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5 ALPHA REDUCTASE METABOLITES & GENOTYPE IN HEALTHY MEN

5 种 α 还原酶代谢物

基本信息

批准号：
2517665
负责人：
ANNA H. WU
金额：
$ 12.89万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-09-15 至 1999-08-31
项目状态：
已结题

项目摘要

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.

前列腺的细胞分裂是由睾丸激素控制的，细胞内转化为其还原形式的双氢睾酮（DHT）。这种转换是由一种酶，5 α- 还原酶（II型），其由单个基因SRD 5A 2编码。最近研究显示较低的5 α-还原酶活性（基于两种 DHT代谢物; 3 α-17 β-雄甾烷葡糖苷酸（3 α-二醇G）和雄酮葡萄糖醛酸苷（A-G）），白色和非洲裔美国男性，这可能解释了前列腺癌在亚洲男性中观察到。这项研究将扩大最近完成的病例对照研究，前列腺癌在非洲裔美国人，白人和亚裔美国人谁是在高、中、低风险的前列腺癌。作为这个案子的一部分- 对照研究，血液标本（血清和淋巴细胞）收集自大约1100名老年非裔美国人、白色人和亚裔美国人对照组男性。血清睾酮、二氢睾酮、性激素结合球蛋白（SHBG）水平测定DHT与睾酮的比率在非洲人中最高美国人，白人居中，亚裔美国人最低，间接支持5 α-还原酶活性种族差异。的这项研究的目的是进一步调查种族 5 α-还原酶活性的差异， 3 α-二醇G和A-G以及确定储存的5 α-还原酶基因型淋巴细胞从生物样本中获得的信息将结合大量的访谈资料以及血清雄激素和SHBG水平之前收集。这将使我们能够：1）研究5 α-还原酶活性的种族/民族差异; 3）研究5 α-还原酶基因型种族/民族差异，4）和确定人口统计学的作用（例如，年龄）和人体测量特性（例如，身体尺寸）、生活方式因素（例如，输精管切除术，身体活动模式、饮食习惯）和前列腺家族史癌症作为5-α-还原酶活性的调节剂。