Dose-dependent effects of isoflavone exposure during early lifetime on development and androgen sensitivity in male Wistar rats.

Scope: The aim of our study was to investigate dose-dependent effects of isoflavone (ISO) exposure during adolescence on the androgen sensitivity of various physiological end points in male Wistar rats.

Methods And Results: During embryogenesis and adolescence, rats were exposed to an ISO-depleted diet (IDD) or one of two diets enriched with different concentrations of a soy-based ISO extract causing plasma concentrations observed averagely (ISO-rich diet [IRD]low) and maximally (IRDhigh) in Asian men. Most of the rats were orchiectomized at postnatal day (PND) 81 and were treated with testosterone propionate (TP) or vehicle from PND 89 to 99. In intact rats (PND 99) body weight, food intake, and fat mass were not influenced by ISO, but serum triglycerides and hepatic fatty acid synthase expression were decreased. Trabecular bone mineral density (BMD) was reduced in IRDlow, but not in IRDhigh rats. Orchiectomy (ORX) induced loss of BMD, which was antagonized by IRDhigh. ISO increased androgen sensitivity of seminal vesicle and levator ani. Besides, ISO plasma levels were reduced by ORX compared to intact and TP-treated rats.

Conclusion: In summary, the results of this study indicate that exposure to ISO during adolescence affects bone homeostasis, lipid metabolism, and modulates androgen sensitivity in young adult male rats.