Effects of castration and androgen replacement on erectile function in a rabbit model

We investigated, in a rabbit model, the effects of castration and testoster one replacement on: 1) the hemodynamics of the corpus cavernosum; 2) alpha- 1 adrenergic receptor protein expression; 3) neural NO synthase protein exp ression and activity; 4) phosphodiesterase type 5 activity; and 5) trabecul ar smooth muscle/connective tissue balance. One week after bilateral orchie ctomy, animals were treated for 7 days with vehicle alone, testosterone, or estradiol. Intact control animals received vehicle only. Systemic arterial blood and intracavernosal pressures (ICP) were measured in each animal bef ore and after electrical stimulation of the cavernosal nerve. alpha(1)-adre nergic receptor protein expression was determined by ligand binding studies . NO synthase expression and activity were determined by Western blot analy ses and conversion of L-arginine to citrulline, respectively. Phosphodieste rase type 5 activity was determined by hydrolysis of guanosine 3',5'-cyclic monophosphate (cGMP) in tissue extracts in the absence or presence of 100 nM sildenafil. Smooth muscle content was assessed by Masson's trichrome sta ining and computer-assisted histomorphometry. Castration significantly redu ced ICP, but it did not alter systemic arterial blood pressure during stimu lation of the cavernosal nerve. Testosterone, but not estradiol, treatment prevented the effects of castration and restored ICP to values similar to t hose obtained in intact animals. Castration reduced expression of alpha(1)- adrenergic receptor, and this reduction was prevented or reversed by testos terone replacement. Neural NO synthase protein expression and total activit y were not altered significantly by castration or after testosterone replac ement. However, phosphodiesterase type 5 activity increased in castrated an imals treated with testosterone. Castration significantly reduced trabecula r smooth muscle content, and this reduction was restored by testosterone (b ut not estradiol) treatment. The results of this study demonstrate that and rogen deprivation alters the functional responses and structure of erectile tissue.