OBJECTIVE: To investigate the expression of insulin-like growth factor binding protein-3 (IGFBP-3) in penile cavernous of streptozotocin (STZ)-induced DM rats and whether downregulation of IGFBP-3 by intracavernosal injection of short hairpin ribonucleic acid (shRNA) targeting IGFBP-3 could improve the erectile function in DM rats.
MATERIALS AND METHODS: Diabetes was induced in rats by intraperitoneal injection of STZ, and the expression of IGFBP-3 in the penile tissue of adult normal and DM male rats was assayed using reverse transcriptase-polymerase chain reaction and Western blot. Next, shRNA-targeting IGFBP-3 and a scramble sequence were injected into the penile corpora cavernosa of DM rats. At 12 weeks after shRNA-IGFBP-3 administration, the intracavernous pressure in response to electrical stimulation of the cavernous nerves was evaluated. The expression of IGFBP-3 was assayed by Western blot. The concentration of cyclic guanosine monophosphate in the corpus cavernosum was assayed by enzyme-linked immunosorbent assay.
RESULTS: At 12 week after intraperitoneal administration of STZ, IGFBP-3 expression had increased in the penis of the DM rat (P < .05) compared with that of the normal control rats. Among the DM rats, IGFBP-3 expression at the messenger RNA and protein level was significantly inhibited 12 weeks after intracavernous administration of IGFBP-3 shRNA (P < .01). At 12 weeks after shRNA-IGFBP-3 injection, intracavernosal pressure was significantly increased in response to cavernous nerve stimulation (P < .05), and an increase in the concentration of cyclic guanosine monophosphate in the corpus cavernous tissue (P < .01) was detected compared with the "randomer" shRNA treatment group.
CONCLUSION: Gene transfer of shRNA-IGFBP-3 could improve erectile function in STZ-induced DM rats by an increase in the cyclic guanosine monophosphate concentration in cavernous tissue.
Written by:
Yang Z, Zhou Z, Wang X, Peng M, Zhou H, Meng Z, Chen D, Wang Y. Are you the author?
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Reference: Urology. 2013 Feb;81(2):464.e11-6.
doi: 10.1016/j.urology.2012.10.045
PubMed Abstract
PMID: 23374841
UroToday.com Investigative Urology Section
