Obesity-associated inflammation induces androgenic to estrogenic switch in the prostate gland.
Obesity-associated inflammation induces androgenic to estrogenic switch in the prostate gland.
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DOI：
10.1038/s41391-020-0208-4
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发表时间：
2020-09
影响因子：
4.8
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Xue B;Wu S;Sharkey C;Tabatabaei S;Wu CL;Tao Z;Cheng Z;Strand D;Olumi AF;Wang Z
我们的患者队列显示，肥胖与 2 型类固醇 5α 还原酶 (SRD5A2) 启动子甲基化和蛋白质表达减少密切相关。对于这一人群前列腺生长的基本机制知之甚少。在这里，我们解决了肥胖、炎症和类固醇激素如何影响良性前列腺增生 (BPH) 发展的问题。我们使用前脂肪细胞、巨噬细胞、原代人前列腺基质细胞、来自高脂肪饮食诱导的肥胖小鼠的前列腺组织，以及从接受经尿道前列腺切除术 (TURP) 的患者收集的 35 个前列腺样本。 RNA 被分离并通过 RT-PCR 定量。提取基因组DNA并测定SRD5A2启动子甲基化。通过高效液相色谱-串联质谱法 (HPLC/MS) 测定性激素。提取蛋白并通过ELISA检测进行测定。在肥胖的前列腺组织中，炎症介质的水平升高。 SRD5A2启动子甲基化被促进，但SRD5A2表达被抑制。炎症介质和饱和脂肪酸协同调节芳香酶活性。肥胖促进前列腺中雄激素向雌激素的转变。我们的研究结果表明，肥胖相关炎症会诱导前列腺中雄激素向雌激素的转换，这可能作为替代疗法的有效策略，用于治疗特定个体中与 BPH 相关的下尿路症状。
Our patient cohort revealed that obesity is strongly associated with steroid-5α reductase type 2 (SRD5A2) promoter methylation and reduced protein expression. The underlying mechanism of prostatic growth in this population is poorly understood. Here we addressed the question of how obesity, inflammation and steroid hormones affect the development of benign prostatic hyperplasia (BPH). We used pre-adipocytes, macrophages, primary human prostatic stromal cells, prostate tissues from high fat diet induced obese mice, and 35 prostate specimens that collected from patients who underwent transurethral resection of the prostate (TURP). RNA was isolated and quantified with RT-PCR. Genome DNA was extracted and SRD5A2 promoter methylation was determined. Sex hormones were determined by High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC/MS). Protein was extracted and determined by ELISA test. In prostatic tissues with obesity, the levels of inflammatory mediators were elevated. SRD5A2 promoter methylation was promoted, but SRD5A2 expression was inhibited. Inflammatory mediators and saturated fatty acid synergistically regulated aromatase activity. Obesity promoted an androgenic to estrogenic switch in the prostate. Our findings suggest that obesity-associated inflammation induces androgenic to estrogenic switch in the prostate gland, which may serve as an effective strategy for alternative therapies for management of lower urinary tract symptoms associated with BPH in select individuals.
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作者：
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