Vasoactive intestinal polypeptide, an erectile neurotransmitter, improves erectile function more significantly in castrated rats than in normal rats.

OBJECTIVE • To investigate the regulatory role of androgen in VIP-mediated erectile effect. Androgen is essential for physiological erection. Vasoactive intestinal polypeptide (VIP) is an important erectile neurotransmitter. While previous studies demonstrated that VIP expression in the penis was androgen-independent, it remains controversial whether androgen has any effect on VIP-mediated erection. MATERIALS AND METHODS • Male SD rats were divided into a control group, a castration group, and a castration-with-testosterone-replacement group. Four weeks later, each group was subdivided into low and high-dose VIP subgroups and subjected to intracavernous injection of 0.5 and 2 µg VIP, respectively. • Erectile function was tested by recording intracavernosal pressure (ICP) and mean arterial blood pressure (MAP) before and after VIP injection. • The expressions of the VIP-receptor (VPAC2), G-protein stimulatory and inhibitory alpha subunits (Gs-α, Gi-α), and PDE3A in rat corpus cavernosum (CC) was qualified by real-time PCR and Western blot analysis. RESULTS • Castration reduced erectile function while testosterone restored it. VIP improved erectile function in a dose-dependent manner. • High-dose VIP significantly enhanced erectile function in castrated rats and there was no difference of ICP/MAP among three groups after injection of high-dose VIP. • Low-dose VIP also resulted in a higher improvement of erectile function in castrated rats, although the ICP/MAP was lower in these rats than in the other two groups. VPAC2 and Gs-α were up-regulated while Gi-α and PDE3A were down-regulated in CC of castrated rats. CONCLUSION • VIP improves erectile function much more significantly in hypogonadal condition, mainly due to the higher expression of VPAC2, Gs-α, and lower expression of Gi-α and PDE3A in CC of castrated rats. Androgen may negatively regulate the erectile effect of VIP.