were shown to be co-expressed in rat intrinsic cardiac ganglial cells.

The Effect of GnRHa Induced Superovulation on Endometrial Morphology and Estrogen Receptor and Progesterone Receptor in Mouse

To evaluate the effect of GnRHa induced superovulation protocol on endometrial morphology and function. Material & Methods Forty ICR mice were randomly allocated into 4 groups, among them, 2 experimental groups were injected with GnRHa+HMG+hCG, another 2 groups were given saline of same volume as control group. The uterine tissues were investigated at 24 h and 48 h after administration (experimental group) or ovulation (control group).The endometrial thickness, the size of gland and glandular lumen, the total area of glandular cells, the average height of glandular epithelium were measured from routine histological slides using computerized image analysis. The SP immunohistochemistry techniques with monoclonal antibodies were employed to semi quantitatively analize the estrogen receptor (ER) and progesterone receptor (PR) in glandular cells. Results The endometrial thickness was not significantly different between experimental groups and control groups at 24 h and 48 h (P>0.05).The average area, perimeter, maximal diameter of single gland and glandular lumen, the total area, average height of glandular epithelium in experimental groups were significantly smaller than those of in control groups at equivalent time stages (all P<0.01). The asynchronous development of gland epithelium and stroma cells, namely, pesudostratified glandular epithelium and predecidual changes of stroma cells were seen at same time in experimental groups. The positive percentage (%) and expression intense of ER and PR in glandular epithelium cells were significantly lower in experimental groups than in control groups (P<0.05). Conclusion The protocol with GnRHa had a negative effect on endometrial histological structure and down regulated the express of ER and PR, suggesting that this protocol effect on the endometrial morphology and function and could not facilitate the formation of a physiologic endometrium completely, which may be one of the causes of low pregnancy rates.

Effects of Jiantaiye (健胎液) on Estrogen Receptor and mRNA Expressions in Uterus of Mice with Embryo Implantation Dysfunction

Objective: To explore the effect of Jiantaiye (健胎液, JTY) on the expression of estrogen receptor (ER) and ER mRNA in uterus of mice with embryo implantation dysfunction. Methods: Embryo implantation dysfunction mouse models were induced with mifepristone and treated with JTY. All animals were sacrificed on day 8 of pregnancy. The endometrial ER and ER mRNA expressions were assessed by immunnohistochemical SP method and semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Results: Area ratio and absorbency of ER in the JTY treated group's gland and stroma were higher than those of the model group, quite similar to those of the normal control's, and ER mRNA expression in treated group's uterus was significantly higher than that in the models, but it was not significantly different from the normal control. Conclusion: JTY improves the endometrial development by increasing ER and ER mRNA expressions of uterus of mice with embryo implantation dysfunction.

Effects of coriaria lactone-activated,astrocyte-conditioned medium on estrogen receptor and progesterone receptor expression in rat cortical and hippocampal neurons

BACKGROUND： Coriaria lactone-activated astrocytes released bioactive substances that eventually caused epilepsy. OBJECTIVE： It has been suggested that activated astrocytes alter the expression of the estrogen receptor and progesterone receptor by releasing bioactive substances during epilepsy, thereby affecting neuronal activity in the brain. This study was designed to observe the expression of the estrogen receptor and the progesterone receptor in rat brain following lateral ventricle injection of coriaria lactone-activated, astrocyte-conditioned medium. DESIGN AND SETTING： This immunohistochemical, randomized, controlled, animal study was conducted at the Department of Pathology, Hospital Affiliated to Binzhou Medical College, China. MATERIAL： Coriaria lactone was provided by Huaxi Pharmaceutical Factory, China. METHODS： Forty adult, healthy, male, Sprague Dawley rats were randomly assigned into two groups. Astrocyte-conditioned medium （10 μ L） was injected into rat lateral ventricle in the control group （n = 8）. Coriaria lactone-activated, astrocyte-conditioned medium （10 μL） was infused into the rat lateral ventricle in the coriaria lactone group （n = 32）. At 2, 4, 8 and 12 hours following injection, rats were sacrificed and subjected to immunohistochemistry. Eight rats were studied at each time point. MAIN OUTCOME MEASURES： Behavioral changes were observed in rats of both groups. Expression of the estrogen receptor and the progesterone receptor in rat cortical and hippocampal neurons was measured using immunohistochemistry. RESULTS： Four hours after injection, estrogen receptor levels in rat cortical and hippocampal neurons were significantly higher in the coriaria lactone group than in the control group （P 〈 0.05）. Progesterone receptor levels were significantly lower in the coriaria lactone group than in the control group （P 〈 0.05）. Seizures were not observed in the control group. In the coriaria lactone group, convulsions appeared 30 minutes after injection; seizures reached grade Ⅲ at 45 minutes rat behavior was nearly normal at 2 hours. CONCLUSION： Activated astrocytes can induce seizures in the rat by enhancing estrogen receptor expression and decreasing progesterone receptor expression in cerebral cortical and hippocampal neurons.

Intricate roles of estrogen and estrogen receptors in digestive system cancers:a systematic review

Gender disparities are evident across different types of digestive system cancers,which are typically characterized by a lower incidence and mortality rate in females compared to males.This finding suggests a potential protective role of female steroid hormones,particularly estrogen,in the development of these cancers.Estrogen is a well-known sex hormone that not only regulates the reproductive system but also exerts diverse effects on non-reproductive organs mediated through interactions with estrogen receptors(ERs),including the classic(ERαand ERβ)and non-traditional ERs[G protein-coupled estrogen receptor(GPER)].Recent advances have contributed to our comprehension of the mechanisms underlying ERs in digestive system cancers.In this comprehensive review we summarize the current understanding of the intricate roles played by estrogen and ERs in the major types of digestive system cancers,including hepatocellular,pancreatic,esophageal,gastric,and colorectal carcinoma.Furthermore,we discuss the potential molecular mechanisms underlying ERα,ERβ,and GPER effects,and propose perspectives on innovative therapies and preventive measures targeting the pathways regulated by estrogen and ERs.The roles of estrogen and ERs in digestive system cancers are complicated and depend on the cell type and tissue involved.Additionally,deciphering the intricate roles of estrogen,ERs,and the associated signaling pathways may guide the discovery of novel and tailored therapeutic and preventive strategies for digestive system cancers,eventually improving the care and clinical outcomes for the substantial number of individuals worldwide affected by these malignancies.

Comprehensive Analysis of Estrogen Receptor 1 Dysregulation in Liver Hepatocellular Carcinoma: Implications for Prognosis and Therapeutic Targeting - A Secondary Publication

The study investigates the expression pattern and regulatory mechanisms of estrogen receptor 1 (ESR1) in liver hepatocellular carcinoma (LIHC) through comprehensive bioinformatics analysis. Utilizing UALCAN and GEPIA2 databases, significant down-regulation of ESR1 expression is observed in LIHC samples compared to normal controls, indicating its potential role in tumor progression. Further analysis reveals consistent down-regulation across different clinical variables including patient age, gender, race, and various stages of LIHC, affirming the regulatory role of ESR1 in tumor development and progression. Additionally, promoter methylation analysis demonstrates hypermethylation of ESR1 in LIHC samples, negatively correlating with its expression. This association persists across different clinical parameters, emphasizing the inverse relationship between ESR1 methylation and expression levels. Survival analysis indicates that up- regulation of ESR1 is associated with better overall survival, suggesting its potential as a prognostic biomarker in LIHC. Furthermore, genetic mutation analysis using cBioPortal reveals a spectrum of alterations in ESR1, including amplification, missense mutation, deep deletion, splice mutation, and truncating mutation, highlighting the genetic complexity of ESR1 in LIHC. These findings collectively contribute to a deeper understanding of ESR1 dysregulation in LIHC and its clinical implications as a potential therapeutic target and prognostic marker.

Clinicopathological Features and Long-Term Prognostic Role of Human Epidermal Growth Factor Receptor-2 Low Expression in Chinese Patients with Early Breast Cancer:A Single-Institution Study

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC.Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups.Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszelχ^(2)test,P<0.001,Pearson’s R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%.Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Changes of Estrogen in Serum and Estrogen Receptor β in the Relevant Brain Regions Following Mating Behavior of the Male Mandarin Vole Microtus mandarinus

In order to investigate the estrogen and estrogen receptor β changes after mating behavior of male mandarin vole （Microtus mandarinus）, the radioimmunoassay （RIA） and immunohistochemistry methods were used to investigate changes of the serum estrogen （E） concentrations, estrogen immunoreactive neurons （E-IRs） and estrogen receptor β immunoreactive neurons （ERβ-IRs） in the relevant brain regions following mating behavior. Fifteen sexually matured male voles were randomly divided into three groups and treated differently： （1） control group： voles were exposed to clean hard-wood shavings （n=5）, （2） exposure group： voles were exposed to the soiled bedding for more than 24h on which estrous females had been placed （n=5）, and （3） mating group： voles were placed with an estrous female for more than 24h （n=5）. The results showed circulating serum E concentrations were significantly higher in the mating group than in the exposure group and the control group, and there were no significant difference between the exposure group and the control group. E-IRs and ERβ-IRs were detected in the following brain regions related to mating behavior： the arcuate nucleus （ARC）, bed nucleus of the stria terminalis （BST）, lateral septal nucleus （LS）, medial amygdaloid nucleus （ME）, medial preoptic area （MPO） and ventromedial hypothalamic nucleus （VMH）. The results showed that there were significantly more E-IRs in the six brain regions in the mating group than in the control group and the exposure group, and there were no significant difference between the exposure group and the control group except for LS. There was no significant difference in ERβ-IRs in the six brain regions among the three groups, and there were some lighter -stained ERβ-IRs in these brain regions. The results suggested that estrogen affect mating activity of male mandarin voles, but ERβ might not play an important role in mating behavior of male mandarin voles. Instead, it might be through other receptors.

Estrogen receptor alpha gene polymorphism associated with type 2 diabetes mellitus and the serum lipid concentration in Chinese women in Guangzhou

Background Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha （ERα） gene （also named ESR1）, including the XbaⅠ and PvuⅡ restriction enzyme polymorphisms of ESR1, which may be involved in disease pathogenesis. The aim of this study was to determine whether ER0t gene polymorphisms are associated with type 2 diabetes mellitus and serum lipid level. Methods Two hundred and ninety-nine patients with type 2 diabetes mellitus were compared with three hundred and forty-one health controls of Guangzhou in China, both were male and postmenopausal female residents at 51--70 years. ESR1 genotyping was performed using polymerase chain reaction （PCR） and PvulI and XbaI restriction fragment length polymorphism （PCR-RFLP） analysis. Results ESR1 allelic frequencies of P, p and X, x alleles were 0.408, 0.592; 0.360, 0.640 in the type 2 diabetes mellitus group and 0.318, 0.682; 0.328, 0.672 in the control group, respectively. In case-control study, there was significant difference in PvuⅡ, but not XbaⅠ, allele frequency between the type 2 diabetes mellitus and control groups （P=0.001 and P=0.122）. When the group was separated into men and women, the difference was significant in women （P〈0.001） but not in men （P=0.854） with the PvulI genotype, and the effect of PvulI variant on the development of type 2 diabetes mellitus was improved with aging. In addition, PvulI genotype was associated with blood glucose [fasting blood glucose （FBG）, postprandial blood glucose （PBG）] and serum lipid [total cholesterol （TC） and low density lipoprotein （LDL）-c] concentration in healthy women. Conclusions PvuII polymorphism of ESRI increases susceptibifity to type 2 diabetes mellitus in Chinese Guangzhou women. ESR1 variants may also impact serum lipid metabolism, which might provide a mechanism connecting ESR1 to type 2 diabetes.

Association of estrogen receptor alpha gene polymorphisms with bone mineral density： a meta-analysis

Background A number of studies have examined the association between estrogen receptor alpha （ESR-a） gene polymorphisms and bone mineral density （BMD）, but previous studies of ESR-a gene Xbal （rs9340799） and Pvull （rs2234693） polymorphisms have been hampered by small sample size, regional restrictions and inconclusive results. Thus a meta-analysis is needed to assess their pooled effects. Methods This study reviewed all published articles indexed in Pubmed using the keywords in the title or abstract. All data were extracted independently by two reviewers using a standard form, the studies were meta-analyzed and minor discrepancies were resolved by authors＇ discussion. Results Twenty seven eligible studies involving 8467 women and 2032 men were identified. The Xbal and Pvull polymorphisms were significantly associated with BMD of the lumbar spine. XX and PP homozygotes had a protective effect in comparison with carriers of the x and p alleles, the effects were more significant in premenopausal women or Western women. At the femoral neck, the results were different. XX served as a protective factor in postmenopausal women, Western women, Western postmenopausal women, and men, while PP was likely to serve as a risk factor in Eastern women, Eastern postmenopausal women, and men. Conclusions The Xbal polymorphism is correlated to BMD at diverse skeletal sites. PP had a protective role for the lumbar spine but might be a risk factor for the femoral neck.

Estrogen receptor a gene PvulI polymorphism and coronary artery disease： a meta-analysis of 21 studies

The association between the estrogen receptor a gene （ESR1） Pvull polymorphism （c.454-397T〉C） and coronary artery disease （CAD） is controversial. Thus, we conducted a meta-analysis to evaluate the relationship. Data were collected from 21 studies encompassing 9926 CAD patients and 16710 controls. Odds ratios （ORs） with 95% confidence intervals （CIs） were used to assess the relationship between Pvull polymorphism and CAD. The poly- morphism in control populations in all studies followed Hardy-Weinberg equilibrium. We found a significant association between ESR1 Pvull polymorphism and CAD risk in all subjects. When the data were stratified by region, a significant association between ESR1 Pvull polymorphism and CAD risk was observed in Asian populations but not in Western populations. The current study suggests that ESR1 Pvull polymorphism has an important role in CAD susceptibility.

Expression of estrogen receptor (ER) -α and -βtranscripts in the neonatal and adult rat cerebral cortex, cerebellum, and olfactory bulb

In the present study expression of estrogen receptor subtype -alpha (ERalpha) and -beta (ERbeta) in the cerebral cortex, cerebellum, and olfactory bulb was investigated and compared between neonatal (1 to approximately 3-days-old) and adult (250 to approximately 350 g) rats, using reverse transcription-polymerase chain reaction (RT-PCR). No ERalpha transcripts were detectable in the adult cerebellum and olfactory bulb, whereas very weak expression of ERalpha was present in the adult cerebral cortex. No significant difference in ERbeta transcripts was detectable between the neonatal and adult rats. While transcripts for both ER subtypes were co-expressed in these brain areas of neonatal rats, although ERalpha expression was significantly weaker than ERbeta. Even in the cerebral cortex known to contain both ER subtypes in adult rats, ERalpha transcripts in neonatal rats were much higher than in adult. These observations provide evidence for the existence of different expression patterns of ERalpha/ERbeta transcripts in these three brain areas between the neonatal and adult rats, suggesting that each ER subtype may play a distinct role in the regulation of differentiation, development, and functions of the brain by estrogen.

Placental expressions of estrogen receptor α,estrogen receptor β in intrahepatic cholestasis of pregnancy

To investigate the association of the expression of estrogen receptor ct, estrogen receptor 13 in placenta with intrahepatic cholestasis of pregnancy （ICP） susceptibility. Methods： In 14 cases of mild ICP, 14 cases of severe ICP and 14 cases of normal cases （control group） with corresponding age and gestation weeks, the expressions of ERa and ERD were detected by means of immunohistochemical method S-P. Results： The mean grey numbers of ERa in each group mentioned above were 151.684±3.76, 149.854±3.69, 153.184±3.18, without significant difference （P〉0.05） The mean grey numbers of ERβ in each group mentioned above were 146.51±3.81, 139.434±9.97, 149.87±4.17, with significant difference （P〉0.05）; the expression of ERI3 of severe ICP group was significantly higher than that of the mild ICP group and the control group （P〈0.05）. The expression of ERβ in every group was higher than that of ERa （P〈0.05）. Conclusion： ERβ maybe play an important part in the etiology and development of ICP

Association of CA Repeat Polymorphism in Estrogen Receptor β Gene with Postmenopausal Osteoporosis in Chinese

Postmenopausal osteoporosis （PMO） is considered a polygenic disease. The estrogen receptor β （ESR2） gene is a candidate mediating the genetic influence on bone mass and the risk of osteoporosis. The aim of this study is to investigate the association of a cytosine-adenine （CA） repeat polymorphism in the fifth intron of the ESR2 gene with PMO in Chinese Han population. The CA repeat polymorphism was genotyped in a case-control study, involving 78 femoral neck PMO patients vs. 122 controls and 108 lumbar spine （L2-4） PMO patients vs. 92 controls. The （CA）n〈22 and （CA）n≥22 alleles were designated short （S） and long （L）, respectively. ESR2 genotype was categorically defined as SS （2 S alleles）, SL （having the mixed S and L alleles）, and LL （2 L alleles）. At both the femoral neck and the L2-4 region, LL genotype and L allele frequencies of the PMO group were significantly higher than those of the control group （P〈0.01）. The subjects with the SL, the LL, and the combined SL and LL genotype had a significant increased risk of PMO when compared with those with the SS genotype （P〈0.05）. After adjustments for age, years since menopause, menopausal age, and body mass index, logistic regression analysis showed that the subjects with the combined SL and LL genotype had increased risk of PMO when compared with those with the SS genotype both at the femoral neck （adjusted OR 4.923, 95% CI 1.986-12.203 , P=0.001） and the L2-4 （adjusted OR 2.267, 95% CI 1.121-4.598, P=0.023）. This extensive association study has identified the ESR2 CA repeat polymorphism to be independently associated with PMO at the femoral neck and the L2-4 in Chinese Han population. The data also suggested that the presence of the L allele may dominantly increase the risk of PMO at the two regions.