Hormones and behavior and the integration of brain-body science.

The investigation of hormones, brain function and behavior over the past 50 years has played a major role in elucidating how the brain and body communicate reciprocally via hormones and other mediators and how this impacts brain and body health both positively and negatively. This is illustrated here for the hippocampus, a uniquely sensitive and vulnerable brain region, study of which as a hormone target has provided a gateway into the rest of the brain. Hormone actions on the brain and hormones generated within the brain are now recognized to include not only steroid hormones but also metabolic hormones and chemical signals from bone and muscle. Moreover, steroid hormones, and some metabolic hormones, and their receptors, are generated by the brain for specific functions that synergize with effects of those circulating hormones. Hormone actions in hippocampus have revealed its capacity, and that of other brain regions, for adaptive plasticity, loss of which needs external intervention in, for example, mood disorders. Early life experiences as well as in utero and transgenerational effects are now appreciated for their lasting effects at the level of gene expression affecting the capacity for adaptive plasticity. Moreover sex differences are recognized as affecting the whole brain via both genetic and epigenetic mechanisms. The demonstrated plasticity of a healthy brain gives hope that interventions throughout the life course can ameliorate negative effects by reactivating that plasticity and the underlying epigenetic activity to produce compensatory changes in the brain with more positive consequences for the body.