You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research (II)1 Apr 2013108 INSULIN-LIKE GROWTH FACTOR-1 AS AN IMPORTANT ENDOGENOUS GROWTH FACTOR FOR THE RECOVERY FROM STRESS URINARY INCONTINENCE IN RATS WITH SIMULATED CHILDBIRTH INJURY Yasuhiro Sumino, Satoru Yoshikawa, Hiromitsu Mimata, and Naoki Yoshimura Yasuhiro SuminoYasuhiro Sumino Oita, Japan More articles by this author , Satoru YoshikawaSatoru Yoshikawa Pittsburgh, PA More articles by this author , Hiromitsu MimataHiromitsu Mimata Oita, Japan More articles by this author , and Naoki YoshimuraNaoki Yoshimura Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1487AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Insulin-like growth factor-1 (IGF-1) plays an important role in cell proliferation, survival and regeneration in various tissues.We previously identified the significant upregulation of exogenous IGF-1 and its receptors is associated with the recovery from stress urinary incontinence (SUI) induced by stimulated childbirth trauma in rats (2012AUA). In the present study, we examined the functional role of endogenous IGF-1 for the recovery from SUI induced by simulated childbirth trauma using an IGF-1 receptor inhibitor. METHODS Simulated birth trauma was induced by vaginal distension (VD) in female SD rats. An IGF-1 receptor antagonist, JB-1 (10 and 100μg/kg/day) or vehicle (saline) was continuously delivered from 1 day before VD using subcutaneous osmotic pumps. At 7, 14 and 21 days after VD, the effect of JB-1 treatment was examined by functional analyses (leak point pressure; LPP, urethral baseline pressure; UBP and urethral responses during passive increment in intravesicular pressure) and biomolecular analyses in urethral tissues (phosphorylation of Akt by Western blotting, apoptotic changes by TUNEL staining and peripheral adrenergic and cholinergic nerve density using immunohistochemistry of tyrosine hydroxylase; TH and vesicular acetylcholine transporter; VAChT, respectively). RESULTS In functional analyses, vehicle-treated rats had significantly reduced LPP, UBP and urethral responses after 7 days, with a recovery to the normal level 14 and 21 days after VD. However, in the JB-1 treated group (100μg/kg/day), LPP, UBP and urethral responses were still significantly reduced 21 days after VD. In biomolecular analyses, TUNEL positive cells were significantly increased in urethral tissues of JB-1 treated rats 7days after VD compared to vehicle-treated rats (P < 0.05). JB-1 treatment also prolonged the decrease of both TH and VAChT expression in urethral tissues (14 and 21 days after VD) although the reduction of positive stained area in vehicle-treated rats returned to normal levels at 14 days after VD (P < 0.05). Phosphorylation of urethral Akt in JB-1 treated rats tended to decrease 7 and 14 days after VD compared to vehicle-treated rats (not significant). CONCLUSIONS Suppression of endogenous IGF-1 activity delayed the recovery from SUI induced by simulated childbirth trauma in rats. Thus, IGF-1 is likely to be an important endogenous mediator for the functional recovery from childbirth-related SUI, suggesting that IGF-1 treatment could be effective for the treatment of SUI in women. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e43-e44 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yasuhiro Sumino Oita, Japan More articles by this author Satoru Yoshikawa Pittsburgh, PA More articles by this author Hiromitsu Mimata Oita, Japan More articles by this author Naoki Yoshimura Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...