Objective: To investigate the effect of low androgen status on mitochondria-associated membranes (MAMs) and its relationship with erectile function.

Methods: A total of 36 eight-week-old male Sprague-Dawley rats were randomly divided into six groups: the control (sham-operated) group, the castration group, the castration + testosterone (cast + T) group, the control + siRNA group, the cast + siRNA group, and the cast + empty vector group. Testosterone propionate (3 mg/kg) was subcutaneously injected into the rats in the cast + T group every other day starting from the second day after the surgery. Four weeks later, lentiviral vectors carrying phosphofurin acidic cluster sorting protein 2 (PACS-2) gene-specific siRNA (1 × 10⁸ TU/ml, 10 µl) were injected into the rats in the siRNA groups. At the sixth week of castration, the ratio of the maximum intracavernous pressure/the mean arterial pressure (ICPmax/MAP), the levels of nitric oxide (NO), endothelial nitric oxide synthase (eNOS), phospho-eNOS (p-eNOS), fatty acid-CoA ligase 4 (FACL-4), PACS-2, and inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) in the penile corpus cavernosum were determined.

Results: The FACL-4, PACS-2, and IP3R1 were primarily localized in the cytoplasm of endothelial cells and part of smooth muscle cells in the corpus cavernosum. The level of NO, the ratio of ICPmax/MAP, and p-eNOS/eNOS were decreased significantly in the castration group compared with the control group (p < 0.01). The expressions of FACL-4, PACS-2, and IP3R1 were increased significantly in the castration group compared with the control group (p < 0.01). The level of NO, the ratios of ICPmax/MAP, and the ratio of p-eNOS/eNOS were increased significantly in the cast + siRNA group compared with the castration group (p < 0.01). The expressions of FACL-4 and PACS-2 were decreased significantly in the cast + siRNA group compared with the castration group (p < 0.01).

Conclusion: Low androgen status upregulated the expressions of patients in MAMs (FACL-4, PACS-2, and IP3R1) in the corpus cavernosum and inhibited the eNOS/NO/cGMP signaling pathway, resulting in impaired erectile function in rats. Erectile function may be improved by inhibiting the high expression of PACS-2 in the corpus cavernosum under low androgen state.