HORMONAL REGULATION OF RAT PROSTATE STEROID RECEPTORS

本研究的长期目标是：1）阐明 特定的类固醇受体蛋白的机制是 在成年前列腺中受尿道调节，2）以确定 成年人的新生儿和青春期前的激素印记 前列腺，和3）阐明印迹之间的关系， 类固醇受体水平和组织功能 生活 该建议的重点是雄激素， 雌激素和孕激素受体（AR，ER和PR） 成年大鼠的腹侧、背侧和侧叶 前列腺 具体目标是：1）确定ER和PR是否 在三个前列腺叶中存在;以表征其 通过饱和结合分析、免疫测定、蔗糖 梯度分析和单克隆抗体阳性验证 抗体;并通过以下方法鉴定和定量其mRNA水平： 与cDNA杂交; 2）检测ER和PR的功能 通过观察它们以高亲和力与核结合的能力， 配体给药后的组分，并且对于ER，诱导 合成特异性蛋白质，如PR; 3）确定 细胞质和细胞核AR、ER和PR水平激素调节 在三个独立的叶通过激素的操纵成年 动物，包括阉割、类固醇替代、类固醇 拮抗剂，肾上腺切除术和垂体移植物; 4）确定 新生儿和青春期前激素暴露对印迹影响 成人前列腺叶的类固醇敏感性， 以确定这些永久性的改变是否部分地 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 背叶和侧叶特异性雄激素调节基因 和RWB使用点杂交来定量它们的mRNA水平。 这些研究与正常和病理性生长有关， 前列腺的发育。 理解差异 调节类固醇受体和受体介导的生长， 这三个独立的脑叶的功能可能有助于解释为什么 腹叶、背叶和侧叶表现出选择性偏好 前列腺腺癌的发展。 而且 外侧叶被认为是类似于外部区域的 人类前列腺癌的起源。 以来 前列腺癌和前列腺增生的发生依赖于类固醇， 比较和对比类固醇受体的控制， 叶可以提供有价值的见解的机制 这个器官的恶性肿瘤

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.