Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education, Miami, Florida 33125, USA.
J Urol. 2012 Apr;187(4):1498-504. doi: 10.1016/j.juro.2011.11.081. Epub 2012 Feb 17.
Benign prostatic hyperplasia often affects aging men. Antagonists of the neuropeptide growth hormone-releasing hormone reduced prostate weight in an androgen induced benign prostatic hyperplasia model in rats. Luteinizing hormone-releasing hormone antagonists also produce marked, protracted improvement in lower urinary tract symptoms, reduced prostate volume and an increased urinary peak flow rate in men with benign prostatic hyperplasia. We investigated the influence of a combination of antagonists of growth hormone-releasing hormone and luteinizing hormone-releasing hormone on animal models of benign prostatic hyperplasia.
We evaluated the effects of the growth hormone-releasing hormone antagonist JMR-132, given at a dose of 40 μg daily, the luteinizing hormone-releasing hormone antagonist cetrorelix, given at a dose of 0.625 mg/kg, and their combination on testosterone induced benign prostatic hyperplasia in adult male Wistar rats in vivo. Prostate tissue was examined biochemically and histologically. Serum levels of growth hormone, luteinizing hormone, insulin-like growth factor-1, dihydrotestosterone and prostate specific antigen were determined.
Marked shrinkage of the rat prostate (30.3%) occurred in response to the combination of growth hormone-releasing hormone and luteinizing hormone-releasing hormone antagonists (p<0.01). The combination strongly decreased prostatic prostate specific antigen, 6-transmembrane epithelial antigen of the prostate, interleukin-1β, nuclear factor-κβ and cyclooxygenase-2, and decreased serum prostate specific antigen.
A combination of growth hormone-releasing hormone antagonist with luteinizing hormone-releasing hormone antagonist potentiated a reduction in prostate weight in an experimental benign prostatic hyperplasia model. Results suggest that this shrinkage in prostate volume was induced by the direct inhibitory effects of growth hormone-releasing hormone and luteinizing hormone-releasing hormone antagonists exerted through their respective prostatic receptors. These findings suggest that growth hormone-releasing hormone antagonists and/or their combination with luteinizing hormone-releasing hormone antagonists should be considered for further development as therapy for benign prostatic hyperplasia.
良性前列腺增生常影响老年男性。神经肽生长激素释放激素拮抗剂可减少大鼠雄激素诱导的良性前列腺增生模型中的前列腺重量。促黄体生成素释放激素拮抗剂也可显著改善下尿路症状，减少前列腺体积，增加良性前列腺增生患者的尿流峰值。我们研究了生长激素释放激素和促黄体生成素释放激素拮抗剂联合应用对良性前列腺增生动物模型的影响。
我们评估了生长激素释放激素拮抗剂 JMR-132（每天 40μg）、促黄体生成素释放激素拮抗剂 cetrorelix（0.625mg/kg）及其联合应用对雄性 Wistar 大鼠体内雄激素诱导的良性前列腺增生的影响。对前列腺组织进行生化和组织学检查。测定血清生长激素、促黄体生成素、胰岛素样生长因子-1、二氢睾酮和前列腺特异性抗原水平。
生长激素释放激素和促黄体生成素释放激素拮抗剂联合应用可显著缩小大鼠前列腺（30.3%）（p<0.01）。该联合显著降低前列腺特异性抗原、6-跨膜上皮抗原前列腺、白细胞介素-1β、核因子-κβ和环氧化酶-2，并降低血清前列腺特异性抗原。
生长激素释放激素拮抗剂与促黄体生成素释放激素拮抗剂联合应用可增强实验性良性前列腺增生模型中前列腺重量的减轻。结果表明，这种前列腺体积的缩小是由生长激素释放激素和促黄体生成素释放激素拮抗剂通过各自的前列腺受体直接抑制作用引起的。这些发现表明，生长激素释放激素拮抗剂及其与促黄体生成素释放激素拮抗剂的联合应用应被视为良性前列腺增生治疗的进一步发展。
