Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit
Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit
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DOI：
10.1530/joe-11-0289
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发表时间：
2012-01-01
影响因子：
4
通讯作者：
Maggi, Mario
中科院分区：
文献类型：
--
作者：
Vignozzi, Linda;Morelli, Annamaria;Maggi, Mario
代谢综合征(METS)和良性前列腺增生症(BPH)/下尿路症状(LUTS)经常相关。他们的共同点之一是性腺功能减退。然而，由于担心潜在的前列腺副作用，补充睾丸素受到限制。研究的目的是确定补充睾丸素是否可以预防甲硫氨酸相关的前列腺改变。我们使用了之前描述的蛋氨酸动物模型，通过给雄性兔子喂高脂饮食(HFD)12周而获得。用睾酮或法尼醇X受体激动剂INT-747治疗HFD兔。以喂饲标准饲料的兔为对照。HFD-动物出现性腺功能减退和所有蛋氨酸代谢综合征的特征：高血糖、葡萄糖耐受不良、血脂异常、高血压和内脏肥胖。此外，HFD动物表现出前列腺炎。免疫组织化学分析表明，HFD可导致前列腺纤维化、缺氧和炎症。在HFD前列腺组织中，多种促炎细胞(IL8、IL6、IL1β和TNFα)、T淋巴细胞(CD4、CD8、Tbet、GATA3和RORGamma t)、巨噬细胞(TLR2、TLR4和STAMP2)、中性粒细胞(乳铁蛋白)、炎症(COX2和RAGE)以及纤维化/肌成纤维细胞活化(TGFβ、SM22α、αSMA、RhoA和ROCK1/ROCK2)的mRNA表达显著增加。睾酮和INT-747治疗阻止了甲硫氨酸的一些特征，尽管只有睾酮使所有由HFD引起的前列腺改变正常化。有趣的是，睾酮和雌二醇血浆水平之间的比率与所有的纤维化和大多数炎症标志物分析都保持着显著的负相关。这些数据表明，睾酮保护兔前列腺免受蛋氨酸诱导的前列腺缺氧、纤维化和炎症的影响，这些都可能在BPH/LUTS的发生/发展中发挥作用。内分泌学杂志(2012)212，71-84
Metabolic syndrome (MetS) and benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) are often associated. One of their common denominators is hypogonadism. However, testosterone supplementation is limited by concerns for potential prostatic side effects. The objective was to determine whether MetS-associated prostate alterations are prevented by testosterone supplementation. We used a previously described animal model of MetS, obtained by feeding male rabbits a high-fat diet (HFD) for 12 weeks. Subsets of HFD rabbits were treated with testosterone or with the farnesoid X receptor agonist INT-747. Rabbits fed a standard diet were used as controls. HFD-animals develop hypogonadism and all the MetS features: hyperglycemia, glucose intolerance, dyslipidemia, hypertension, and visceral obesity. In addition, HFD-animals show a prostate inflammation. Immunohistochemical analysis demonstrated that HFD-induced prostate fibrosis, hypoxia, and inflammation. The mRNA expression of several proinflammatory (IL8, IL6, IL1 beta, and TNF alpha), T lymphocyte (CD4, CD8, Tbet, Gata3, and ROR gamma t), macrophage (TLR2, TLR4, and STAMP2), neutrophil (lactoferrin), inflammation (COX2 and RAGE), and fibrosis/myofibroblast activation (TGF beta, SM22 alpha, alpha SMA, RhoA, and ROCK1/ROCK2) markers was significantly increased in HFD prostate. Testosterone, as well as INT-747, treatment prevented some MetS features, although only testosterone normalized all the HFD-induced prostate alterations. Interestingly, the ratio between testosterone and estradiol plasma level retains a significant, negative, association with all the fibrosis and the majority of inflammatory markers analyzed. These data highlight that testosterone protects rabbit prostate from MetS-induced prostatic hypoxia, fibrosis, and inflammation, which can play a role toward the development/progression of BPH/LUTS. Journal of Endocrinology (2012) 212, 71-84