|
PWS Articles PWS Research
Other |
[ Printable Page | Edit ]
J Endocrinol. 2001 Sep;170(3):591-9. Nutritional factors, especially phytoestrogens, have been extensively studied for their potential beneficial effects against hormone-dependent and age-related diseases. The present study describes the short-term effects of dietary phytoestrogens on regulatory behaviors (food/water intake, locomotor activity and body weight), prostate weight, prostate 5alpha-reductase enzyme activity, reproductive hormone levels, and testicular steroidogenic acute regulatory peptide (StAR) levels in adult Sprague-Dawley rats. Animals were fed either a phytoestrogen-rich diet containing approximately 600 microg/g isoflavones (as determined by HPLC) or a phytoestrogen-free diet. After 5 weeks of consuming these diets, plasma phytoestrogen levels were 35 times higher in animals fed the phytoestrogen-rich vs phytoestrogen-free diets. Body and prostate weights were significantly decreased in animals fed the phytoestrogen-rich diet vs the phytoestrogen-free fed animals; however, no significant change in prostate 5alpha-reductase enzyme activity was observed between the treatment groups. Locomotor activity levels were higher in the phytoestrogen-rich vs the phytoestrogen-free animals during the course of the treatment interval. Plasma testosterone and androstenedione levels were significantly lower in the animals fed the phytoestrogen-rich diet compared with animals fed the phytoestrogen-free diet. However, there were no significant differences in plasma LH or estradiol levels between the diet groups. Testicular StAR levels were not significantly different between the phytoestrogen-rich vs the phytoestrogen-free fed animals. These results indicated that consumption of dietary phytoestrogens resulting in very high plasma isoflavone levels over a relatively short period can significantly alter body and prostate weight and plasma androgen hormone levels without affecting gonadotropin or testicular StAR levels. The findings of this study identify the biological actions of phytoestrogens on male reproductive endocrinology and provide insights into the protective effects these estrogen mimics exert in male reproductive disorders such as benign prostatic hyperplasia and prostate cancer. From the full text article: ... [P]lasma testosterone levels were approximately 50% lower in animals fed the Phyto-600 compared with animals fed the Phyto-free diet. ... To further determine the pattern of steroidogenesis in the Phyto-600 and Phyto-free animals, plasma androstenedione and estradiol levels were also measured by RIA (Table 4). A significant decrease in plasma androstenedione levels was observed in the animals fed the Phyto-600 diet compared with the Phyto-free fed animals (Table 4). The plasma androstenedione concentrations showed the same pattern as that of the plasma testosterone levels, being significantly lower in animals fed the Phyto-600 diet (Table 4). However, in the case of androstenedione, there was a much greater reduction in the Phyto-600 animals vs the Phyto-free fed animals when compared with the testosterone results. Conversely, when plasma estradiol levels were determined, no significant differences were observed between the two groups of animals (Table 4). [...] ... The circulating plasma phytoestrogen concentration of animals fed the Phyto-600 diet (2200 ng/ml) is similar to that in people eating a typical Asian diet (of approximately 1 ìM). ... [...] Long-term dietary studies where animals have been exposed to phytoestrogens show influences on prostate and other markers of reproductive development (Sharma et al. 1992, Makela et al. 1995a, Zhang et al. 1997). When reproductive organs were examined, Phyto-600 fed animals displayed a significant reduction in ventral prostate weight compared with Phyto-free fed animals. The mechanism for this change is unknown but may relate to changes in steroid hormone status within the prostate itself by effects on the levels of enzymes regulating steroid hormone production. It is known that phytoestrogens can inhibit prostate 5alpha-reductase enzyme activity in vitro (Evans et al. 1995), but our studies did not find significant alterations in prostate 5alpha-reductase enzyme activity after feeding the Phyto-600 diet that could account for the changes in prostate weight. However, the Phyto-600 fed animals had significantly lower plasma androgen levels when compared with the Phyto-free fed animals. This reduction in testosterone could account for the reduced prostate weight in these animals, because the ventral prostate is androgen sensitive. In previous (longer term) studies, changes in androgen levels were not noted (Sharma et al. 1992, Makela et al. 1995a, Zhang et al. 1997); however, circulating phytoestrogen levels were not measured in these studies and, therefore, such differences are difficult to reconcile. Additionally, we have previously observed a similar pattern of circulating testosterone reduction in animals on the Phyto-600 diet (at approximately 40–50% of Phytofree values) in three independent studies under the same experimental conditions, representing an n of 39 rats per treatment group. Another possible explanation for this finding is that phytoestrogens have the ability to inhibit the aromatase enzyme in peripheral tissues (Kellis & Vickery 1984, Ibrahim & Abul-Hajj 1990, Adlercreutz et al. 1994, Wang et al. 1994) and the apparent protection phytoestrogens have against BPH and PCa may be via the reduction in local estrogen formation since estrogenic agents are known to be mitogenic (vom Saal et al. 1997, Griffiths et al. 1998, Farnsworth 1999, Shibata et al. 2000, Yaono et al. 2000). On the other hand, the inter-conversion of testosterone to androstenedione is regulated by the activity of 17beta-hydroxysteroid dehydrogenase, an enzyme that has been shown to be influenced by phytoestrogens (Makela et al. 1995b). Changes in plasma androstenedione levels with the Phyto-600 diet were much lower compared with those observed for testosterone by dietary treatments, suggesting that the substrate supply or enzyme regulation for testosterone synthesis may be affected by the phytoestrogen-rich diet. No changes in plasma LH or estradiol levels were observed between the Phyto-600 animals and the Phyto-free fed animals that could account for the changes in the observed testosterone levels. Finally, in an attempt to determine whether phytoestrogens may alter cholesterol delivery into the steroidogenic pathway, we measured StAR activity but found no significant differences in testicular StAR levels between the Phyto-600 and the Phyto-free groups. However, it is possible that the 30 kDa StAR protein analyzed in these experiments may not represent newly synthesized StAR and thus the protein measured would not be active in cholesterol transfer (Townson et al. 1996). It is also possible that the effects of phytoestrogens may be manifested at the level of protein kinase activity in the prostate. It is known that genistein decreases tyrosine phosphorylation in endocrine tissue (Fioravanti et al. 1998). Finally, the decrease in testosterone levels in the Phyto-600 animals remains to be explained but represents a consistent observation (Sharma et al. 1992, Landstrom et al. 1998). It is possible that phytoestrogens affect the biosynthetic pathways for androgen production by an unknown mechanism. [...] Categories: 2001, Endocrine, Sexual development, Androgens, Androstenedione, Testosterone |