Castration increases PGE 2 release from the bladder epithelium in male rats

• DOI: 10.1016/j.lfs.2017.10.037
• Publication Date: 2017-11-08T16:15:20Z
• Authors: Hideaki Ito; Dong Wang; Xinmin Zha; So Inamura; Masaya Seki; Minekatsu Taga; Osamu Yokoyama
• Keywords: Male; Cyclooxygenase 2 Inhibitors; Interleukin-1beta; Urinary Bladder; Real-Time Polymerase Chain Reaction; Dinoprostone; Epithelium; Rats; 3. Good health; Rats, Sprague-Dawley; 03 medical and health sciences; Adenosine Triphosphate; 0302 clinical medicine; Cyclooxygenase 2; Nerve Growth Factor; Cyclooxygenase 1; Animals; Castration; Urothelium

Androgen deprivation therapy has been widely used for the treatment of prostate cancer. While sexual side effects including decreased sexual desire and function are well studied, there are only limited reports about its influences on lower urinary tract symptoms. The aim of this study is to clarify the influences of castration in male rats.Ten-week-old male rats were divided into treatment group (bilateral orchiectomy) and control group (sham surgery). Two-months after the surgery, adenosine triphosphate (ATP), prostaglandin E2 (PGE2), and nerve growth factor (NGF) released from stretched bladder epithelium were measured by luciferin-luciferase assay or ELISA. The mRNA levels of bladder cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were determined by real-time PCR. The protein level of bladder COX-2 was analyzed by western blot analysis. Bio-Plex Pro cytokine assay was performed to quantify the level of proinflammatory cytokine interleukin (IL)-1β in the bladder.The PGE2 release from stretched bladder epithelium was significantly increased after castration, which increased more than 50% compared with control. On the other hand, those of ATP and NGF were not different from those of the controls. Testosterone replacement restored the PGE2 increase. Castration significantly increased bladder IL-1β protein level and COX-2 at both mRNA and protein levels, whereas caused no marked changes in the COX-1 mRNA level.These findings suggest that castration induces inflammation in the rat bladder, which causes elevated PGE2 release from bladder epithelium and may finally contribute to the disruption of bladder storage function.