Oestrogen and benign prostatic hyperplasia: effects on stromal cell proliferation and local formation from androgen
Oestrogen and benign prostatic hyperplasia: effects on stromal cell proliferation and local formation from androgen
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DOI：
10.1677/joe-07-0470
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发表时间：
2008-06-01
影响因子：
4
通讯作者：
Habib, Fouad K.
中科院分区：
文献类型：
--
作者：
Ho, Clement K. M.;Nanda, Jyoti;Habib, Fouad K.
雌激素被认为是良性前列腺增生（BPH）的一个原因。先前的动物研究得出的假设是，雌激素可以刺激前列腺生长，导致前列腺增生。在人类中，雌激素在BPH发病机制中的确切作用目前尚不清楚。我们研究了雌二醇对培养的前列腺增生细胞增殖的直接影响。雌二醇（10（-7）和10(-6)M）适度促进基质细胞增殖；这种刺激被抗雌激素ICI 182 780拮抗，表明雌激素受体（ER）介导的机制。相比之下，雌二醇对培养的上皮细胞的增殖没有影响。研究了基质细胞对雌激素反应的参数，包括两种ER亚型的表达和芳香化酶活性。免疫组织化学和western blot分析证实了培养基质细胞中ER(3 mRNA的表达，半定量RT-PCR证实了基质细胞中ER β mRNA的表达高于ER α mRNA。芳香酶，一种将雄激素前体转化为雌激素的酶，也被检查了。在基质细胞中检测到芳香化酶mRNA和活性，而在培养的上皮细胞中检测不到，这表明雌激素浓度可以调节BPH基质的机制。综上所述，这些发现支持了雌激素在BPH发病机制中起作用的假设，BPH是一种以基质过度生长为主要特征的疾病。
Oestrogens have been implicated as a cause of benign prostatic hyperplasia (BPH). Previous animal studies led to the hypothesis that oestrogens can stimulate prostate growth, resulting in hyperplasia of the gland. In humans, the precise role of oestrogens in BPH pathogenesis is currently unclear. We investigated the direct effects of oestradiol on the proliferation of BPH-derived prostate cells in culture. Oestradiol (10(-7) and 10(-6) M) moderately increased the proliferation of stromal cells in culture; this stimulation was antagonised by anti-oestrogen ICI 182 780, indicating an oestrogen receptor (ER)-mediated mechanism. By contrast, oestradiol had no effects on the proliferation of epithelial cells in culture. Parameters that can determine the response of stromal cells to oestrogens, including expression of the two ER subtypes and aromatase activity, were investigated. ER(3 expression in stromal cells in culture was demonstrated by immunohistochemistry and western blot analysis, and was confirmed by semi-quantitative RT-PCR showing higher expression of ER beta than ER alpha mRNA in stromal cells. Aromatase, the enzyme that converts androgen precursors to oestrogens, was also examined. Aromatase mRNA and activity were detected in stromal, but not epithelial cells in culture, suggesting a mechanism whereby oestrogen concentrations can be regulated in the BPH stroma. Taken together, these findings support the hypothesis that oestrogens play a role in the pathogenesis of BPH, a disease characterised predominantly by stromal overgrowth.