title: Long-term oral administration of 5α-reductase inhibitor attenuates erectile function by inhibiting autophagy and promoting apoptosis of smooth muscle cells in corpus cavernosum of aged rats.
abstract: OBJECTIVE
  To investigate the effects and mechanisms of long-term treatment of 5α-reductase inhibitors (5ARIs) on erectile organ structure and function in aged rats.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hypertension, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Min-Guan
authors.initials: MG
authors.lastname: Zhang
authors.forename: Xian-Jin
authors.initials: XJ
authors.lastname: Wang
authors.forename: Zhou-Jun
authors.initials: ZJ
authors.lastname: Shen
authors.forename: Ping-Jin
authors.initials: PJ
authors.lastname: Gao
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology*; D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D009130:Muscle, Smooth / Q000187:drug effects* / Q000648:ultrastructure; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009929:Organ Size; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D010413:Penis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000378:metabolism; D013997:Time Factors
chemical_list: D058891:5-alpha Reductase Inhibitors; D003094:Collagen; D013196:Dihydrotestosterone; D008869:Microtubule-Associated Proteins; D052250:Nitric Oxide Synthase Type III; D013739:Testosterone; C526109:Anxa3 protein, rat; C496316:Nos3 protein, rat