Nassis L, Frauman A G, Ohishi M, Zhuo J, Casley D J, Johnston C I, Fabiani M E
Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, VIC 3084, Australia.
J Pathol. 2001 Dec;195(5):571-9. doi: 10.1002/path.999.
Benign prostatic hyperplasia (BPH) is the most common hyperplastic disease in man and it is characterized by increased cellular growth (stromal and epithelial hyperplasia) and enhanced local sympathetic tone, both of which are known to be augmented by activation of the renin-angiotensin system (RAS) in other tissues. Angiotensin-converting enzyme (ACE) is an integral component of the RAS that is responsible for the production of the active peptide angiotensin II from the inactive precursor angiotensin I. The present study was undertaken to map the anatomical localization of ACE protein and messenger ribonucleic acid (mRNA) in the normal human prostate and to establish whether their expression is pathologically altered in BPH. Human prostate samples were obtained at post-mortem and histologically defined as normal or hyperplastic. ACE protein binding/expression was determined by in vitro autoradiography and immunohistochemistry using the ACE-specific radioligand [125I]-MK351A and a mouse anti-ACE polyclonal antibody, respectively, whereas the spatiotemporal distribution of ACE mRNA was determined by in situ hybridization using 35S-labelled oligonucleotide probes. ACE protein was localized to the glandular epithelium in the human prostate. ACE binding and immunostaining were increased in BPH compared with normal (non-hyperplastic) prostate specimens [X-ray film autoradiography: normal 873+/-48 dpm/mm2 (n=8) vs. BPH 1631+/-274 dpm/mm2 (n=6), p<0.05; emulsion autoradiography: normal 3.1+/-0.5 grains/mm2 (n=6) vs. BPH 32.8+/-8.6 grains/mm2 (n=5), p<0.01]. ACE mRNA was also localized to glandular epithelial cells in the human prostate with a significant increase in ACE mRNA expression in BPH compared with the normal prostate [normal 11.04+/-2.03 grains/cell (n=220 cells total) vs. BPH 22.29+/-1.34 grains/cell (n=198 cells total), p<0.05]. The findings of the present study suggest that ACE is localized to the glandular epithelium of the human prostate and that its expression, at both protein and mRNA level, is aberrantly increased in BPH. These data support the concept that hyperactivity of the local RAS in the prostate may be involved in the pathogenesis of BPH.
良性前列腺增生（BPH）是男性最常见的增生性疾病，其特征是细胞生长增加（基质和上皮增生）以及局部交感神经张力增强，已知这两者在其他组织中都会因肾素-血管紧张素系统（RAS）的激活而增强。血管紧张素转换酶（ACE）是RAS的一个组成部分，负责将无活性的前体血管紧张素I转化为活性肽血管紧张素II。本研究旨在确定正常人类前列腺中ACE蛋白和信使核糖核酸（mRNA）的解剖定位，并确定它们的表达在BPH中是否发生病理改变。在尸检时获取人类前列腺样本，并通过组织学确定为正常或增生。分别使用ACE特异性放射性配体[125I]-MK351A和小鼠抗ACE多克隆抗体，通过体外放射自显影和免疫组织化学来测定ACE蛋白结合/表达，而使用35S标记的寡核苷酸探针通过原位杂交来测定ACE mRNA的时空分布。ACE蛋白定位于人类前列腺的腺上皮。与正常（非增生性）前列腺标本相比，BPH中ACE结合和免疫染色增加[X射线胶片放射自显影：正常873±48 dpm/mm2（n = 8），BPH为1631±274 dpm/mm2（n = 6），p < 0.05；乳胶放射自显影：正常3.1±0.5颗粒/mm2（n = 6），BPH为32.8±8.6颗粒/mm2（n = 5），p < 0.01]。ACE mRNA也定位于人类前列腺的腺上皮细胞，与正常前列腺相比，BPH中ACE mRNA表达显著增加[正常11.04±2.03颗粒/细胞（共220个细胞），BPH为22.29±1.34颗粒/细胞（共198个细胞），p < 0.05]。本研究结果表明，ACE定位于人类前列腺的腺上皮，并且其在蛋白和mRNA水平的表达在BPH中异常增加。这些数据支持前列腺局部RAS功能亢进可能参与BPH发病机制的观点。
