HORMONAL REGULATION OF RAT PROSTATE STEROID RECEPTORS

这次调查的长期目标是：1)澄清 特定类固醇受体蛋白的作用机制 荷尔蒙在成人前列腺中的调节，2)确定 成人的新生儿和青春期前激素印记 3)阐明印迹与前列腺癌之间的关系。 成人期的类固醇受体水平和组织功能 生活。这项建议侧重于雄激素之间的关系， 雌激素和孕激素受体(AR、ER和PR) 成年大鼠分离的腹叶、背叶和侧叶 前列腺。具体目标是1)确定ER和PR是否 存在于三个前列腺叶中；以表征它们的 饱和结合分析、免疫分析、蔗糖的性质 用单抗进行梯度分析和阳性验证 抗体；并通过下列方法鉴定和定量它们的mRNA水平 与cDNA杂交；2)检测ER和PR的功能 通过观察它们与核高亲和力结合的能力 配基给药后的成分，对于内质网，诱导 合成特定的蛋白质，如PR；3)确定 细胞内和核内AR、ER、PR水平的激素调节 在三个独立的脑叶中，通过对成虫的荷尔蒙调节 动物，包括去势、类固醇替代、类固醇 拮抗剂、肾上腺切除和垂体移植；4)确定 新生儿和青春期前激素暴露对印记的影响 分离的成人前列腺叶和前列腺的类固醇敏感性 以确定这些永久性改变是否在一定程度上是由 通过类固醇受体；5)确定激素调节是否 类固醇受体的印记改变了 背叶和侧叶特异的雄激素调节基因，M-40 和RWB用斑点杂交法对其mRNA水平进行定量。 这些研究与正常和病理性生长和 前列腺癌的发育。了解两者的区别 类固醇受体的调节和受体介导的生长和 三个单独的脑叶的功能可能有助于解释为什么 腹叶、背叶和侧叶表现为选择性偏爱 用于前列腺癌的发展。此外， 侧叶被认为类似于 人类前列腺癌病变的发源地。自.以来 前列腺癌和良性前列腺增生症的发生依赖于类固醇， 类固醇受体调控的比较与对比 这些脑叶可能会提供有价值的洞察机制。 这个器官的恶性病变。

The long range objectives of this investigation are 1) to elucidate the mechanisms by which specific steroid receptor proteins are hormonally regulated in the adult prostate gland, 2) to determine the neonatal and prepubertal hormone imprints of the adult prostate, and 3) to elucidate the relationship between imprinting, steroid receptor levels, and tissue functionality during adult life. This proposal focuses on the relationships among androgen, estrogen and progesterone receptors (AR, ER and PR) within the separate ventral, dorsal and lateral lobes of the adult rat prostate. The specific aims are 1) to determine if ER and PR are present within the three prostate lobes; to characterize their properties by saturation binding analysis, immunoassays, sucrose gradient analysis and positive verification with monoclonal antibodies; and to identify and quantitate their mRNA levels by hybridization with cDNA; 2) to test the functionality of ER and PR by observing their ability to bind with high affinity to nuclear components following ligand administration, and, for ER, to induce synthesis of specific proteins such as PR; 3) to determine the hormonal regulation of cytosolic and nuclear AR, ER and PR levels in the three separate lobes via hormonal manipulations of the adult animal including castration, steroid replacements, steroid antagonists, adrenalectomy, and pituitary grafts; 4) to determine the role of neonatal and prepubertal hormone exposure on imprinting the steroid sensitivity of the separate adult prostate lobes and to determine if these permanent alterations are mediated in part by the steroid receptors; 5) to determine if hormonal regulation and imprinting of steroid receptors alters the expression of the dorsal and lateral lobe-specific, androgen-regulated genes, M-40 and RWB using dot-hybridization to quantitate their mRNA levels. These studies are related to the normal and pathologic growth and development of the prostate gland. Understanding the differential regulation of steroid receptors and receptor-mediated growth and function of the three separate lobes may help explain why the ventral, dorsal and lateral lobes exhibit selective predilection for the development of prostatic adenocarciroma. Moreover, the lateral lobe is believed to be analogous to the outer region of the human prostate where cancerous lesions originate. Since the development of prostatic cancer and BPH are steroid-dependent, comparing and contrasting the control of steroid receptors among the lobes may provide valuable insights into the mechanisms of malignancy in this organ.