A previous study demonstrate that chronic tadalafil administration (2 mg/kg per day) was able to prevent some, but not all, penile alterations induced by long-term (3 months) bilateral cavernous neurotomy (BCN) in the rat. In particular, in vitro acetylcholine responsiveness and reduced eNOS and nNOS expression were not preserved, while PDE5 down-regulation, along with muscle/fiber ratio and hypoxygenation (hypoxyprobe) were significantly restored by chronic tadalafil (J Sex Med 2006 3 419431). During the course of the previous study a reduction of testis weight from BCN rats was noticed. Aim of this study is to clarify the role of androgens in BCN.
SpragueDawley rats were divided in 5 groups: a) control, b) BCN, c) BCN+tadalafil (2 mg/kg per day), d) BCN+testosterone (T, 30 mg/kg per week), e) BCN+tadalafil +T and parameters were recorded as before (J Sex Med 2006 3 419431), including hormonal values. Castrated SD rats was used as control.
BCN reduced testis weight, number of Leyding cells, gene expression of the sterodogenetic enzyme 3β-HSD, prostate weight and circulating T, while LH concentration resulted unchanged, suggesting BCN-induced hypogonadotropic hypogonadism. Hypoxygenation, still present in some cavernous endothelial cell in BCN+tadalafil, was completely absent in T-substituted rats. T alone or in combination with tadalafil rescued PDE5 gene level up to control and normalized hyper-sensitivity to the nitric oxide donor SNP. More importantly, T treatment restored eNOS expression and acetylcholine responsiveness. Conversely, nNOS gene expression resulted still down-regulated in T-treated (w or w/o tadalafil) BCN rats.
We described for the first time the presence of hypogonadotropic hypogonadism in long-term BCN, and demonstrated that T substitution can ameliorate the positive effect of chronic tadalafil administration fully restoring penile oxygenation and responsiveness to acetylcholine. The possibility that hypogonadism complicate the radical prostatectomy-associated deleterious effect on penile activity in humans should be tested in forthcoming studies.
03 - 07 May 2008
European Society of Endocrinology