title: Therapeutic effects of IGF-1 on stress urinary incontinence in rats with simulated childbirth trauma.
abstract: OBJECTIVE
  We examined the effect of IGF-1 in a rat model of stress urinary incontinence induced by simulated childbirth trauma.
  
  
  METHODS
  Simulated birth trauma was induced by vaginal distension in female Sprague Dawley® rats. Four, 7, 14 and 28 days after distension we performed functional assessment by measuring leak point pressure, urethral baseline pressure and the urethral response during a passive increment in intravesical pressure. The expression of IGF-1 and IGF1R mRNA and protein in damaged tissues was examined by real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. Thereafter hrIGF-1 (50 and 150 μg/kg per day) was continuously delivered from 1 day before distension using subcutaneous osmotic pumps. Four and 7 days after distension the effect of hrIGF-1 treatment was examined by functional analysis of leak point pressure, urethral baseline pressure and the urethral response as well as Western blot and histological analysis.
  
  
  RESULTS
  After 4 and 7 days rats with vaginal distension had significantly decreased leak point pressure, urethral baseline pressure and urethral responses. IGF-1 and IGF1R mRNA and protein levels were significantly increased in urethral and pudendal nerves 4 and 7 days after distension. IGF-1 treated groups showed significant improvement in leak point pressure, urethral baseline pressure and urethral responses 4 and 7 days after distension. Moreover, IGF-1 treatment increased Akt phosphorylation and induced cellular proliferation and antiapoptotic effects in the urethra.
  
  
  CONCLUSIONS
  IGF-1 treatment accelerated recovery from stress urinary incontinence induced by simulated childbirth trauma in association with activation of the Akt signal transduction pathway in rats. This suggests that IGF-1 has therapeutic potential for stress urinary incontinence in women.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Urology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sumino
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yoshikawa
authors.affiliation: Department of Urology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Mimata
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Electronic address: nyos@pitt.edu.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D036861:Delivery, Obstetric / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D014550:Urinary Incontinence, Stress / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I
keywords: ELISA; GAPDH; IGF-1; IGF-1 receptor; IGF1R; LPP; PBS; PCR; RT-PCR; SUI; UBP; VD; enzyme-linked immunosorbent assay; glyceraldehyde-3-phosphate dehydrogenase; hr; human recombinant; insulin-like growth factor 1; insulin-like growth factor-1; leak point pressure; parturition; phosphate buffered saline; polymerase chain reaction; reverse transcriptase-PCR; stress; stress urinary incontinence; urethra; urethral baseline pressure; urinary incontinence; vagina; vaginal distension