Low Androgen Status Inhibits Erectile Function By Promoting ENOS Uncoupling In Rat Corpus Cavernosum

Objective:To investigate whether low androgen ststus affects erectile function of rat cavernous by regulating eNOS uncoupling.Methods:Thirty-six 8-week-old male Sprague-Dawley?SD?rats were randomly divided into 6 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?,8-week castration+T group?8w-cast+T?.Testicles were surgically removed as castration.3mg/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.Results:The level of serum testosterone,BH₄/BH₂ level,NO content and GTPCH1 decreased significantly in the castration group ?4w-cast:1.63±0.17nmol/L;1.49±0.06;6.81±0.48unmol/gprot;0.85±0.06,8w-cast:0.44±0.03nmol/L;0.7±0.04;3.3±0.61unmol/gprot;0.57±0.12?compared with sham-operated groups?4w-sham:20.71±0.55 nmol/L;3.63±0.19;11.27±0.8unmol/gprot;1,8w-sham:20.63±0.47nmol/L;3.55±0.15;11.75±1.98unmol/gprot;1.00±0.03?and castration+testoserone groups?4w-cast+T:20.91±0.84nmol/L;3.56±0.12;12.08±1.98nmol/gprot;1.03±0.04,8w-cast+T:20.65±0.37nmol/L;3.68±0.17;12.67±0.6unoml/gprot;0.99±0.04??p<0.05?,and 8w-cast was significantly lower than the 4w-cast?p<0.01?.Tthe ratio of eNOS monomers/dimers,the expression of 3NT and NOX2 increased significantly in the castration group?4w-cast:1.01±0.04;53.72±2.12pg/mg;1.42±0.10,8w-cast:1.58±0.02;80.42±2.48pg/mg;1.88±0.19?compared with sham-operated groups?4w-sham:0.58±0.05;38.57±1.35pg/mg;1,8w-sham:0.59±0.02;38.91±0.79mg/pg,0.98±0.07?and castration+testoserone groups?4w-cast+T:0.59±0.02;39.56±2.51pg/mg;1.01±0.10,8w-cast+T:0.58±0.05;36.82±3.34pg/mg;1.02±0.07??p<0.01?,and8w-cast was significantly higher than 4w-cast?p<0.01?.The expression of DHFR in 4w-cast?1.26±0.02?increased significantly compared with 4w-sham?1?and 4w-cast+testoserone?0.97±0.04??P<0.01?,the expression of DHFR in8w-cast?0.85±0.03?is significantly lower than 8w-sham?0.98±0.02?and8w-cast+testoserone?0.98±0.06??p<0.01?and DHFR content in 8w-cast dercreased obviously compared with that in 4w-cast.The ratio of ICPmax/MAP under 3V and 5V in cast groups?3V:4w-cast:0.41±0.02,8w-cast:0.24±0.02,5V:4w-cast:0.55±0.03;8w-cast:0.40±0.01?were significantly lower than that in sham-operated groups?3V:4w-sham:0.66±0.02,8w-sham:0.66±0.04,5V:4w-sham:0.83±0.03,8w-sham:0.85±0.02?and castration+T groups?3V:4w-cast+T:0.65±0.03,8w-cast+T:0.67±0.03,5V:4w-cast+T:0.83±0.01;8w-cast+T:0.81±0.03??p<0.01?,the ICPmax/MAP ratio under 3V and 5V in 8w-cast was dercreased obviously compared with that in 4w-cast?p<0.01?.Conclusion: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.