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Expression of oestrogen receptor-α and oestrogen receptor-β in prostate cancer

Chinese Medical Journal 2007年第18期120卷 1611-1615页

作者： YANG Guo-sheng WANG Ying WANG Ping CHEN Zhao-dian Department of Urology （Yang GS Wang P and Chen ZD）Operating Room （Wang Y） First Affiliated Hospital ZhejiangUniversity School of Medicine Hangzhou 310003 China

Background Recent studies have suggested that estrogens are involved in normal and abnormal prostate growth, though their exact role is still controversial. oestrogens exert inhibitory and stimulatory effects on prostate gland, but the expression of oestrogen receptor-α （ERα） and oestrogen receptor-β （ERβ） in malignant prostate tissue remains unresolved. We determined ERa and ERβ in prostate cancer and investigated the relationship between expression of ER and pathological features of prostate carcinoma. Methods Thirty-two cases of prostate cancer, 12 cases of normal prostate tissue and 32 cases of benign prostate hyperplasia were analyzed for the expression of ERa and ERβ using semiquantitative, reverse transcription polymerase chain reaction （RT-PCR） and the products sequenced. Results Comparisons of the normal, hyperplastic and tumour prostate tissues indicated an overexpression of ERa in tumour specimens （P〈0.01）. However, the expression of ERβ significantly reduced in tumour tissues compared with normal and hyperplastic specimens （P〈0.01）, suggesting that severe pathological features of prostate cancer were associated with lower ERβ expression. Spearman analysis showed negative correlation between ERβ expression and tumour stage, grade （-0.67, -0.43, respectively, both P〈0.05）, and a positive correlation between ERα expression and tumour stage, grade （0.51, 0.57, respectively, both P〈0.01）. Our analysis also showed that hormone refractory, prostate cancer, compared with hormone dependent, prostate cancer, displayed a decreased expression of ERβ （P〈0.01） and an increased expression of ERa. Conclusions ERα and ERβ may play important roles in the development of prostate cancer. The decrease in ERβ expression is associated with higher Gleason grade tumours and prostate cancer with higher metastatic potential. The loss of ERβ could be one of the key processes leading to uncontrolled growth of prostate epithelial cells.

关键词： oestrogen prostatic neoplasms prostatic hyperplasia

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Sex differences and effects of oestrogen in rat gastric mucosal defence

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World Journal of Gastroenterology 2017年第3期23卷 426-436页

作者： Richard Shore Hakan Bjorne Yoko Omoto Anna Siemiatkowska Jan-Ake Gustafsson Mats Lindblad Lena Holm Department of Clinical Sciences Intervention and Technology(CLINTEC)Karolinska InstitutetS-14186 StockholmSweden Function Perioperative Medicine and Intensive Care Karolinska University HospitalS-17176 StockholmSweden Department of Physiology and Pharmacology Karolinska InstitutetS-17177 StockholmSweden Department of Endocrine and Breast Surgery Graduate School of Medical ScienceKyoto Prefectural University of Medicine 465 Kajii-choHirokoji AgaruKawaramachi-doriKamigyo-kuKyoto 602-0841Japan Department of Medical Cell Biology Uppsala UniversityS-75123 UppsalaSweden Center of Nuclear Receptors and Cell Signalling University of HoustonHoustonTX 77004United States Department of Clinical Sciences Intervention and Technology(CLINTEC)Karolinska InstitutetS-14186 StockholmSweden

AIM To evaluate sex differences and the effects of oestrogen administration in rat gastric mucosal *** Sex differences in gastric mucus thickness and accumulation rate, absolute gastric mucosal blood flow using microspheres, the integrity of the gastric mucosal epithelium in response to a chemical irritant and the effects of oestrogen administration on relative gastric mucosal blood flow in an acute setting was assessed in an in vivo rat experimental model. Subsequently, sex differences in the distribution of oestrogen receptors and calcitonin gene related peptide in the gastric mucosa of animals exposed to oestrogen in the above experiments was evaluated using *** The absolute blood flow in the GI-tract was generally higher in males, but only significantly different in the corpus part of the stomach (1.12 ± 0.12 m L/min·g in males and 0.51 ± 0.03 m L/min·g in females) (P = 0.002). After removal of the loosely adherent mucus layer the thickness of the firmly adherent mucus layer in males and females was 79 ± 1 μm and 80 ± 3 μm respectively. After 60 min the mucus thickness increased to 113 ± 3 μm in males and 121 ± 3 μm in females with no statistically significant difference seen between the sexes. Following oestrogen administration(0.1 followed by 1 μg/kg·min), mean blood flow in the gastric mucosa decreased by 31% [68 ± 13 perfusion units (PFU)] in males which was significantly different compared to baseline(P = 0.02). In females however, mean blood flow remained largely unchanged with a 4% (5 ± 33 PFU) reduction. The permeability of the gastric mucosa increased to a higher level in females than in males (P = 0.01) after taurocholate challenge. However, the calculated mean clearance increase did not significantly differ between the sexes [0.1 ± 0.04 to 1.1 ± 0.1 m L/min·100 g in males and 0.4 ± 0.3 to 2.1 ± 0.3 m L/min·100 g in females(P = 0.065)]. There were no significant differences between 17β-Estradiol treated males (me

关键词： Sex differences Gastric mucosal defence Blood flow oestrogen Gastric physiology Mucus

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Effect of oestrogen on Ros production and MCP-1 expression in ovariectomized salt-loaded Dahl salt-sensitive rats

Effect of oestrogen on Ros production and MCP-1 expression i...

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2008北京国际生理科学学术大会

作者： SHIGEMOTO Fujii HIROAKI Kosaka Department of Cardiovascular Physiology Medical FacultyKagawa UniversityKagawaJapan

Introduction Although the cardioprotective benefits of oestrogens appear to be well-established,the mechanism of this effect remains ***-1 is found to be a major factor in the development of atherosclerosis and is implicated in the pathogenesis of vascular *** previously demonstrated an antioxidant treatment decrease the overexpression of MCP-1 in hypertensive Dah1 salt-sensitive *** this study,we propose that oestrogen may inhibit the atherosclerotic process by modulate the expression of MCP-1 and this may be related to an antioxidative effect of *** To investigate the effects of oestrogen supplementation after ovariectomy on systolic blood pressure,production of reactive oxygen species(ROS)and expression of mRNA of monocyte chemoattractant protein 1(MCP-1)on different sodium content diet in the female Dah1 salt-sensitive *** At 8 weeks of age,DSS female rats were ovariectomized or sham-operated and were fed either high NaCl(8%,HS)or normal NaCl(0.24%,N)*** rats were treated with 17β-estradiol for 4 weeks. The systolic blood pressure was measured by tail-cuff *** production in aorta was determined with the use of lucigenin *** expression of MCP-1 mRNA was assessed by reverse transcription -polymerase chain *** expresion of MCP-1,and macrophage infiltration were examined by immunohistochemical *** The systolic blood pressure and superoxide production in aorta of ovariectomized rats was significantly higher than that of sham-operated rats with high salt diet,and both of these increases was suppressed by estrogen *** loading significantly interacted on the expression of ***-1 mRNA expression in aorta was significantly enhanced by salt loading in ovariectomized rats,which was counteracted by oestrogen *** increased MCP-1 protein expression and ED1-positive cells mainly in the media and adventitia of aorta,as we

关键词： MCP-1 ROS oestrogen hypertension

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The differential effects of prostate stromal cells derived from different zones on prostate cancer epithelial cells under the action of sex hormones

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Asian Journal of Andrology 2011年第6期13卷 798-805页

作者： Qi Jiang Bang-Min Han Fu-Jun Zhao Yan Hong Shu-Jie Xia Department of Urology Shanghai First People＇s Hospital Institute of Urology Shanghai Jiao Tong University Shanghai 200080 China

It is well known that prostate cancer （PCa） occurs predominantly in the peripheral zone （PZ）, whereas benign prostatic hyperplasia （BPH） typically develops in the transition zone. To identify possible mechanisms underlying zonal differences, we compared the effects of prostate stromal cells derived from the peripheral zone （PZsc） and the transition zone （TZsc） on a PCa epithelial cell line （PC3） in the presence of sex hormones. First, we observed that androgen receptor （AR） mRNA was more highly expressed in PZsc than TZsc when the cells were treated with dihydrotestosterone （DHT） and β-oestradiol （E2）（P〈0.05）. By ELISA, we looked for differences in the secretion of peptide growth factors from PZsc and TZsc. We found that keratinocyte growth factor （KGF） secretion increased with increasing concentrations of DHT （P〉0.01） and was higher in PZsc than TZsc. Under treatment with DHT plus E2, PZsc secreted more transforming growth factor-β1 （TGF-β1） than TZsc, but this pattern was reversed when the cells were treated with E2 only. With increasing concentrations of DHT, insulin-like growth factor-1 （IGF-1） secretion increased in PZsc but decreased in TZsc. To further characterize the effects of PZsc and TZsc on PC3 cells, we developed a coculture model and performed MTT assays, Western blot analysis and real-time RT-PCR. We found that PZsc promoted PC3 cell proliferation and progression better than TZsc, particularly when treated with 10 nmoll^- 1 DHT plus 10 nmoll^-1 E2. In conclusion, our data suggest that PZsc may have a greater capacity to induce PCa development and progression than TZsc via growth factors regulated by sex hormones. These findings provide possible mechanisms underlying zonal differences in prostate diseases, which may aid the search for novel therapeutic targets for PCa.

关键词： androgen growth factor oestrogen prostate cancer stromal cell

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The association of aromatase （CYP19） gene variants wil sperm concentration and motility

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Asian Journal of Andrology 2011年第2期13卷 292-297页

作者： Leandros Lazaros Nectaria Xita Apostolos Kaponis Elissavet Hatzi Nicolaos Plachouras Nicolaos Sofikitis Konstantinos Zikopoulos Ioannis Georgiou Genetics and IVF Unit Department of Obstetrics and Gynaecology Medical School University of Ioannina Ioannina 45110 Greece Department of Endocrinology MedicalSchool University of Ioannina Ioannina 45110 Greece Department of Urology Medical School University of Ioannina Ioannina 45110 Greece

The irreversible transformation of androgens into oestrogens is catalysed by cytochrome P450 aromatase. In the present study, we explored the contribution of the （TTTA）n polymorphism in the aromatase gene （CYP19） to sperm concentration and motility. Ninety normozoospermic and 60 oligospermic men were examined during infertility examinations. DNA was extracted from spermatozoa, and the CYP19（TTTA）n polymorphism was genotyped by PCR. Genotype analysis revealed six CYP19（TTTA）n alleles with 7-12 repeats. The allelic distribution of the CYP19（TTTA）n polymorphism differed between normozoospermic and oligospermic men （P〈0.01）. Oligospermic men less frequently had long CYP19 alleles than did normozoospermic men （25 and 37.8%, respectively; P〈0.02）. The higher frequency of short CYP19alleles in oligospermic men compared to normozoospermic men （43.3 and 28.3%, respectively; P〈0.01） was primarily due to the distribution of the CYP19 （TTTA）7 allele. The CYP19 （TTTA）7 allele was associated with lower sperm concentration in normozoospermic men {P〈0.01） and in the total study population {P〈0.01）; it was also associated with lower sperm motility in normozoospermic men （P〈0.05） and in the total study population （P〈0.01）. In conclusion, the CYP19 （TTTA）7 allele probably impairs aromatase activity, which in turn alters aromatase and oestrogen levels in the testis, leading to decreased sperm concentration and motility. These findings support the significance of cytochrome P450 aromatase in human spermatogenesis and consequently in semen quality.

关键词： androgen male infertility oestrogen semen quality spermatogenesis

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The influence of sex steroid hormones on the response to trauma and burn injury

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Burns & Trauma 2017年第3期5卷 173-185页

作者： K Al-Tarrah N Moiemen JM Lord Institute of Inflammation and Ageing Birmingham University Medical School B152TT Birmingham UK Scar Free Foundation Centre for Burns Research University Hospital Birmingham Foundation Trust B152WB Birmingham UK Scar Free Foundation Centre for Burns Research University Hospital Birmingham Foundation Trust B152WB Birmingham UK Institute of Inflammation and Ageing Birmingham University Medical School B152TT Birmingham UK

Trauma and related sequelae result in disturbance of homeostatic mechanisms frequently leading to cellular dysfunction and ultimately organ and system failure. Regardless of the type and severity of injury, gender dimorphism in outcomes following trauma have been reported, with females having lower mortality than males, suggesting that sex steroid hormones (SSH) play an important role in the response of body systems to trauma. In addition, several clinical and experimental studies have demonstrated the effects of SSH on the clinical course and outcomes following injury. Animal studies have reported the ability of SSH to modulate immune, inflammatory, metabolic and organ responses following traumatic injury. This indicates that homeostatic mechanisms, via direct and indirect pathways, can be maintained by SSH at local and systemic levels and hence result in more favourable prognosis. Here, we discuss the role and mechanisms by which SSH modulates the response of the body to injury by maintaining various processes and organ functions. Such properties of sex hormones represent potential novel therapeutic strategies and further our understanding of current therapies used following injury such as oxandrolone in burn-injured patients.

关键词： Burn Trauma Sex hormones Sex steroid hormones Testosterone Estradiol oestrogen

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The role of nitric oxide in cancer

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Cell Research 2002年第Z2期 311-320页

作者： WEIMING XU, Li ZHI LIU, MARILENA LOIZIDOU, MOHAMED AHMED, IAN G CHARLES Wolfson Institute for Biomedical Research, Cruciform Building, Gower Street, UCL, London, WC1 E 6AUUK Department of Surgery, Charles Bell House, 67-73 Riding House Street, UCL, London W1W 7EJ, UK

Nitric oxide (NO) is a pleiotropic regulator, critical to numerous biological processes, including va-sodilatation, neurotransmission and macrophage-mediated immunity. The family of nitric oxide synthases (NOS) comprises inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS). Interestingly, various studies have shown that all three isoforms can be involved in promoting or inhibiting the etiology of cancer. NOS activity has been detected in tumour cells of various histogenetic origins and has been associated with tumour grade, proliferation rate and expression of important signaling components associated with cancer development such as the oestrogen receptor. It appears that high levels of NOS expression (for example, generated by activated macrophages) may be cytostatic or cytotoxic for tumor cells, whereas low level activity can have the opposite effect and promote tumour growth. Paradoxically therefore, NO (and related reactive nitrogen species) may have both genotoxic and angiogenic pro

关键词： nitric oxide oestrogen cancer p53 PARP DNA-PKcs.

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Colorectal cancers and chlorinated water

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World Journal of Gastrointestinal Oncology 2016年第4期8卷 402-409页

作者： Ahmed Mahmoud El-Tawil Department of Surgery University Hospital Birmingham

Published reports have revealed increased risk of colorectal cancers in people exposed to chlorinated drinking water or chemical derivatives of chlorination. oestrogen plays a dual positive functions for diminishing the possibilities of such risk by reducing the entrance, and increasing the excretion, of these chemicals. In addition, there are supplementary measures that could be employed in order to reduce this risk further, such as boiling the drinking water, revising the standard concentrations of calcium, magnesium and iron in the public drinking water and prescribing oestrogen in susceptible individuals. Hypo-methylation of genomic DNA could be used as a biological marker for screening for the potential development of colorectal cancers.

关键词： Chlorinated drinking water oestrogen Sex hormones Gender Colorectal cancers Trihalomethanes Carcinogenesis DNA hypo-methylation

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