Aromatase and regulating the estrogen:androgen ratio in the prostate gland
Aromatase and regulating the estrogen:androgen ratio in the prostate gland
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DOI：
10.1016/j.jsbmb.2009.10.015
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发表时间：
2010-02-28
影响因子：
4.1
通讯作者：
Risbridger, Gail P.
中科院分区：
文献类型：
--
作者：
Ellem, Stuart J.;Risbridger, Gail P.
虽然雄激素和雌激素都在前列腺中发挥重要作用，但它们的联合作用-特别是它们的平衡-对于维持成年期前列腺健康和组织稳态至关重要。在男性中，血清睾酮水平在21岁至85岁之间下降约35%，而雌二醇水平保持不变或增加。这种雄激素：雌激素（T：E）比例的变化与良性和恶性前列腺疾病的发展有关。雄激素产生雌激素是由芳香化酶介导的，芳香化酶的异常表达在许多组织的恶性发展中起着关键作用。正常前列腺在间质内表达芳香化酶，而在恶性肿瘤中存在上皮表达的诱导，改变了启动子利用。这可能最终导致与疾病发展相关的T：E比例改变。雌激素和T：E平衡在前列腺中的作用由于雌激素受体α和β的差异作用而进一步复杂化。ER α的刺激导致异常增殖、炎症和癌前病变;而ER β的激活似乎对细胞增殖有有益的影响，并对癌发生有假定的保护作用。总体而言，这些数据表明，正常前列腺的稳态涉及雄激素和雌激素之间的微调平衡。这已经确定了雌激素，除了雄激素之外，作为维持正常前列腺健康的组成部分，也是前列腺疾病的重要介质。(C)2009爱思唯尔有限公司保留所有权利。
Although androgens and estrogens both play significant roles in the prostate, it is their combined action - and specifically their balance - that is critically important in maintaining prostate health and tissue homeostasis in adulthood. In men, serum testosterone levels drop by about 35% between the ages of 21 and 85 while estradiol levels remain constant or increase. This changing androgen:estrogen (T:E) ratio has been implicated in the development of benign and malignant prostate disease.The production of estrogens from androgens is mediated by the aromatase enzyme, the aberrant expression of which plays a critical role in the development of malignancy in a number of tissues. The normal prostate expresses aromatase within the stroma, while there is an induction of epithelial expression in malignancy with altered promoter utilisation. This may ultimately lead to an altered T:E ratio that is associated with the development of disease.The role of estrogen and the T:E balance in the prostate is further complicated by the differential actions of both estrogen receptors, alpha and beta. Stimulation of ER alpha leads to aberrant proliferation, inflammation and pre-malignant pathology; whereas activation of ER beta appears to have beneficial effects regarding cellular proliferation and a putative protective role against carcinogenesis.Overall, these data reveal that homeostasis in the normal prostate involves a finely tuned balance between androgens and estrogens. This has identified estrogen, in addition to androgens, as integral to maintaining normal prostate health, but also as an important mediator of prostate disease. (C) 2009 Elsevier Ltd. All rights reserved.