Characterization a model of prostatic diseases and obstructive voiding induced by sex hormone imbalance in the Wistar and Noble rats

Chronic nonbacterial prostatitis associated with lower urinary tract symptoms (LUTS) is a prevalent condition in men. One potential pathophysiological factor is change in sex hormone, testosterone and estrogen, balance. Inflammation, cancer and obstructive voiding has been induced in the Noble rat strain by altering levels of sex hormones. We evaluated if imbalance of sex hormones could induce comparable diseases also in a less estrogen sensitive Wistar strain rats. Subcutaneous testosterone (830 µg/day) and 17β-estradiol (83 µg/day) hormone pellets were used in male Wistar and Noble strain rats to induce prostatic diseases. The rats were followed for 13 and 18 weeks. Urodynamical measurements were performed at the end of the study under anesthesia. Prostates were collected for further histological analysis. A panel of cytokines were measured from collected serum samples. Noble rats exhibited stromal and glandular inflammation after 13 weeks that progressed into more severe forms after 18 weeks of hormonal treatment. CD68-positive macrophages were observed in the stromal areas and inside the inflamed acini. CD163-positive macrophages were present in the stromal compartment but absent inside inflammatory foci or prostate acini. Thirteen-week hormonal treatment in Noble rats induced obstructive voiding, which progressed to urinary retention after 18-weeks treatment. In the Wistar rats 18-week treatment was comparable to the 13-week-treated Noble rats judged by progression of prostatic inflammation, being also evident for obstructive voiding. Incidence of PIN-like lesions and carcinomas in the periurethal area in Noble rats were high (100%) but lower (57%) and with smaller lesions in Wistar rats. Serum cytokines leptin, CCL5, and VEGF concentrations showed a decrease in the hormone-treated rats compared to placebo-treated rats. Prostate inflammation and obstructive voiding developed also in the Wistar rats but more slowly than in Noble rats. Male non-castrated Wistar strain rats may thus be suitable to use in studies of pathophysiology and hormone-dependent prostate inflammation and obstructive voiding.