ADRENERGIC REGULATION OF HUMAN PROSTATE GROWTH

描述(摘自申请者摘要)：良性前列腺 增生(BPH)主要是一种间质增生性疾病。平滑 肌肉(SM)是前列腺间质的主要成分。因此，它是 良性前列腺增生症的进展可能需要平滑肌的增殖。在……里面 许多平滑肌组织中，收缩蛋白的状态受基因调控 在增殖过程中被调节，失去正常的收缩 活跃生长过程中的蛋白质和收缩蛋白质的重新获得 一旦增长受阻。关于表型还知之甚少。 间质SM细胞在BPH发生发展过程中的调控作用 此外，治疗，特别是封锁对SM的影响 表型尚不清楚。在初步研究中，他们已经证明 确诊为良性前列腺增生症的男性有平滑肌去分化的证据 流程，与过去但不是正在进行的SM扩散兼容。在……里面 此外，他们已经证明，封锁显著影响 Sm表型。他们建议对SM表型的表达进行表征 标记物，包括肌球蛋白重链和钙调蛋白，以确定 在自然历史过程中，平滑肌表型发生了变化 良性前列腺增生症的进展。此外，他们将扩大或初步研究，以 确定α-肾上腺素能在多大程度上调节SM表型 信号转导通路。他们将利用两个独特的组织库来 这些研究。首先，大量正常和增生性前列腺 来自不同年龄段的男性，作为德克萨斯州西南部银行的一部分 美国国立卫生研究院奥布莱恩中心储存库及来自美国国立卫生研究院的前列腺药物治疗 允许进行纵向观察的症状(MTOPS)临床试验 与临床转归的相关性。量化 利用RT_PCR、免疫组织化学和形态计量学分析 解决以下具体目标：(1)建立和验证方法 适用于多中心试验的存档组织分析；(2)确定 BPH自然病程中SM表型的变化； (3)确定SM表型是否受α-肾上腺素能调节 信号；(4)利用前列腺SM培养系统，阐明其调控 α1a肾上腺素能刺激在前列腺SM生长和发育中的作用 差异化。

DESCRIPTION (Adapted from the Applicant's Abstract): Benign prostate hyperplasia (BPH) is primarily a disease of stromal proliferation. Smooth muscle (SM) is a major component of prostatic stroma. Therefore, it is likely that the progression of BPH requires smooth muscle proliferation. In many smooth muscle tissues, the state of contractile protein gene regulation is modulated during proliferation, with a loss of normal contractile proteins during active growth and a re-acquisition of contractile proteins once growth has been arrested. Little is known regarding the phenotypic modulation of stromal SM cells during the initiation and progression of BPH. In addition, the impact of therapy, specifically a blockade, on the SM phenotype is unknown. In preliminary studies, they have demonstrated that men with established BPH have evidence of a smooth muscle de-differentiation process, compatible with past but not ongoing SM proliferation. In addition, they have demonstrated that a blockade significantly affects the SM phenotype. They propose to characterize the expression of SM phenotypic markers, including myosin heavy chain and caldesmon, to determine whether the smooth muscle phenotype is altered during the natural history and progression of BPH. In addition, they will expand or preliminary studies to determine to what extent the SM phenotype is regulated by alpha adrenergic signal transduction pathways. They will utilize two unique tissue banks for these studies. First, a large number of normal and hyperplastic prostates from men of a variety of age groups banked as part of the UT Southwestern NIH O'Brien Center Repository and from the NIH Medical Therapy of Prostate Symptoms (MTOPS) clinical trial which will permit longitudinal observation of single patients in correlation with clinical outcome. Quantitative RT_PCR, immunohistochemical and morphometric analysis will be utilized to address the following specific aims: (1) to establish and validate methods of archived tissue analysis suitable for a multi-center trial; (2) to define changes in the SM phenotype which occur during the natural history of BPH; (3) to determine whether the SM phenotypes is modulated by alpha adrenergic signals; (4) using a prostate SM culture system, elucidate the regulatory role of alpha1A adrenergic stimulation in prostatic SM growth and differentiation.