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Effects of Estrogen Receptor β Stimulation in a Rat Model of Non‐Bacterial Prostatic Inflammation
Author(s) -
Mizoguchi Shinsuke,
Mori Kenichi,
Wang Zhou,
Liu Teresa,
Funahashi Yasuhito,
Sato Fuminori,
DeFranco Donald B.,
Yoshimura Naoki,
Mimata Hiromitsu
Publication year - 2017
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23320
Subject(s) - cystometry , medicine , prostate , hyperplasia , inflammation , saline , lower urinary tract symptoms , estrogen receptor , urinary bladder , endocrinology , estrogen , stimulation , overactive bladder , agonist , urology , receptor , pathology , cancer , alternative medicine , breast cancer
BACKGROUND There is increasing evidence showing that chronic non‐bacterial prostatic inflammation is involved in the pathogenesis of benign prostatic hyperplasia (BPH) and male lower urinary tract symptoms (LUTS). It has also been reported that estrogen receptor β (ERβ) could have an immunoprotective role in prostatic tissue. Therefore, we investigated the effect of ERβ‐activation on not only prostatic inflammation, but also bladder overactive conditions in a rat model with nonbacterial prostatic inflammation. METHODS Male Sprague‐Dawley rats (8 weeks, n = 15) were divided into three groups: sham‐saline group (n = 5), formalin‐vehicle group (n = 5), and formalin‐treatment group (n = 5). The sham‐saline group had sham operation and 50 μl normal saline injected into each ventral lobe of the prostate. The formalin‐vehicle group had 50 μl 5% formalin injection into bilateral ventral lobes of the prostate. The formalin‐treatment group was treated with 3α‐Adiol (a selective ERβ agonist precursor) at a dose of 3 mg/kg daily from 2 days before induction of prostatic inflammation, whereas formalin‐vehicle rats received vehicle (olive oil). In each group, conscious cystometry was performed on day 28 after intraprostatic formalin injection or sham treatment. After cystometry, the bladder and prostate were harvested for evaluation of mRNA expression and histological analysis. RESULTS In cystometric investigation, the mean number of non‐voiding contractions was significantly greater and voiding intervals were significantly shorter in formalin‐vehicle rats than those in sham‐saline rats ( P < 0.05). In RT‐qPCR analysis, mRNA expression of NGF, P2X2, and TRPA1 receptors was significantly increased in the bladder mucosa, and mRNA expression of TNF‐α, iNOS and COX2 in the ventral lobes of prostate was significantly increased in formalin‐vehicle rats compared with sham‐saline rats ( P < 0.05). In addition, relative mRNA expression ratio of ERβ to ERα (ERβ/ERα) in the ventral lobes of prostate was significantly decreased in formalin‐vehicle rats compared with sham‐saline rats ( P < 0.05). These changes were ameliorated by 3α‐Adiol administration in formalin‐treatment rats. CONCLUSIONS These results indicate that ERβ activation by 3α‐Adiol administration, which normalized the ERβ/ERα expression ratio in the prostate, can improve not only prostatic inflammation, but also bladder overactivity. Therefore, ERβ agonists might be useful for treating irritative bladder symptoms in patients with symptomatic BPH associated with prostatic inflammation. Prostate 77:803–811, 2017 . © 2017 Wiley Periodicals, Inc.