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estrogen receptor gene polymorphism in a Chinese population with multiple sclerosis

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Neural Regeneration Research 2011年第19期6卷 1488-1492页

作者： Qingli Sun Ruping Xie Yu Fu Xiaogang Li Dongsheng Fan Department of Neurology Peking University Third Hospital Beijing 100191 China

This study sought to elucidate the role of the Pvull and Xbal polymorphisms of the estrogen receptor gene in 74 Chinese patients with multiple sclerosis, and 95 ethnicity-matched controls, using polymerase chain reaction-restriction fragment-length polymorphism analysis. The results revealed that the P allele of Pvull was significantly more prevalent in multiple sclerosis patients compared with controls （P = 0.019）. While distribution frequencies were significantly increased in female multiple sclerosis patients compared with female controls （P = 0.044）, no significant difference was observed between male patients and controls （P〉 0.05）. Frequencies of Ppxx genotypes were significantly higher in multiple sclerosis patients compared with controls （24.3% vs 12.8%, P = 0.025）. Genotypes and alleles of the estrogen receptor were not associated with age, number of attacks or expanded disability status scale scores of patients with multiple sclerosis. These findings indicate that the Pvull but not the Xbal polymorphism in the estrogen receptor gene is associated with susceptibility to multiple sclerosis in the Chinese population. In addition, women with P allele appear to be particularly susceptible to multiple sclerosis.

关键词： estrogen receptor gene polymorphism multiple sclerosis case-control study

estrogen receptor-NEGATIVE BREAST CANCER CELLS TRANSFECTED WITH estrogen receptor EXHIBIT DECREASED TUMOUR PROGRESSION AND SENSITIVITY TO GROWTH INHIBITION BY estrogen

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Chinese Medical Sciences Journal 1997年第1期12卷 11-14页

作者：邵志敏江明余黎明韩企夏沈镇宙 Department of Surgery Cancer Hospital Shanghai Medical University Shanghai 200032.

Breast cancer containing estrogen receptors (ER ) are responslve to antiestrogen treatment and have a better prognosis compared with ER-negative tumors. The loss of estrogen receptors appears to be associated with a progression to less clifferentiated cells. We transfected the human ER into the ER-negative breast cancer cell line MDA MD 231 cells. We found that expresslon of adequate ER is strong associated with the ability of human breast cancer cell growth inhibition and progression. Compared with nontransfected or mock-trans fected cells, ER-transfected cells exhibited growth slower, forming smaller colonles in soft agar and growth inhibited by estrogen and tamoxifen. Therefore reactivation or transfection of the estrogen receptor gene can be considered as therapeutic approaches to hormone-independent breast cancer.

关键词： estrogen receptor breast cancer stable transfection

Cancer therapy using natural ligands that target estrogen receptor beta

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Chinese Journal of Natural Medicines 2015年第11期13卷 801-807页

作者： Gangadhara R Sareddy Ratna K.Vadlamudi Department of Obstetrics and Gynecology University of Texas Health Science Center at San Antonio Cancer Therapy & Research Center University of Texas Health Science Center at San Antonio

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.

关键词： estrogen receptor estrogen receptor beta Tumor suppressor ER beta agonists Liquiritigenin S-equol Genistein

17β-Estradiol Regulates SKP2 Expression in Cultured Immature Boar Sertoli Cells Mainly via estrogen receptor β,cAMP-PKA and ERK1/2

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Journal of Integrative Agriculture 2014年第4期13卷 827-836页

作者： WANG Xian-zhong ZHU Feng-wei WANG Yong WANG Yi ZHANG Jiao-jiao ZHANG Jia-hua Chongqing Key Laboratory of Forage & Herbivore College of Animal Science and TechnologySouthwest University

estrogen plays an important role in regulating testicular Sertoli cell number. Furthermore, S-phase kinase-associated protein 2 （SKP2） plays a central role in mammalian cell cycle progression. The objective of this study was to determine whether 17β-estradiol can regulate the expression of SKP2, and the Sertoli cell cycle, via estrogen receptor β （ERβ）, the cyclic adenosine monophosphate （cAMP）-protein kinase A （PKA） and extracellular signal-regulated kinase （ERK1/2） pathway. When cultured immature boar Sertoli cells were treated with 17β-estradiol, a time-dependent increase in SKP2 mRNA and protein level was observed by real-time PCR and Western blot, and 17β-estradiol activity peaked at 30 min. Treatment with ICI182780 and ERβ antagonist reduced 17β-estradiol-induced expression of SKP2 and proliferating cell nuclear antigen （PCNA）, while increasing the protein concentration of p27kip1. However, the effect of ERa antagonist on these parameters was lower than that of ICI 182780 and ERβ. Forskolin had a similar effect as 17β-estradiol on the expression of SKP2, PCNA and p27kip1, Rp-cAMP, H-89 and U0126 treatment reduced 17β-estradiol-induced changes, while H-89 also inhibited ERK1/2 activation. Therefore, 17β-estradiol mainly regulates SKP2 mRNA and protein expression via ERβ-cAMP-PKA and ERK1/2 activation. SKP2 and PCNA expression were positively correlated, while increased SKP2 expression likely resulted in p27kip1 degradation.

关键词： 17β-estradiol Sertoli cell SKP2 estrogen receptor cAMP-PKA ERK1/2

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

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Asian Journal of Andrology 2012年第4期14卷 546-555页

作者： Ming Chen Chiuan-Ren Yeh Chih-Rong Shyr Hsiu-Hsia Lin Iun Da Shuyuan Yeh Departments of Urology and Pathology University of Rochester Medical Center Rochester New York 14642 USA Sex Hormone Research Center China Medical University Hospital Taichung 40402 Taiwan China

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 *** 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.

关键词： Cre-loxP estrogen receptor knockout prostate stromal-epithelial interaction

17β-Estradiol Regulates Cultured Immature Boar Sertoli Cell Proliferation via the cAMP-ERK1/2 Pathway and the estrogen receptor β

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Agricultural Sciences in China 2010年第8期9卷 1201-1210页

作者： WANG Xian-zhong ZHAO Bo-chuan ZHOU Yu-lan ZHOU Yin-tao MA Kai-ge ZHANG Jia-hua Chongqing Key Laboratory of Forage ＆ Herbivore College of Animal Science and Technology Southwest University Chongqing 400716P.R. China

estrogen plays an important role in regulating Sertoli cell number in the testis. The objective of the study was to identify whether 17β-estradiol affected the proliferation of cultured, immature boar Sertoli cells via the estrogen receptor β （ERβ） and the cAMP-extracellular signal-regulated kinase （ERK1/2） pathway. Low levels （10-10-10-8 mol L-1） of 17β-estradiol increased cell number, but high levels （10-7-10-6 mol L-1） decreased it （P〈0.05）. Sertoli cell number began to recover for an additional 24 h in the medium without 17β-estradiol （10-6 mol L-l）（P〉0.05）. The effects of 17β-estradiol （10-9 mol L-1） peaked at the first 24 h （P〈0.05）. 17β-estradiol activated ERK1/2 from 5 min to 24 h, but the activiy of ERK1/2 began to decrease after 4 h. Both PD98059 and U0126, two ERK inhibitors, blocked cell division （P〈0.05）. 17β-estradiol （10-10-10-6 mol L-1） dose-dependently increased cAMP production （P 〈 0.05）, and both 17β-estradiol （10-9 mol L-1） and forskolin, which increases cAMP levels, induced cell proliferation and activated ERK1/2 （P〈 0.05）. Rp-cAMP, an antagonist of cAMP, blocked this 17β-estradiol activity （P〈 0.05）. Two estrogen receptor antagonists, ICI 182780 and ERβ antagonist （ERβAnt）, reduced Sertoli cell number, cAMP production and ERK1/2 activation （P〈 0.05）, but ERaAnt did not （P〉 0.05）. Therefore, 17β- estradiol mainly promotes pig Sertoli cell proliferation via ERβ to induce cAMP production and ERK activation to promote cell proliferation.

关键词： 17β-estradiol Sertoli cell cell proliferation estrogen receptor ERK1/2

estrogen and oxytocin involvement in social preference in male mice:a study using a novel long-term social preference paradigm with aromatase,estrogen receptor-αand estrogen receptor-β,oxytocin,and oxytocin receptor knockout male mice

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Integrative Zoology 2018年第6期13卷 698-710页

作者： Mumeko C.TSUDA Kazuyo NAGATA Shoko SAGOSHI Sonoko OGAWA Laboratory of Behavioral Neuroendocrinology University of TsukubaTsukubaIbarakiJapan

Certain aspects of social behavior help animals make adaptive decisions during encounters with other *** mice choose to approach another conspecific,the motivation and preference behind the interaction is not well *** and oxytocin are known to influence a wide array of social behaviors,including social motivation and social *** present study investigated the effects of estrogen and oxytocin on social preference using aromatase(ArKO),estrogen receptor(ER)α(αERKO),ERβ(βERKO),oxytocin(OTKO),oxytocin receptor(OTRKO)knockout and their respective wild-type(WT)male *** were presented with gonadally-intact versus castrated male(IC),intact male versus ovariectomized female(IF),or intact male versus empty cage(IE)stimuli sets for 5 *** showed no preference for either stimuli in IC and IF and intact male preference in IE,but ArKO mice preferred a castrated male or an ovariectomized female,or had no preference for either stimulus in IC,IF and IE stimuli sets,respectively,suggesting reduced intact male preference.αandβWT mice preferred a castrated male,showed no preference,and preferred an intact male in IC,IF and IE,respectively.αERKO mice displayed similar modified social preference patterns as ArKO,whereas the social preference ofβERKO mice remained similar toβ*** preferred a castrated male whereas OTKO,OTRWT and OTRKO mice failed to show any preference in IC and none showed preference for either stimuli in ***,these findings suggest that estrogen regulates social preference in male mice and that impaired social preference in oxytocin-deficient mice may be due to severe deficits in social recognition.

关键词： aromatase estrogen receptor oxytocin receptor social motivation social preference

PI3K/mTOR mediate mitogen-dependent HDAC1 phosphorylation in breast cancer:a novel regulation of estrogen receptor expression

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Journal of Molecular Cell Biology 2015年第2期7卷 132-142页

作者： Simona Citro Claudia Miccolo Laura Meloni Susanna Chiocca Department of Experimental Oncology European Institute of OncologyIFOM-IEO Campusvia Adamello 1620139 MilanItaly Department for Molecular Biomedical Research Technologiepark Zwijnaarde927 VIB west9052 GhentBelgium

Histone deacetylase 1(HDAC1)is an important epigenetic controller involvedin transcriptional regulation throughmodification of chromatin *** and epigenetic changes and deregulation of signal transduction pathways have been implicated in the development of breast *** of estrogen receptor a(ERa)expression is one of the mechanisms behind the acquisition of endocrine *** and increased hormone and growth factor receptor signaling in breast cancer cells contribute to resistance to endocrine *** HDACs and the PI3K/mTOR signaling pathway are becoming promising targets in breast cancer,reversing also acquired hormone *** we show how mitogens,activating the PI3K/mTOR pathway,trigger the phosphorylation of HDAC1 in breast cancer cells,which is completely dependent on the activity of the p70 S6 kinase(S6K1).Our findings show that S6K1,overexpressed in many breast cancers,controls HDAC1-dependent transcriptional regulation of ERa levels upon mitogenic stimuli,controlling HDAC1 recruitment to the ERa ***,cell treatment with both mTOR and HDACs inhibitors shows an additive effect in inhibiting breast cancer *** confirms the novel cross-talk between the HDAC1 and PI3K pathways with clinical implications towards the treatment of this malignant disease.

关键词： breast cancer estrogen receptor HDAC1/mTOR/PI3K/S6K1

Zearalenone toxicosis on reproduction as estrogen receptor selective modulator and alleviation of zearalenone biodegradative agent in pregnant sows

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Journal of Animal Science and Biotechnology 2022年第4期13卷 1222-1232页

作者： Jianchuan Zhou Lihong Zhao Shimeng Huang Qingxiu Liu Xiang Ao Yuanpei Lei Cheng Ji Qiugang Ma State Key Laboratory of Animal Nutrition College of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China Sichuan tieqilishi Food Co. LtdMianyang 610000Sichuan provinceChina.

Background:Zearalenone(ZEA)is a resorcylic acid lactone derivative derived from various Fusarium species that are widely found in food and *** molecular structure of ZEA resembles that of the mammalian hormone 17β-oestradiol,thus zearalenone and its metabolites are known to compete with endogenous hormones for estrogen receptors binding sites and to activate transcription of oestrogen-responsive ***,the effect of long-term low-dose ZEA exposure on the reproductive response to Bacillus subtilis ANSB01G culture for first-parity gilts has not yet been *** study was conducted to investigate the toxic effects of ZEA as an estrogen receptor selective modulator and the alleviating effects of Bacillus subtilis ANSB01G cultures as ZEA biodegraders in pregnant sows during their first ***:A total of 80 first-parity gilts(Yorkshire×Landrace)were randomly assigned to four dietary treatments during gestation:CO(positive control);MO(negative control,246μg ZEA/kg diet);COA(CO+*** ANSB01G culture with 2×10^(9)CFU/kg diet);MOA(MO+*** ANSB01G culture with 2×10^(9)CFU/kg diet).There were 20 replications per treatment with one gilt per *** low-dose ZEA naturally contaminated diets disordered most of reproductive hormones secretion and affected estrogen receptor-αand estrogen receptor-βconcentrations in serum and specific organs and led to moderate histopathological changes of gilts,but did not cause significant detrimental effects on reproductive *** addition of Bacillus subtilis ANSB01G culture to the diet can effectively relieve the competence of ZEA to estrogen receptor and the disturbance of reproductive hormones secretion,and then ameliorate toxicosis of ZEA in ***:Collectively,our study investigated the effects of feeding low-dose ZEA on reproduction in pregnant sows during their first *** low-dose ZEA could modulate estrogen receptor-αand-βconcentrations in specific organs,ca

关键词： Bacillus subtilis ANSB01G estrogen receptor Mycotoxin biodegradation Pregnant sows Reproductive performance ZEA