雄激素对高盐饮食状态下雄性大鼠血管内皮功能的影响

目的 探讨不同水平雄激素对高盐饮食状态下雄性大鼠血管内皮功能的影响.方法 雄性Wistar大鼠32只随机分为4组,每组各8只:假手术组(Sham),去势组(Cas),去势后补充睾酮组(TC),去势后补充睾酮和氟他胺组(FTC).各组均以8％NaCl高盐颗粒饲料喂养,Sham组施以假手术,Cas、TC及FTC组均施以去势手术.TC及FTC组予以丙酸睾酮(TP) 2mg/(kg·2d)皮下注射,FTC组同时予以氟他胺1mg/(kg·d)灌胃,持续8周.尾动脉脉压法测定各组实验前、实验4周、实验8周后尾动脉血压,8周后酶联免疫吸附测定法(ELISA)测定血清中睾酮(T)、内皮素1(ET-1)的浓度,比色法测定血浆中一氧化氮(NO)水平.结果 (1)与Sham组血压相比,Cas组和FTC组明显下降[Cas组:(124.8±4.4) vs(135.9±3.7) mmHg,P＜0.01;FTC组:(127.7±3.0)vs(135.9±3.7) mmHg,P＜ 0.01];与基础血压相比,Sham组和TC组明显升高(P＜0.01);(2)与Sham组T浓度相比,Cas组的明显下降[(0.26±0.02) vs (3.15±0.54) μg/L,P＜ 0.01],而FTC组明显升高[(5.47±1.29) vs(3.15±0.54) μg/L,P＜0.01];(3)与Sham组血清ET-1浓度相比,Cas组和FTC组明显下降[Cas组:(0.77±0.23) vs(1.08±0.15)μg/L,P＜0.01;FTC组:(0.80±0.21) vs(1.08±0.15) μg/L,P＜0.05]; TC组差异无统计学意义(P＞0.05);(4)与Sham组NO浓度相比,Cas组和FTC组明显升高[Cas组:(42.37±15.74)vs(17.20±7.32) mmol/L,P＜0.01; FTC组:(33.44±8.50) vs(17.20±7.32) mmol/L,P＜0.01];TC组差异无统计学意义(P＞0.05).结论 高盐饮食下,雄激素水平的变化可能影响雄性大鼠血管内皮功能.     

Kinetics of testosterone recovery in clinically localized prostate cancer patients treated with radical prostatectomy and subsequent short-term adjuvant androgen deprivation therapy

Androgen deprivation therapy (ADT) is a standard treatment for metastatic, recurrent and locally advanced prostate cancer (PCa). The aim of this study is to investigate the timing and extent of testosterone recovery in clinically localized PCa patients treated with radical prostatectomy (RP) and subsequent short-term adjuvant ADT. A total of 95 localized PCa patients underwent RP and 9-month adjuvant ADT were included in this prospective study. Serum testosterone level was measured before adjuvant ADT, at ADT cessation, and at 1, 3, 6, 9 and 12 months after cessation of ADT. A Cox proportional hazards model was used to assess variables associated with the time of testosterone normalization. The results showed that median patient age was 67 years and median testosterone level before adjuvant ADT was 361 (230–905) ng dl⁻¹. All patients finished 9-month adjuvant ADT and achieved castrate testosterone level. At 3 months after ADT cessation, testosterone recovered to supracastrate level in 97.9% patients and to normal level in 36.9% patients. The percentage of patients who recovered to normal testosterone level increased to 66.3%, 86.3% and 92.6% at 6, 9 and 12 months, respectively. Cox regression model found that higher baseline testosterone level (≥300 ng dl⁻¹) was the only variable associated with a shorter time to testosterone normalization (hazard ratio: 1.98; P = 0.012). In conclusion, in most patients, testosterone recovered to supracastrate level at 3 months and to normal level at 12 months after 9-month adjuvant ADT cessation. Patients with higher baseline testosterone level need shorter time of testosterone normalization.     

The effect of diet-induced insulin resistance on DNA methylation of the androgen receptor promoter in the penile cavernosal smooth muscle of mice

Population studies have suggested an association between diabetes and the symptoms of testosterone deficiency. Recently, the expression of the androgen receptor (AR) has been shown to be decreased in diabetic patients. Furthermore, diabetes has been shown to induce global methylation. In this study, we used an animal model to investigate whether diabetes results in increased methylation of the AR promoter and whether these changes are associated with the decreased expression of AR in penile cavernosal smooth muscle tissue. Twenty C57BL/6J mice were divided into two groups, receiving either high- (mature diabetic) or low- (mature control) caloric meals for 14 weeks. Another 10 mice were killed at 1 week (young control). Animals in the mature diabetic group showed decreased testosterone levels, although this was not statistically significant. In both control groups, no significant methylation was observed in the AR promoter region CpG island (−85 to +339). In the mature diabetic group, significant methylation was observed at +185 and +200 of the AR promoter. These changes were associated with increased homeostatic model assessment for insulin resistance (HOMA-IR) and decreased corpus cavernosal tissue mass and expression of AR mRNA and protein. We conclude that in these animals, insulin resistance increased the methylation of the GC-rich regions of the AR promoter, leading to decreased AR expression.