Department of Hypertension, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Urology. 2013 Sep;82(3):743.e9 -15. doi: 10.1016/j.urology.2013.02.045. Epub 2013 Jul 19.
To investigate the effects and mechanisms of long-term treatment of 5α-reductase inhibitors (5ARIs) on erectile organ structure and function in aged rats.
Thirty 16-month-old male rats were assigned to 2 groups: untreated or treated with 5ARIs. After 16 weeks, the erectile function was measured after electrical stimulation of the cavernous nerve. The weights and histopathologic features of the corpus cavernosum were examined. The levels of autophagy, apoptosis, and protein expression were also recorded.
In the 5ARI-treatment group, the plasma and intraprostatic dihydrotestosterone concentration was lowered by 52.1% and 57.3%, respectively, and the weight of the corpus cavernosum and prostate had decreased by 22.4% and 35.6%, respectively. The in vivo erectile response to electrical stimulation of the cavernous nerve had decreased significantly in the 5ARI-treatment group (P <.001). Masson's staining, immunohistochemistry, and Western blot all demonstrated decreased smooth muscle and increased collagen deposition and decreased endothelial nitric oxide synthase and LC3-II protein expression in the corpus cavernosum of the 5ARI-treatment group. Using transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, decreased autophagy, aggravated ultrastructural injury of mitochondria, and increased apoptosis were observed in the cavernous smooth muscle cells from the rats in the 5ARI-treatment group.
Long-term 5ARI treatment did attenuate the erectile function of aged rats. The mechanisms might have been the decreased rate of autophagy and an increased rate of apoptosis in the cavernous smooth muscle cells, suggesting a new role for androgen in maintaining the structural and functional integrity of the erectile organ. Additional studies are necessary to demonstrate the mechanisms of dihydrotestosterone in regulating the autophagy and apoptosis of the cavernous smooth muscle cells.
研究 5α-还原酶抑制剂（5ARIs）长期治疗对老年大鼠阴茎器官结构和功能的影响及其机制。
将 30 只 16 月龄雄性大鼠分为未治疗组或 5ARIs 治疗组。16 周后，用电刺激海绵体神经测量勃起功能。检查海绵体的重量和组织病理学特征。还记录了自噬、凋亡和蛋白表达的水平。
在 5ARI 治疗组中，血浆和前列腺内二氢睾酮浓度分别降低了 52.1%和 57.3%，海绵体和前列腺的重量分别降低了 22.4%和 35.6%。电刺激海绵体神经时，5ARI 治疗组的体内勃起反应明显下降（P<.001）。Masson 染色、免疫组织化学和 Western blot 均显示 5ARI 治疗组海绵体平滑肌减少，胶原沉积增加，内皮型一氧化氮合酶和 LC3-II 蛋白表达减少。电镜和末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记法显示，5ARI 治疗组海绵体平滑肌细胞自噬减少，线粒体超微结构损伤加重，凋亡增加。
长期 5ARI 治疗可减弱老年大鼠的勃起功能。其机制可能是海绵体平滑肌细胞自噬率降低和凋亡率增加，提示雄激素在维持勃起器官的结构和功能完整性方面具有新的作用。需要进一步的研究来证明二氢睾酮调节海绵体平滑肌细胞自噬和凋亡的机制。
