REGULATION OF PROSTATE GROWTH BY NEURAL FACTORS

描述（改编自申请人的摘要）： 正常和异常的前列腺生长被认为在很大程度上 通过内分泌机制。 其他因素也与前列腺 包括生长因子和基质上皮细胞 交互. 然而，直到最近，很少有人注意到 自主神经系统（ANS）在前列腺生长中的作用， 在正常和异常条件下的差异。 我们最近有 在动物模型中的实验证据支持了 前列腺素促进前列腺增生和萎缩的选择性 操纵副交感神经（增生）和交感神经（萎缩） 神经支配 这个建议是基于这样的假设，即ANS具有 重要的，恒定的和广泛的调节作用的分化和 前列腺的功能 下面详细描述的实验设计如下： 让人知道这部小说的存在和机制 神经调节影响前列腺的生长，使用的模型，在我们 实验室 本研究设计旨在检验以下总体假设： 这种神经调节机制的扰动导致 前列腺神经支配和自主神经功能亢进在附近的非扰动 前列腺组织导致增长。 的扰动 通过选择性神经切除术的前列腺神经支配导致腺体宽度增加 神经生长因子和其他可能的生长因子。 这诱导了NGF 增加未受干扰的前列腺组织中的自主神经过度支配 导致局部神经递质水平增加， 分裂和减少前列腺细胞凋亡。 这些神经调节 变化最终导致前列腺增生。 要解决的具体目标是：1）测试假设， 神经支配诱导前列腺广泛的NGF增加。 2)检验这一假设 神经操纵会导致未受干扰的前列腺神经支配过度 组织. 3)验证神经生长因子是导致增生的假设 通过直接作用于前列腺细胞或通过使用基质和 大鼠前列腺上皮细胞培养技术。 4)检验这一假设 过度神经支配的增生是由于前列腺 细胞增殖和减少的凋亡。 使用这个模型可以探索了解前列腺的局限性， 神经调节，探讨神经营养对外分泌腺的影响 发展，并可能发现新的方法来影响前列腺 疾病

DESCRIPTION (Adapted from the Applicant's Abstract): The factors inducing both normal and abnormal prostate growth have been considered to act largely via endocrine mechanisms. Other factors have been implicated in prostate development including growth factors and stromal-epithelial cell interactions. However, until recently, little attention has been paid to the role of the autonomic nervous system (ANS) in prostate growth and differentiation under normal and abnormal conditions. We have recent experimental evidence in an animal model that supports a significant role of the ASN in promoting both prostate hyperplasia and atrophy by the selective manipulation of the parasympathetic (hyperplasia) and sympathetic (atrophy) innervation. This proposal is based upon the hypothesis that the ANS has an important, constant and broad regulatory role on the differentiation and function of the prostate gland. The experiments detailed below are designed to make known both the existence of and the mechanism(s) by which this novel neuroregulation influences prostate growth using a model developed in our lab. This research design is structured to test the overall hypothesis that perturbations of this neural regulatory mechanism lead to an increase in prostate innervation and autonomic hyperactivity in nearby in non-perturbed prostate tissues resulting in increased growth. The perturbation of the prostate innervation by selective neurectomy leads to a gland wide increase in nerve growth factor and possibly other growth factors. This induced NGF increases autonomic hyperinnervation in the un-perturbed prostate tissue resulting in an increase in local neurotransmitter levels by increasing cell division and decreasing prostatic apoptosis. These neural regulatory changes culminate in prostatic hyperplasia. The Specific Aims to be addressed are: 1) Test the hypothesis that innervation induces prostate wide increases in NGF. 2) Test the hypothesis that neural manipulation induces hyperinnervation in non-perturbed prostate tissue. 3) Test the hypothesis that NGF is responsible for the hyperplasia by direct action on prostate cells or via hyperinnervation using stromal and epithelial cell culture techniques of rat prostates. 4) Test the hypothesis that the hyperplasia of hyperinnervation occurs by an increase of prostate cell proliferation and reduced apoptosis. Using this model allows one to explore the limits of understanding prostatic neuroregulation, to explore neurotrophic influences on exocrine gland development, and to possibly uncover novel methods to influence prostate disease.