Regulation of Male Sex Hormone Levels by Soy Isoflavones in Rats Mi-Ae Yi, Hyun M. Son, Jung-Soon Lee, Chong-Suk Kwon, Jin Kyu Lim, Young Keun Yeo, Young Sik Park, and Jong-Sang Kim Abstract: Several studies have suggested that soybean in- take is associated with a lower risk of prostate cancer. How- ever, the mechanism of prostate cancer prevention by soybeans remains unclear. Because prostate cancer is re- ported to have an association with an increased level of dihydrotestosterone (DHT) and soybean isoflavones are known to inhibit 5a-reductase, which is involved in the con- version of testosterone to DHT, the effects of soybean extract and isoflavones on the plasma levels of male sex hormones were investigated using male rats. In Experiment I, Sprague- Dawley rats were fed diets with and without soy flour; in Ex- periment II, rats were fed diets containing 2% soy methanol extract or 0.2% semipurified isoflavones or a control diet. The study showed a reduction of plasma DHT along with an increase in total plasma androgen in rats fed soy flour or semipurified isoflavones for 1 wk. These results suggest that soy isoflavone intake may reduce plasma DHT level. Introduction Epidemiological studies show a lower incidence of hor- mone-related cancer in Asians, including Koreans, Japanese, and Chinese, than in their Western counterparts (1,2). Most Asians eat a low-fat, high-fiber diet that is a rich source of phytoestrogens, and there is an extremely low incidence of prostate cancer. The soy-based foods included in this diet may play a role in decreasing the prevalence of prostate can- cer in Asian communities (3,4). The isoflavone levels are much higher in the prostatic fluid from Hong Kong and Chi- nese men who consume soybeans than in Portuguese and British men (3). In animal models, most studies investigat- ing the effects of soybeans show a reduced tumorigenesis (5). For instance, a soy-containing diet was reported to re- duce the severity of prostatitis in rats (6) and prevent the de- velopment of dysplastic lesions of the prostate in neonatal diethylstilbestrol-treated mice (7). Recently, soy isoflavones have been shown to inhibit the growth of transplantable hu- man prostate carcinoma and tumor angiogenesis in mice, thereby suggesting multiple interacting mechanisms in pros- tate cancer inhibition (8). In its early stages, prostate cancer is hormone dependent, with castration causing tumor regres- sion (9). Meanwhile, isoflavones of soy origin may play a major role in the promotion and growth of prostate cancer by modulating the metabolism of sex hormones. Genistein and daidzein, the main isoflavones in soybeans, are known to in- hibit 5a-reductase in vitro (9). This enzyme is involved in the conversion of testosterone to 5a-dihydrotestosterone (DHT), the main prostatic androgen responsible for the de- velopment of prostate cancer (1,10). Therefore, there is a strong possibility that soy isoflavones generate a significant effect on the DHT level, inasmuch as they are known to be strong inhibitors of 5a-reductase. This communication reports that soy flour and isofla- vones tended to lower the level of plasma DHT with a lim- ited effect on the total androgen level in rats. In addition, a significant amount of isoflavones was retained in the plasma from rats fed an isoflavone-supplemented diet. Materials and Methods Animals and Diets Male Sprague-Dawley rats (Korean Experimental Ani- mal Center, Umsung, South Korea; 200–300 g body wt) were housed individually in stainless steel cages and divided into two and three experimental groups for two rounds of ex- periments with 8 or 10 rats per group. The animals were maintained at 22 ± 2°C on a 12:12-h light-dark cycle (lights on at 0700) with free access to food and water. The diet com- positions used in Experiment I are presented in Table 1. Au- toclaved soy flour was blended into the powdered diet at 442.7 g/kg diet. In Experiment II, the rats in the control group were fed ad libitum an AIN-76 diet containing 200 g of casein, 3 g of DL-methionine, 150 g of corn starch, 500 g of sucrose, 50 g of cellulose, 50 g of corn oil, 35 g of mineral mixture, 10 g of vitamin mixture, and 2 g of choline bitartrate per kilogram diet. The treatment groups were fed an AIN-76 diet in which the cornstarch was partially re- NUTRITION AND CANCER, 42(2), 206–210 Copyright © 2002, Lawrence Erlbaum Associates, Inc. J.-S. Lee, J. K. Lim, Y. K. Yeo, Y. S. Park, and J.-S. Kim are affiliated with the Department of Animal Science and Biotechnology, Kyungpook National University, Taegu 702-701, South Korea. M.-A. Yi is and H. M. Son was affiliated with the School of Food Science, Inje University, Kimhae 621-749, South Korea. C.-S. Kwon is affiliated with the Department of Food Science and Nutrition, Andong National University, Andong 760-380, South Korea.