Effects of dutasteride in a rat model of chemically induced prostatic inflammation-Potential role of estrogen receptor β.

Background: Dutasteride administration reportedly improves lower urinary tract symptoms in patient with chronic, histologically-identified prostatic inflammation, potentially through estrogen receptor β (ERβ), activation of which has anti-inflammatory effects in the prostate tissue. Therefore, we investigated the effect of dutasteride on intraprostatic inflammatory responses and bladder activity using a rat model of chemically induced prostatic inflammation.

Methods: Male Sprague-Dawley rats at 10 weeks old were used. Prostatic inflammation was induced by 5% formalin injection into ventral lobes of the prostate and saline was injected in the control group (control, n = 5). Rats with prostatic inflammation were divided into dutasteride therapy (dutasteride, n = 5) and placebo groups (placebo, n = 5). Dutasteride was administrated at a dose of 0.5 mg/kg daily from 2 days before induction of prostatic inflammation whereas placebo rats received vehicle only. Twenty-eight days later, cystometry was performed in a conscious condition to measure non-voiding contractions (NVCs), intercontraction intervals (ICI) and postvoid residual volume (RV). After cystometry, the prostate was excised for analysis of messenger RNA (mRNA) expression levels of ERα, ERβ, interleukin-1β (IL-1β), and IL-18 by quantitative polymerase chain reaction.

Results: The mean number of NVCs was significantly greater in placebo group than that of control group without prostatic inflammation (p < .05), and ICI were significantly decreased in placebo group compared with control group (p < .05). On the contrary, there was no significant change in NVCs or ICI between control and dutasteride groups. RV was not significantly different among three groups. Gene expression levels of ERα, IL-1β, and IL-18 was significantly increased in placebo rats compared with control rats (p < .05), but not significantly different between control and dutasteride rats. On the other hand, the mRNA expression level of ERβ was significantly decreased in placebo rats (p < .05), but not in dutasteride rats, compared with control rats.

Conclusion: Dutasteride treatment improved not only prostatic inflammation evident as increased gene expression levels in IL-1β and IL-18, but also bladder overactivity shown by increased NVCs during bladder filling. These therapeutic effects were associated with the restored expression of anti-inflammatory ERβ. Therefore, dutasteride might be effective via ERβ modulation for the treatment of prostatic inflammation in addition to its previously known, anti-androgenic effects on benign prostatic hyperplasia.