431 AGING AND ITS IMPACT ON URINARY BLADDER: MOLECULAR FEATURES OF HORMONAL THERAPY ON THE SENESCENCE

Abstract

INTRODUCTION AND OBJECTIVES: The occurrence of lower urinary tract symptoms and morphological changes in the urinary bladder is verified in elderly men very often. Steroid hormone receptors (SHRs) influence mitogenic signaling pathways, apoptosis, cell cycle, and it has long been known that incidence of bladder cancer in men is several times greater than in women. This study characterizes and -dystroglycans ( -DG, -DG), androgen receptor (AR), and -estrogen receptors ( ER, ER), matrix metalloproteinase 9 (MMP-9) and insulin-like growth factor receptor (IGFR-1) reactivities in the urinary bladder of elderly rats under hormonal imbalance. METHODS: Twenty male (senile) 10 month old Sprague-Dawley rats were divided into groups (5 animals per group): the ControlSenile group received 5mL/kg peanut oil; the Testosterone-Senile group received 5mg/kg testosterone cypionate; the Estrogen-Senile group received 25 g/kg 17 -estradiol, every other day for 30 days. The Castrated-Senile group underwent surgical castration. Five 4 month old rats were included as Young group to comparative parameter. Urinary bladder was collected and processed for immunohistochemical and blood for hormonal analyses at the end of experimental period. RESULTS: The Young group showed intensified ER, ER, DG, DG reactivities and weak AR, IGFR-1, MMP-9 reactivities. Weak ER, ER, DG, DG and moderate AR, IGFR-1, MMP-9 reactivities were verified in the Control-Senile group. The CastratedSenile group showed weak AR, IFGR-1, MMP-9 and moderate ER, ER, DG, DG reactivities. After testosterone therapy, intensified AR, IGFR-1, MMP-9, and moderate ER, ER and weak DG, DG reactivities were verified. The estrogen therapy showed intensified ER, ER, DG, DG, moderate AR and weak IGFR-1, MMP-9 reactivities. Increased hormone serum levels were verified in hormone replacement groups. CONCLUSIONS: Based on the important role of dystroglycans in the maintenance of tissue integrity and involvement of MMP-9 and IGFR-1 in proliferative processes, it could be concluded that estrogen therapy in the senile rats affected directly the molecular features in the urothelium of the urinary bladder. Testosterone therapy, AR and IGFR-1 reactivities were an important pathway in cellular mitosis occurrence, which could be fundamental element involved in bladder disease process. The ER and ER reactivities pointed to an important role for maintenance of the structural balance of the urinary bladder.