Insulin-like growth factor-1 restores erectile function in aged rats: modulation the integrity of smooth muscle and nitric oxide-cyclic guanosine monophosphate signaling activity.
BACKGROUND
Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. We have confirmed that gene transfer of IGF-1 to the penis could improve erectile capacity. However, there are some limitations in gene therapies, such as toxicity or a risk of insertional mutagenesis. Protein treatment may be another choice for decreasing these risks.


OBJECTIVE
To investigate whether intracavernosal injection of IGF-1 protein can restore erectile function in the aging rat.


METHODS
Erectile responses, morphological changes, and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathways-related marker were determined.


METHODS
Ten young (4 months) and 30 old (24 months) Sprague-Dawley male rats were enrolled in this study. The old rats were divided into three groups: vehicle-only (N = 10), IGF-1 1 microg/kg (N = 10) and IGF-1 10 microg/kg treatment group (N = 10). After 4 and 8 weeks of single IGF-1 injection treatment, intracavernous pressure (ICP) responses with electrical stimulation to the cavernous nerve were evaluated. The percent of smooth muscle in corpus cavernosum tissue, the expression of mRNA and protein of endothelial nitric oxide synthase (eNOS) were also evaluated. The activity of nitric oxide synthase (NOS) and concentration of guanosine 3',5'-cyclic-monophosphate (cGMP) that act upon the major NO-cGMP signaling pathways in penile tissue were also analyzed.


RESULTS
After IGF-1 treatment, the ICP responses was significantly increased as the young control group in both the IGF-1 1 microg/kg and the IGF-1 10 microg/kg group compared with the vehicle-only group at 4 and 8 weeks (P < 0.05). Masson's trichrom staining showed the percentage of cavernosal smooth muscle was increased in IGF-1 treatment group. IGF-1 increased e-NOS expression. NOS activities and cGMP concentrations were also significantly increased in IGF-1 treatment rats.


CONCLUSIONS
IGF-1 improved erectile function in aged rats via restoration the integrity of smooth muscle of corpus cavernosum and modulation of NO-cGMP pathways.
Pu
Xiao-Yong
XY
Guangdong Provincial People's Hospital-Department of Urology, Cancer Center and The Medical Research Center, Guangdong, Guangzhou, China.
Wang
Xing-Huan
XH
Gao
Wai-Chen
WC
Yang
Zhong-Hua
ZH
Li
Shi-Lin
SL
Wang
Huai-Peng
HP
Wu
Yi-Long
YL
D000375:Aging / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure; D006152:Cyclic GMP / Q000378:metabolism*; D004558:Electric Stimulation; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000503:physiopathology; D007150:Immunohistochemistry; D007267:Injections; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010413:Penis / Q000294:innervation / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D012333:RNA, Messenger; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D006152:Cyclic GMP