title: Insulin-like growth factor-1 restores erectile function in aged rats: modulation the integrity of smooth muscle and nitric oxide-cyclic guanosine monophosphate signaling activity.
abstract: BACKGROUND
  Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. We have confirmed that gene transfer of IGF-1 to the penis could improve erectile capacity. However, there are some limitations in gene therapies, such as toxicity or a risk of insertional mutagenesis. Protein treatment may be another choice for decreasing these risks.
  
  
  OBJECTIVE
  To investigate whether intracavernosal injection of IGF-1 protein can restore erectile function in the aging rat.
  
  
  METHODS
  Erectile responses, morphological changes, and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathways-related marker were determined.
  
  
  METHODS
  Ten young (4 months) and 30 old (24 months) Sprague-Dawley male rats were enrolled in this study. The old rats were divided into three groups: vehicle-only (N = 10), IGF-1 1 microg/kg (N = 10) and IGF-1 10 microg/kg treatment group (N = 10). After 4 and 8 weeks of single IGF-1 injection treatment, intracavernous pressure (ICP) responses with electrical stimulation to the cavernous nerve were evaluated. The percent of smooth muscle in corpus cavernosum tissue, the expression of mRNA and protein of endothelial nitric oxide synthase (eNOS) were also evaluated. The activity of nitric oxide synthase (NOS) and concentration of guanosine 3',5'-cyclic-monophosphate (cGMP) that act upon the major NO-cGMP signaling pathways in penile tissue were also analyzed.
  
  
  RESULTS
  After IGF-1 treatment, the ICP responses was significantly increased as the young control group in both the IGF-1 1 microg/kg and the IGF-1 10 microg/kg group compared with the vehicle-only group at 4 and 8 weeks (P < 0.05). Masson's trichrom staining showed the percentage of cavernosal smooth muscle was increased in IGF-1 treatment group. IGF-1 increased e-NOS expression. NOS activities and cGMP concentrations were also significantly increased in IGF-1 treatment rats.
  
  
  CONCLUSIONS
  IGF-1 improved erectile function in aged rats via restoration the integrity of smooth muscle of corpus cavernosum and modulation of NO-cGMP pathways.
authors: Guangdong Provincial People's Hospital-Department of Urology, Cancer Center and The Medical Research Center, Guangdong, Guangzhou, China.
authors: Xiao-Yong
authors: XY
authors: Pu
authors: Xing-Huan
authors: XH
authors: Wang
authors: Wai-Chen
authors: WC
authors: Gao
authors: Zhong-Hua
authors: ZH
authors: Yang
authors: Shi-Lin
authors: SL
authors: Li
authors: Huai-Peng
authors: HP
authors: Wang
authors: Yi-Long
authors: YL
authors: Wu
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure; D006152:Cyclic GMP / Q000378:metabolism*; D004558:Electric Stimulation; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000503:physiopathology; D007150:Immunohistochemistry; D007267:Injections; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010413:Penis / Q000294:innervation / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D012333:RNA, Messenger; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D006152:Cyclic GMP