(066) A Low Androgen State Impairs Erectile Function by Suppressing EPAC1 in Rat Corpus Cavernosum Penis

Abstract Introduction The relationship among exchange proteins activated by cAMP 1(EPAC1), androgen and erectile function is still unknown. Objective To explore whether EPAC1 expresses in penile corpus cavernosum of rats and how EPAC1 affects erectile function under low androgenic conditions. Methods Thirty 8-week-old healthy male rats were randomly divided into six groups (n=5): sham operation (sham), castrated, castrated + testosterone replacement (castrated + T), sham + EPAC1 over-expression lentivirus (sham + EPAC1), castrated + empty lentivirus vector (castrated + empty vector), and castrated + EPAC1. Four weeks after the operation, the lentivirus vectors carrying the EPAC1 gene were injected into the corpus cavernosum penis tissues of the sham + EPAC1 and castrated + EPAC1 groups (1×108TU/ml, 20 μl per rat). A week after injection, the ratio of maximum intracavernous pressure to mean arterial pressure (ICPmax/MAP) and the levels of serum testosterone (T), nitric oxide (NO), the active form of ras homolog gene family, member A (RhoA-GTP), protein kinase B (AKT), phospho-AKT (p-AKT), endothelial nitric oxide synthase (eNOS), phospho-eNOS (p-eNOS), p-AKT/AKT, p-eNOS/eNOS and EPAC1 levels were measured. Results EPAC1 is primarily located in the cytoplasm of endothelial cells and smooth muscle cells in the rat corpus cavernosum penis. In comparison to the sham group, the T, ICPmax/MAP and NO levels of the castrated group were notably reduced (p < 0.01). Meanwhile, the RhoA-GTP concentration in the castrated + EPAC1 group was reduced in comparison with the castrated + empty vector group (p < 0.01). Compared with the castrated + empty vector group, the p-AKT/AKT, EPAC1 and p-eNOS/eNOS levels in the castrated + EPAC1 group were significantly increased (p < 0.05). Conclusions Androgen deficiency can suppress EPAC1 expression in the penile corpus cavernosum of rats, while the up-regulation of which can improve the erectile function of castrated rats. Disclosure Yes, this is sponsored by industry/sponsor: This study was supported by the Research Foundation of the Department of Human Resources and Social Security of Sichuan Province of Returned Scholars grant 2019-76. Clarification: No industry support in study design or execution.