Abstract
OBJECTIVE: To investigate whether variable coding sequence protein A1 (Vcsa1) is down-regulated in rat models of diabetes and ageing, and to investigate the role of Vcsa1 in erectile function, as Vcsa1 is the most down-regulated gene in the corpora of a rat model of neurogenic erectile dysfunction (ED). MATERIALS AND METHODS: Quantitative reverse-transcriptase polymerase-chain reaction was used to determine Vcsa1 expression in the corpora of rats in three models of ED, i.e. streptozotocin-induced diabetes, retired breeder (old), and neurogenic (bilaterally ligated cavernosal nerves), and in control rats. To confirm a physiological role of Vcsa1 in erectile function, we carried out gene transfer studies using a plasmid in which Vcsa1 was expressed from a cytomegalovirus promoter (pVAX-Vcsa1). This plasmid was injected intracorporally into old rats, and the effect on physiology of corporal tissue was analysed by intracorporal/blood pressure (ICP/BP) measurement and histological analysis, and compared with the effects of a positive control plasmid (pVAX-hSlo, which we previously reported to restore erectile function in diabetic and ageing rats) and a negative control plasmid (pVAX). RESULTS: In each rat model of ED there was a significant down-regulation of the Vcsa1 transcript of at least 10-fold in corporal tissue. Remarkably, intracorporal injection with 80 microg pVAX-Vcsa1 caused priapism, as indicated by visible prolonged erection, histological appearance, and elevated resting ICP/BP. Lower doses of pVAX-Vcsa1 (5 and 25 microg) increased ICP/BP over that in untreated controls. CONCLUSION: These results show that Vcsa1 has a role in erectile function and might be a molecular marker for organic ED. The role of Vcsa1 in erectile function suggests that it could represent a novel therapeutic target for treating ED.