PROSTATIC ANDROGEN RECEPTORS--FORM AND FUNCTION

前列腺雄激素受体——形式和功能

基本信息

批准号：
3175396
负责人：
VIRENDRA B MAHESH
金额：
$ 9.09万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-07-01 至 1989-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3175396
关键词：
aging androgens density gradient ultracentrifugation dihydrotestosterone electrofocusing gel electrophoresis hormone receptor hormone therapy laboratory rat male castration neoplasm /cancer therapy prolactin prostate prostate neoplasms protein biosynthesis steroid hormone

项目摘要

These studies are designed to examine the significance within prostatic tissue of androgen receptor species which, by virtue of differences in their avidity for androgenic ligands, may function as regulators of the responsiveness of androgen-sensitive cells. In pursuit of our observation that two such cytoplasmic forms of this receptor do co-exist, we propose to define various physicochemical properties of these forms, as well as any others which may occur, including especially nuclear and heat-transformed cytoplasmic moieties. The emphasis will be on comparative aspects of interaction with androgens, and susceptibility to interconversion by a cytoplasmic factor which has been discovered and which will be purified and characterized further. The relative levels of the different receptor forms will be assessed under a variety of experimentally-induced changes in endogenous hormonal milieu, including castration-replacement, aging, and administration of assorted types of steroid hormones and prolactin. We will exploit the ability to separate the cytoplasmic receptor forms by ammonium sulfate fractionation in experiments wherein the dynamics of nuclear uptake and mechanisms of nuclear retention of receptor will be explored. Patterned induction of specific protein synthesis in response to androgen will be investigated as a function of the relative receptor-dictated responsiveness of the cells; these analyses are an outgrowth of preliminary observations which suggest a potentially important correlation. While not within the scope of this initial stage of the project, the implications of these studies with respect to defining a relationship between functional androgen receptor concentration and prediction of responsiveness of human prostatic cancer to endocrine therapy will certainly constitute the next major phase of this work.

这些研究旨在检查前列腺内的重要性雄激素受体物种的组织，由于差异它们对雄激素配体的亲和力，可能起到调节作用雄激素敏感细胞的反应性。为了追求我们的观察该受体的两种细胞质形式确实共存，我们建议定义这些形式的各种物理化学性质，以及任何其他可能发生的情况，特别是核和热转变细胞质部分。重点将放在比较方面与雄激素的相互作用，以及对相互转化的敏感性已发现并将被纯化和纯化的细胞质因子进一步表征。不同受体形式的相对水平将在各种实验引起的变化下进行评估内源性激素环境，包括去势替代、衰老和施用各种类型的类固醇激素和催乳素。我们将利用分离细胞质受体形式的能力实验中硫酸铵分级分离的动力学受体的核摄取和核保留机制将是探索过。响应特定蛋白质合成的模式化诱导雄激素将作为相对的函数进行研究细胞受体决定的反应性；这些分析是初步观察的结果表明潜在的重要相关性。虽然不属于该初始阶段的范围项目，这些研究对于定义功能性雄激素受体浓度与功能性雄激素受体浓度之间的关系人类前列腺癌对内分泌治疗的反应性预测肯定会构成这项工作的下一个主要阶段。