AB228. Research on the mechanism of androgen replacement therapy improving erectile dysfunction in castrated rats

OBJECTIVE: To investigate the mechanism of androgen replacement therapy (ART) improving erectile dysfunction (ED) in castrated rats. METHODS: We randomly divided 40 8-week-old healthy male SD rats into 4 groups: group A was the control, and rats of the group B, C and D were castrated, then rats in the groups C and D were treated with different concentrations of testosterone undecanoate orally every day (C: 10 mg/kg, D: 20 mg/kg), while other groups with 0.9% NS instead. 8weeks’ treatment later, we determined the level of serum testosterone and assessed the erectile function of rats. Western blot, immunohistochemistry were performed to detect the level of target proteins. RESULTS: (I) The level of serum testosterone and erectile function (Max ICP/MAP): group Bwas significantly lower than group A, C and D, and group D was higher compared with group C; (II) effect of castration and ART on endothelial cells and androgen receptor (AR)/vascular endothelial growth factor (VEGF)/cyclin A pathway: the expression of CD31, vWF and AR/VEGF/cyclin A in group B were lower than group A, C and D, and group D was higher compared with group C; (III) effect of castration and ART on corpus cavernosum smooth muscle cells (CCSMCs) and TGF-β/S1P2/RhoA/ROCK pathway: the expression of α-sma in group B were lower than group A, C and D, and group D was higher compared with group C; while the expression of TGF-β/S1P2/RhoA/ROCK1 were higher in group B than group A, C and D, and group D was lower compared with group C. CONCLUSIONS: ART can improve ED in castrated rats through promoting the proliferation of corpus cavernosum endothelial cells by activating AR/VEGF/cyclin A pathway; decreasing the contraction of CCSMCs and corporal fibrosis by inhibiting TGF-β/S1P2/RhoA/ROCK pathway, which provides reference for revealing the mechanism of ART treating ED associated late-onset hypogonadism.