Effects of estrogen receptor modulators on cytoskeletal proteins in the central nervous system

Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1（MAP1）, MAP2, neurofilament 38（NF38） by different mechanisms of action and at different levels： neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects.

Expressions of estrogen receptor subtypes and c-met proto-oncogene in endometrial carcinoma and their correlation

Objective To investigate the expressions of estrogen receptor(ER)subtypes and c-met proto-oncogene in human endometrial carcinomas and to assess the clinical significance of ER and c-met in this carcinoma.Methods Reverse transcription PCR(RT-PCR)was used to detect the expressions of ERα,ERβ and c-met proto-oncogene mRNA in 30 samples of endometrial carcinoma and 11 samples of normal endometrium.Results The expression of ERα in endometrial carcinoma(0.70±0.40)was significantly reduced in comparison to that in normal endometrium(1.14±0.56,P<0.05).A similar finding was made for the expression of ERβ in carcinoma(0.24±0.18)versus normal tissues(0.48±0.20,P<0.05).In contrast,c-met mRNA expression was increased in endometrial carcinoma(1.45±0.72)compared to that in normal endometrium(0.42±0.31,P<0.01).A decrease tendency of the expression of ERα was also found from Stage Ⅰ(0.82±0.41)to a more severe Stag Ⅱ-Ⅲ of endometrial carcinoma(0.42±0.17,P<0.05).The analysis of ERα and ERβ mRNA revealed a decrease tendency from shallow to deep invasion of the uterine muscles(P<0.05).We found that the expressions of ERα and ERβ were negatively correlated with c-met proto-oncogene with a coefficient correlation of-0.63(P<0.01)and-0.32(P<0.05),respectively.Conclusion ERα and ERβ are both involved in mutagenic action of carcinogen.C-met proto-oncogene plays an important role in the carcinogenesis and development of endometrial carcinoma.C-met and ER expressions show a negative correlation in the development of endometrial carcinoma.

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

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.

The Relationship of CyclinD1 and Estrogen Receptor Expression in the Process of Proliferation and Metastasis in Breast Neoplasm

The role of CyclinD1 and estrogen receptor (ER) in the process of proliferation and metastasis of breast neoplasm and their relationship were studied. The expression levels of CyclinD1 and ER in the tissue samples were detected by using flow cytometry and L SAB immunohistochemistry staining, respectively. The results showed that CyclinD1 and ER expression levels in breast cancer were significantly higher than in benign breast neoplasm (P<0.05). The CyclinD1 expression levels in stage I was much lower than in stages Ⅱ, Ⅲ, Ⅳ (P<0.05). The positive rate of ER was not related with tumor size, lymph node metastasis and TNM stage (P>0.05), but the CyclinD1 expression level in ER (+) group was significantly higher than in ER (-) group (P<0.05). It was concluded that CyclinD1 expression level might be obviously related with the proliferation and metastasis of breast neoplasm and ER.

Estrogen Receptor α and β Expressions in Hypothalamus-pituitary-ovary Axis in Rats Exposed Lactationally to Soy Isoflavones and Bisphenol A

Objectives This paper aims to investigate the uterotrophic activities of lactational exposure to combination of soy isoflavones （SIF） and bisphenol A （BPA） and to examine estrogen receptor α （ERα） and estrogen receptor β （ERβ） expressions in hypothalamus-pituitary-ovary axis and uterus.Methods Maternal rats that were breeding about 8 litters were randomly divided into four groups with seven dams in each group.Dams in different treatment groups received corn oil （control）,150 mg/kg BW of SIF,150 mg/kg BW of BPA or combination of 150 mg/kg BW of SIF and 150 mg/kg BW of BPA,respectively,from postnatal day 5 to 11 （PND5-11） by gavage.On PND12 and PND70,10 female litters were killed and hypothalamus,pituitary,ovary and uterus were collected.ERα and ERβ expressions in these organs were detected with Western blotting assay.And vaginal opening time and estrus cycle were examined in animals fed for PND70.Results On PND12,the relative uterine weight of rats treated with ISF or BPA or their combination was significantly higher than that of untreated rats （P〈0.05）.But the relative uterine weight of rats in the co-exposure group was slightly lower than that in the group only exposed to SIF or BPA.On PND 70,however,the relative uterine weight in each treatment group was not statistically different from that in the control group （P〈0.05）.Vaginal opening time and estrus cycle in groups treated with SIF or BPA or their combination were similar to those in the control group （P〈0.05）.Exposure to SIF or BPA or their combination could up-regulate or down-regulate ERα and ERβ expressions in hypothalamus,pituitary,ovary and uterus on PND12 and PND70.These regulation patterns for ERα and ERβ were different in different organs at different time points.Conclusion Lactational exposure to ISF or BPA or their combination could induce uterotrophic responses in neonate rats,which disappeared in later life.But these data fail to suggest a possibility for synergic actions between SIF and BPA.It was also demonstrated that the uterotrophic effects of SIF and BPA exposure might,at least,involve modification of ERα or ERβ expressions in the hypothalamus-pituitary-ovary axis.

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)

The Relationship of the Expression of Estrogen Receptor in Cartilage Cell and Osteoarthritis Induced by Bilateral Ovariectomy in Guinea Pig

To investigate the estrogen receptor（ER） expression in cartilage cell in the development of oste0arthritis induced by bilateral ovariectomy in guinea pig and to find their relationship. 30 two-month-old female guinea pigs were randomly divided into two groups （n=15 each） ： sham operation （control）group and ovariectomized group （OVX）; Scanning electorne microscope （SEM） and transmission electron microscope （TEM） were obtained to analysis the cartilage degeneration of the hind limb knee joint after 6 and 12 weeks of ovariectomy. Dextran-Coated-Charcoal （DCC） was taken to quantitively detect the expression of ER. The serum levels of estrogen and gestone were detected by immune contest assay. The results showed that ER do exist in the cartilages of the guinea pigs, with higher expression in the control group than in OVX group at the same time point （P〈0. 05）. It was increased also at 12 th week after operation than that of preoperation. The blood serum levels of estrogen and gestone showed a similar tendency to the expression of ER. Joint cartilage degeneration detected by SEM and TEM could be found at 6 th week, but severe degenerative lesions at 12 th week in the OVX group compared with the control group （P〈0.01）. The data suggested that bilateral ovariectomy in guinea pig lead to severe os.teoarthritis which mighgt be related to the lower serum level of estrogen and the downregulation of the expression of ER in the cartilage also.

Age-related decrease in aromatase and estrogen receptor （ERα and ERβ） expression in rat testes： protective effect of low caloric diets

Aim： To examine the effects on rat aging of caloric restriction （CR1） and undernutrition （CR2） on the body and on testicular weights, on two enzymatic antioxidants （superoxide dismutase and catalase）, on lipid peroxidation and on the expression of testicular aromatase and estrogen receptors （ER）. Methods： CR was initiated in 1-month-old rats and carried on until the age of 18 months. Results： In control and CR2 rats an age-related decrease of the aromatase and of ER （α and β） gene expression was observed; in parallel a diminution of testicular weights, and of the total number and motility of epididymal spermatozo was recorded. In addition, aging in control and CR2 rats was accompartied by a significant decrease in testicular superoxide dismutase, catalase activities, and an increase in lipid peroxidation level （thiobarbituric acid reactive substance）, associated with alterations of spermatogenesis. Conversely, caloric restriction-treatment exerted a protective effect and all the parameters were less affected by aging. Conclusion： These results indicate that during aging, a low caloric diet （not undernutrition） is beneficial for spermatogenesis and likely improves the protection of the cells via an increase of the cellular antioxidant defense system in which aromatase/ ER could play a role. （Asian J Andro12008 Mar; 10： 177-187）

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.

Estrogen receptor beta treats Alzheimer's disease

In vitro studies have shown that estrogen receptor β can attenuate the cytotoxic effect of amyloid protein on PC12 cells through the Akt pathway without estrogen stimulation. In this study, we aimed to observe the effect of estrogen receptor β in Alzheimer＇s disease rat models established by intraventricular injection of amyloid β protein. Estrogen receptor β lentiviral particles delivered via intraventricular injection increased Akt content in the hippocampus, decreased interleukin-1β mRNA tumor necrosis factor a mRNA and amyloid β protein levels in the hippocampus, and improved the learning and memory capacities in AIzheimer＇s disease rats. Estrogen receptor β short hairpin RNA lentiviral particles delivered via intraventricular injection had none of the above impacts on AIzheimer＇s disease rats. These experimental findings indicate that estrogen receptor β, independent from estrogen, can reduce inflammatory reactions and amyloid β deposition in the hJppocampus of AIzheimer＇s disease rats, and improve learning and memory capacities. This effect may be mediated through activation of the Akt pathway.

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.

Design, Synthesis and Biological Evaluation of 2-Aroyl-3-aryl-6,7-dihydro-5H-furo[3,2-g]chromen Derivatives as a Novel Series of Estrogen Receptor Modulators

Based on the principles of the bioisosterism, combination of the active substructures of selective estrogen receptor modulators which are currently therapeutic agents available for the prevention and treatment of various estrogen dependent diseases, and structural optimization, a novel series of 2-aroyl-3-aryl-6,7-dihydro-5H-furo[3,2-g]- chromen derivatives was designed as potent selective estrogen receptor modulators via molecular docking. The target compounds have been synthesized, and characterized by 1R, proton NMR, ESI-MS, elemental analysis and evaluated for their antitumor activity against human osteosarcoma U2OS-EGFP-4FI2G cell line. Some target compounds showed good inhibition effects on U2OS-EGFP-4F12G cell line and the preliminary structure-activity relationships were discussed.

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.

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

Background:Zearalenone(ZEA)is a resorcylic acid lactone derivative derived from various Fusarium species that are widely found in food and feeds.The 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 genes.However,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 investigated.This 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 parity.Results: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+B.subtilis ANSB01G culture with 2×10^(9)CFU/kg diet);MOA(MO+B.subtilis ANSB01G culture with 2×10^(9)CFU/kg diet).There were 20 replications per treatment with one gilt per replicate.Feeding 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 performance.The 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 gilts.Conclusions:Collectively,our study investigated the effects of feeding low-dose ZEA on reproduction in pregnant sows during their first parity.Feeding low-dose ZEA could modulate estrogen receptor-αand-βconcentrations in specific organs,cause disturbance of reproductive hormones and vulva swelling,and damage organ histopathology and up-regulate apoptosis in sow models.Diet with Bacillus subtilis ANSB01G alleviated negative effects of the ZEA on gilts to some extent.

Effect of Compound Recipe Gengniankang (更年康) on Senile Sexual Hormone and Expression of Estrogen Receptor in Bone of Climacteric Female Rats

Objective： To compare the therapeutic effect of Compound Recipe Gengniankang （更年康, GNK） with that of hormone replacement treatment （HRT） on climacteric female rats with osteoporosis, and to investigate the roles of estrogen and estrogen receptors in the mechanism of osteoporosis. Methods： Climacteric female rats with osteoporosis were chosen and divided into three groups （GNK group, HRT group and control group）. Apoptosis of ovarian granulose cells was measured by terminal-deoxynucleotidyl transferae mediated nick end labeling （TUNEL） assay. Serum level of estrdiol （E2）, follicle stimulating hormone （FSH）, luteinizing hormone （LH） were determined by the method of radioimmunoassay （RIA）. Reverse transcriptase polymerase chain reaction （RT-PCT） technology was used to evaluate the expression of estrogen receptor （ER） in bone. Bone mineral density （BMD） was measured by double energy X-ray absorption （DEXA）. Results： In the climacteric rats, BMD, serum E2, ER mRNA expression in bone decreased remarkably, and serum FSH, LH and apoptosis of ovarian granulose cells increased obviously. After treating with GNK, all the indexes were reversed except serum E2. The increase of E2 was not significant. Conclusion： GNK is effective on climacteric osteoporosis female rats. Its role is performed not by increasing serum E2 but by enhancing ER in the bone and inhibiting apoptosis of ovarian granulose cells. GNK can deter further exhaustion of ovarian function.

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.

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.

Overexpression of estrogen receptor beta alleviates the toxic effects of beta-amyloid protein on PC12 cells via non-hormonal ligands

After binding to the estrogen receptor, estrogen can alleviate the toxic effects of beta-amyloid protein, and thereby exert a therapeutic effect on Alzheimer＇s disease patients. Estrogen can increase the incidence of breast carcinoma and endometrial cancer in post-menopausal women, so it is not suitable for clinical treatment of Alzheimer＇s disease. There is recent evidence that the estrogen receptor can exert its neuroprotective effects without estrogen dependence. Real-time quantitative PCR and flow cytometry results showed that, compared with non-transfected PC12 cells, adenovirus-mediated estrogen receptor β gene-transfected PC12 cells exhibited lower expression of tumor necrosis factor a and interleukin 1β under stimulation with beta-amyloid protein and stronger protection from apoptosis. The Akt-specific inhibitor Abi-2 decreased the anti-inflammatory and anti-apoptotic effects of estrogen receptor β gene-transfection. These findings suggest that overexpression of estrogen receptor β can alleviate the toxic effect of beta-amyloid protein on PC12 cells, without estrogen dependence. The Akt pathway is one of the potential means for the anti-inflammatory and anti-apoptotic effects of the estrogen receptor.

Estrogen receptor gene polymorphism in a Chinese population with multiple sclerosis

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.

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.