Presentation Authors: Xiaolong Wang, Yiming Wang, Christian Gratzke, Anna Ciotkowska, Qingfeng Yu, Ruixiao Wang*, Bingsheng Li, Frank Strittmatter, Christian G. Stief, Martin Hennenberg, Munich, Germany
Introduction: Leptin is a metabolic peptide hormone produced by adipocytes, with assumed roles in proflieration of prostate cancer cells and of prostate cells in animal models of benign prostatic hyperplasia (BPH). Thus, a role of leptin as a molecular link connecting BPH and lower urinary tract symptoms (LUTS) suggestive of BPH with metabolic syndrom appears possible/feasible, but is still unknown. In fact, a connection between metabolic syndrome and BPH/LUTS is becoming increasingly evident from epidemiologic studies. Key factors of LUTS suggestive of BPH are an increased prostate smooth muscle tone, and prostate enlargement, which may both contribute to bladder outlet obstruction. Here, we examined the effects of leptin on contraction of human prostate smooth muscle and on growth of stromal cells.
Methods: Human prostate tissues were obtained from patients undergoing radical prostatectomy. Contractions of prostate strips were studied in an organ bath, using tissues from n=5 patients for each control and leptin group. Proliferation and viability of human prostate stromal cells (WPMY-1) were assessed by EdU and CCK-8 assays (five independent experiments for each). Mitochondrial-related apoptosis was examined by near-infrared (NIR) fluorescent dye and analysis by flow cytometry (FACS).
Results: Electric field stimulation induced frequency-dependent, neurogenic contractions of human prostate tissues. These contractions were enhanced concentration-dependently by leptin (50 nM, 100 nM), which was significant using 100 nM of leptin (p < 0.05 at 16 Hz for leptin vs. control, with 47Â±7% of KCl-induced contraction in control, and 99.8Â±22% in leptin group). As shown by CCK-8 assay, leptin increased the viability of WPMY-1 cells, which was observed at different concentrations (6.25-50 ng/ml), and with similar levels of viability at all concentrations. Leptin-induced proliferation (24 h) was confirmed by EdU assay (p=0.024 at 25 ng/ml leptin, with 54 Â±8.8% of cells under proliferation in control group, and 68 Â±5.9% in leptin-stimulated cells). Leptin (25 ng/ml) increased NIR stain intensity in FACS analysis (p=0.035), reflecting attenuated apoptosis in WPMY-1 cells.
Conclusions: Leptin promotes smooth muscle contraction and growth of stromal cells in the human prostate, suggesting that leptin might be an important factor aggravating LUTS/BPH in obese male patients. Patients suffering from metabolic syndrom plus LUTS/BPH may profit from leptin management. The leptin system in LUTS/BPH merits further consideration.
Source of Funding: Deutsche Forschungsgemeinschaft (DFG), Chinese Scholarship Council (CSC)