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.

前列腺中的细胞分裂由睾丸激素控制细胞内转化为其还原形式的二氢睾丸激素（DHT）。这种转化由单个酶5alpha-代谢控制还原酶（II型），由单个基因SRD5A2编码。最近的研究表明，较低的5Alpha-还原酶活性（基于两种血清水平 DHT代谢产物； 3alpha-17beta-androstanediol葡萄糖醛酸（3alpha-Diol g）与年轻人相比白人和非裔美国人可能解释了较低的发病率在亚洲男性中观察到的前列腺癌。这项研究将扩大有关最近完成的病例对照研究非裔美国人，白人和亚裔美国人的前列腺癌前列腺癌的高，中级和低风险。作为此案的一部分 - 对照研究，血液标本（血清和淋巴细胞）是从中收集的大约1100名非裔美国人，白人和亚裔美国人对照男子。睾丸激素，DHT，性激素结合球蛋白（SHBG）的血清水平为决定。 DHT与睾丸激素的比率最高美国人，中间是白人，在亚裔美国人中最低，提供 5Alpha-还原酶活性中种族差异的间接支持。这拟议研究的目标是进一步研究种族通过测量储存的血清水平的5α-还原酶活性的差异 3Alpha-Diol G和A-G，并确定5Alpha-还原酶基因型淋巴细胞。从生物标本获得的信息将与大量的面试信息以及血清结合雄激素和SHBG水平先前收集。这将使我们能够：1）研究5Alpha-还原酶活性的种族/种族差异； 3）研究5Alpha-还原酶基因型的种族/种族差异，4）和确定人口统计学（例如年龄）和人体测量学的作用特征（例如体型），生活方式因素（例如，输精管切除术，体育锻炼模式，饮食习惯）和前列腺家族史癌症作为5-α-还原酶活性的修饰剂。