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

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 � 10⁸TU/ml, 10 �l) 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.

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).

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.