Introduction: Although there has been increasing evidence that indicates positive relationship between metabolic syndrome and emergence in benign prostatic hyperplasia (BPH), the detailed pathophysiological mechanism is still unknown. Estrogen, which is increased in obese patients, is considered to be one of the key factors in development of BPH and G protein-coupled estrogen receptor (GPER) has been reported to be implicated in symptomatic BPH. To elucidate a role of GPER signaling in development of BPH, we evaluated changes in prostatic weight and inflammatory profiles in the prostate by GPER inhibition using high fat diet induced obesity rat model.
Methods: Male Wistar rats (8 weeks old) were divided into three groups; rats with normal diet group (ND, n=6), rats with high fat diet induced obesity group (HFD, n=6), and HFD treated by G15 (G15, n=6) which is GPER antagonist. The high fat diet contains 32% fat. These rats were maintained for twelve weeks followed by two weeks treatment by oral administration of placebo or G15 (0.1mg/kg) daily. Lateral lobes of prostate were harvested to assess prostatic weight, histological change and mRNA expression of GPER, IL1ß, TGFß, ERK1/2 by qPCR.
Results: HFD showed significantly increased body weight, visceral fat and prostatic weight as well as significant upregulation of gene expressions in GPER, IL1ß, TGFß, and ERK1/2 compared to ND. Hematoxylin and eosin (HE) staining showed inflammatory cell infiltration in prostatic tissue section from HFD. In contrast, HFD treated by G15 demonstrated significantly decreased prostatic weight in association with downregulation of IL1ß, TGFß and ERK1/2 compared to HFD with placebo. mRNA expression of GPER was not significantly changed between HFD and G15 group.
Conclusions: We demonstrated improvement of prostatic enlargement and inflammation by GPER inhibition, which suggest GPER signaling has an important role in development of BPH in obese patients. Therefore, GPER inhibition could be an therapeutic target of BPH with metabolic syndrome.