5 ALPHA REDUCTASE METABOLITES & GENOTYPE IN HEALTHY MEN

5 种 α 还原酶代谢物

• 批准号: 2112594
• 负责人: ANNA H. WU
• 金额: $ 12.57万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-15 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2112594
• 关键词: blood chemistry; diet; dihydrotestosterone; enzyme activity; family genetics; human genetic material tag; human population study; human subject; lifestyle; male; neoplasm /cancer epidemiology; neoplasm /cancer genetics; prostate neoplasms; racial /ethnic difference; radioimmunoassay; sex sterilization; statistics /biometry; steroid hormone metabolism; testosterone

Cell division in the prostate is controlled by testosterone after intracellular conversion to its reduced form dihydrotestosterone (DHT). This conversion is metabolically controlled by a single enzyme, 5alpha- reductase(type II), which is encoded by a single gene, SRD5A2. Recent studies show lower 5alpha-reductase activity (based on serum levels of two DHT metabolites; 3alpha-17beta-androstanediol glucuronide (3alpha-diol G) and androsterone glucuronide (A-G)) in young Asian men compared to young white and African-American men which may explain the lower incidence of prostate cancer observed in Asian men. This study will expand on a recently completed case-control study on prostate cancer in African-American, whites, and Asian-Americans who are at high, intermediate, and low risk of prostate cancer. As part of this case- control study, blood specimens (sera and lymphocytes) were collected from some 1100 older African-American, white and Asian-American control men. Serum levels of testosterone, DHT, sex-hormone binding globulin (SHBG) were determined. Ratios of DHT to testosterone were highest in African Americans, intermediate in whites and lowest in Asian-Americans, providing indirect support of ethnic differences in 5alpha-reductase activity. The objectives of the proposed study are to further investigate ethnic differences in 5alpha-reductase activity by measuring stored sera levels of 3alpha-diol G and A-G and determining 5alpha-reductase genotypes in stored lymphocytes. The information obtained from the biological specimens will be combined with a large amount of interview information as well as serum androgen and SHBG levels previously gathered. This will allow us to: 1) investigate racial/ethnic differences in 5alpha-reductase activity; 3) investigate racial/ethnic differences in 5alpha-reductase genotype, 4) and identify the role of demographic (e.g., age) and anthropometric characteristics (e.g., body size), lifestyle factors (eg. vasectomy, physical activity patterns, dietary habits), and family history of prostate cancer as modifiers on 5-alpha-reductase activity.

前列腺癌的细胞分裂是由睾丸激素控制的。 细胞内转化为还原形式的双氢睾酮(DHT)。 这种转化是由一种单一的酶-5α-代谢控制的。 还原酶(II型)，由单基因SRD5A2编码。近期 研究表明较低的5α-还原酶活性(基于两种血清水平 DHT代谢物；3α-17β-雄烷二醇葡萄糖醛酸苷(3α-二醇G) 和雄酮葡萄糖醛酸苷(A-G))在年轻亚洲男性中的比较 白人和非裔美国男性，这可能解释了为什么 在亚洲男性中观察到前列腺癌。 这项研究将在最近完成的一项病例对照研究的基础上展开 非洲裔美国人、白人和亚裔美国人中的前列腺癌 前列腺癌的高、中、低风险。作为此案的一部分- 对照研究，血液样本(血清和淋巴细胞)采集自 大约1100名年长的非裔美国人、白人和亚裔美国人控制着男性。 血清睾酮、DHT、性激素结合球蛋白(SHBG)水平 下定决心。在非洲，双羟色胺与睾丸素的比率最高 美国人，白人居中，亚裔美国人最低，提供 间接支持5α-还原酶活性的种族差异。这个 拟议研究的目标是进一步调查种族 通过测量储存的血清水平来衡量5α-还原酶活性的差异 3α-二醇G和A-G与储藏中5种α-还原酶基因分型 淋巴细胞。从生物样本中获得的信息将 结合了大量的采访信息以及血清 之前收集的雄激素和SHBG水平。这将使我们能够：1) 调查5α-还原酶活性的种族/民族差异；3) 调查5α-还原酶基因的种族/民族差异，4)和 确定人口统计(例如，年龄)和人体测量的作用 特征(例如，体型)、生活方式因素(例如输精管结扎术， 体力活动模式、饮食习惯)和前列腺癌家族史 癌症作为5-α-还原酶活性的修饰物。