【摘要翻译】雌二醇受体上调和生长因子表达的关系

[文题]Relationship between upregulated oestrogen receptors and expression of growth factors in cultured, human, prostatic stromal cells exposed to estradiol or dihydrotestosterone

雌二醇受体上调与生长因子表达的关系：对在雌二醇或双氢睾酮中进行体外培养的人类前列腺间质细胞的研究结果
[来源]Prostate Cancer And Prostatic Diseases
[年、卷、期、页]Volume 7, Issue 1 , 2004, Pages 57-62
[作者]Smith, P; Rhodes, N P; Ke, Y; Foster, C S
[原文摘要]
Abstract
This study investigated the hypothesis that, in benign prostatic hyperplasia (BPH), upregulated oestrogen receptors (ER) and the action of androgens differentially regulate expression of stromal growth factors. Eight human prostatic stromal cell strains were subjected to a procedure to upregulate their ER by exposing them to 1 micromol 17beta-estradiol for 10 days followed by passage and growth in the absence of steroids. Four of the cell strains instead received 100 nmol dihydrotestosterone for 48 h. Immunoexpression of ERalpha, AR and six growth factors was quantified by flow cytometry in each case. Expression of ERalpha was significantly increased in six of eight cell strains. Expressions of six growth factors (FGF-2, FGF-7, IGF-1, TGF-beta(1) NGF and e NOS) were elevated but only for FGF-7 was it significant. There was a significant positive correlation between the change in ERalpha and the change in FGF-2 and FGF-7, but not the other growth factors. Exposure to dihydrotestosterone reduced expression of ERalpha and all six growth factors, compared with oestrogen-treated cells but not significantly. It is concluded that upregulated ERalpha in prostatic stroma may have a greater modulating influence on synthesis of certain growth factors than the direct action of androgens and, by enhancing synthesis of FGF-2 and FGF-7, could play a significant role in the development of BPH.Prostate Cancer and Prostatic Diseases (2004) 7, 57-62. doi:10.1038/sj.pcan.4500692 [Journal Article; In English; England]

[中文译文]
本研究为了证实这样一个假设：在良性前列腺增生病人中，上调雌二醇受体及雄激素水平，会通过不同的机制来调节间质生长因子的表达。本文通过将8个基质细胞株在含有1umol的17β雌二醇中培养10天，然后将其转入去除类固醇激素的培养基中进行传代和培养的方法来上调ER。另外4个细胞株直接在含有100nmol的双氢睾酮中培养48小时。用流式细胞计量术来检测每一组中ERA，AR和六种生长因子的定量免疫表达强度。结果发现在8个细胞株中，有6个的ERA有明显增加，六种生长因子(FGF-2, FGF-7, IGF-1, TGF-beta(1) NGF and e NOS)的表达也有增加，但只有FGF-7有显著性意义。ERα和FGF-2与FGF-7成正相关，而与其它的生长因子无关。和雌激素处理组相比，暴露在双氢睾酮中的细胞株ERα和六种生长因子都有所下降，但是没有显著性差别。结论是雌二醇通过上调前列腺基质内ERα来刺激特定生长因子的合成可能超过雄激素的直接刺激作用，而且，通过刺激FGF-2和FGF-7的合成，雌二醇在前列腺增生，前列腺癌和前列腺疾病的发病中起着重要作用。
评论：
近几年来，雌激素在良性前列腺增生的发病机制越来越受体研究者的重视，现已达成共识：雌激素肯定在良性前列腺增生的发生中起作重要作用，不论是单独的还是和雄激素协同的。但是雌激素致良性前列腺增生的机制研究一直没有进展，多数倾向于通过雌激素和ER结合后导致基质中特定的生长因子合成增加来促使良性前列腺增生的发生发展。至于究竟哪些因子起重要重要作用，国内外有较大争论。翻译本文的目的，一是它提供了一种较简单的上调ER的方法，并且用将免疫标记和流式细胞检测术结合在一起，方便的检测了多种生长因子的表达，这种方法值得借鉴。二是因为雌激素的作用本身有争论，想提出来大家讨论，我下学期的课题可能是这个，还望大家多指教。