Lack of adiponectin and adiponectin receptor 1 contributes to benign prostatic hyperplasia.

Shi Fu,Huan Xu,Qi Chen,Chong Liu,Zhong Wang,Juan Zhou,Yanbo Chen,Meng Gu,Xiang Wan

doi:10.18632/oncotarget.19877

Abstract

PURPOSEThe incidence of benign prostatic hyperplasia increases among obese individuals, but few studies have fully explained the underlying mechanisms. Adiponectin has drawn much attention in recent years due to its protective role in obesity-related diseases. Here we aimed to investigate the possible molecular mechanisms and clinical significance of adiponectin in relation to benign prostatic hyperplasia.METHODSWe analyzed data from 98 Chinese men, including 48 BPH cases and 50 controls in a case-control study. Then, we utilized a tissue microarray analysis to examine expression of AdipoR1 and p-p90RSK in normal and hyperplastic prostate tissues. These studies were followed by various in vitro approaches to examine the anti-proliferation effect and signaling pathways of adiponectin involved in benign prostatic hyperplasia.RESULTSLower serum adiponectin levels were independently associated with larger prostate volume and an increased risk of benign prostatic hyperplasia. Benign prostatic hyperplasia tissues had a decreased expression of AdipoR1 and increased expression of p-p90RSK compared with normal prostate tissues. in vitro, adiponectin inhibited the proliferation of prostatic epithelial and stromal cells and arrested cells in the G0/G1 phase by decreasing phosphorylation of the MEK-ERK-p90RSK axis.CONCLUSIONSOur results suggest a possible negative regulatory mechanism in which adiponectin signaling antagonizes ERK-mediated cell proliferation, and a deficiency in adiponectin could facilitate the proliferation of prostate cells and consequently contribute to benign prostatic hyperplasia.

Highlights

Benign prostatic hyperplasia (BPH) is recognized as the most common pathologic condition in aging men and primarily leads to lower urinary tract symptoms (LUTS)
Lower serum adiponectin levels were independently associated with larger prostate volume and an increased risk of benign prostatic hyperplasia
Benign prostatic hyperplasia tissues had a decreased expression of AdipoR1 and increased expression of p-p90RSK compared with normal prostate tissues. in vitro, adiponectin inhibited the proliferation of prostatic epithelial and stromal cells and arrested cells in the G0/G1 phase by decreasing phosphorylation of the MEK-ERK-p90RSK axis

Summary

Introduction

Benign prostatic hyperplasia (BPH) is recognized as the most common pathologic condition in aging men and primarily leads to lower urinary tract symptoms (LUTS). Increasing evidence suggests that obesity plays a key role in the development of BPH [3, 4], but the relationships between these two conditions are still poorly understood. Numerous studies have found that people with obesityrelated diseases have decreased expression of Adiponectin receptors in the lesion tissues [9]. Several studies have shown that adiponectin receptors are expressed in prostate cancer tissues and cell lines [10, 11]. This suggests an underlying role of adiponectin in the physiological or pathological processes of prostate diseases

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