EFFECTS OF AGING ON THE ANDROGEN SENSITIVITY OF SEX ACCESSORY TISSUES

前列腺细胞增生发生在背叶和侧叶， 而不是老年布朗挪威鼠的腹侧脑叶。 这些 研究结果表明，棕色挪威大鼠的雄激素敏感性 前列腺具有叶特异性和年龄依赖性。 所以我们提出 研究生长调节中的年龄特异性变化， 分化细胞的结构和功能在老化布朗挪威 探讨前列腺增生的发病机制。 的 该提案的具体目标是：1）我们将测量血清， 睾酮（T）及其活性代谢产物的组织浓度 双氢睾酮（DHT）和雌二醇（E2），并确定 无论是雄激素或雌激素受体的变化，5 α- 还原酶或芳香化酶活动发生在每个叶; 2）我们将 确定年龄相关的内在变化是否发生在 影响雄激素敏感性。 我们将 雄激素受体结合，5 α-还原酶 活性和DHT水平或芳香酶活性和E2水平， 青年和老年大鼠，并确定是否细胞的具体结构和 功能受到影响; 3）我们将确定是否年龄依赖性 叶特异性差异发生在细胞死亡和细胞 单独去势后或雄激素 4）我们将确定是否叶特异性细胞 增生与年龄相关的变化的幅度或 睾丸激素产生的时间模式。 增长 将评估腹侧、侧侧和背侧前列腺叶内的 组织重量;细胞结构显微镜检查 上皮内细胞数量的形态学和体视学分析 和间质室;并通过北方印迹法 雄激素特异性mRNA和特异性蛋白质的Western印迹 受体和5 α-还原酶在所有组织，前列腺，背部 腹侧、背侧和侧前列腺中的蛋白I和probasin 叶，分别。 生长因子及其受体将被 与雄激素敏感性和细胞内 形态学 免疫细胞化学和原位RNA杂交 将用于定位基因产物的细胞特异性表达。

Prostatic cell hyperplasia occurs in the dorsal and lateral lobes, but not the ventral lobe, of the aging Brown Norway rat. These findings suggest that androgen sensitivity of the Brown Norway rat prostate is lobe-specific and age-dependent. Therefore, we propose to investigate age-specific changes in the regulation of growth and differentiated cell structure and function in aging Brown Norway rats to elucidate the mechanisms of prostatic hyperplasia. The specific aims of this proposal are: 1) we will measure serum and tissue concentrations of testosterone (T), and its active metabolites dihydrotestosterone (DHT) and estradiol (E2) and determine whether changes in androgen or estrogen receptors, 5alpha- reductase or aromatase activities occur within each lobe; 2) we will determine whether age-associated intrinsic changes occur within each lobe to affect androgen sensitivity. We will pharmacologically alter androgen receptor binding, 5alpha-reductase activity and DHT levels or aromatase activity and E2 levels in young and old rats and determine whether cell specific structure and function is affected; 3) we will determine whether age-dependent and lobe-specific differences occur in cell death and cell proliferation following castration alone or when androgen is replaced; and 4) we will determine whether lobe-specific cellular hyperplasia is related to age-dependent changes in the magnitude or temporal pattern of testicular testosterone production. Growth within the ventral, lateral and dorsal prostate lobes will be assessed by tissue weight; cell structure by microscopic examination of call morphology and stereologic analysis of cell number within epithelial and stromal compartments; and function by Northern blots of specific mRNAs and Western blots of specific proteins for androgen receptor and 5alpha-reductase in all tissues, for prostate in, dorsal protein I and probasin in the ventral, dorsal and lateral prostate lobes, respectively. Growth factors and their receptors will be related to changes in androgen sensitivity and in cellular morphology. Immunocytochemistry and in situ RNA hybridization will be used to localize cell-specific expression of gene products.