title: Castration impairs erectile organ structure and function by inhibiting autophagy and promoting apoptosis of corpus cavernosum smooth muscle cells in rats.
abstract: OBJECTIVE
  The aim of this study was to determine the changes and underlying mechanisms of erectile organ structure and function in castrated rats. In addition, the regulatory effects of an androgen on autophagy and apoptosis in corpus cavernosum smooth muscle cells (CCSMCs), especially the regulatory effect of androgen on the BECN 1-Bcl-2 interaction, were investigated.
  
  
  METHODS
  Male Sprague-Dawley rats were divided into three groups (30/group): control group, castration group, and castration with testosterone supplementation group. The erectile function was examined both in vivo and in vitro, by electric stimulation of the cavernous nerve and corpus cavernosum strip bath test, respectively. Transmission electron microscopy, TUNEL assay, Masson's trichrome staining, immunohistochemistry, and western blotting were performed to determine the levels of autophagy and apoptosis, and the structural changes in corpus cavernosum.
  
  
  RESULTS
  Compared with control group, the castration group showed (1) lower erectile function: lower intracavernosal pressure/mean arterial pressure ratio, lower systolic and diastolic capability of corporal strips, and reduced expressions of eNOS and nNOS; (2) greater fibrosis: decreased smooth muscle/collagen ratio, lower expression of α-SMA, and higher expression of TGF-β1; (3) inhibited autophagy: decreased autophagosomes, lower expressions of BECN1 and LC3-II; and (4) enhanced apoptosis: higher apoptotic index and decreased Bcl-2/Bax ratio. Testosterone supplementation partially improved the effects of castration.
  
  
  CONCLUSIONS
  Castration attenuates erectile function and induces corporeal fibrosis by inhibiting autophagy and promoting apoptosis of CCSMCs in rats. Therefore, our study highlights the important role of androgens in maintaining the integrity of the structure and function of corpus cavernosum in rats through counter-regulation of autophagy and apoptosis, mainly by regulating BECN 1-Bcl-2 interaction.
authors.affiliation: Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, District of Huangpu, Shanghai, 200025, China.
authors.forename: Xian-Jin
authors.initials: XJ
authors.lastname: Wang
authors.forename: Tian-Yuan
authors.initials: TY
authors.lastname: Xu
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Xia
authors.forename: Shan
authors.initials: S
authors.lastname: Zhong
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Zhang
authors.forename: Zhao-Wei
authors.initials: ZW
authors.lastname: Zhu
authors.forename: Dong-Rui
authors.initials: DR
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Fan
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.forename: Min-Guang
authors.initials: MG
authors.lastname: Zhang
authors.forename: Zhou-Jun
authors.initials: ZJ
authors.lastname: Shen
mesh_terms: D000728:Androgens / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D007172:Erectile Dysfunction / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009919:Orchiectomy / Q000009:adverse effects*; D010413:Penis / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000728:Androgens; D051017:Apoptosis Regulatory Proteins; D013739:Testosterone; D019001:Nitric Oxide Synthase