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Sex Steroid Receptors in Male Human maaaer: Expression and Biological Function

机译:男性人类中的类固醇受体:表达和生物学功能。

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Introduction. In male, lower urinary tract symptoms (LUTS) have been associated, beside benign prostatic hyper-plasia, to some unexpected comorbidities (hypogonadism, obesity, metabolic syndrome), which are essentially characterized by an unbalance between circulating androgens/estrogens. Within the bladder, LUTS are linked to RhoA/Rho-kinase (ROCK) pathway overactivity. Aim. To investigate the effects of changing sex steroids on bladder smooth muscle. Methods. ERalpha, ERbeta, GPR30/GPER1 and aromatase mRNA expression was analyzed in male genitourinary tract tissues, and cells isolated from bladder, prostate, and urethra. Estrogen and Gl effect on RhoA/ROCK signaling output like cell migration, gene expression, and cytoskeletal remodeling, and [Ca~(2+)]; was also studied in hB cells. Contractile studies on bladder strips from castrated male rats supplemented with estradiol and testosterone was also performed. Main Outcome Measures. The effects of classical (ERalpha, ERbeta) and nonclassical (GPR30/GPER1) estrogen receptor ligands (17beta-estradiol and G1, respectively) and androgens on RhoA/ROCK-.mediated cell functions were studied in hB cells. Contractility studies were also performed in bladder strips from castrated male rats supplemented with testosterone or estradiol. Results. Aromatase and sex steroid receptors, including GPR30, were expressed in human bladder and mediates several biological functions. Both 17beta-estradiol and G1 activated calcium transients and induced RhoA/ROCK signaling (cell migration, cytoskeleton remodeling and smooth muscle gene expression). RhoA/ROCK inhibitors blunted these effects. Estrogen-, but not androgen-supplementation to castrated rats increased sensitivity to the ROCK inhibitor, Y-27632 in isolated bladder strips. In hB cells, testosterone elicited effects similar to estrogen, which were abrogated by blocking its aromatization through letrozole. Conclusion. Our data indicate for the first time that estrogen-more than and...
机译:介绍。在男性中,除了良性前列腺增生外,下尿路症状(LUTS)还与一些意想不到的合并症(性腺功能减退,肥胖,代谢综合征)有关,这些合并症的主要特征是循环中的雄激素/雌激素不平衡。在膀胱内,LUTS与RhoA / Rho激酶(ROCK)通路过度活跃有关。目标。调查改变性类固醇对膀胱平滑肌的影响。方法。分析了男性泌尿生殖道组织以及从膀胱,前列腺和尿道分离的细胞中的ERalpha,ERbeta,GPR30 / GPER1和芳香化酶mRNA的表达。雌激素和Gl对RhoA / ROCK信号输出的影响,如细胞迁移,基因表达和细胞骨架重塑以及[Ca〜(2+)];在hB细胞中也进行了研究。还对去势雄性大鼠补充雌二醇和睾丸激素的膀胱条进行了收缩研究。主要观察指标。在hB细胞中研究了经典(ERalpha,ERbeta)和非经典(GPR30 / GPER1)雌激素受体配体(分别为17beta-雌二醇和G1)和雄激素对RhoA / ROCK介导的细胞功能的影响。还对cast割的雄性大鼠补充睾丸激素或雌二醇的膀胱试纸进行了收缩性研究。结果。芳香酶和包括GPR30在内的性类固醇受体在人膀胱中表达,并介导多种生物学功能。 17β-雌二醇和G1均激活钙瞬变并诱导RhoA / ROCK信号传导(细胞迁移,细胞骨架重塑和平滑肌基因表达)。 RhoA / ROCK抑制剂减弱了这些作用。去势大鼠补充雌激素,但不补充雄激素,增加了对孤立的膀胱条中ROCK抑制剂Y-27632的敏感性。在hB细胞中,睾丸激素引起的作用类似于雌激素,后者通过来曲唑阻断其芳香化作用而被废止。结论。我们的数据首次表明,雌激素超过...

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