Effects of Intracavernosal IGF-1 Gene Delivery on Erectile Function in the Aging Rat

Park, Kwangsung; Kang, Taek Won; Kim, Min Kyung; Kim, Kyung Keun; Ahn, Kyuyoun; Ryu, Soo Bang

Abstract

PURPOSE: Insulin like Growth Factor-1 (IGF-1) promotes the proliferation and migration of penile cavernous smooth muscle cells in rats. The goal of this study was to investigate the effects of an intracavernosal injection of the IGF-1 gene on the erectile function in the aging rat.
MATERIALS AND METHODS
Corpus cavernosum smooth muscle cells (CCSMCs) were primarily cultured from Sprague-Dawley rats (16 wks). IGF-1 cDNA was subcloned into pcDNA3.1, and this expression plasmid transfected into CCSMCs. Two, three and four days after transfection, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analyses were carried out to quantify the transfection efficiency. In an in vivo study, male F344 rats (n=28) were divided into 2 groups; the young (5 months; n=7) and the old (20-21 months; n=21) groups. The old group was further divided into control (n=7) and treatment groups (n=14). The treatment group was given a single intracavernosal injection of DNA-liposome complex (pcDNA alone and pcDNA/IGF-1; 2mug or 4mug in 7 animals each). After 4 weeks of treatment, the erectile function and corpus cavernosal histology were evaluated by hemodynamic study and histomorphometric analysis, respectively.
RESULTS
When the CCSMCs were transfected with IGF-1, the IGF-1 mRNA and protein were overexpressed compared to the control. After 4 weeks of treatment, the ratio of the peak intracavernosal pressure to systemic arterial pressure increased in the treatment group (66.3+/- 4.3% with 2mug, 65.4+/- 10.2% with 4mug), but without statistical significance (p>0.05) compared to the control group (55.5+/- 16.7%). The percentage of cavernosal smooth muscle also slightly increased in the treatment group (14.1+/-1.7% with 2mug), but without statistical significance (p>0.05) compared to the control group (13.2+/-1.2%).
CONCLUSIONS
IGF-1 mRNA and IGF-1 protein were overexpressed in the rat corpus cavernosum smooth muscle cells due to IGF-1 gene delivery. However, lipid-mediated intracavernosal gene delivery of IGF-1 did not significantly improve the erectile function in the aging rat.