814 SONIC HEDGEHOG REGULATES PENILE MORPHOLOGY IN PROSTATECTOMY AND DIABETIC PATIENTS

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research (I)1 Apr 2013814 SONIC HEDGEHOG REGULATES PENILE MORPHOLOGY IN PROSTATECTOMY AND DIABETIC PATIENTS Nicholas Angeloni, Christopher Bond, Kevin McVary, and Carol Podlasek Nicholas AngeloniNicholas Angeloni Chicago, IL More articles by this author , Christopher BondChristopher Bond Chicago, IL More articles by this author , Kevin McVaryKevin McVary Chicago, IL More articles by this author , and Carol PodlasekCarol Podlasek Chicago, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.380AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Erectile dysfunction (ED) is a debilitating medical condition and current treatments are ineffective in patients with cavernous nerve (CN) injury, due to penile remodeling and apoptosis. Sonic hedgehog (SHH) is a critical regulator of penile smooth muscle and apoptosis that is decreased in rat prostatectomy and diabetic ED models. SHH inhibition in the penis induces apoptosis and ED, and SHH treatment at the time of CN injury suppresses smooth muscle apoptosis and promotes regeneration of erectile function. Thus SHH treatment has significant translational potential as an ED therapy if similar mechanisms underlie ED development in patients. In this study we quantify SHH protein and morphological changes in corpora cavernosal tissue of control, prostatectomy and diabetic patients and hypothesize that decreased SHH protein is an underlying cause of ED development in prostatectomy and diabetic patients. METHODS Human corpora cavernosal tissue was obtained from patients undergoing penile implant to treat ED in prostatectomy (n=21), diabetic (n=20) and Peyronie's (control, n=13) patients. Quantification of SHH protein was performed by Western analysis. SHH localization was examined by immunohistochemical analysis and insitu hybridization. Smooth muscle and apoptosis were quantified by Western analysis for α-ACTIN, trichrome and TUNEL. RESULTS Shh RNA was synthesized in corpora cavernosal smooth muscle and SHH protein was also active in smooth muscle, indicating autocrine signalling. Precursor and active SHH protein were significantly decreased 40% and 44% in prostatectomy and 40% and 39% in diabetic patients. Apoptosis was increased 23% in prostatectomy and 27% in diabetic patients and was observed primarily in corpora cavernosal smooth muscle. Trichrome stain showed decreased smooth muscle/collagen in prostatectomy and diabetic patients. This was confirmed by quantification of alpha-ACTIN/GAPDH, which decreased ∼ 50% in prostatectomy and diabetic patients. CONCLUSIONS Parallel morphological changes and decreased SHH protein were observed in animal models of ED and in ED patients that have had a prostatectomy or were diabetic. Since localized SHH treatment is effective in suppressing neuropathy-induced apoptosis and ED in rat models, SHH treatment has the potential to be similarly effective in prostatectomy and diabetic patients. The increased apoptotic index long after initial injury is suggestive of ongoing remodeling that may be manipulatable. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e334-e335 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nicholas Angeloni Chicago, IL More articles by this author Christopher Bond Chicago, IL More articles by this author Kevin McVary Chicago, IL More articles by this author Carol Podlasek Chicago, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...