Effects of Castration and Androgen Replacement on Erectile Function in a Rabbit Model

Abstract

We investigated, in a rabbit model, the effects of castration and testosterone replacement on: 1) the hemodynamics of the corpus cavernosum; 2) alpha-1 adrenergic receptor protein expression; 3) neural NO synthase protein expression and activity; 4) phosphodiesterase type 5 activity; and 5) trabecular smooth muscle/connective tissue balance. One week after bilateral orchiectomy, 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 before and after electrical stimulation of the cavernosal nerve. Alpha1-adrenergic receptor protein expression was determined by ligand binding studies. NO synthase expression and activity were determined by Western blot analyses and conversion of L-arginine to citrulline, respectively. Phosphodiesterase 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 staining and computer-assisted histomorphometry. Castration significantly reduced ICP, but it did not alter systemic arterial blood pressure during stimulation of the cavernosal nerve. Testosterone, but not estradiol, treatment prevented the effects of castration and restored ICP to values similar to those obtained in intact animals. Castration reduced expression of alpha1-adrenergic receptor, and this reduction was prevented or reversed by testosterone replacement. Neural NO synthase protein expression and total activity were not altered significantly by castration or after testosterone replacement. However, phosphodiesterase type 5 activity increased in castrated animals treated with testosterone. Castration significantly reduced trabecular smooth muscle content, and this reduction was restored by testosterone (but not estradiol) treatment. The results of this study demonstrate that androgen deprivation alters the functional responses and structure of erectile tissue.

Influence of serum testosterone on urinary continence and sexual activity in patients undergoing radical prostatectomy for clinically localized prostate cancer

“…Moreover, a trophic effect of T on penile architecture has also been shown by in vivo data in different animal species and ex vivo data extrapolated from rabbits. 24,27 For all the aforementioned reasons, treatment of hypogonadism restores impaired penile erections in experimental animal models, as well as in the clinical setting. Conversely, administration of testosterone to otherwise eugonadal individuals is ineffective.…”

The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease

“…41 Testosterone is a key central and peripheral modulator of erectile function in animal studies. [42][43][44][45] Consistent with these observations, a single-center study of 1050 men seeking new consultation for sexual dysfunction found that 36% had hypogonadism. 46 Buvat and Bou Jaoude, 47 in a compilation of data from 7000 men with ED in 9 large series, reported serum testosterone levels less than 300 ng/dL (to convert to nmol/L, multiply by 0.0347) in 12%, including 4% before and 15% after age 50 years.…”

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

“…Previous studies in animal models suggest that androgen deprivation reversibly alters the structure and function of the cavernous tissue (Traish and Kim 2005) and results in critical increase in the number of apoptotic trabecular SM cells, which compromise the veno-occlusive mechanism and erectile function (Shabsigh 1997;Traish et al 1999Traish et al , 2007. Nevertheless, the exact mode of androgen action in the regulation of erectile function in human remains unknown.…”