Passos Gabriela Reolon, Ghezzi Ana Carolina, Antunes Edson, de Oliveira Mariana Gonçalves, Mónica Fabiola Zakia
Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.
Front Pharmacol. 2021 Feb 12;12:626155. doi: 10.3389/fphar.2021.626155. eCollection 2021.
The lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) are highly prevalent worldwide. Clinical and experimental data suggest that the incidence of LUTS-BPH is higher in patients with vascular-related disorders such as in pelvic ischemia, obesity and diabetes as well as in the ageing population. Obesity is an important risk factor that predisposes to glucose intolerance, insulin resistance, dyslipidemia, type 2 diabetes mellitus and cardiovascular disorders. Prospective studies showed that obese men are more likely to develop LUTS-BPH than non-obese men. Yet, men with greater waist circumferences were also at a greater risk of increased prostate volume and prostate-specific antigen than men with lower waist circumference. BPH is characterized by an enlarged prostate and increased smooth muscle tone, thus causing urinary symptoms. Data from experimental studies showed a significant increase in prostate and epididymal adipose tissue weight of obese mice when compared with lean mice. Adipose tissues that are in direct contact with specific organs have gained attention due to their potential paracrine role. The prostate gland is surrounded by periprostatic adipose tissue (PPAT), which is believed to play a paracrine role by releasing growth factors, pro-inflammatory, pro-oxidant, contractile and anti-contractile substances that interfere in prostate reactivity and growth. Therefore, this review is divided into two main parts, one focusing on the role of adipokines in the context of obesity that can lead to LUTS/BPH and the second part focusing on the mediators released from PPAT and the possible pathways that may interfere in the prostate microenvironment.
良性前列腺增生(BPH)继发的下尿路症状(LUTS)在全球范围内高度流行。临床和实验数据表明,在患有血管相关疾病(如盆腔缺血、肥胖和糖尿病)的患者以及老年人群中,LUTS-BPH的发病率更高。肥胖是导致葡萄糖不耐受、胰岛素抵抗、血脂异常、2型糖尿病和心血管疾病的重要危险因素。前瞻性研究表明,肥胖男性比非肥胖男性更容易发生LUTS-BPH。然而,腰围较大的男性比腰围较小的男性患前列腺体积增大和前列腺特异性抗原升高的风险也更高。BPH的特征是前列腺增大和平滑肌张力增加,从而导致尿路症状。实验研究数据显示,与瘦小鼠相比,肥胖小鼠的前列腺和附睾脂肪组织重量显著增加。与特定器官直接接触的脂肪组织因其潜在的旁分泌作用而受到关注。前列腺被前列腺周围脂肪组织(PPAT)包围,据信PPAT通过释放生长因子、促炎、促氧化、收缩和抗收缩物质发挥旁分泌作用,这些物质会干扰前列腺的反应性和生长。因此,本综述分为两个主要部分,一部分关注肥胖背景下脂肪因子在导致LUTS/BPH方面的作用,第二部分关注PPAT释放的介质以及可能干扰前列腺微环境的途径。