Planz B, Wang Q, Kirley S D, Lin C W, McDougal W S
Department of Urology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
J Urol. 1998 Nov;160(5):1850-5. doi: 10.1016/s0022-5347(01)62431-5.
Growth and development of the prostate are androgen dependent and mainly influenced by stromal-epithelial interaction. It is believed that indirect androgenic activation of paracrine factors like keratinocyte growth factor (KGF) in the prostatic stroma influences the growth of epithelial cells. In this study we investigated the role androgen plays in stromal cell growth and stimulation of KGF in the human prostate.
Stromal cells were derived from explant primary culture of human normal or benign prostatic tissue. The effect of different dihydrotestosterone (DHT) concentrations on cell proliferation was measured using 3[H]thymidine incorporation assay. The effect of DHT on levels of KGF protein was determined by Western blotting. The effect of DHT on levels of KGF gene expression was measured by various cycles of polymerase-chain-reaction (PCR) and multiplex PCR.
Characterization of stromal cells showed epithelial cells less than 9.5% in all passages. DHT stimulated human prostate stromal cells in a dose dependent fashion over a concentration range of 0.001-10 nM. Immunocytochemical evaluation of KGF after DHT exposure showed a higher staining intensity. Relative quantitation of Western blotting showed a 1.93-fold increase in KGF protein in the androgen treated stromal cells. At 1 nM DHT conventional and multiplex PCR revealed a significant stimulation of the KGF mRNA expression.
These data show for the first time that androgen stimulates cell proliferation as well as KGF protein and gene expression in human prostate stromal cells. This supports the hypothesis that androgen-induced stromal-derived KGF stimulates prostate epithelial cell growth.
前列腺的生长和发育依赖雄激素，主要受基质 - 上皮相互作用影响。据信，前列腺基质中旁分泌因子如角质形成细胞生长因子（KGF）的间接雄激素激活会影响上皮细胞的生长。在本研究中，我们调查了雄激素在人前列腺基质细胞生长和KGF刺激中的作用。
基质细胞来源于人正常或良性前列腺组织的外植体原代培养。使用3[H]胸苷掺入法测量不同二氢睾酮（DHT）浓度对细胞增殖的影响。通过蛋白质印迹法测定DHT对KGF蛋白水平的影响。通过聚合酶链反应（PCR）和多重PCR的不同循环来测量DHT对KGF基因表达水平的影响。
基质细胞的特征表明，所有传代中上皮细胞少于9.5%。在0.001 - 10 nM的浓度范围内，DHT以剂量依赖方式刺激人前列腺基质细胞。DHT暴露后对KGF的免疫细胞化学评估显示染色强度更高。蛋白质印迹的相对定量显示，雄激素处理的基质细胞中KGF蛋白增加了1.93倍。在1 nM DHT时，常规PCR和多重PCR显示KGF mRNA表达有显著刺激。
这些数据首次表明雄激素刺激人前列腺基质细胞的细胞增殖以及KGF蛋白和基因表达。这支持了雄激素诱导的基质来源KGF刺激前列腺上皮细胞生长的假说。
