The effects of testosterone replacement on penile structure and erectile function after long-term castration in adult male rats

Short periods of testosterone suppression have been shown to reduce trabecular smooth muscle content and increase interstitial connective tissue accumulation in animal models. However, the long-term effects of testosterone suppression remain unclear. The aim of this study was to evaluate the long-term effects of testosterone suppression on penile structure and erectile function in rats. Subjects were divided into two groups by observation period (short-period group (group I), 12 weeks; long-period group (group II), 20 weeks). Each group comprised three different subgroups (10 rats each): sham-operated control, surgical castration, and testosterone replacement (4 weeks after an 8-week castration period). Group II subgroups included a sham control, surgical castration, and testosterone replacement (4 weeks after a 16-week castration period). Erectile function was assessed by measuring intracavernosal pressure in response to cavernous nerve stimulation, and expression of the endothelial nitric oxide synthase (eNOS) protein was determined by western blot analysis. Serum testosterone values were measured via radioimmunoassay. The results indicated that serum testosterone level, penile length and girth, cavernosal smooth muscle content, and eNOS activity decreased significantly in castrated animals. These effects were rescued by testosterone undecanoate injection. Erectile function was normalized over 4 weeks in rats that received androgen replacement. Expression of eNOS was decreased in the corpus cavernosum of castrated animals compared with controls, while androgen replacement normalized the expression of eNOS. These results were consistently observed regardless of the duration of androgen deprivation. Thus, these data suggest that androgen regulates the expression of eNOS in the rat penile corpus cavernosum and confirm the importance of androgens in the maintenance of erectile function. Additionally, long-term androgen deprivation does not induce irreversible structural or erectile functional changes in sexually mature adult male rats.