Effect of androgen replacement therapy on erectile function through histological recovery in castrated rats

Abstract

ABSTRACT Introduction Androgens are essential for physical activity in males and normal erectile function. Reportedly, androgen deficiency causes erectile dysfunction through tissue damage in the corpus cavernosum. We previously reported that delayed androgen replacement therapy improved erectile function in rats through histological recovery. Objective To investigate the mechanism of the recovery process by androgen replacement therapy in rats. Methods Twelve-week-old male Wistar ST rats were used in this study. The rats were assigned to the following groups: castrated (Cast), castrated with subcutaneous administration of testosterone undecanoate (25 mg/kg; Cast+T), and sham (Sham). Cast+T rats received subcutaneous doses of testosterone, beginning from 4 weeks after castration, whereas Sham and Cast rats received only the vehicle. Erectile function was assessed by evaluating intracavernosal pressure (ICP) and mean arterial pressure (MAP) after electrical stimulation of the cavernous nerve at 1, 2, 4, and 8 weeks after testosterone administration. mRNA expression of histological factors (Cavin-1, Cavin-2, Cavin-3, α-SMA, VEGF-R, ICAM-1, and TGF-β1) was tested using real-time PCR. Results The ratio of ICP to MAP was 0.26 ± 0.04 in the 4th week for the Cast group, and the erectile function was significantly lower than that of the Sham group (0.61 ± 0.03; p <0.05). On the other hand, in the Cast+T group, it changed over time from 0.41 ± 0.06 in the 1st week, 0.44 ± 0.04 in the 2nd week, 0.48 ± 0.04 in the 4th week, to 0.70 ± 0.03 in the 8th week, and erectile function was significantly improved 8 weeks after the testosterone administration (p <0.05). The Cavin-1 and Cavin-2 mRNA expressions were increased in the Cast+T group compared to the Cast group at all times (P <0.01). α-SMA, VEGF-R, ICAM-1, and TGF-β1 mRNA expressions were also increased in the Cast+T group, as compared to the Cast group (P <0.01). Conclusions In this study, we identified that androgen replacement therapy in rats would improve ED. This may be because the administration of testosterone improved histological recovery. It has been reported that these caveolae-related factors control the invagination structure of the cell membrane, and that caveolae in endothelial cells are also involved in the production of nitric oxide (NO), which might contribute to the therapeutic effect of androgen replacement therapy. Increase in the expression of these caveolae-related factors may regenerate smooth muscle and corpus cavernosum structures. Disclosure Work supported by industry: no.