CHARACTERIZATION OF THE CANINE AND RAT PROSTATE

犬和​​大鼠前列腺的特征

• 批准号: 6296462
• 负责人: CHUNG LEE
• 金额: $ 9.06万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6296462
• 关键词: androgen receptor; benign prostate hyperplasia; cell differentiation; cell growth regulation; cell population study; connective tissue stroma; disease /disorder model; dogs; epithelium; growth factor; growth factor receptors; immunocytochemistry; in situ hybridization; laboratory rabbit; laboratory rat; model design /development; prostate; tissue /cell culture

The objective of the present project is to use animal models to study the biology of benign prostatic growth. Since animal systems offer a greater degree of flexibility than the human counterpart in manipulation of host conditions, these studies can be conducted to complement findings obtained from studies using human prostates and to widen the scope of the investigation in which reproducible manipulation in host conditions is difficult to accomplish in a human system. The rat prostate will be used extensively in the present proposal, because a great deal of information on the biology of the rat prostate has been available. The canine prostate is also an important model, because dogs are the only species other than man known to develop BPH during aging. Both in vivo and in vitro experiments will be proposed. We will use the in vivo experiments to further characterize the newly recognized prostatic ductal system in which a regional variation in morphological and functional activity of epithelial and stromal cells was observed along the ductal system of the rat prostate. There was also a regional distribution of cell proliferation, differentiation, and degeneration in this ductal system. This regional variation in cellular activities offers an opportunity for us to study the regional variation in the distribution of androgen receptors and growth factors, and to correlate these parameters with cellular growth, differentiation, and degeneration under normal homeostatic conditions and under altered growth conditions. The in vitro experiments mainly involve culture of stromal or epithelial cells of either the rat prostate or the canine prostate. This system will allow us to study the effect of the extracts of growing prostates on the cultured cells in an attempt to identify the natural growth factors in the prostate. It will also allow us to identify the factors associated with the growing prostate that can have an impact on the biological behavior of the cultured cells in terms of proliferation and differentiation. We may use the same system to study the effect of extracts from the regressing prostate in an attempt to identify the factors responsible for prostatic regression. Results of our preliminary study indicated that TGF-beta may be linked to programmed cell death for prostatic epithelial cells. Information generated from these studies should serve as basis for future studies using the human prostate.

本项目的目标是使用动物模型来研究 良性前列腺生长生物学。因为动物系统提供了更大的 在操纵宿主方面比人类对手灵活的程度 条件，这些研究可以进行，以补充所获得的结果 来自使用人类前列腺的研究，并扩大了 在宿主条件下可重复操作的研究 在人类系统中很难完成。大鼠前列腺将被用来 在本提案中广泛使用，因为有大量关于 大鼠前列腺癌的生物学研究已经有了进展。狗的前列腺是 也是一个重要的模型，因为狗是除人类之外唯一的物种 已知在衰老过程中会患上良性前列腺增生症。包括体内和体外实验 将会被提出。我们将利用体内实验进一步 描述新发现的前列腺管系统 上皮细胞形态和功能活性的区域差异 沿大鼠前列腺导管系统可见间质细胞。 细胞增殖也有区域分布， 在这个导管系统中的分化和退化。这个地区 细胞活动的变化为我们提供了一个研究 雄激素受体分布与生长发育的区域差异 因素，并将这些参数与细胞生长相关联， 在正常的动态平衡条件下分化、退化和 在改变的生长条件下。体外实验主要包括 大鼠前列腺间质细胞或上皮细胞的培养 狗的前列腺。这一系统将使我们能够研究 生长中的前列腺提取物对培养细胞的影响 确定前列腺中的自然生长因子。它还将允许我们 以确定与生长的前列腺相关的因素 对培养细胞生物学行为的影响 增殖分化。我们可以使用相同的系统来研究 退行性前列腺液的作用 影响前列腺癌退行性变的因素。我们的结果是 初步研究表明，转化生长因子-β可能与程序化细胞有关 前列腺上皮细胞死亡。从这些数据中生成的信息 这项研究应该成为未来利用人类前列腺进行研究的基础。