| Phytoestrogens are plant-derived estrogen-like molecules. They have received a great deal of investigative attention due to their potential beneficial effects on hormone-dependent cancers, cardiovascular disease, osteoporosis, and perimenopausal symptoms. Of all the phytoestrogens, soy-derived isoflavones are the most abundant in human and experimental rodent diets and the most studied in clinical and animal research. We examined the influence of dietary soy isoflavones on metabolism, stress/pain response, and neuronal cell death/survival in rats fed diets containing different levels of soy isoflavones. We found that consumption of soy isoflavones significantly decreased body weight, adipose deposition, serum insulin and leptin levels, core/skin body temperature, but increased food/water intake, hypothalamic neuropeptide Y (NPY), serum thyroid hormone and uncoupling protein-1 mRNA levels in brown adipose tissue. Furthermore, we observed an apparent dose-dependent relationship between body weight/skin temperature and the isoflavone concentrations of the diets, where body weight/skin temperature decreased as a function of increasing isoflavone levels in the diets. However, no changes in thermal pain threshold or serum corticosterone/ACTH levels after activation of the HPA stress axis were observed in chemically-induced estrous ovariectomized (OVX) rats. Finally, the effects of soy isoflavones on neuronal apoptosis and survival in vivo were investigated. We showed evidence for the neuroprotective potential of dietary soy isoflavones in the amygdala, frontal cortex, hippocampus and medial basal hypothalamus (MBH). Furthermore, consumption of soy isoflavones significantly increased neuronal apoptosis in adult male anteroventral periventricular nucleus (AVPV), which is smaller in male rats than in females. Moreover, estrogen receptor beta, but not estrogen receptor alpha, was found to mediate apoptosis in AVPV by consumption of soy isoflavones. In summary, these results suggest that consumption of soy isoflavones alters several parameters involved in maintaining body homeostatic balance (such as energy expenditure, feeding behavior, and metabolic/neuroendocrine function) and neuronal cell death/survival. These findings were previously unknown, and may shed light on the prevention of obesity and hot flashes in humans. In addition, they suggest mechanisms for a possible impact on neural function, behavioral changes, and brain aging. |
