Effects of Estrogen Receptor β Stimulation in a Rat Model of Non‐Bacterial Prostatic Inflammation

Abstract

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.

Long‐lasting bladder overactivity and bladder afferent hyperexcitability in rats with chemically‐induced prostatic inflammation

“…Among these models, intraprostatic injection of chemicals (such as formalin, carrageenan, zymosan, or complete Freund adjuvant) is a convenient and effective approach. Our previous studies showed that a rat model of formalin‐induced prostatic inflammation developed molecular changes similar to those identified in human BPH specimens and exhibits 13 at 1 week after intraprostatic formalin injection . Schwartz et al also reported that bladder afferent pathways were sensitized in a 4‐week mouse model of prostatitis induced by intraprostatic zymosan injection possibly due to cross‐organ sensitization between the prostate and bladder.…”

“…Rats were housed in under a 12/12 hours reversed light‐dark cycle. In our previous studies, we utilized 5% formalin solution to induce prostatic inflammation . In this study, we increased the formalin concentration to 10% to examine whether prostatic inflammation induced by injection of 10% formalin solution (50 μL) into each of bilateral ventral lobes of the prostate can induce the long‐lasting effects on bladder function and bladder afferent activity.…”

Bladder overactivity and afferent hyperexcitability induced by prostate‐to‐bladder cross‐sensitization in rats with prostatic inflammation

“…; Mizoguchi et al . ). However, detailed functional and molecular mechanisms underlying bladder dysfunction following prostatic inflammation remain to be elucidated.…”

“…Rodent models of non-bacterial or bacterial prostatic inflammation show bladder overactivity evident by frequent voiding (Chen et al 2010;Lee et al 2015;Schwartz et al 2016;Mizoguchi et al 2017). However, detailed functional and molecular mechanisms underlying bladder dysfunction following prostatic inflammation remain to be elucidated.…”

Inflammatory pathway employed by Red Maca to treat induced benign prostatic hyperplasia in rats

“…There is increasing evidence that chronic nonbacterial prostatic inflammation may be involved in the pathogenesis of BPH (Mizoguchi et al, 2017). Almost, all BPH specimens present inflammatory infiltrates during histologic examination, and data suggest that BPH is an immune inflammatory disease (Kramer, Mitteregger, & Marberger, 2007).…”