Santner S J, Albertson B, Zhang G Y, Zhang G H, Santulli M, Wang C, Demers L M, Shackleton C, Santen R J
Department of Medicine, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey 17033, USA.
J Clin Endocrinol Metab. 1998 Jun;83(6):2104-9. doi: 10.1210/jcem.83.6.4898.
Clinically apparent prostate cancer occurs more commonly among Caucasians living in Western countries than in Chinese in the Far East. Prior studies demonstrated diminished facial and body hair and lower levels of plasma 3 alpha-androstanediol glucuronide and androsterone glucuronide in Chinese than in Caucasian men. Based upon these findings, investigators postulated that Chinese men could have diminished 5 alpha-reductase activity with a resultant decrease in prostate tissue dihydrotestosterone levels and clinically apparent prostate cancer. An alternative hypothesis suggests that decreased 3 alpha-androstanediol glucuronide and androsterone glucuronide levels might reflect reduced production of androgenic ketosteroid precursors as a result of genetic or environmental factors. The present study examined 5 alpha-reductase activity, androgenic ketosteroid precursors, and the influence of genetic and environmental/dietary factors in groups of Chinese and Caucasian men. We found no significant differences in the ratios of 5 beta-:5 alpha-reduced urinary steroids (a marker of 5 alpha-reductase activity) between Chinese subjects living in Beijing, China, and Caucasians living in Pennsylvania. To enhance the sensitivity of detection, we used an isotopic kinetic method to directly measure 5 alpha-reductase activity and found no difference in testosterone to dihydrotestosterone conversion ratios between groups. Then, addressing the alternative hypothesis, we found that the Caucasian subjects excreted significantly higher levels of individual and total androgenic ketosteroids than did their Chinese counterparts. To distinguish genetic from environmental/dietary factors as a cause of these differences, we compared Chinese men living in Pennsylvania and a similar group living in Beijing, China. We detected a reduction in testosterone production rates and total plasma testosterone and sex hormone-binding levels, but not in testosterone MCRs in Beijing Chinese as a opposed to those living in Pennsylvania. Comparing Pennsylvania Chinese with their Caucasian counterparts, we detected no significant differences in total testosterone, free and weakly bound testosterone, sex hormone-binding globulin levels, and testosterone production rates. Taken together, these studies suggest that environmental/dietary, but not genetic, factors influence androgen production and explain the differences between Caucasian and Chinese men.
临床显性前列腺癌在居住于西方国家的白种人中比在远东地区的中国人中更为常见。先前的研究表明，与白种男性相比，中国男性面部和身体毛发减少，血浆3α-雄烷二醇葡糖苷酸和雄酮葡糖苷酸水平较低。基于这些发现，研究人员推测中国男性可能5α-还原酶活性降低，导致前列腺组织二氢睾酮水平下降及临床显性前列腺癌。另一种假设认为，3α-雄烷二醇葡糖苷酸和雄酮葡糖苷酸水平降低可能反映了由于遗传或环境因素导致的雄激素性酮类固醇前体生成减少。本研究调查了中国和白种男性群体中的5α-还原酶活性、雄激素性酮类固醇前体以及遗传和环境/饮食因素的影响。我们发现，居住在中国北京的中国人与居住在宾夕法尼亚州的白种人之间，5β-:5α-还原尿类固醇的比率（5α-还原酶活性的标志物）没有显著差异。为提高检测的敏感性，我们使用同位素动力学方法直接测量5α-还原酶活性，发现两组之间睾酮向二氢睾酮的转化率没有差异。然后，针对另一种假设，我们发现白种受试者排泄的个体及总雄激素性酮类固醇水平显著高于中国受试者。为区分导致这些差异的遗传因素与环境/饮食因素，我们比较了居住在宾夕法尼亚州的中国男性和居住在中国北京的类似群体。我们发现，与居住在宾夕法尼亚州的男性相比，北京的中国男性睾酮生成率、总血浆睾酮和性激素结合水平降低，但睾酮代谢清除率没有降低。将宾夕法尼亚州的中国男性与其白种对应人群进行比较，我们发现总睾酮、游离及弱结合睾酮、性激素结合球蛋白水平和睾酮生成率没有显著差异。综上所述，这些研究表明，影响雄激素生成的是环境/饮食因素而非遗传因素，并解释了白种男性与中国男性之间的差异。
