Effect of baicalein on the expression of glutamate receptor related protein in PC12 cells damaged by Aβ 25-35 / 国际中医中药杂志

Objective:To study the effect of baicalein on the expression of glutamate receptor related protein in PC12 cells injured by Aβ 25-35. Methods:PC12 cells were divided into control group, model group, estradiol group and baicalein group with different concentrations. The survival condition of PC12 cells in each group were detected by thiazole blue (MTT). PC12 cells were divided into control group, model group, estradiol group and baicalein group. The control group and model group were cultured with DMEM medium, and the estradiol group was added with 1×10 -3 μmol/L estradiol DMEM medium, baicalein group was added with 1 μmol/L baicalein DMEM medium. After 2 hours of intervention, 20 μmol/L Aβ 25-35 was added to the model group, estradiol group and baicalein group with induced PC12 cell injury. After 22 hours of intervention, flow cytometry was used to detect the apoptosis of PC12 cells. The expression of estrogen receptor β (ER β), phosphorylated c-Jun N-terminal kinase (p-JNK/JNK) and ionic receptor N-methyl-D-aspartate receptor 1 (NMDAR1), glutamate receptor 2 (GluR2) and calcium/calmodulin dependent protein kinase Ⅱ (CaMK Ⅱ) were detected by Western blot. Results:Compared with model group, 1 μmol/L baicalein significantly increased the proliferation rate [(95.80±2.47)% vs. (64.34±3.84)%]. The apoptosis rate of PC12 cells[(7.83±0.67)% vs. (12.84±0.91)%] was significantly decreased in baicalein group ( P<0.01). The expression of NMDAR1 (0.582±0.012 vs. 0.352±0.012), GluR2(0.538±0.017 vs. 0.355±0.006), ER β (0.362±0.015 vs. 0.262±0.018) in baicalein group were significantly increased ( P<0.01), the expression of p-JNK/JNK (0.476±0.013 vs. 0.752±0.014) and CaMK Ⅱ(0.499±0.019 vs. 0.670±0.016) in baicalein group were significantly decreased ( P<0.01). Conclusions:Baicalein has a protective effect on PC12 cells injured by Aβ 25-35. Its mechanism may be related to the inhibition of p-JNK/JNK activity by activating ERβ and regulating the expression of glutamate receptor related protein.

Immunoexpression of estrogen receptor-? and progesterone receptor in prostate adenocarcinoma, does it inhibit neoplastic proliferation and invasion?

Context: The roles of estrogen and progesterone in human prostate carcinogenesis have been only recently recognized. Aims: This study was conducted to evaluate the expressions of esterone receptor-beta (ER-?), progesterone receptor (PR), and Ki-67 in benign and malignant lesions of the prostate. Settings and Design: The study was conducted at a tertiary care hospital. It was an analytical cross-sectional study. Materials and Methods: We selected a total of 39 cases including 26 cases of benign prostatic hyperplasia and 13 cases of adenocarcinoma prostate. The proportion of cases showing expression for ER-?, PR, and Ki-67 was noted for both groups. A difference in immunoexpression between benign and malignant cases was evaluated. Association between receptor expression and Gleason grade was evaluated for malignant cases. Statistical Analysis Used: To compare the difference in expressions of ER-?, PR, and Ki-67 Mann–Whitney U test was used. Association between ER-?, PR, and Ki-67 expression and Gleason grade was analyzed using the Chi-square test. Results: ER-? expression was seen in all benign and malignant cases, whereas the majority of the malignant cases (61.54%) were negative for progesterone expression. Epithelial expressions of ER-? and PR were significantly higher in benign as compared with malignant lesions. Malignant cases showed a significantly higher expression of Ki-67. However, we did not find any association between the expressions of these markers with Gleason grade. Conclusions: The expressions of ER-? and PR were significantly higher in the epithelium in benign cases as compared with malignant cases. Ki-67 expression was significantly higher in the malignant group as compared with the benign group.

Mechanism of traditional Chinese medicine balancing Yin-Yang by targeting ERα/ERβ and its application in treatment of menopausal syndrome / 中国中药杂志

The coordination and unification of Yin and Yang are the basis of normal human life activities. Along with the age growth and aging of the body, women will suffer from menopausal syndrome during menopause. In addition to the significant changes in the genital system, there are also pathological manifestations in estrogen target points including bone, nerve and cardiovascular systems, due to the imbalance of Yin and Yang. Besides the insufficiency of estrogen, the main cause of menopausal syndrome is the changes in the response of target organs to estrogen. In other words, the biological effects mediated by estrogen receptor(ER) alpha and beta subtypes in target cells are often different or even opposite; the changes of expression level and ratio of ERα and ERβ are also important causes for the abnormal estrogenic effects in target organs and the imbalance of Yin and Yang of the body. Therefore, on one hand, the therapeutic mechanism of drugs is ER-mediated estrogenic effect. On the other hand, the drugs have a regulatory effect on ER subtype expression in target cells and Yin-Yang state in target organs and even organisms, so as to cause further changes in the response of target cells to estrogen or estrogenic components, and exert its therapeutic effects. This paper reviews the pharmacological mechanism of gynecological traditional Chinese medicine in harmonizing Yin and Yang in estrogen-positive target cells and the clinical efficacy in the following aspects, including estrogen and its mechanism, the estrogenic effect of ER in traditional Chinese medicine and the mechanism of ER subtype in balancing Yin and Yang and mediating and regulating the main target tissues in menopausal syndrome treatment.

Effects of estrogen on bicarbonate secretion of duodenal mucosa / 中华消化杂志

Objective@#To study the effects of estrogen on bicarbonate secretion of duodenal mucosal, and to observe estrogen receptor (ER) subtypes of estrogen.@*Methods@#Sixteen 4-week-old male C57 mice were divided into control group and estrogen group, with eight mice in each group. The mice serum level of estrogen was detected by chemiluminescence. The expression of cystic fibrosis transmembrane conductance regulator (CFTR), solute carrier family 26 (SLC26) A3 and SLC26A6 in the duodenum tissues were determined by real-time polymerase chain reaction (RT-PCR). After SCBN cells treated with estrogen, ERα and ERβ blocking agent, and transfected with silenced ERα and ERβ for 24 and 48 hours, the expression levels of CFTR, SLC26A3 and SLC26A6 mRNA in cells were detected by RT-PCR. The effects of estrogen before and after silenced ERα and ERβ on bicarbonate secretion of SCBN cells were observed by high-speed ion imaging system. T test and rank sum test were used for statistical analysis.@*Results@#Compared with that of control group, the serum estrogen level of estrogen group was significantly high ((4 874±942) pmol/L vs. (657±187) pmol/L, t=-11.579, P<0.01). The expression levels of CFTR, SLC26A3 and SLC26A6 mRNAs in duodenum tissues of estrogen group were higher than those of control group (0.856±0.302 vs. 0.452±0.246, 2.910±1.680 vs. 1.120±0.540, 1.272±0.667 vs. 0.319±0.114), and the differences were statistically significant (t=-2.317, -2.483 and -3.721, all P<0.05). Compared with those treated with estrogen for 24 and 48 hours, the levels of CFTR mRNA and SLC26A6 mRNA were lower after the ERβ blocking agent were added into estrogen for 24 and 48 hours (CFTR mRNA: 0.171±0.059 vs. 0.522±0.260 and 0.111±0.014 vs. 0.578±0.297; SLC26A6 mRNA: 0.486±0.289 vs. 1.118±0.571 and 0.492±0.231 vs. 1.551±0.605), and the differences were statistically significant (tCFTR mRNA=2.974 and 2.655, tSLC26A6 mRNA=2.393 and 3.272; all P<0.05). Compared with those of silenced ERα group, the levels of CFTR mRNA, SLC26A3 mRNA and SLC26A6 mRNA were higher after ERα silenced and then added estrogen for 24 and 48 hours (24 h: 5.073±2.270 vs. 1.185±0.494, 1.796±1.168 vs. 0.468±0.108 and 3.085±1.357 vs. 0.706±0.347; 48 h: 5.025±1.998 vs. 1.185±0.494, 1.557±0.653 vs. 0.468±0.108 and 3.290±1.750 vs. 0.706±0.347), and the differences were statistically significant (t24 h=-4.122, -2.773 and -4.162, t48 h=-4.604, -4.034 and -3.250; all P<0.05). Compared with that of silenced ERα group, the bicarbonate secretion increased after ERα silenced and then added estrogen for 24 and 48 hours (0.72±0.17 and 1.15±0.25 vs. 0.35±0.17), and pH also elevated, and the differences were statistically significant (t=-6.516 and -12.387, both P<0.01).@*Conclusion@#Estrogen mainly up-regulates the expression of bicarbonate transporter protein in duodenal mucosal epithelial cells through ERβ, and promotes the bicarbonate secretion of duodenal mucosa.

Effects of estrogen on bicarbonate secretion of duodenal mucosa / 中华消化杂志

Objective To study the effects of estrogen on bicarbonate secretion of duodenal mucosal , and to observe estrogen receptor (ER) subtypes of estrogen.Methods Sixteen 4-week-old male C57 mice were divided into control group and estrogen group , with eight mice in each group .The mice serum level of estrogen was detected by chemiluminescence .The expression of cystic fibrosis transmembrane conductance regulator (CFTR), solute carrier family 26 (SLC26) A3 and SLC26A6 in the duodenum tissues were determined by real-time polymerase chain reaction ( RT-PCR).After SCBN cells treated with estrogen , ERαand ERβblocking agent, and transfected with silenced ER αand ERβfor 24 and 48 hours, the expression levels of CFTR, SLC26A3 and SLC26A6 mRNA in cells were detected by RT-PCR.The effects of estrogen before and after silenced ER αand ERβon bicarbonate secretion of SCBN cells were observed by high-speed ion imaging system.T test and rank sum test were used for statistical analysis .Results Compared with that of control group , the serum estrogen level of estrogen group was significantly high ((4 874 ±942) pmol/L vs.(657 ±187) pmol/L,t＝-11.579, P?0.01). The expression levels of CFTR, SLC26A3 and SLC26A6 mRNAs in duodenum tissues of estrogen group were higher than those of control group (0.856 ±0.302 vs.0.452 ±0.246, 2.910 ±1.680 vs.1.120 ±0.540, 1.272 ± 0.667 vs.0.319 ±0.114), and the differences were statistically significant ( t ＝-2.317,-2.483 and-3.721, all P?0.05).Compared with those treated with estrogen for 24 and 48 hours, the levels of CFTR mRNA and SLC26A6 mRNA were lower after the ERβblocking agent were added into estrogen for 24 and 48 hours (CFTR mRNA: 0.171 ±0.059 vs.0.522 ±0.260 and 0.111 ±0.014 vs.0.578 ±0.297; SLC26A6 mRNA:0.486 ±0.289 vs.1.118 ±0.571 and 0.492 ±0.231 vs.1.551 ±0.605), and the differences were statistically significant (tCFTR mRNA＝2.974 and 2.655, tSLC26A6 mRNA＝2.393 and 3.272; all P?0.05).Compared with those of silenced ERαgroup, the levels of CFTR mRNA, SLC26A3 mRNA and SLC26A6 mRNA were higher after ERα silenced and then added estrogen for 24 and 48 hours (24 h: 5.073 ±2.270 vs.1.185 ±0.494, 1.796 ±1.168 vs.0.468 ±0.108 and 3.085 ±1.357 vs.0.706 ±0.347; 48 h: 5.025 ±1.998 vs.1.185 ±0.494, 1.557 ± 0.653 vs.0.468 ±0.108 and 3.290 ±1.750 vs.0.706 ±0.347), and the differences were statistically significant (t24 h＝-4.122,-2.773 and -4.162, t48 h ＝-4.604,-4.034 and -3.250; all P?0.05).Compared with that of silenced ERαgroup, the bicarbonate secretion increased after ER αsilenced and then added estrogen for 24 and 48 hours (0.72 ±0.17 and 1.15 ±0.25 vs.0.35 ±0.17), and pH also elevated, and the differences were statistically significant (t＝-6.516 and -12.387, both P?0.01).Conclusion Estrogen mainly up-regulates the expression of bicarbonate transporter protein in duodenal mucosal epithelial cells through ER β, and promotes the bicarbonate secretion of duodenal mucosa .

Effects of metformin on the expression of estrogen synthetase and ER mRNA in uterine leiomyoma tissues / 中华妇产科杂志

Objective To elucidate whether metformin could regulate the mRNA expression level of estrogen synthetase and ER in human uterine leiomyoma tissues. Methods (1) Seventeen pairs of uterine leiomyoma tissues and adjacent myometrium (>2 cm) were collected from patients underwent hysterectomy in Peking University First Hospital between December 2016 and January 2017. Real-time PCR was used to measure the mRNA expression level of estrogen synthetase [including cytochrome P450 cholesterol side chain cleavage enzyme (P450scc), cytochrome P450 17 α-hydroxylase (P450c17), 3-beta-hydroxysteroid dehydrogenase type 2 (3β-HSD-2), 17-beta-hydroxysteroid dehydrogenase type 1 (17β-HSD-1) and aromatase cytochrome P450 (P450arom)] and ER (including ERα and ERβ) in the uterine leiomyoma tissues and adjacent myometrium. (2) Uterine leiomyoma cells derived from uterine leiomyoma tissues were identified by immunocytochemistry method and cultured to the third generation. The treatment groups were cultured with different concentrations of metformin (10, 50 and 100 μmol/L) for 48 hours, and the control group was cultured with deionized water for 48 hours. The mRNA expression level of estrogen synthetase and estrogen receptor subtypes were measured by real-time PCR. Results (1) P450scc, P450c17, 3β-HSD-2, 17β-HSD-1, P450arom mRNA median expression levels were 112, 4, 13, 42 and 194 in the uterine leiomyoma tissues, and were respectively 114, 5, 11, 32 and 6 in the myometrium. Compared to those of the myometrium, 3β-HSD-2 and P450arom mRNA expression levels in the uterine leiomyoma tissue were significantly higher (P<0.05), while there were no significant change of mRNA expression levels among P450scc, P450c17 and 17β-HSD-1 (P>0.05). ERα and ERβ mRNA median expression levels were 208 and 116 in the uterine leiomyoma tissues, and were 24 and 95 in the myometrium. Compared to that of the myometrium, ERα mRNA level in the uterine leiomyoma tissue was significantly higher (P=0.001), while there were no significant change of ERβ mRNA level (P=0.193). (2) After cultured with different concentrations of metformin (10, 50 and 100 μmol/L), the P450arom mRNA levels in the uterine leiomyoma tissues were 9 ± 4, 8 ± 5 and 8 ± 3 respectively in the treatment groups and was 16 ± 5 in the control group. Compared to that of the control group, P450arom mRNA expression levels in the treatment groups were significantly declined (P<0.05). There were no significant different change of mRNA expression levels among 3β-HSD-2, ERα and ERβ between the treatment groups and the control group (P>0.05). Conclusions Metformin could down-regulate the mRNA expression level of aromatase in the uterine leiomyoma cells. These results indicate that metformin may inhibit the local estrogen synthesis and therefore suppress the development of uterine leiomyoma.

Evaluation of estrogen receptor expression in low-grade and high-grade astrocytomas

SUMMARY OBJECTIVE: This study aims to compare estrogen receptor expression between low and high-grade astrocytomas. METHOD: A study using paraffin blocks of glial tumors from the Anatomy Pathology archives of São Marcos Hospital was carried out and began after approval by the Review Board of the Federal University of Piaui. Specimens were histochemically marked with an anti-ER alpha antibody. Brown-stained nuclei were considered positive, regardless of reaction intensity. Data were statistically analyzed using the Mann-Whitney test and Spearman's correlation. Statistical significance was established at p<0.05. RESULTS: The mean percentage of nuclei stained with anti-ER alpha in low-and high-grade astrocytomas was 0.04 and zero, respectively, while Spearman's correlation showed a strong negative association between low and high-grade tumors (p<0.001) and (r= −0.67), respectively. CONCLUSION: In the current study, estrogen receptor expression was positive only in low-grade astrocytomas and nil in high-grade astrocytomas, showing that ER expression declines with the grade of tumor malignancy.

RESUMO OBJETIVO: O objetivo deste estudo é comparar a expressão do receptor de estrogênio entre astrocitomas de baixo e alto grau. MÉTODO: Foi realizado um estudo usando blocos de parafina de tumores gliais dos arquivos de Anatomia Patológica do Hospital São Marcos e iniciado após aprovação pelo Comitê de Ética da Universidade Federal do Piauí. Os espécimes foram marcados histoquimicamente com anticorpo anti-ER alpha. Os núcleos corados em marrom foram considerados positivos, independentemente da intensidade da reação. Os dados foram analisados estatisticamente utilizando o teste de Mann-Whitney e a correlação de Spearman. A significância estatística foi estabelecida em p<0,05. RESULTADOS: A porcentagem média de núcleos corados com anti-ER alfa em astrocitomas de baixo e alto grau foi de 0,04 e zero, respectivamente, enquanto a correlação de Spearman mostrou uma forte correlação negativa entre tumores de baixa e alta qualidade (p<0,001) e (r=-0,67), respectivamente. CONCLUSÕES: No presente estudo, a expressão do receptor de estrogênio foi positiva apenas em astrocitomas de baixo grau e nula em astrocitomas de alto grau, mostrando que a expressão de ER diminui com o grau de malignidade tumoral.

Protctive effects of Angelicin on UVB-induced HDF cells damage and its mechanism / 国际中医中药杂志

Objective To study the effect of Angelicin on proliferation activity and anti-aging related protein expression of human HDF cells and its mechanism. Methods According to the random number table method, the cells were divided into blank group, model group, estradiol group, Angelicin group, estrogen receptor antagonist+estradiol group, estrogen receptor antagonist+Angelicin group, and P38 pathway blocker group. Different groups were given the according drugs respectively for 24 h. Except the blank group, all the groups of cells were given UVB irradiation with a dose of 150 mJ/cm2. The MTT assay was used to detect cell proliferation rate. The Western blot was used to detect the expression levels of COLⅠ, MMP-1, ERβ, P38 and p-P38 in cells, and the MMP-1 mRNA expression was detected by real-time fluorescent quantitative PCR.Results Compared with the model group, the proliferation rate of HDF cells significantly increased in Angelicin(10,1,0.1 and 0.01 μmol/L groups)(P<0.01);The protein expression of COLⅠ (0.326 ± 0.006 vs. 0.176 ± 0.007),ERβ(0.281 ± 0.011 vs.0.143 ± 0.006)significantly increased(P<0.01),and the expression of MMP-1(0.256 ± 0.006 vs.0.395 ± 0.006)and p-P38(0.224 ± 0.003 vs.0.318 ± 0.005)significantly decreased (P<0.01) in Angelicin 10 μmol/L group. Compared with 10 μmol/L Angelicin group, the protein expression of estrogen receptor antagonist+Angelicin group ERβ(0.120 ± 0.007 vs.0.281 ± 0.011)significantly decreased and MMP-1mRNA(1.377 ± 0.012 vs.1.024 ± 0.010)significantly increased(P<0.01).Conclusions The Angelicin may degrade MMP-1 through the ER-P38 MAPK signaling pathway,and then promote collagen synthesis, to achieve the purpose of prevention and treatment of photoaging.

Estrogen-induced and Expression Repressed via Estrogen Receptor Beta in MC3T3-E1 Cells / 中华医学杂志(英文版)

<p><b>Background</b>Estrogen, as an important hormone in human physiological process, is closely related to bone metabolism. The aim of this study was to investigate the mechanism of estrogen on osteoblasts metabolism in MC3T3-E1 cells.</p><p><b>Methods</b>We treated the MC3T3-E1 cells with different concentrations of β-estradiol (0.01, 0.1, 1, and 10 nmol/L), observed the morphological changes of the cells, and detected the cell's proliferation and apoptosis of MC3T3-E1 cells. Two transcriptome libraries were constructed and sequenced. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to confirm the differentially expressed genes (DEGs), and then treated the MC3T3-E1 cells with estrogen receptor (ER) inhibitors α and β, respectively, and then examined the expression of Tgfbr1 and Bmpr1a genes. The promoter of Tgfbr1 and Bmpr1a gene was analyzed, and the ER response elements were identified. Finally, ChIP was used to verify the binding of ER to Tgfbr1 and Bmpr1a promoter.</p><p><b>Results</b>In the high-concentration β-estradiol treatment group (1 nmol/L and 10 nmol/L), there was no significant difference in the morphology of the cells under the microscope, 1 nmol/L and 10 nmol/L treated group appeared statistically significant difference in cell apoptosis and proliferation (P < 0.05 and P < 0.01, respectively). We found 460 DEGs compared with the control group. Among the DEGs, there were 66 upregulated genes and 394 downregulated genes. Gene ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that many bone metabolism-related biological processes and cell signaling pathways were disordered. The qRT-PCR verification showed that the expressions of Tgfbr1- and Bmpr1a-related genes in bone metabolism pathway in the 10 nmol/L treatment group were significantly decreased (P < 0.05). ER β was involved in the inhibitory effect of Tgfbr1 and Bmpr1a genes. The bioinformatics of the promoter found that there were three ER response elements in the promoter of Tgfbr1, and there were two ER response elements in Bmpr1a promoter regions. ChIP experiments showed that estrogen could enhance the binding of ERs to Tgfbr1 and Bmpr1a genes.</p><p><b>Conclusions</b>Estrogen can promote the apoptosis and proliferation of osteoblasts simultaneously, and the mechanism may be the joint action of transforming growth factor-beta, Wnt, mitogen-activated protein kinase, and nuclear factor-kappaB bone metabolism-related signaling pathway. Estrogen inhibits the expression of Tgfbr1 and Bmpr1a genes through ER β and affects the metabolism of MC3T3-E1 osteoblasts.</p>

Expression and significance of estrogen receptor- β and tyrosine kinase receptor- B in endometriosis associated ovarian cancer / 中国医师进修杂志

Malignant transformation of ovarian endometriosis is known as endometriosis associated ovarian cancer (EAOC). However, the carcinogenic pathways by which EAOC develops remained poorly understood, and numerous studies found the risk factors of malignant transformation. Recent studies have provided evidence that estrogen receptor-β(ER-β) can influence the proliferation, motility and apoptosis of ovarian cancer cells. The signal pathway of tyrosine kinase receptor-B (TrkB)/brain-derived neurotrophic factor (BDNF) has a direct relation with the endometriosis, and its anti-anoikis plays a prerequisite role in proliferation of cancer. In the nervous system, estradiol and estrogen receptor can be combined through a variety of ways to promote BDNF/TrkB high expression and activity enhancement. Therefore,the relationship between high-risk factors of malignant transformation and ER-β expression and ER-β and TrkB/BDNF signal pathways need to be explored in EAOC.

Effects of acacetin on T47D cell proliferation / 中国药理学通报

Aim To investigate the effect of acacetin on cell proliferation and the influence of acacetin on estrogen receptor expression in vitro.Methods The proliferation rates and the cell cycle changes of acace-tin-treated T47D cells were measured by sulforhodam-ine B(SRB)assay and flow cytometry,respectively. Moreover,the mRNA expressions of estrogen receptor-alpha(ERα),estrogen receptor-beta(ERβ)and pro-liferating antigen(Ki67)were determined by quantita-tive real time PCR (qPCR).Western blot was em-ployed to detect the ERαand ERβprotein expression. Results Acacetin significantly promoted the prolifera-tion and increased the amount of cells arrested in S and G2 /M phase under the concentration of 0.001 ~1 0μmol·L -1 .Ki67 mRNA level and the ERαprotein level in T47D cells were remarkably upregulated after acacetin treatment.To clarify which estrogen receptors played a role in acacetin induced the proliferation of T47D cells,the combination treatment of acacetin and ERαinhibitor (MPP)/ERβ inhibitor (PHTPP) was employed.We found that MPP could reverse the cell proliferation,the cell arrested in S and G2 /M phase and the increased Ki67 mRNA level induced by acace-tin.PHTPP also alleviated the T47D cell proliferation induced by acacetin,whereas no significant changes were found in cell cycle and Ki67 mRNA level.Con-clusion Acacetin stimulates the cell proliferation of T47D cells in the concentration from 0.001 μmol · L -1 to 1 0 μmol·L -1 ,which is mainly mediated by ERα.

Expression of estrogen and progesterone receptors in astrocytomas: a literature review

Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression.

Analysis of polymorphisms in Interleukin 10, NOS2A, and ESR2 genes in chronic and aggressive periodontitis

Abstract The objective of this study was to investigate the association between single nucleotide polymorphisms (SNPs) in the IL10, NOS2A, and ESR2 genes and chronic periodontitis (CP) and aggressive periodontitis (AgP). Three groups of patients underwent periodontal and radiographic evaluations: CP (n = 61), AgP (n = 50), and periodontally healthy (control group=61). Genomic DNA was extracted from oral epithelial cells and used for genotyping by real-time polymerase chain reaction using TaqMan® probes. The investigated SNPs were: -1087G > A, -819C > T and -592C > A in the IL10; +2087G > A in the NOS2A, and +1730G > A in the ESR2 gene. Differences in genotype and allele frequencies of each polymorphism and some individual characteristics were analyzed using the chi-square test and multivariate logistic regression analysis. Analysis of SNPs and haplotypes in the IL10 and SNP in the ESR2 gene did not present any significant association with AgP or CP. The +2087G allele of the NOS2A gene tended to be significantly associated with periodontal disease. Patients carrying the genotype +2087GG in the NOS2A gene were genetically protected against the development of CP (p = 0.05; OR = 0.44; 95%CI = 0.20-0.95). This result showed greater significance when patients with AgP and CP were combined (total PD) (p = 0.03; OR = 0.46; 95%CI = 0.23-0.92). In conclusion, the studied Brazilian population had a significantly higher frequency of the GG genotype for the +2087 SNP in the NOS2A gene in individuals without periodontitis, although statistical significance was not maintained after multiple logistic regression.

The relationship between the incidence of melasma and estrogen gene polymorphism / 天津医药

Objective To investigate the relationship between estrogen gene polymorphism and the incidence of melasma. Methods A total of 56 patients with chloasma blepharoplasty surgery (case group) and 39 healthy women with eyelid blepharoplasty (control group) were included in this study. The expression of estrogen receptor (ER) was detected by immunohistochemistry. The ERαgene PvuⅡand XbaⅠrestriction site polymorphisms and RsaⅠand AluⅠrestriction site polymorphism of ERβ gene were detected by PCR-restriction fragment length polymorphism (PCR-RFLP) analysis in two groups. The relationship between the incidence of ER and the score of melasma was analysed. Results Results of immunohistochemistry showed that there were positive expressions of ERα and ERβ in dermal fibroblasts and endothelial cells of case group, while there was weak expressions of ERα and ERβ in control group. Spearman correlation analysis showed that there was a positive correlation between ERα, ERβ and melasma score (rs=0.462 and 0.512, P<0.05). There was a significant difference in distribution of ERαgene XbaⅠgenotype between two groups (P<0.05). With xx genotype reference, the value of OR exposed to X allele (Xx+XX) was 2.23 (95%CI:1.41-3.89, P<0.05). There was a significant difference in ERβ gene AluⅠ genotypes between two groups (P<0.05 ). With aa genotype reference, the value of OR exposed to the A allele (AA+Aa) was 1.58 (95% CI: 1.21-4.29, P<0.05). There was a significant difference in RsaⅠgenotype distribution between two groups (P<0.05). With reference rr genotype, the value of OR exposed to R allele (RR+Rr) was 2.37 (95%CI:1.19-6.33, P<0.05). Conclusion The incidence of melasma is related with XbaⅠERαgenotype, ERβ gene AluⅠ, RsaⅠ genotype polymorphisms. The gene mutations increase the risk of incidence of melasma. Persons with Xx, Aa and RR genotypes are susceptible to melasma.

Cancer therapy using natural ligands that target estrogen receptor beta / 中国天然药物

Estrogen receptor beta (ERβ) is one of the two key receptors (ERα, ERβ) that facilitate biological actions of 17β-estradiol (E2). ERβ is widely expressed in many tissues, and its expression is reduced or lost during progression of many tumors. ERβ facilitates estrogen signaling by both genomic (classical and non-classical) and extra-nuclear signaling. Emerging evidence suggests that ERβ functions as a tissue-specific tumor suppressor with anti-proliferative actions. Recent studies have identified a number of naturally available selective ERβ agonists. Targeting ERβ using its naturally available ligands is an attractive approach for treating and preventing cancers. This review presents the beneficial actions of ERβ signaling and clinical utility of several natural ERβ ligands as potential cancer therapy.

The association study on the polymorphisms of estrogen receptor α and β genes and systemic lupus erythematosus in Chinese Han cohort of Yunnan Province / 中华风湿病学杂志

Objective To analyze the association of polymorphisms of estrogen receptor (ER) α and β genes with systemic lupus erythematosus (SLE) in Chinese Han cohort of Yunnan Province.Methods XbaⅠ and Pvu Ⅱ of ERα gene,Rsa Ⅰ and Alu Ⅰ of ERβ gene were typed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 697 SLE patients and 638 healthy controls.The frequency distribution of the alleles and genotypes were analyzed by Hardy-Weinberg equilibrium test and x2 test.Results ① For ERα gene,the frequency of minor allele of Pvu Ⅱ C in SLE patients was significantly higher than healthy controls (x2=15.427,P=0.001);the allele frequencies of XbaⅠ in SLE patients showed no significant difference compared with healthy controls (P＞0.05).The frequency of minor genotype of Pvu Ⅱ CC in SLE patients was significantly higher than healthy controls (x2=17.371,P=0.011).The frequency of two locus haplotype AATT in SLE patients was significantly lower than healthy controls (x2=6.333,P=0.012);the frequency of the two locus haplotype AACC in SLE patients was significantly higher than healthy controls (x2=7.771,P=0.038).② For ERβ gene,the frequency of minor allele RsaⅠ A in SLE patients was significantly lower than healthy controls (x2=12.595,P=0.013);the allele frequencies of Alu Ⅰ in SLE patients showed no significant differences compared with the healthy controls (P＞0.05).The frequency of minor genotype AA of Rsa Ⅰ in SLE patients was significantly higher than healthy controls (x2=41.456,P=0.000).The frequency of two locus haplotype AAGG in SLE patients was significantly higher than healthy controls (x2=37.063,P=0.000).The frequency of the two locus haplotype AAGA in SLE patients was significantly lower than healthy controls(x2=21.086,P=0.001).③ Pvu Ⅱ C was related with splenomegaly (x2=4.212,P＜0.05).The two locus haplotype AGTC of Xba Ⅰ and Pvu Ⅱ was related with edema (x2=7.898,P＜0.05).Conclusion There are associations between the polymorphisms of ERα and ERβ genes and SLE.The ERα and ERβ genes may be the susceptible genes for SLE in Yunnan Han Chinese Cohort.

Efeitos da participação de esteroides-like provenientes da poluição atmosférica no epitélio das vias aéreas em camundongos machos e fêmeas / Effects of the participation of steroid-like compounds from air pollution in the airway epithelium of male and female mice

O epitélio nasal é a primeira porção do sistema respiratório a entrar em contato com o ambiente externo. Partículas da poluição do ar, principalmente os compostos orgânicos absorvidos, podem atuar como liberadores endócrinos. O receptor aril hidrocarboneto (AhR) é um importante competidor dos receptores de estrógeno-beta (ERbeta) que regulam a transcrição do gene para enzimas de metabolização xenobióticas (enzimas do citocromo P450). O objetivo deste estudo é identificar e quantificar ERbeta, AhR, CYP1A1, CYP1A2, CYP1B1 e o perfil de muco no epitélio nasal de camundongos machos e fêmeas em diferentes fases do ciclo estral. Camundongos BALB/c machos (n=32) e fêmeas (n=84) foram expostos ao ar ambiente e ao MP2,5 concentrado a 600 ug.m-³ em um concentrador de partículas ambientais (CPAs). As fêmeas foram divididas de acordo com as fases do ciclo estral: proestro, estro e diestro. O epitélio nasal foi avaliado por RT-PCR e imuno-histoquímica para análise de expressão de ERbeta (proteína), Erbeta-1 e Erbeta-2 (gene), AhR (proteína e gene) e Cyp1a1, Cyp1a2 and Cyp1b1 (gene). A quantificação de muco neutro - Periodic Acid Schiff's (PAS+) e ácido - Alcian Blue (AB+) foi avaliada por morfometria. As exposições foram realizadas durante 5 dias/semana, por 45 ± 55 dias. A expressão de Erbeta-2 RNAm apresentou diferenças em resposta à exposição ao CPAs (p=0,016), bem como uma diminuição em fêmeas, quando comparadas aos camundongos machos (p=0,036). A expressão de Cyp1b1 RNAm foi significantemente menor no grupo exposto ao CPAs, em relação ao grupo exposto ao ar ambiente nas fêmeas em diestro (p=0,036). A expressão de Erbeta foi aumentada no epitélio nasal de fêmeas em estro expostas ao CPAs (p=0,005) e a expressão de AhR foi menor em fêmeas em proestro expostas ao CPAs (p=0,048). A exposição ao CPAs levou ao aumento do conteúdo de muco ácido em camundongos machos (p=0,048), o qual diminuiu em fêmeas (p=0,040), quando comparados ao grupo ar ambiente. Este estudo mostrou...

The nasal epithelium is the first portion of the respiratory system to reach contact with the external environment. Air pollution particles, mainly the organic compounds absorbed into them, may act as endocrine releasers. The aryl hydrocarbon (AhR) receptor is an important competitor of estrogenic receptors-beta (ERbeta) that regulate transcription of gene coding for xenobiotic-metabolizing enzymes (cytochrome P450 enzymes). The aim of this study is to identify and quantify in the nasal epithelium of male and female mice in different estrous cycle phases related with ERbeta, AhR, CYP1A1, 1A2, 1B1 and the mucus profile. Male (n=32) and female (n=84) BALB/c mice were exposed to ambient air and PM2.5 concentrated at 600 ug.m-³ in an ambient particle concentrator with a particulate matter diameter of 2.5 um (PM2.5). Females were subdivided in three estrous cycles: proestrus, estrus and diestrus. Nasal epithelium was evaluated through RT-PCR and immunohistochemistry for the expression of ERbeta (protein), Erbeta-1 and Erbeta-2 (gene expression), AhR (protein and gene expression) and Cyp1a1, Cyp1a2 and Cyp1b1 (gene expression). Morphometry was applied for evaluation of mucus profile: acid - Alcian Blue (AB+) and neutral - Periodic Acid Schiff's (PAS+). Exposure happened for 5 days/week, for 45 ± 55 days. There were differences in Erbeta-2 mRNA in response to exposition to CPAs (p=0.016), and a significant decrease in female compared male mice (p=0.036). Cyp1b1 mRNA was significantly smaller in the CPAs-exposed group compared with the ambient air group in diestrus female mice (p=0.036). The ERbeta expression increased in the nasal epithelium of CPAs-exposed females in the estrus cycle (p=0.005), and the AhR expression decreased in the proestrus cycle of CPAs-exposed females (p=0.048). The exposure to the CPAs led to an increase in the acidic content of mucus in male mice (p=0.048), and decreased in female mice (p=0.040), compared to the ambient air group. This...

Evaluation of the estrogenic effects of Rehmannia glutinosa Libosch / 中国药学杂志

OBJECTIVE: To screen the estrogenic effects of fresh Radix Rehmanniae, dried Radix Rehmanniae, Radix Rehmanniae Praeparata and the leaves of Rehmannia glutinosa Libosch. METHODS: Mouse uterine weight test and MCF-7 cell proliferation assay were used to evaluate the estrogenic effects of the four kinds of Chinese traditional herbs. ICI182, 780 antagonnist assay and reporter gene assay were adopted to explore the mechanism of action of fresh and dried Radix Rehmanniae. In reporter gene assay, HEK293 cells were cotranfected with pERE-TAL-luc, pβgal-Control, pCXN2-hERα or pCXN2-hERβ, and the expression of reportr gene luc was controlled by ERE. RESULTS: Mouse uterine weight test showed that compared with the control group, fresh and dried Radix Rehmanniae could increase the uterus index of premature female mice, and both of them could promote the proliferation of MCF-7 cells. Co-incubation of MCF-7 cells with estrogen receptor blocker ICI182, 780 abolished the inductive effect of the proliferation. The reporter gene controlled by ERE technology showed that when mediated by ERβ, the normalized luciferase activity of the two groups were significantly higher than the activity of the control group. CONCLUSION: Fresh and dried Radix Rehmanniae have estrogenic activities which are mainly mediated by ERβ. Fresh Radix Rehmanniae has higher estrogenic activity than dried Radix Rehmanniae. Radix Rehmanniae Praeparata does not have estrogenic activity. The estrogenic activity may change during the processing process of Rehmannia glutinosa Libosch.

Effects of MSH2 gene re-expression on estrogen induced-apoptosis of colon cancer cells LOVO / 中华消化杂志

Objective To observe the effects of MSH2 gene re expression on estrogen-induced apoptosis of colon cancer cells LOVO,and to explore its mechanisms.Methods According to different plasmid and whether with estradiol intervention,colon cancer LOVO cells were divided into empty plasmid with ethanol group,empty plasmid with estradiol group,MSH2 with ethanol group,MSH2 with estradiol group,estrogen receptor (ER) β with ethanol group,ERβ with estradiol group,ERβ with MSH2 and ethanol group and ERβ with MSH2 and estradiol group,and received corresponding treatment.The expression of MSH2,ERβ protein and apoptosis related caspase 3 protein were detected by Western blotting.Cell viability was measured by cell counting kit-8.Cell DNA fragments of each group were isolated with apoptosis DNA fragments isolation kit.And the DNA ladder was observed.The rate of apoptosis was detected by flow cytometer.Single factor variance analysis was performed for comparison among multiple groups,and t test was used for comparison between the two groups.Results After transfection,the expression of the MSH2 and ERβ at protein level in LOVO cells significantly increased and neither of their expression was effected by estradiol.The expression levels of caspase 3 cleavaged active fragments of ERβ with estradiol group and ERβ with MSH2 and ethanol group were higher than other groups,and there was no significant difference between these two groups.The LOVO cell viability of empty plasmid with ethanol group,empty plasmid with estradiol group,MSH2 with ethanol group,MSH2 with estradiol group,ERβ with ethanol group,ERβ with estradiol group,ERβ with MSH2 and ethanol group and ERβ with MSH2 and estradiol group was 1.72 ±0.25,1.74 ± 0.31,1.77 ± 0.35,1.74±0.33,1.70±0.34,1.02±0.48,1.71±0.31 and 1.07±0.18,respectively,and the differences between the groups were statistically significant (F=3.791,P＜0.05).Among them,the LOVO cell viability of ERβ with estradiol group was lower than that of ERβ with ethanol group,accordingly,that of ERβ with MSH2 and estradiol group was lower than that of ERβ with MSH2 and ethanol group,that of ERβ with estradiol group was lower than that of empty plasmid with estradiol group,that of ERβ with MSH2 and estradiol group was lower than that of MSH2 with estradiol group,and the differences were statistically significant (t=3.158,3.075,3.648,3.253,all P＜0.05).DNA ladder formed from DNA fragments of apoptosis cells was seen in ERβ with estradiol group and ERβ with MSH2 and estradiol group.The apoptosis rate of empty plasmid with ethanol group,empty plasmid with estradiol group,MSH2 with ethanol group,MSH2 with estradiol group,ERβ with ethanol group,ERβ with estradiol group,ERβ with MSH2 and ethanol group and ERβ with MSH2 and estradiol group was 7.86±0.19,7.87±0.39,8.39±1.02,9.05±1.54,7.54±0.99,19.77±2.35,7.76±1.32 and 19.30±1.75,respectively,and the differences between groups were statistically significant (F=45.436,P＜0.05).Among them,the apoptosis rate of ERβ with ethanol group was lower than that of ERβ with estradiol group,that of ERβ with MSH2 and ethanol group was lower than that of ERβ with MSH2 and estradiol group,that of empty plasmid with estradiol group was lower than that of ERβ with estradiol group,that of ERβ with MSH2 and estradiol group was lower than that of MSH2 with estradiol group,and the differences were statistically significant (t =8.260,9.133,8.596,7.617,all P＜ 0.05).Conclusions Estrogen may promote colon cancer cell apoptosis through ERβ pathway.The process of apoptosis maybe related with caspase protein,MSH2 may not be involved in the regulation of this signal pathway.

Prognostic Value of Sex-Hormone Receptor Expression in Non-Muscle-Invasive Bladder Cancer

PURPOSE: We investigated sex-hormone receptor expression as predicting factor of recurrence and progression in patients with non-muscle invasive bladder cancer. MATERIALS AND METHODS: We retrospectively evaluated tumor specimens from patients treated for transitional cell carcinoma of the bladder at our institution between January 2006 and January 2011. Performing immunohistochemistry using a monoclonal androgen receptor antibody and monoclonal estrogen receptor-beta antibody on paraffin-embedded tissue sections, we assessed the relationship of immunohistochemistry results and prognostic factors such as recurrence and progression. RESULTS: A total of 169 patients with bladder cancer were evaluated in this study. Sixty-threepatients had expressed androgen receptors and 52 patients had estrogen receptor beta. On univariable analysis, androgen receptor expression was significant lower in recurrence rates (p=0.001), and estrogen receptor beta expression was significant higher in progression rates (p=0.004). On multivariable analysis, significant association was found between androgen receptor expression and lower recurrence rates (hazard ratio=0.500; 95% confidence interval, 0.294 to 0.852; p=0.011), but estrogen receptor beta expression was not significantly associated with progression rates. CONCLUSION: We concluded that the possibility of recurrence was low when the androgen receptor was expressed in the bladder cancer specimen and it could be the predicting factor of the stage, number of tumors, carcinoma in situ lesion and recurrence.