PROSTATIC ANDROGEN RECEPTORS--FORM AND FUNCTION

这些研究旨在检查前列腺内的意义 雄激素受体种类的组织，由于在 它们对雄激素配体的亲合力，可能作为调节剂发挥作用， 雄激素敏感细胞的反应性。 根据我们的观察 这种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，特别是核和热转化 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 已经发现并将被纯化的细胞质因子， 特征进一步。 不同受体形式的相对水平 将在各种实验诱导的变化下进行评估， 内源性激素环境，包括去势替代，衰老， 给予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， 在实验中，硫酸铵分馏的动力学 核摄取和受体的核保留机制将是 探讨了 特异性蛋白质合成的模式化诱导 将研究雄激素作为相对 细胞的受体决定的反应性;这些分析是一个 初步观察的结果表明， 相关性 虽然不属于这一初步阶段的范围， 项目，这些研究的影响，以确定一个 功能性雄激素受体浓度与 前列腺癌内分泌治疗反应性的预测 将是这项工作的下一个主要阶段。

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.