Intracavernous growth differentiation factor-5 therapy enhances the recovery of erectile function in a rat model of cavernous nerve injury.

Abstract

INTRODUCTION:

Neurogenic erectile dysfunction remains a serious complication in the postprostatectomy population. Effective protective and regenerative neuromodulatory strategies are needed.

AIM:

To determine the effect of growth differentiation factor-5 (GDF-5) on erectile function and its mechanism in a rat model of cavernous nerve (CN) injury.

MAIN OUTCOME MEASURES:

Erectile function was assessed by CN electrostimulation at 4 weeks. Penile tissues were examined by real-time polymerase chain reaction (PCR) and immunohistochemical analyses.

METHODS:

Forty-eight male Sprague-Dawley rats were randomly divided into six equal groups: one group underwent sham operation (uninjured controls), while five groups underwent bilateral CN crush. Crush-injury groups were treated at the time of injury with intracavernous injection of a slow-release suspension of liquid microparticles containing no GDF-5 (vehicle), 0.4 microg (low concentration), 2 microg (intermediate concentration), or 10 microg GDF-5 (high concentration). One untreated group served as injured controls.

RESULTS:

GDF-5 enhanced erectile recovery and significantly increased intracavernous pressure in the low and intermediate-concentration groups vs. injured controls. Low-concentration GDF-5 demonstrated the best functional preservation, as the intracavernous pressure increase in this group did not differ significantly from uninjured controls. A dose-response relationship was confirmed for the effects of GDF-5 in penile tissue. Low-concentration GDF-5 showed better preservation of the penile dorsal nerves and antiapoptotic effects in the corpus cavernosum (P < 0.05 vs. injured controls). Although high concentration GDF-5 did not confer meaningful erectile recovery, this dose was more effective at decreasing transforming growth factor-beta than low-concentration GDF-5.

CONCLUSIONS:

Intracavernous injection of low (0.4 microg) or intermediate-concentration GDF-5 (2 microg) was effective in preserving erectile function in a rat model of neurogenic erectile dysfunction. The underlying mechanism appears to involve neuron preservation and antiapoptosis.

• Authors: Thomas M Fandel, Anthony J Bella, Guiting Lin, Kavirach Tantiwongse, Ching-Shwun Lin, Jens Pohl, Tom F Lue
• Journal: The journal of sexual medicine (J Sex Med) Vol. 5 Issue 8 Pg. 1866-75 (Aug 2008) ISSN: 1743-6109 [Electronic] Netherlands
• PMID: 18564148 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Growth Differentiation Factor 5
• RNA, Messenger
• Transforming Growth Factor beta
• Nitric Oxide Synthase

Topics

• Animals
• Apoptosis (drug effects)
• Blood Pressure (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Erectile Dysfunction (drug therapy, pathology)
• Gene Expression (drug effects)
• Growth Differentiation Factor 5 (administration & dosage)
• In Situ Nick-End Labeling
• Injections
• Male
• Nerve Crush
• Nitric Oxide Synthase (metabolism)
• Penile Erection (drug effects)
• Penis (blood supply, drug effects, innervation, pathology)
• Peripheral Nerve Injuries
• RNA, Messenger (genetics)
• Rats
• Rats, Sprague-Dawley
• Transforming Growth Factor beta (genetics)