Sexual Medicine and Andrology Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy.
J Endocrinol. 2012 Jan;212(1):71-84. doi: 10.1530/JOE-11-0289. Epub 2011 Oct 18.
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, IL1β, and TNFα), T lymphocyte (CD4, CD8, Tbet, Gata3, and ROR γt), macrophage (TLR2, TLR4, and STAMP2), neutrophil (lactoferrin), inflammation (COX2 and RAGE), and fibrosis/myofibroblast activation (TGFβ, SM22α, αSMA, 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.
代谢综合征（MetS）和良性前列腺增生（BPH）/下尿路症状（LUTS）常相关。它们的一个共同特征是性腺功能减退。然而，由于担心潜在的前列腺副作用，睾酮补充受到限制。目的是确定 MetS 相关的前列腺改变是否可以通过睾酮补充来预防。我们使用了先前描述的 MetS 动物模型，该模型通过给雄性兔子喂食高脂肪饮食（HFD）12 周来获得。HFD 兔子的亚组接受了睾酮或法尼醇 X 受体激动剂 INT-747 的治疗。喂食标准饮食的兔子作为对照。HFD 动物会出现性腺功能减退和所有 MetS 特征：高血糖、葡萄糖耐量受损、血脂异常、高血压和内脏肥胖。此外，HFD 动物还表现出前列腺炎症。免疫组织化学分析表明，HFD 诱导的前列腺纤维化、缺氧和炎症。几种促炎（IL8、IL6、IL1β 和 TNFα）、T 淋巴细胞（CD4、CD8、Tbet、Gata3 和 RORγt）、巨噬细胞（TLR2、TLR4 和 STAMP2）、中性粒细胞（乳铁蛋白）、炎症（COX2 和 RAGE）和纤维化/肌成纤维细胞激活（TGFβ、SM22α、αSMA、RhoA 和 ROCK1/ROCK2）标志物的 mRNA 表达在 HFD 前列腺中显著增加。睾酮和 INT-747 治疗均可预防一些 MetS 特征，但只有睾酮能使所有 HFD 诱导的前列腺改变正常化。有趣的是，睾酮和雌二醇血浆水平的比值与所有纤维化和大部分分析的炎症标志物呈显著负相关。这些数据表明，睾酮可保护兔前列腺免受 MetS 引起的前列腺缺氧、纤维化和炎症的影响，这可能对 BPH/LUTS 的发展/进展起作用。
