Low androgen status inhibits erectile function by inducing eNOS uncoupling in rat corpus cavernosum.

Abstract

The number of erectile dysfunction (ED) patients is increasing annually. How to improve the effectiveness of ED treatment is an important issue for the field of andrology. To investigate whether low androgen status impairs the erectile function of rats by regulated endothelial nitric oxide synthase (eNOS) uncoupling. Thirty-six 8-week-old male Sprague Dawley (SD) rats were randomly divided into six groups as follows: 4-week sham-operated group (4w-sham), 4-week castration group (4w-cast), 4-week castration+testosterone (T) group (4w-cast+T), 8-week sham-operated group (8w-sham), 8-week castration group (8w-cast), and 8-week castration+T group (8w-cast+T). Three mg/kg of T was subcutaneously injected every other day in castration+T groups. The ratio of the maximum intracavernous pressure/the mean arterial pressure (ICPmax/MAP), the level of serum T, dihydrobiopterin(BH2 ), tetrahydrobiopterin (BH4 ), nitric oxygen(NO), 3-nitrotyrosine(3NT), dihydrofolate reductase (DHFR), guanosine triphosphate cyclohydrolase 1 (GTPCH1), nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), and eNOS monomers/dimers in the corpus cavernosum were detected. The ratio of ICPmax/MAP and BH4 /BH2 , the level of serum T, NO, and GTPCH1 decreased significantly in castration groups compared with sham-operated groups and castration+T groups (P<.05) and decreased significantly in 8w-cast group compared with 4w-cast group (P<.05). The expression of 3NT and NOX2 and the ratio of eNOS monomers/dimers increased significantly in castration groups compared with sham-operated groups and castration+T groups (P<.01) and increased significantly in 8w-cast group compared with 4w-cast group (P<.01). The expression of DHFR in 4w-cast group was significantly higher than that in 4w-sham group and 4w-cast+T group (P<.01) and in 8w-cast group was significantly lower than that in 8w-sham group and 8w-cast+T group (P<.01). Low androgen status induces eNOS uncoupling by reducing BH4 /BH2 and increasing 3NT. Due to the decreased NO production, the erectile function of the rats was impaired.