AB154. Testosterone improves erectile function through regulation of nicotinamide adenine dinucleotide phosphate-oxidase and cyclooxygenase-2 expression in castrated rats

Objective: Testosterone significantly improves hypogonadal-related erectile dysfunction (ED). However, the molecular mechanisms are poorly understood. The purpose of this study was to explore the effect and mechanism of testosterone in castrated rats.

Methods: Forty male Sprague-Dawley rats were randomized to 4 groups (control, sham-operated, castration and castration-with-testosterone-replacement). After 2 months, reactive oxygen species (ROS) production was measured by dihydroethidium (DHE) staining. Erectile function was tested by recording intracavernosal pressure (ICP) and mean arterial blood pressure (MAP). Protein expression levels were examined by Western blot.

Results: Castration reduced erectile function, and testosterone restored it. The concentrations of testosterone, cyclic guanosine mono-phosphate (cGMP) and cyclic adenosine monophosphate (cAMP) were lower in castrated rats than in controls, and testosterone restored these decreases (each P<0.05). The expression levels of cyclooxygenase-2 (COX-2), prostacyclin synthase (PTGIS or PGIS), endothelial nitric oxide synthase (eNOS) and phospho-eNOS were reduced in castrated rats compared with controls. The expression levels were significantly elevated in rats treated with testosterone (each P<0.05). The expression levels of p40phox and p67phox were increased in castrated rats, and testosterone significantly reduced these increases (each P<0.05). ROS production was markedly enhanced in castrated rats, and testosterone administration reversed this effect (P<0.05).

Conclusions: Testosterone can ameliorate ED after castration by reducing ROS production and increasing activity of the eNOS/cGMP and COX-2/PTGIS/cAMP signaling pathways.

Keywords: Testosterone; erectile dysfunction (ED); NADPH oxidase; reactive oxygen species (ROS)