ERα Expression Levels Research Articles

Inhibiting ERα expression in the medial amygdala increases prosocial behavior in male meadow voles (Microtus pennsylvanicus)

This study tested the hypothesis that site-specific estrogen receptor alpha (ERα) expression is a critical factor in the expression of male prosocial behavior and aggression. Previous studies have shown that in the socially monogamous prairie vole (Microtus ochrogaster) low levels of ERα expression, in the medial amygdala (MeA), play an essential role in the expression of high levels of male prosocial behavior and that increasing ERα expression reduced male prosocial behavior. We used an shRNA adeno-associated viral vector to knock down/inhibit ERα in the MeA of the polygynous male meadow vole (M. pennsylvanicus), which displays significantly higher levels of ERα in the MeA than its monogamous relative. Control males were transfected with a luciferase expressing AAV vector. After treatment males participated in three social behavior tests, a same-sex dyadic encounter, an opposite-sex social preference test and an alloparental test. We predicted that decreasing MeA ERα would increase male meadow vole’s prosocial behavior and reduce aggression. The results generally supported the hypothesis. Specifically, MeA knockdown males displayed lower levels of defensive aggression during dyadic encounters and increased levels of overall side-x-side physical contact with females during the social preference test, eliminating the partner preference observed in controls. There was no effect on pup interactions, with both treatments expressing low levels of alloparental behavior. Behaviors affected were similar to those in male prairie voles with increased ERα in the BST rather than the MeA, suggesting that relative changes of expression within these nuclei may play a critical role in regulating prosocial behavior.

Effect of estradiol on fibroblasts from postmenopausal idiopathic carpal tunnel syndrome patients.

Fibrosis of the subsynovial connective tissue (SSCT) is a characteristic finding in patients with idiopathic carpal tunnel syndrome (CTS). Idiopathic CTS frequently occurs in postmenopausal women; therefore, female steroid hormones, especially estrogens, may be involved in its development. In this study, we evaluated the effect of the estradiol on the expression of genes and proteins related to fibrosis of SSCT fibroblasts from patients with idiopathic CTS. This study included 10 postmenopausal women (mean age 76 years). Fibroblasts derived from SSCT were treated with estradiol (10-4 -10-12 M), and the expression levels of TGF-β-responsive genes were evaluated. The relationships between the expression of untreated estrogen receptor α (ERα) and ERβ and changes in gene expression due to estradiol treatment were examined by quantitative real-time polymerase chain reaction. The effects of 10-4 M estradiol on collagen type I (Col1) and collagen type III (Col3) protein expression levels were also evaluated by fluorescent staining. The relationships between ERα/β and Col1/3 expression were evaluated by immunohistochemical staining. The reduction in Col1A1 mRNA expression due to estradiol treatment was positively correlated with ERα expression (r = 0.903, p < 0.01). At the protein level, expression of Col1 and Col3 were down-regulated. These results indicated that ERα-mediated signaling may be involved in the regulation of Col1A1, and its regulatory effect may be dependent on the ERα expression level. The accurate evaluation of ERα expression level in the SSCT of individual patients with idiopathic CTS might guide the effective use of new estrogen replacement therapy.

Effects of puerarin on estrogen-regulated gene expression in gonadotropin-releasing hormone pulse generator of ovariectomized rats

Effects of puerarin on the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator function is investigated, for the first time, in ovariectomized rats at the level of mRNA expression of estrogen-responsive genes, e.g., estrogen receptor (ER), GnRH and its receptor (GnRHR). Rats were treated orally for 90 days either with a soy-free diet containing two different doses of puerarin (low dose of 600 mg/kg and high dose of 3000 mg/kg) or estradiol benzoate (E2B) at either low dose (4.3 mg/kg) or high dose (17.3 mg/kg). Levels of mRNA expression in the medial preoptic area/anterior hypothalamus (MPOA/AH), mediobasal hypothalamus/median eminence (MBH/ME) and adenohypophysis were measured by quantitative TaqMan® real-time RT-PCR. Plasma levels of luteinizing hormone (LH) and prolactin (PRL) were measured by radioimmunoassay. In the MPOA/AH, both puerarin and E2B decreased ERα mRNA levels without any significant changes in ERβ and GnRH mRNA levels. Both puerarin and E2B did not significantly alter the expression levels of ERα, ERβ and GnRHR in the MBH/ME. E2B exerted significant effects on the down-regulation of adenohypophyseal GnRHR mRNA transcripts and serum LH levels. Puerarin did not cause significant changes in pituitary GnRHR mRNA transcripts and serum LH and PRL levels. This is the first study to demonstrate that in ovariectomized rat models of ovarian hormone deprivation, puerarin acted as a weak estrogen-active compound in the hypothalamic GnRH pulse generator through the downregulation of MPOA/AH ERα mRNA expression.

A sorafenib-sparing effect in the treatment of thyroid carcinoma cells attained by co-treatment with a novel isoflavone derivative and 1,25 dihydroxyvitamin D3

BackgroundSorafenib improves progression-free survival in patients with progressive radioactive iodine-refractory differentiated thyroid carcinoma, but causes severe side effects. Estrogens may accelerate thyroid carcinoma cell growth. Our group recently reported that isoflavone derivative 7-(O)-carboxymethyl daidzein conjugated to N-t-boc-hexylenediamine (cD-tboc), a novel anti-estrogenic compound, retards the growth of both thyroid carcinoma cell lines and cultured human carcinoma cells. Vitamin D receptor (VDR) is expressed in malignant cells and responds to 1,25 dihydroxyvitamin D3 (1.25D) by decreased proliferative activity in vitro. The purpose of this study was to examine the effects of vitamin D metabolites (VDM) on the expression of estrogen receptors (ERs), VDR, and 1OHase mRNA, and to evaluate the inhibitory effect of low doses of sorafenib in combination with cDtboc and VDM on cell proliferation in cultured human papillary thyroid carcinoma (PTC). MethodsIn 19 cultured PTC specimens and 19 normal thyroid specimens, harvested during thyroidectomies from the same patients, expression levels of ERα, ERβ, VDR, and 1 alpha-hydroxylase (1OHase) mRNA (by quantitative real-time PCR) were determined at baseline and after treatment with VMD. Cell proliferation was determined by measurement of 3[H] thymidine incorporation after treatment with sorafenib alone, sorafenib with added 1.25D or cD-tboc, and sorafenib with both 1.25D and cD-tboc added. Results1,25D increased mRNA expression of all tested genes in the malignant and normal thyroid cells, while the ERα mRNA of the normal cells was unaffected. 1.25D dose-dependently inhibited cell proliferation in the malignant cells. The inhibitory effect of sorafenib on cell proliferation in the malignant cells was amplified after the addition of cDtboc and 1.25D, such that the maximal inhibition was not only greater, but also had been attained at a 10-fold lower concentration of sorafenib (20 μg/ml). This inhibition was similar to that of the generally used concentration of sorafenib (200 μg/ml) alone. ConclusionsThe demonstration that low concentrations of cDtboc and 1.25D markedly amplify the inhibitory effect of sorafenib on the growth of human PTC supports the use of a 10-fold lower concentration of sorafenib. The findings may promote a new combination treatment for progressive radioactive iodine-refractory PTC.

DNA Methylation Status of the Estrogen Receptor α Gene in Canine Mammary Tumors.

Estrogen receptor α (ERα) has an important role in mammary carcinogenesis, prognosis, and treatment. In human and canine mammary cancer, the most aggressive tumors show loss of ERα expression, which in human breast cancer has been attributed to methylation of the cytosine followed by guanine (CpG) island within the estrogen receptor α gene ( ESR1) promoter. This study aimed to investigate the role of ESR1 CpG island (CGI) methylation in ERα expression in canine mammary tumors. Twenty-one canine mammary samples were sorted into three groups: malignant tumor (n = 9), benign tumor (n = 8), and normal gland (n = 4). Immunohistochemical analysis and reverse-transcription quantitative real-time PCR were performed to assess ERα expression and ESR1 mRNA levels. The methylation status was determined using sodium-bisulfite-treated DNA sequencing. All normal mammary glands and benign tumors showed high ERα expression (score range, 5-8). Six of the nine malignant tumors did not show ERα expression (score 0), two had score 2, and one had score 4. Lower ERα ( P < .005) and ESR1 mRNA levels ( P < .005) were found in malignant mammary tumors than in the other two groups. Canine ESR1 has an intragenic and non-promoter-associated CGI, different from humans. No significant variation in methylation percentage was observed among the groups, suggesting that ESR1 is not regulated by DNA methylation, unlike that in humans. This difference should be considered in further research using ERα as a biomarker for mammary tumors in canine studies on ERα-targeting therapy.

Normalization of serum corticosterone, testosterone levels, and testicular estrogen receptor-α expression in Wistar rats subjected to restraint stress — Beneficial effects of olive oil supplementation

Many Stressors have been reported to affect male reproduction. Stress-induced elevated glucocorticoids that affect testosterone synthesis in Leydig cells. Consequently, spermatogenesis is impaired. Several studies reported that olive oil (OO) supplementation had beneficial effects on semen analysis. We aimed to evaluate the effect of restraint stress on serum testosterone, serum follicle stimulating hormone (FSH) levels and the expression of testicular estrogen receptor-α (ERα) in Wistar rats. Also, we investigated whether OO supplementation might modulate the effect of restraint stress or not. 27 adult male Wistar rats were subdivided into 4 groups: control group (n = 7), restraint stress group (RS) (n = 7), restraint stress group receiving OO supplementation (RS + OO) (n = 7), olive oil supplemented group (OO) (n = 6). Serum corticosterone, FSH, testosterone, testicular cholesterol, semen fructose levels, and testicular ERα, expression were measured to all study groups. We revealed that RS group had higher corticosterone, testicular cholesterol levels and lower ERα expression, semen fructose levels in comparison to the control group (p < 0.05). While RS + OO group had lower corticosterone, cholesterol levels and higher testosterone, ERα expression, and semen fructose levels compared to RS group. We concluded that stress decreases testicular ERα expression and semen fructose level. While olive oil alleviates that inhibitory effect.

TRANSCRIPTION FACTOR BRN-3α AND PROSTATE CANCER, RELATION WITH HORMONE RECEPTORS AND AKT/M-TOR SIGNALING PATHWAY ACTIVATION

Introduction. The transcription factor Brn-3α (product of the POU4F1) plays a significant role in carcinogenesis. The purpose of the study was to investigate Brn-3α, AR, ERα expressions in tissues of benign prostatic hyperplasia and prostate cancer as well as to determine their association with AKT/mTOR signaling pathway activation. Material and methods . The study included 30 patients with locally advanced prostate cancer and 15 patients with benign prostatic hyperplasia. The expression levels of Brn-3α, AR, ERα and the components of AKT/m-TOR signaling pathway were determined using RT-PCR assay. Results. Overexpression of Brn-3α in prostate cancer tissues was found to be associated with high level of ERα mRNA. High expression of AR was revealed in tissues of benign prostatic hyperplasia and prostate cancer. High expression levels of AKT, m-TOR and PTEN were observed in prostate cancer tissues. However, no significant changes in PTEN mRNA level were found in tissues of prostatic hyperplasia. Conclusion. Brn-3α transcription factor was associated with prostate cancer and accompanied with high expression levels of ERα, AKT and m-TOR.

The feasibility of 18F-FES and 18F-FDG microPET/CT for early monitoring the effect of fulvestrant on sensitizing docetaxel by downregulating ERα in ERα+ breast cancer.

Our study aimed to investigate the feasibility of PET/CT for monitoring the influence of fulvestrant on sensitizing docetaxel by downregulating ERα in ERα+ breast cancer. Docetaxel-insensitive ERα+ breast cancer cells (DIS-ZR751) were established, identified and cultured. ERα expression, toxicity and viability of DIS-ZR751 were analyzed before and after treatment in vitro. DIS-ZR751-bearing nude mice were randomly divided into four groups according to different treatments: blank (DIS-ZR751), docetaxel (DIS-ZR751+DOC), fulvestrant (DIS-ZR751+FUL), and combination treatment (DIS-ZR751+DOC+FUL). 18F-FES and 18F-FDG microPECT/CT scans were performed before and 7, 14days after treatment. Absolute %ID/gmax was calculated. ERα expression level and growth rate of DIS-ZR751 were higher than control group and decreased dramatically after docetaxel and fulvestrant combination treatment. 18F-FES and 18F-FDG PET/CT imaging in vivo revealed that ERα expression in DIS-ZR751 treated with fulvestrant, and tumor activity in DIS-ZR751 treated with combination drugs decreased as early as 7days after treatment. 18F-FES and 18F-FDG PET/CT were feasible for early monitoring the effect of fulvestrant on sensitizing docetaxel by downregulation of ERα in ERα+ breast cancer noninvasively.

Seasonal expressions of androgen receptor, estrogen receptors and cytochrome P450 aromatase in the uteri of the wild Daurian ground squirrels (Spermophilus dauricus).

The reproductive tissues including the uterus undergo dramatic changes in seasonal breeders from the breeding to non-breeding seasons. Classically, sex steroid hormones play important roles in the uterine morphology and functions. To clarify the relationship between sex steroid hormones and seasonal changes in the uterine morphology and functions, the wild Daurian ground squirrels (Spermophilus dauricus) were used as seasonal breeder model. And the immunolocalizations and expression levels of androgen receptor (AR), estrogen receptors α and β (ERα and ERβ) and cytochrome P450 aromatase (P450arom) were investigated in the uteri of the wild Daurian ground squirrels in the breeding (April) and the non-breeding (June) seasons via immunohistochemistry, Western blot and RT-PCR. Histologically, the uterine weight, the thickness of endometrium and the glandular density were significantly higher in the uteri of the breeding season than those of the non-breeding season. In both seasons, the immunostaining of AR was only presented in stromal cells of the uteri; the positive staining of ERα and ERβ were localized in stromal cells and glandular cells; P450arom was merely immunolocalized in glandular cells. The protein and mRNA expression levels of ERα, ERβ and P450arom were higher in the uteri of the breeding season than those of the nonbreeding season; conversely, the expressions of AR were higher in the uteri of the non-breeding season comparing with those of the breeding season in both protein and mRNA levels. The AR: ER ratio in the uteri of the non-breeding season exceeded the AR: ER ratio in the uteri of the breeding season in the wild Daurian ground squirrels. These results suggested that seasonal changes in the expression levels of AR, ERs and P450arom might be correlated with the uterine morphology and histology changes, and estrogen may play an important autocrine/paracrine role in regulating the uterine functions of the wild Daurian ground squirrels.

Overexpression of Endometrial Estrogen Receptor-Alpha in The Window of Implantation in Women with Unexplained Infertility.

BackgroundFailure in the endometrial receptivity may account for a significant number of infertility cases including unexplained infertility in women. Reduction in the endometrial estrogen receptor-alpha (ER-α) expression during implantation may be a critical event that coincides with the expression of specific genes and the formation of a receptive endometrium. The aim of the present study was to assess the expression of ER-α in the mid-secretory phase in the endometrium of women with unexplained infertility.Materials and MethodsThis case-control study was carried out on randomly selected fertile (n=10) and infertile (n=16) women whose source of infertility remained unexplained. We evaluated the expression of ER-α and glycode-lin-A (GdA) through mRNA level measurement with real-time polymerase chain reaction (PCR) in the endometrium of fertile women and patients suffering from unexplained infertility and fertile women. Endometrial biopsies of each subject were collected during a single menstrual cycle 7 days after the peak of luteinizing hormone (LH+7).ResultsEndometrial expression level of ER-α was significantly (P<0.05) higher in the patients with unexplained infertility compared to the control. Significantly (P<0.05) lower levels of GdA expression were seen in women with unexplained infertility. A statistically non-significant negative correlation was observed between ER-α and GdA mRNA expression.ConclusionOur findings demonstrate that reduction in the endometrial GdA expression is associated with elevated expression of ER-α in mid-luteal phase. Disruption in the endometrial ER-α expression, which leads to defects in uterine receptivity, may contribute to unexplained infertility.

Genistein and daidzein treatments differently affect uterine homeostasis in the ovary-intact middle-aged rats

This study aimed to investigate the effects of soy isoflavones, genistein (GEN) and daidzein, (DAI) on the uterine function in ovary-intact middle-aged rats. GEN and DAI (35mg/kg) were subcutaneously administrated to acyclic (12-month-old) Wistar females, daily, for 4weeks. Control group received either vehicle (olive oil and ethanol, 9:1) or remained intact. We found that GEN and DAI differently affect uterine morphophysiology. GEN significantly increased the uterine wet weight which was associated with hyperplastic changes, revealed by stereological and histomorphometrical analyses. Also, PCNA immunoexpression was increased, whereas expression of apoptotic marker (caspase-3) was decreased. Protein and gene expressions of ERα were down-regulated, while PR and ERβ were up-regulated after GEN application. Also, GEN caused an increase of LAC and VEGF mRNA expression, together with an up-regulation of Akt activity. In contrast, DAI did not change the uterine wet weight and stereological features of the main uterine compartments as well as LAC and VEGF gene expression. Absence of hyperplastic changes were illustrated by an increase in caspase-3 immunoexpression, associated with reduced PCNA expression. DAI up-regulated only the expression of ERβ, while the expression levels of ERα and PR remain unaffected. Also, DAI inhibited the activation of Akt due to down-regulation of phosphorylated and total form of Akt protein expression. Compared to GEN, DAI did not promote events associated with the endometrial cell proliferation in the conducted study, figuring as the compound with a potential safety profile, which justifies further investigation.

Effects of Atrial Natriuretic Peptide on p53 and Estrogen Receptor in Breast Cancer Cells.

The atrial natriuretic peptide (ANP) hormone is secreted by cardiac atrial myocytes and acts to regulate blood pressure homeostasis in humans. Previous research indicates ANP treatment significantly decreases the proliferation of human prostate cancer cells, pancreatic adenocarcinoma, and breast cancer cells. Minimal studies have been conducted with regard to ANP regulating tumor suppressor genes and steroid hormone receptors in breast cancer cells. Our study analyzed the effects of ANP in combination with 17β-estradiol (E2) and antiestrogen treatments on p53 and ERα levels in T-47D breast cancer cells. Preliminary studies through Western blot analysis showed that ANP treatment decreases p53 and ERα expression levels in a concentration-dependent (10–100 nM) manner. Treatment with ANP alone, at a 100 nM concentration, causes a decrease of p53 and ERα expression compared with Cs (control stripped), but with E2 and antiestrogen combinations, expression of both protein levels decreased compared with treatments without ANP. Combined treatment with E2, an estrogen antagonist, and ANP decreased cellular proliferation compared with treatments without ANP, except in the case of raloxifene (RAL). Our studies indicate that ANP has potential as a therapeutic breast cancer treatment and should inspire further studies on the molecular mechanism of ANP in T-47D breast cancer cells.

Inhibitory effects of 17β-estradiol or a resveratrol dimer on hypoxia-inducible factor-1α in genioglossus myoblasts: Involvement of ERα and its downstream p38MAPK pathways.

Deficiency in the functioning of the genioglossus, which is one of the upper airway dilator muscles, is an important cause of obstructive sleep apnea/hypopnea syndrome (OSAHS). Estrogens have been reported to inhibit hypoxia-inducible factor-1α (HIF-1α) expression in hypoxia, regulating its target genes and exerting protective effects on the genioglossus in chronic intermittent hypoxia (CIH). This study aimed to investigate the role of 17β-estradiol (E2) and a resveratrol dimer (RD) on HIF-1α and the underlying mechanism. Mouse genioglossus myoblasts were isolated and cultured, and the estrogen receptor α (ERα) shRNA lentivirus was used for gene knockdown. Then MTT assay was used to determine the effects of E2 and RD on the viability of the cells. Cells in different groups were treated with different agents (E2, or RD, or E2 and SB203580), incubated under normoxia or hypoxia for 24 h, and then expression levels of HIF-1α, ERα, ERβ, total-p38 MAPK and phospho-p38 MAPK were detected. We observed that both E2 and RD inhibited the overexpression of HIF-1α induced by hypoxia at the mRNA and protein levels, and these effects were eliminated by genetic silencing of ERα by RNAi. In addition, we found that E2 activated p38 MAPK pathways to inhibit HIF-1α expression. On the whole, ERα may be responsible for downregulation of HIF-1α by E2 or RD via activation of downstream p38 MAPK pathways.

Hypoxia induced phosphorylation of estrogen receptor at serine 118 in the absence of ligand

The estrogen receptor (ER) plays an important role in breast cancer development and progression. Hypoxia modulates the level of ERα expression and induces ligand-independent transcriptional activation of ERα, which is closely related with the biology of breast carcinomas. Since phosphorylation itself affects the transcriptional activity and stabilization of ERα, we examined changes in ERα phosphorylation under hypoxic conditions. Hypoxia induced phosphorylation of ERα at serine residue 118 (S118) in the absence of estrogen through the mitogen-activated protein kinase (MAPK)/ERK1/2 pathway. Cell proliferation was significantly decreased under normoxia or hypoxia when ERα harboring the S118A mutation was overexpressed. Our previous studies showed that ER degradation is the most prominent phenomenon under hypoxia. E2-induced ER protein downregulation is dependent on phosphorylation of S118. However, hypoxia-induced ERα degradation did not involve S118 phosphorylation. Our study implies the existence of a differential mechanism between E2 and hypoxia-mediated ERα protein degradation. Understanding the mechanistic behavior of ER under hypoxia will likely facilitate understanding of endocrine therapy resistance and development of treatment strategies for breast cancer.

The study of endometrium at gestational days 5 and 15 in dairy goats (Capra hircus)

Endometrium receptivity, an absolutely necessary part of successful embryo implantation, and several morphological and biochemical endometrial receptivity biomarkers have already been studied and proposed in some animals. However, to our knowledge, no such a study has as yet been undertaken in dairy goat. In the present study, the serum and uterus of dairy goat were studied at gestational days 5 and 15, the estrogen (E2) and progesterone (P4) concentrations in serum were determined by electrochemiluminescence immunoassay, the surface topography of endometrium was observed by scanning electron microscopy. Furthermore, the estrogen receptors (ER), prolactin (PRL), some marker genes of receptive endometrium, and cell proliferation and apoptosis in the uterus were also detected. Well-formed pinopodes were found on the surface of endometrium at day 15 with higher E2 and P4 concentrations in the serum and higher estrogen receptors ERα and ERβ expression levels and a lower PRL level in the endometrium. Moreover, some expression levels of marker genes of receptive endometrium (OPN, VEGF, LIF, PRLR) were increased at day 15 compared to day 5, but no significant differences were observed in the cell proliferation and apoptosis in the uterus. The results showed that the endometrium reached the receptive state at gestational day 15 in dairy goats.

Reduced hippocampal IL-10 expression, altered monoaminergic activity and anxiety and depressive-like behavior in female mice subjected to chronic social instability stress

Evidence indicates that release of pro-inflammatory cytokines induced by social stress contributes to affective disorders. Additionally, there are known sex differences in both the stress response and the stressors that can elicit this response. In this regard, the chronic social instability (CSI) rodent model of stress appears to be the best fit for the social nature of females. This study analyzed the effects of CSI on female mouse behavior, hippocampal cytokine expression, tryptophan metabolism and monoaminergic activity. The activity of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes were also measured. Results showed a decrease in sucrose consumption in stressed subjects, indicative of anhedonic behavior and an increase in climbing activity in the forced swimming test (FST) and in whisking behavior, which have been associated with anxiety. Decreased interleukin-10 (IL-10) expression was found in the hippocampus of the stressed mice, while no differences in pro-inflammatory cytokine expression and tryptophan (TRYP), kynurenine (KYN) or 3-hydroxy kynurenine (3-HK) levels were found. Increased hippocampal serotoninergic and noradrenergic activity was observed in stressed mice. The higher plasma corticosterone and lower hypothalamic glucocorticoid receptor (GR) expression levels showed an increase in HPA activity after CSI. No differences were found in the plasma estradiol levels or the central estrogen receptors (ERα and ERβ) expression levels. These data indicate that the CSI stress-induced behavioral and physiological changes associated with anxiety and depressive disorders. Although additional studies are warranted, the results suggest an involvement of anti-inflammatory cytokines in the biobehavioral effects of social stress in female mice.

Involvement of estrogen receptor β in androgen receptor-induced growth inhibition in prostate cancer PC-3 cells.

Previous studies have suggested that changes in sex hormone receptor expression may be associated with the initiation and progression of prostate cancer (PCa). Therefore, the present study aimed to investigate the association and possible pathways between two sex hormone receptors and PCa by measuring the expression levels of the androgen receptor (AR) and the estrogen receptor subtypes alpha (ERα) and beta (ERβ) in prostatic cancer PC-3 cell lines. The pcDNA3.1-hERβ plasmid was transfected into PC-3 cell lines. The expression levels of AR, ERα and ERβ were detected at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR) and quantitative PCR (qPCR). The results demonstrated that the expression levels of AR, ERβ and ERα were downregulated to different degrees: ERβ test group vs. PC-3 cell group (P=0.000; 95% confidence interval: 0.9803–1.6331). ERβ and AR expression was detected continuously in the PC-3 cells, but the expression of ERα was not. AR expression levels exhibited an upward trend whilst the expression of ERβ demonstrated a marked downward trend. There is a correlation between the expression levels of ERβ and the incidence of PCa, and ERβ may inhibit the growth of PC-3 cell lines by regulating the expression levels of AR. ERβ may provide a novel target for PCa therapies.

Small leucine zipper protein functions as a negative regulator of estrogen receptor α in breast cancer

The nuclear transcription factor estrogen receptor α (ERα) plays a critical role in breast cancer progression. ERα acts as an important growth stimulatory protein in breast cancer and the expression level of ERα is tightly related to the prognosis and treatment of patients. Small leucine zipper protein (sLZIP) functions as a transcriptional cofactor by binding to various nuclear receptors, including glucocorticoid receptor, androgen receptor, and peroxisome proliferator-activated receptor γ. However, the role of sLZIP in the regulation of ERα and its involvement in breast cancer progression is unknown. We found that sLZIP binds to ERα and represses the transcriptional activity of ERα in ERα-positive breast cancer cells. sLZIP also suppressed the expression of ERα target genes. sLZIP disrupted the binding of ERα to the estrogen response element of the target gene promoter, resulting in suppression of cell proliferation. sLZIP is a novel co-repressor of ERα, and plays a negative role in ERα-mediated cell proliferation in breast cancer.

Effects of low dose of bisphenol A on the proliferation and mechanism of primary cultured prostate epithelial cells in rodents.

Bisphenol A (BPA) is a well-known endocrine disruptor compound (EDC) that aggravates testosterone-induced benign prostate hyperplasia by increasing the relative weight of the ventral and dorsolateral prostate in rats. This phenomenon is primarily attributed to the exogenous estrogen effect of BPA. However, the direct effect of BPA on prostate cells has not been characterized. The present study investigated the proliferative effect and possible mechanisms of action of BPA on the prostatic epithelium of rats. The ventral prostate epithelial cells were cultured in vitro and the proliferation effects of BPA on cells were studied. The cells were identified as prostatic epithelial cells, and cell viability, cell apoptosis and the expressions of androgen receptors (AR) and estrogen receptors (ER), were detected. It was observed that 0.01–1 nM BPA promoted cell growth, with 1 nM BPA inducing the greatest increase in the rate of cell growth. However, BPA-treated cells exhibited no marked morphological changes compared with the control group. The cell apoptosis rate in each BPA-treated group was lower compared with the control group. The expression levels of ERα and ERβ increased, but the expression of AR decreased. The present study demonstrated that environmental exposure to BPA directly promoted the proliferation of prostate cells in rats through increasing the expression of estrogen receptors, reducing the expression of androgen receptors of the cells and decreasing apoptosis-induced cell death.

Postpartum estrogen withdrawal impairs GABAergic inhibition and LTD induction in basolateral amygdala complex via down-regulation of GPR30

Postpartum estrogen (E2) withdrawal is known to be a particularly vulnerable time for depressive symptoms. In this study, ovariectomized (OVX) mice were treated with co-administration of estradiol benzoate and progesterone (E2/P4) followed by administration of E2 alone (E2) and a subsequent E2 withdrawal (EW) to mimic the hormonal changes during pregnancy and postpartum. The objective of this study was to investigate the influence of E2 withdrawal after hormone-simulated pregnancy on synaptic function and plasticity in basolateral amygdala complex (BLA). In comparison to control mice, EW mice spent less time in the central portion of open-field test and open arms of elevated plus-maze. Excitatory postsynaptic potentials (EPSPs) slopes at external capsule BLA synapse were reduced in E2/P4-mice, recovered in E2-mice, and increased in EW-mice. EW-mice showed a significant increase in duration of EPSPs and paired-pulse inhibition (PPI) with multi-spike responses of EPSPs and impairment of long-term depression (LTD) induction, which were corrected by GABAAR agonist muscimol. Levels of estrogen receptor (ER) GPR30, ERα and ERβ expression in BLA of EW-mice were lower than those in control mice. The bath-application of GPR30 agonist G-1 in BLA of EW-mice recovered the GABAAR-mediated inhibition and LTD indication, but ERβ agonist DPN or ERα agonist PPT could not. A single BLA-injection of G-1 rather than DPN or PPT in EW-mice could partially relieve the anxiety-like behaviors. The results indicate that postpartum E2 withdrawal causes dysfunction of GABAAR-mediated inhibition in the BLA through reducing GPR30 expression, which impairs LTD induction and causes anxiety-like behaviors.