Crone J K, Burnett A L, Chamness S L, Strandberg J D, Chang T S
Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Androl. 1998 May-Jun;19(3):358-64.
Nitric oxide synthase (NOS) is expressed in the prostate of various species, including humans. NOS catalyzes the production of nitric oxide (NO), which may function in prostatic smooth-muscle relaxation. To investigate further the role of NO in the prostate, we examined neuronal NOS expression in the aging canine prostate, after hormonal perturbation, and correlated these results with histopathologic findings. The study comprised the following treatment groups: intact dogs (treatment group 1, n = 6); dogs who were castrated at 7 days of age and received testosterone and estrogen replacement at 2 years of age (treatment group 2, n = 10); and dogs who were castrated at 2 years of age and received testosterone and estrogen replacement at 2 years of age (treatment group 3, n = 9). Studies were done on prostates removed from dogs after euthanasia at 6 years of age. In treatment group 1, complex benign prostatic hyperplasia (BPH) was observed in all specimens. In treatment group 2, atrophy was observed in 70%, normal prostate with small areas of hyperplasia in 20%, and BPH in 10% of specimens. In treatment group 3, atrophy was observed in 78%, normal histology with small areas of hyperplasia in 11%, and BPH in 11% of specimens. Neuronal NOS localizations were confirmed by western blot analysis and by immunohistochemistry in 0% and 17%, respectively, of specimens in treatment group 1, in 60% and 70%, respectively, of specimens in treatment group 2, and in 67% and 71%, respectively, of specimens in treatment group 3. Neuronal NOS immunoreactivity was localized in histologically normal prostates of four intact, young-adult control dogs (2 years of age). For all treatment groups, neuronal NOS immunoreactivity was confirmed by western blot in 86% of atrophic prostates but in no prostates with BPH (P < 0.001), and it was confirmed by immunohistochemistry in 75% of atrophic prostates but in only 13% of prostates with BPH (P < 0.02). These data suggest that, in the canine prostate, NO release relates to growth and pathology. Low levels of neuronal NOS expression in BPH tissue, compared with higher levels in atrophic tissue, suggest that neuronal NOS expression is down-regulated in the prostate with benign cellular proliferation whereas it is maintained or possibly up-regulated in the prostate with prostatic involution. Whether altered neuronal NOS expression contributes to the pathogeneses of BPH and prostatic involution or whether it occurs as a consequence of these processes requires further investigation.
一氧化氮合酶（NOS）在包括人类在内的多种物种的前列腺中均有表达。NOS催化一氧化氮（NO）的生成，而NO可能在前列腺平滑肌舒张中发挥作用。为了进一步研究NO在前列腺中的作用，我们检测了老龄犬前列腺在激素干扰后的神经元型NOS表达，并将这些结果与组织病理学发现进行关联。该研究包括以下治疗组：未阉割犬（治疗组1，n = 6）；7日龄时阉割并在2岁时接受睾酮和雌激素替代治疗的犬（治疗组2，n = 10）；以及2岁时阉割并在2岁时接受睾酮和雌激素替代治疗的犬（治疗组3，n = 9）。研究在6岁安乐死后从犬身上取出的前列腺上进行。在治疗组1中，所有标本均观察到复杂的良性前列腺增生（BPH）。在治疗组2中，70%的标本观察到萎缩，20%的标本为正常前列腺伴小面积增生，10%的标本为BPH。在治疗组3中，78%的标本观察到萎缩，11%的标本组织学正常伴小面积增生，11%的标本为BPH。通过蛋白质免疫印迹分析和免疫组织化学分别在治疗组1的0%和17%的标本中、治疗组2的60%和70%的标本中以及治疗组3的67%和71%的标本中证实了神经元型NOS的定位。在4只未阉割的年轻成年对照犬（2岁）组织学正常的前列腺中检测到神经元型NOS免疫反应性。对于所有治疗组，通过蛋白质免疫印迹在86%的萎缩性前列腺中证实了神经元型NOS免疫反应性，但在BPH前列腺中未证实（P < 0.001），通过免疫组织化学在75%的萎缩性前列腺中证实了该反应性，但在BPH前列腺中仅13%的标本中证实（P < 0.02）。这些数据表明，在犬前列腺中，NO释放与生长和病理状态相关。与萎缩组织中较高水平相比，BPH组织中神经元型NOS表达水平较低，这表明在良性细胞增殖的前列腺中神经元型NOS表达下调，而在前列腺 involution中其表达维持或可能上调。神经元型NOS表达的改变是导致BPH和前列腺 involution发病的原因，还是这些过程的结果，需要进一步研究。
