Nicholas L. Angeloni and Christopher W. Bond have contributed equally to the manuscript.
The Role of Hedgehog-Interacting Protein in Maintaining Cavernous Nerve Integrity and Adult Penile Morphology
Version of Record online: 9 JUN 2009
© 2009 International Society for Sexual Medicine
The Journal of Sexual Medicine
Volume 6, Issue 9, pages 2480–2493, September 2009
How to Cite
Angeloni, N. L., Bond, C. W., Monsivais, D., Tang, Y. and Podlasek, C. A. (2009), The Role of Hedgehog-Interacting Protein in Maintaining Cavernous Nerve Integrity and Adult Penile Morphology. Journal of Sexual Medicine, 6: 2480–2493. doi: 10.1111/j.1743-6109.2009.01349.x
Grant Sponsor: National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, Grant number DK068507 and DK079184.
- Issue online: 26 AUG 2009
- Version of Record online: 9 JUN 2009
- Cavernous Nerve;
- Hedgehog-Interacting Protein;
- Erectile Dysfunction;
- Penile Differentiation;
- Sonic Hedgehog;
- Nitric Oxide
Introduction. Sonic hedgehog (SHH) is an essential regulator of smooth muscle apoptosis in the penis that has significant clinical potential as a therapy to suppress post-prostatectomy apoptosis, an underlying cause of erectile dysfunction (ED). Thus an understanding of how SHH signaling is regulated in the adult penis is essential to move the field of ED research forward and to develop new treatment strategies. We propose that hedgehog-interacting protein (HIP), which has been shown to bind SHH protein and to play a role in SHH regulation during embryogenesis of other organs, is a critical regulator of SHH signaling, penile morphology, and apoptosis induction.
Aims. We have examined HIP signaling in the penis and cavernous nerve (CN) during postnatal differentiation of the penis, in CN-injured, and a diabetic model of ED.
Methods. HIP localization/abundance and RNA abundance were examined by immunohistochemical (IHC) analysis and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in Sprague-Dawley rats between the ages of 7 and 92 days old, in CN-injured Sprague-Dawley rats and in BioBreeding/Worcester diabetic rats. HIP signaling was perturbed in the pelvic ganglia and in the penis and TUNEL assay was performed in the penis. CN tie, lidocaine, and anti-kinesin experiments were performed to examine HIP signaling in the CN and penis.
Results. In this study we are the first to demonstrate that HIP undergoes anterograde transport to the penis via the CN, that HIP perturbation in the pelvic ganglia or the penis induces apoptosis, and that HIP plays a role in maintaining CN integrity, penile morphology, and SHH abundance.
Conclusions. These studies are significant because they show HIP involvement in cross-talk (signaling) between the pelvic ganglia and penis, which is integral for maintenance of penile morphology and they suggest a mechanism of how nerves may regulate target organ morphology and function. Angeloni NL, Bond CW, Monsivais D, Tang Y, and Podlasek CA. The role of hedgehog-interacting protein in maintaining cavernous nerve integrity and adult penile morphology. J Sex Med 2009;6:2480–2493.