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Objective: The aim of this study was determine whether intracavernosal injection (ICI) of insulin-like growth factor-1 (IGF-1) protein can improve corpus cavernosal smooth muscle relaxation in aging rats., Materials and Methods: Ten young (4-month-old) and 30 old (24-month-old) Sprague-Dawley male rats were enrolled in the study. The old rats were divided into three groups: vehicle-only (n = 10), IGF-1 1 µg/kg (n = 10) and IGF-1 10 µg/kg treatment groups (n = 10). After 4 weeks of single IGF-1 injection treatment, strips of corporal tissue were precontracted with phenylephrine, and dose-response curves were generated to evaluate endothelial-dependent [acetylcholine (ACh)], endothelial-independent [sodium nitroprusside (SNP)] and electrical field stimulation (EFS) vasoreactivity. The changes in percentage of cavernosal smooth muscle and the concentration of nitric oxide (NO) in penile tissue were also evaluated., Results: After IGF-1 treatment, the vasoreactivity was significantly improved in both the 1 µg/kg and the 10 µg/kg treatment groups compared with the vehicle-only group at 4 weeks in response to ACh, SNP and EFS (all p < 0.05). The percentage of cavernosal smooth muscle was increased in the IGF-1 treatment groups. The NO concentrations were increased after IGF-1 treatment., Conclusions: These data demonstrate that ICI of IGF-1 can improve vasoreactivity via endothelium-dependent and endothelial-independent mechanisms in the corpus cavernosum of the aging rat.

Objective: To observe the secretion of insulin-like growth factor-1 (IGF-1) in corpus cavernosum smooth muscle cells (CCSMCs) in rats of different ages and explore the possible relationship of IGF-1 with aging-related erectile dysfunction (ED)., Methods: We primarily cultured CCSMCs of rats aged 4, 12 and 24 months, and identified them by immunohistochemistry. We quantitatively cultured the CCSMCs in 6-well culture plates, determined the levels of IGF-1 secreted from the CCSMCs by enzyme immunoassay (EIA) and analyzed the effect of age on the IGF-1 level., Results: CCSMCs were successfully cultured in vitro. The level of IGF-1 secreted from the CCSMCs was decreased with the increase of age, with 7.1 ng/10(5) cells in the 4-month-old group, 2.2 ng/10(5) cells in the 12-month group, and 1.9 ng/10(5) cells in the 24-month group, with statistically significant differences among the three groups (P < 0.01)., Conclusion: The secretion of IGF-1 is reduced with the increase of age, and the decreased expression of IGF-1 might be associated with aging-related ED.

Objective: To explore the effects of gene transfer of insulin like growth factor-1 (IGF-1) on the penis of senile rats and the altered levels of mRNA and protein of endothelial nitric oxide synthase (eNOS)., Methods: Ten young (4 months) and 20 senile (24 months) Sprague-Dawley male rats were selected. The senile rats were divided into 2 groups: phosphate buffer solution (PBS)-only (n = 10) and 100 µg IGF-1 plasmid treatment group (n = 10). After a 4-week injection of IGF-1, the responses of intracavernous pressure (ICP) with electrical stimulation to the cavernous nerve and systemic mean arterial pressure (MAP) were evaluated. In the control and transfected senile rats, the levels of eNOS mRNA and protein were examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively., Results: The ICP/MAP and total ICP were significantly higher in the young control group versus the PBS-only group at Week 4 (P < 0.05). The ICP/MAP and total ICP were significantly higher in the young control group and the 100 µg IGF-1 treatment group versus the PBS-only group at Week 4 (P < 0.05). The levels of mRNA and protein of eNOS were higher in the 100 µg IGF-1 treatment group versus the PBS-only group at Week 4 (0.62 ± 0.16 vs 0.25 ± 0.08, 0.71 ± 0.19 vs 0.27 ± 0.09, both P < 0.05, respectively)., Conclusion: The gene therapy of IGF-1 can ameliorate erectile functions and improve the levels of mRNA and protein of eNOS in senile rats.

Growth factors have a universal bioactivity. Gene therapy is a new strategy in dealing with erectile dysfunction (ED). This paper presents an overview on the value of growth factors, particularly the vascular epithelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1), in the treatment of ED.

Objective: To investigate the best dose and the long-term effect of the human insulin-like growth factor-1 (hIGF-1) gene injection into the penis of aged rats., Methods: Included in this study were 10 young (4 months old) and 40 aged (24 months old) Sprague-Dawley male rats, the latter equally divided into a PBS control and a 10 microg, a 100 microg and a 1 000 microg hIGF-1 injection group. Electrical stimulation was conducted 4 and 8 weeks after hIGF-1 injection into the penile corpus cavernous of the rats to detect the intracavernous pressure (ICP) and mean arterial pressure (MAP). Dose - and time -associated therapeutic results were analyzed and the mRNA expression of hIGF-1 determined by RT - PCR., Results: ICP, MAP and total ICP were significant decreased by electrical stimulation in the aged rats as compared with the young ones (P < 0.05), statistically increased in the three hIGF-1 dose groups in comparison with the PBS controls (P < 0.05), and showed no obvious difference between the young rats and the latter two dose groups at 4 and 8 weeks. Although less obvious effect was achieved in the 10 microg group than in the young rats, the therapeutic result was still of significance. The mRNA expression of the hIGF-1 gene was confirmed in all the hIGF-1 treated rats., Conclusion: The hIGF-1 therapy can improve erectile function in aged rats, 100 microg suffices for effective erection and the effect may last at least 8 weeks for a single dose.

Introduction: 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., Aim: To investigate whether intracavernosal injection of IGF-1 protein can restore erectile function in the aging rat., Main Outcome Measures: 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.

Aim: To determine whether adenoviral gene transfer of insulin like growth factor-1 (IGF-1) to the penis of streptozotocin (STZ)-induced diabetic rats could improve erectile capacity., Methods: THE STZ diabetic rats were transfected with AdCMV-betagal or AdCMV-IGF-1. These rats underwent cavernous nerve stimulation to assess erectile function and their responses were compared with those of age-matched control rats 1 to 2 days after transfection. In control and transfected STZ diabetic rats, IGF-1 expression were examined by reverse transcription polymerase chain reaction (RT-PCR), Western blot and histology. The penis beta-galactosidase activity and localization of the STZ diabetic rats were also determined., Results: One to two days after transfection, the beta-galactosidase was found in the smooth muscle cells of the diabetic rat penis transfected with AdCMV-betagal. One to 2 days after administration of AdCMV-IGF-1, the cavernosal pressure, as determined by the ratio of maximal intracavernous pressure-to-mean arterial pressure (ICP/MAP) and total intracavernous pressure (ICP), was increased in response to cavernous nerve stimulation. Transgene expression was confirmed by RT-PCR, Western blot and histology., Conclusion: Gene transfer of IGF-1 significantly increased erectile function in the STZ diabetic rats. These results suggest that in vivo gene transfer of IGF-1 might be a new therapeutic intervention for the treatment of erectile dysfunction (ED) in the STZ diabetic rats.