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

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

亮丙瑞林对ER阳性绝经前乳腺癌化疗患者卵巢功能及骨密度的影响

目的:探讨亮丙瑞林对雌激素受体(ER)阳性绝经前乳腺癌化疗患者卵巢功能及骨密度(BMD)的影响。方法:选取2020年1月—2022年8月丰城市人民医院收治的82例ER阳性绝经前乳腺癌患者的病历资料进行回顾性分析,根据治疗方式分为化疗组(n=41)和亮丙瑞林组(n=41)。化疗组患者予以AC-T辅助化疗,亮丙瑞林组在化疗组的基础上联合亮丙瑞林治疗。比较两组患者疗效、卵巢功能、BMD及月经情况。结果:亮丙瑞林组的总有效率高于化疗组(P<0.05)。治疗后,两组血清雌二醇(E2)水平均明显降低,血清促黄体生成素(LH)、卵泡刺激素(FSH)水平均明显升高(P<0.05);亮丙瑞林组患者的血清LH、FSH水平均明显高于化疗组,血清E2水平明显低于化疗组(P<0.05)。治疗后,两组左髋部、腰椎的BMD水平均明显降低(P<0.05);两组比较差异均无统计学意义(P>0.05)。亮丙瑞林组的闭经时间、月经恢复正常时间均较化疗组短,月经复潮率较化疗组高(P<0.05)。结论:亮丙瑞林可保护ER阳性绝经前乳腺癌化疗患者卵巢功能,可有效提高疗效,但可能会导致患者BMD下降,需要在治疗期间注意监测BMD变化,降低骨质疏松发生风险。

乳腺癌ER、AR表达与术前MRI征象的相关性分析

目的探讨乳腺癌ER、AR表达与术前MRI征象的相关性。方法收集甘肃省妇幼保健院2019年1月至2022年1月乳腺癌患者共计234例,依据术后免疫组化将其分为ER、AR双表达组、共计155例,ER、AR非双表达组、共计79例,采用Sperman及两独立样本t检验对ER、AR双表达与术前MRI征象进行单因素相关性分析,筛选存在统计学意义的MRI征象并进行多因素Logistic相关性分析。结果乳腺癌AR、ER表达与肿瘤形态之间差异无统计学意义(均P>0.05),与瘤体直径、环形强化及瘤周水肿之间差异具有统计学意义(均P<0.05),乳腺癌AR、ER双表达者肿瘤直径更小,环形强化及瘤周水肿更少见,二元Logistic回归分析表明环形强化(OR=0.421,P=0.041),瘤周水肿(OR=0.505,P=0.025)与乳腺癌AR、ER双表达相关。结论术前MRI征象与乳腺癌AR、ER双表达有较好的相关性,乳腺癌AR、ER双表达者瘤周水肿、环形强化少见,肿瘤组织学分级低,侵袭性弱。

Estrogen receptors in gastric cancer:Advances and perspectives

Worldwide, gastric cancer is one of the most common malignancies with high mortality. Various aspects of thedevelopment and progression of gastric cancer continue to be extensively investigated in order to further our understanding and provide more effective means for the prevention, diagnosis, and treatment of the disease. Estrogen receptors(ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. There are two distinct forms of ERs, namely ERα and ERβ, with several alternative-splicing isoforms for each. They show distinct tissue distribution patterns and exert different biological functions. Dysregulation of ERs has been found to be associated closely with many diseases, including cancer. A number of studies have been conducted to investigate the role of ERs in gastric cancer, the possible mechanisms underlying these roles, and the clinical relevance of deregulated ERs in gastric cancer patients. To date, inconsistent associations of different ERs with gastric cancer have been reported. These inconsistencies may be caused by variations in in vitro cell models and clinical samples, including assay conditions and protocols with regard to different forms of ERs. Given the potential of the deregulated ERs as diagnostic/prognostic markers or therapeutic targets for gastric cancer, it will be important to identify/confirm the association of each ER isoform with gastric cancer, to determine the specific roles and interactions that these individual ER isoforms play under specific conditions in the development and/or progression of gastric cancer, and to elucidate precisely these mechanisms. In this review, we summarize the achievements from early ER studies in gastric cancer to the most up-to-date discoveries, with an effort to provide a comprehensive understanding of the role of ERs roles in gastric cancer and its possible mechanisms. Furthermore, we propose directions for future investigations.

Prognostic implications of estrogen receptor 1 and vascular endothelial growth factor A expression in primary gallbladder carcinoma

AIM: To investigate the prognostic significance of estrogen receptor 1(ER1) and vascular endothelial growth factor A(VEGF-A) expression in primary gallbladder carcinoma(GBC) to identify new prognostic markers for this malignancy.METHODS: Using immunohistochemistry, we investigated ER1 and VEGF-A expression in 78 GBC and 78 cholelithiasis(CS) tissues. The results were correlated with clinicopathological features. Univariate and multivariate analyses were performed to evaluate the relationship between ER1 and VEGF-A expression and patients' prognosis. Further Kaplan-Meier survival analysis was also performed. RESULTS: ER1 and VEGF-A expression was significantly higher in GBC compared with CS(47/78 vs 28/78, P < 0.05; 51/78 vs 33/78, P < 0.05). ER1 expression was correlated with gender(P < 0.05) and VEGF-A expression was correlated with tumor differentiation in GBC patients(P < 0.05). In univariate analysis, age and tumor node metastasis(TNM) stage were factors associated with GBC prognosis(P < 0.05). Although there was no statistical difference between the expression of ER1 or VEGF-A and overall survival, the high expression of ER1 combined with VEGF-A predicted a poor prognosis for GBC patients(16.30 ± 1.87 vs 24.97 ± 2.09, log-rank P < 0.05). In multivariate analysis, combined expression of ER1 and VEGF-A and TNM stage were independent prognostic factors for GBC patients(P < 0.05).CONCLUSION: Combined expression of ER1 and VEGF-A is a potential prognostic marker for GBC patients. Clinical detection of ER1 and VEGF-A in surgically resected GBC tissues would provide animportant reference for decision-making of postoperative treatment programs.

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, estrogen receptors, and hepatocellular carcinoma: Are we there yet?

A protective role of the sex steroid hormone estrogenin hepatocellular carcinoma(HCC) was suggested a few decades ago according to clinical data showing higher HCC morbidity and mortality among males. Several recent studies further confirmed the anti-cancer effects of estrogen in the liver. However, it remains to be identified how to exploit estrogen signalling within clinical settings for HCC treatment. There are several unresolved issues related to the estrogen pathway in liver cells. The main problems include the absence of a clear understanding of which estrogen receptor(ER) isoform is predominantly expressed in normal and malignant liver cells, the ER isoform expression difference between males and females, and which ER isoform should be targeted when designing HCC therapy. Some of those questions were recently addressed by Iyer and coauthors. The current editorial review critically analyses the study by Iyer et al(WJG, 2017) that investigated the expression of ER subtypes in liver samples collected from patients with a healthy liver, hepatitis C virus cirrhosis, and HCC. ER presence was evaluated in association with gender, intracellular localization, inflammation marker NF-kB, and proliferation-related effector cyclin D1. The study limitations and advantages are discussed in light of recent advances in the HCC and estrogen signalling areas.

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.

Role of estrogen receptor β selective agonist in ameliorating portal hypertension in rats with CCl4-induced liver cirrhosis

AIM: To investigate the role of diarylpropionitrile(DPN), a selective agonist of estrogen receptor β(ERβ), in liver cirrhosis with portal hypertension(PHT) and isolated hepatic stellate cells(HSCs).METHODS: Female Sprague-Dawley rats were ovariectomized(OVX), and liver cirrhosis with PHT was induced by CCl4 injection. DPN and PHTPP, the selective ERβ agonist and antagonist, were used as drug interventions. Liver fibrosis was assessed by hematoxylin and eosin(HE) and Masson's trichrome staining and by analyzing smooth muscle actin expression. Hemodynamic parameters were determined in vivo using colored microspheres technique. Protein expression and phosphorylation were determined by immunohistochemical staining and Western blot analysis. Messenger RNA levels were analyzed by quantitative real-time polymerase chain reaction(q RT-PCR). Collagengel contraction assay was performed using gel lattices containing HSCs treated with DPN, PHTPP, or Y-27632 prior to ET-1 addition. RESULTS: Treatment with DPN in vivo greatly lowered portal pressure and improved hemodynamic parameters without affecting mean arterial pressure, which was associated with the attenuation of liver fibrosis and intrahepatic vascular resistance(IHVR). In CCl4-treated rat livers, DPN significantly decreased the expression of Rho A and ROCK Ⅱ, and even suppressed ROCK Ⅱ activity. Moreover, DPN remarkedly increased the levels of endothelial nitric oxide synthase(e NOS) and phosphorylated e NOS, and promoted the activities of protein kinase G(PKG), which is an NO effector in the liver. Furthermore, DPN reduced the contractility of activated HSCs in the 3-dimensional stress-relaxed collagen lattices, and decreased the ROCK Ⅱ activity in activated HSCs. Finally, in vivo /in vitro experiments demonstrated that MLC activity was inhibited by DPN.CONCLUSION: For OVX rats with liver cirrhosis, DPN suppressed liver Rho A/ROCK signal, facilitated NO/PKG pathways, and decreased IHVR, giving rise to reduced portal pressure. Therefore, DPN represents a relevant treatment choice against PHT in cirrhotic patients, especially postmenopausal women.

Current medical treatment of estrogen receptor-positive breast cancer

Approximately 80% of breast cancers(BC) are estrogen receptor(ER)-positive and thus endocrine therapy(ET) should be considered complementary to surgery in the majority of patients. The advantages of oophorectomy, adrenalectomy and hypophysectomy in women with advanced BC have been demonstrated many years ago, and currently ET consist of(1) ovarian function suppression(OFS), usually obtained using gonadotropinreleasing hormone agonists(Gn RHa);(2) selective estrogen receptor modulators or down-regulators(SERMs or SERDs); and(3) aromatase inhibitors(AIs), or a combination of two or more drugs. For patients aged less than 50 years and ER+ BC, there is no conclusive evidence that the combination of OFS and SERMs(i.e., tamoxifen) or chemotherapy is superior to OFS alone. Tamoxifen users exhibit a reduced risk of BC, both invasive and in situ, especially during the first 5 years of therapy, and extending the treatment to 10 years further reduced the risk of recurrences. SERDs(i.e., fulvestrant) are especially useful in the neoadjuvant treatment of advanced BC, alone or in combination with either cytotoxic agents or AIs. There are two types of AIs: type Ⅰ are permanent steroidal inhibitors of aromatase, while type Ⅱ are reversible nonsteroidal inhibitors. Several studies demonstrated the superiority of the third-generation AIs(i.e., anastrozole and letrozole) compared with tamoxifen, and adjuvant therapy with AIs reduces the recurrence risk especially in patients with advanced BC. Unfortunately, some cancers are or became ET-resistant, and thus other drugs have been suggested in combination with SERMs or AIs, including cyclin-dependent kinase 4/6 inhibitors(palbociclib) and mammalian target of rapamycin(m TOR) inhibitors, such as everolimus. Further studies are required to confirm their real usefulness.

Association between estrogen receptor β gene Rsa1 polymorphism and depressive disorder in peri-menopausal and menopausal women

Objective: To investigate estrogen receptor β (ERβ) gene Rsa1 polymorphism and concentration of estrogen, FSH and LH in serum in peri-menopausal and menopausal women with depressive disorder. Methods: Seventy-four peri-menopausal and menopausal women with depressive disorder met ICD-10 and CCMD-3 assessment criteria for depressive disorder were recruited. ERβ gene Rsa1 polymorphism was analyzed with PCR-RFLP. Serum levels of estrogen, FSH and LH were measured by magnetism-ELISA. Results: The respective frequency of ERβ gene Rsa1 polymorphism was no significant difference between women with depressive disorder and the healthy women (χ 2=1.106,P>0.05). The serum level of estrogen was lower in women with depressive disorder than in the healthy women (P<0.05). No difference was found for FSH and LH between two groups. Conclusion: ERβ gene Rsa1 polymorphism may be not associated with depressive disorder in the peri-menopausal and menopausal women. The serum level of estrogen is associated with depressive disorder in the peri-menopausal and menopausal women.

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.

Estrogen receptors as the novel therapeutic biomarker in non-small cell lung cancer

Although a wide range of studies have addressed the relationship between estrogen receptor(ER) expression and prognosis in non-small cell lung cancer(NSCLC), that relationship remains controversial. This is in large part because there is no consensus on the rate of ER expression in NSCLC or on the intracellular distribution of ER expression. This suggests that establishing the relationship between ER expression and prognosis will require standardization of the antibodies used as well as the definition of a positive response. For example, it is supposed from previous studies that ERs in the cytoplasm and nucleus have different relationships to prognosis than ERs in the cytoplasm. Moreover, ER signaling in NSCLC is known to be affected by aromatase, progesterone receptor and epidermal growth factor receptor mutation. However, there has been little functional analysis these mutants and subtypes. This review will focus on what is known about the role of ERs in NSCLC and whether ER can be a useful prognostic marker or therapeutic target in NSCLC.

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)

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.

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.

Polyubiquitination inhibition of estrogen receptor alpha and its implications in breast cancer

Estrogen receptor alpha(ERα) is detected in more than 70% of the cases of breast cancer. Nuclear activity of ERα, a transcriptional regulator, is linked to the development of mammary tumors, whereas the extranuclear activity of ERα is related to endocrine therapy resistance. ERα polyubiquitination is induced by the estradiol hormone, and also by selective estrogen receptor degraders, resulting in ERα degradation via the ubiquitin proteasome system. Moreover, polyubiquitination is related to the ERα transcription cycle, and some E3-ubiquitin ligases also function as coactivators for ERα. Several studies have demonstrated that ERα polyubiquitination is inhibited by multiple mechanisms that include posttranslational modifica-tions, intera-ctions with coregula-tors, a-nd forma-tion of specific protein complexes with ERα. These events are responsible for an increase in ERα protein levels and deregulation of its signaling in breast cancers. Thus, ERα polyubiquitination inhibition may be a key factor in the progression of breast cancer and resistance to endocrine therapy.

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）

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.