A single low dose of cadmium exposure induces benign prostate hyperplasia like condition in rat: A novel benign prostate hyperplasia rodent model

Abstract

Abnormal prostate growth is the most prevalent pathological sign in aged human males, as reflected by high incidence of benign prostate hyperplasia (BPH) and prostate cancer. In spite of the high prevalence, the etiology and pathophysiology of BPH is unclear due to the lack of any established rodent model for study. It has been demonstrated that the cadmium (Cd) mimics the activity of androgen or estrogen by interacting with the steroid hormone receptors in the prostate and elicits BPH, but the specific receptor which binds to Cd is still unknown. Our lab studies with BPH patients highlighted a strong co-relation between smokings with increased Cd content. Changes in the maximum urinary flow rate (Qmax) and prostatic acid phosphatase (PAP) level further supports that Cd can induce BPH like condition. Therefore, the present study was aimed to induce BPH like condition in rats by Cd administration. The dose of cadmium was standardized in an age- and time-dependent manner, which was further examined by prostate weight, histology, and PAP levels that elucidated the pathogenesis of BPH. Further to understand the molecular basis, steroid hormone receptor antagonist experiment was performed. Gene expression and immunohistochemistry data suggest that Cd induces hyperplasia like condition by activating the androgen receptor and estrogen receptor-α and suppresses the action of estrogen receptor-β. The experimental model used here is a cost effective, less time consuming and potentially valuable tool for investigating the respective functions of epithelial and stromal hormone receptors. The applicability of this model would be helpful in understanding the pathogenesis of BPH and its progression.