Improvement in erectile dysfunction after insulin-like growth factor-1 gene therapy in diabetic rats

Abstract

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. 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. 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. 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.