Testosterone modulates endothelial progenitor cells in rat corpus cavernosum.

Abstract

To investigate the effects of testosterone on cavernosal endothelial progenitor cells (EPCs) in a castrated rat model. In all, 45 male Sprague-Dawley rats (12-weeks old) were divided into control, surgical castration, and castration with testosterone replacement groups. The rats were castrated under ketamine anaesthesia, and testosterone was administered by daily subcutaneous injection of 3 mg/kg testosterone propionate. The corpus cavernosum was obtained after perfusion with 10 mL saline via the abdominal aorta 4 weeks later. The expression of EPC-specific markers [cluster of differentiation 34 (CD34), fetal liver kinase 1 (Flk1), and vascular endothelial (VE)-cadherin] was evaluated by flow cytometry analysis and immunofluorescence staining. CD34+/Flk1+ and CD34+/VE-cadherin+ cells were detected in the cavernosal sinusoidal endothelial space. Flow cytometry analysis showed that CD34 and Flk1 double positive cells (EPCs) comprised ≈3.79% of the corpus cavernosum in normal rats. The percentage of EPC marker-positive cells decreased significantly in the castration group (2.8%; P < 0.05) and was restored to 3.56% after testosterone supplementation. Confocal microscopy revealed that the numbers of CD34+/Flk1+ and CD34+/VE-cadherin+ cells decreased in castrated rats compared with controls, but were similar to control levels in rats receiving testosterone replacement. The EPC markers were expressed in the cavernosal sinusoidal endothelial space, and the numbers of resident EPCs were regulated by testosterone. These results suggest that testosterone replacement therapy may improve erectile function by modulating EPCs in patients with hypogonadism.