Testosterone Improves Erectile Function Through Inhibition Of Reactive Oxygen Species Generation And Increasing The Activity Of COX-2/PTGIS/cAMP Signal Pathway In Castrated Rats

Part I Testosterone improves erectile function through inhibition of reactive oxygen species generation in castrated ratsObjective:Testosterone significantly improves hypogonadal-related erectile dysfunction(ED).However,the molecular mechanisms are poorly understood.The purpose of this study was to explore the effect and mechanisms of testosterone in castrated rats.Methods:Forty male Sprague-Dawley rats were randomized to 4 groups(control,sham-operated,castration and castration-with-testosterone-replacement).After 1 month,reactive oxygen species(ROS)production was measured by dihydroethidium(DHE)staining.Erectile function was tested by recording intracavernosal pressure(ICP)and mean arterial blood pressure(MAP).Relative protein expression levels were assessed by Western bloting.Results:Castration reduced erectile function,and testosterone restored it.The concentrations of testosterone,dihydrotestosterone(DHT),cyclic guanosine mono-phosphate(cGMP)were lower in castrated rats than in controls,and testosterone restored these decreases(each P<0.05).The expression levels of endothelial nitric oxide synthase(eNOS)and phospho-eNOS(Ser1177)were reduced in castrated rats compared with controls.The expression levels were significantly elevated in rats treated with testosterone(each P<0.05).The expression levels of p40phox and p67phox were increased in castrated rats,and testosterone significantly reduced these increases(each P<0.05).ROS production was markedly enhanced in castrated rats,and testosterone treatment reversed this increase(P<0.05).Conclusions:Testosterone can ameliorate ED after castration by reducing ROS production and increasing activity of the NO/cGMP signal pathway.Part II Testosterone improves erectile function through increasing the activity of COX-2/PTGIS/cAMP signal pathway in Castrated RatsObjective:The purpose of this study was to explore the effect and mechanisms of testosterone in castrated rats.Methods:Forty male Sprague-Dawley rats were randomized to 4 groups(control,sham-operated,castration and castration-with-testosterone-replacement).After 1 month,erectile function was tested by recording intracavernosal pressure(ICP)and mean arterial blood pressure(MAP).Protein expression levels were examined by Western blot.Masson’s trichrome staining was used to determine collagen content and smooth muscle in penile tissues.TUNEL assay was ued to assess the degree of apoptosis.Results:Castration reduced erectile function,and testosterone restored it.The concentrations of testosterone,dihydrotestosterone(DHT)and cyclic adenosine monophosphate(cAMP)were lower in castrated rats than in controls,and testosterone restored these decreases(each P<0.05).The expression levels of cyclooxygenase-2(COX-2),prostacyclin synthase(PTGIS or PGIS)were reduced in castrated rats compared with controls.The expression levels were significantly elevated in rats treated with testosterone(each P<0.05).The expression levels of TGF-β1 and the ratio of Bax/Bcl-2 were increased in castrated rats,and testosterone significantly reduced these increases(each P<0.05).The collagen/smooth muscle content ratio was markedly enhanced in penile tissues in MED group and the degree of apoptosis in MED group was obviously increased,as demonstrated by the increased Bax/Bcl-2 ratio,testosterone significantly reduced the collagen/smooth muscle content ratio and apoptosis(each P<0.05).Conclusions:Testosterone can ameliorate ED after castration by reducing fibrosis and apoptosis and increasing activity of the COX-2/PTGIS/cAMP signal pathway.Objective: The metabolic syndrome,a disease arising from the world-wide epidemic of obesity,is manifested as insulin resistance,hypertension,hyperlipidaemia,and diabetes,Metabolic Syndrome is a risk factor for erectile dysfunction(ED),but the underlying mechanisms are unclear.The aims of this study were to del;ermine the underlying mechanisms of the metabolic syndrome-related ED(MED).Methods: Sprague-Dawley rats rendered obese by feeding a very high fat diet for 6 months.After 6 months,body weight,plasma insulin(insulin-resistance),glucose levels and plasma lipid were assessed.An apomorphine test was conduchd to confirm MED.Erectile responses were evaluated by dekrmining mean arterial blood pressure(MAP)and intracavernosal pressure(ICP)with electrical stimulation of the cavernous nerve.Levels of protein expression were examined by Western Blot and Immunohistochemistry.Results: The levels of body weight,blood glucose,plasma insulin and plasma total cholesterol were increased in metabolic syndrome rats when compared to those of control rats(P<0.05).The ratio of Maximum ICP-to-MAP(Max ICP/MAJP)and the concentration of cyclic guanosine mono-phosphate(cGMP)was significantly decreased in MED rats,compared to that of age-matched control rats(P<0.05).Expression levels of p110 a,p-Aktl(iyr308)/Akt and p-eNOS(Serll77)/eNOS were reduced,compared to those of coniTol rats(P<0.05).Conelusions: The present study demonstrates that down-regulation of PI3K/Akt/eNOS signal pathway was involved in MED.