Background/Aims: Scarce data exist on the effects of soy isoflavones (IF) on bone during peripuberty, a known ‘window of opportunity’ for bone consolidation. Our aim was to determine the skeletal, reproductive, and serum estradiol (E2)/estrogenic activity response of consuming naturally-occurring soy protein-associated IF during peripuberty. Methods: Weanling (∼3 weeks old), female rats were placed on one of four nutritionally-complete dietary regimens in which protein (200 g/kg diet) was provided as casein or soy protein isolates containing either 0.11 (Low IF), 2.16 (Med IF), or 3.95 (High IF) mg total aglycone isoflavones/g protein for 8 weeks, during which body weights and estrus cycling were recorded. Results: Bone growth and density were unaffected by soy intake while the reproductive tissues showed a slight response (greater uterine weights of the Med and High IF groups). Despite suppression of E2 concentrations in the High IF group, total circulating estrogenic activity was unaltered. Moreover, in the High IF group, E2 was significantly depressed compared with bioassayable estrogenic activity, suggesting negative feedback inhibition of E2 by the elevated circulating levels of IF. Conclusions: This suppression in E2 with maintenance of total serum estrogenicity in the High IF group may explain the lack of effect observed in the skeletal tissues.

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