Sonic Hedgehog, Apoptosis, and the Penis

Abstract

Smooth muscle apoptosis in the penis is common in prostatectomy patients and animal models of erectile dysfunction (ED). A critical regulator of smooth muscle apoptosis in the penis is the secreted protein Sonic hedgehog (SHH). Since SHH protein treatment of the penis prevents cavernous nerve (CN) injury-induced apoptosis, SHH has the potential to treat post-prostatectomy apoptosis. However, little is known about how SHH signaling is regulated in the adult penis. The goal of this review is to examine what is known about SHH signaling in the penis, to offer insight as to how SHH inhibition induces apoptosis in penile smooth muscle, and to define the role of the SHH pathway in maintaining CN integrity. Information presented in this review was derived from a literature search using the National Library of Medicine PubMed Services. Search terms included SHH, apoptosis, smooth muscle, penis, ED, pelvic ganglia, corpora cavernosa, CN, regeneration, Schwann cell, neural activity, and transport. In this review, we have discussed the role of the CN in regulation of SHH abundance and apoptosis induction in the penis, and have examined the function and localization of SHH signaling in the CN. There is substantial potential to develop SHH for delivery to the penis of prostatectomy patients at the time of surgery in order to prevent apoptosis induction and long-term ED development. Studies are in progress that will identify if SHH may be used as a regenerative therapy to speed CN regeneration.