5 ALPHA REDUCTASE METABOLITES & GENOTYPE IN HEALTHY MEN

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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.