Intracavernous growth differentiation factor-5 therapy enhances the recovery of erectile function in a rat model of cavernous nerve injury.
BACKGROUND
Neurogenic erectile dysfunction remains a serious complication in the postprostatectomy population. Effective protective and regenerative neuromodulatory strategies are needed.


OBJECTIVE
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.


METHODS
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.
University of California, San Francisco-Urology, San Francisco, CA 94143-0738, USA.
Thomas M
TM
Fandel
Anthony J
AJ
Bella
Guiting
G
Lin
Kavirach
K
Tantiwongse
Ching-Shwun
CS
Lin
Jens
J
Pohl
Tom F
TF
Lue
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D055428:Growth Differentiation Factor 5 / Q000008:administration & dosage*; D020287:In Situ Nick-End Labeling; D007267:Injections; D008297:Male; D009409:Nerve Crush; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000098:blood supply / Q000187:drug effects / Q000294:innervation* / Q000473:pathology; D059348:Peripheral Nerve Injuries; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000235:genetics
D055428:Growth Differentiation Factor 5; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019001:Nitric Oxide Synthase