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Neural Influences on Sonic Hedgehog and Apoptosis in the Rat Penis¹

Department of Urology,³ Northwestern University Medical School, Chicago, Illinois 60611 Children's Memorial Hospital,⁴ Chicago, Illinois 60614

ABSTRACT

The role of sonic hedgehog (SHH) in maintaining corpora cavernosal morphology in the adult penis has been established; however, the mechanism of how SHH itself is regulated remains unclear. Since decreased SHH protein is a cause of smooth muscle apoptosis and erectile dysfunction (ED) in the penis, and SHH treatment can suppress cavernous nerve (CN) injury-induced apoptosis, the question of how SHH signaling is regulated is significant. It is likely that neural input is involved in this process since two models of neuropathy-induced ED exhibit decreased SHH protein and increased apoptosis in the penis. We propose the hypothesis that SHH abundance in the corpora cavernosa is regulated by SHH signaling in the pelvic ganglia, neural activity, or neural transport of a trophic factor from the pelvic ganglia to the corpora. We have examined each of these potential mechanisms. SHH inhibition in the penis shows a 12-fold increase in smooth muscle apoptosis. SHH inhibition in the pelvic ganglia causes significantly increased apoptosis (1.3-fold) and decreased SHH protein (1.1-fold) in the corpora cavernosa. SHH protein is not transported by the CN. Colchicine treatment of the CN resulted in significantly increased smooth muscle apoptosis (1.2-fold) and decreased SHH protein (1.3-fold) in the penis. Lidocaine treatment of the CN caused a similar increase in apoptosis (1.6-fold) and decrease in SHH protein (1.3-fold) in the penis. These results show that neural activity and a trophic factor from the pelvic ganglia/CN are necessary to regulate SHH protein and smooth muscle abundance in the penis.

apoptosis, cavernous nerve, erectile dysfunction, male sexual function, penis

¹Supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grants DK068507 and DK062970.

Correspondence: ²Carol Podlasek, Department of Urology, Northwestern University, Tarry Building 16-703, 303 E. Chicago Ave., Chicago, IL 60611. FAX: 312 908 7275; e-mail: cap325{at}northwestern.edu