Estrogen Actions on Brain and Behavior: Recent Insights and Future Challenges

Recent advances in our knowledge of estrogen action in the brain suggest that this steroid is not solely an endocrine factor but plays important but hitherto largely unrecognized physiological and pathophysiological roles that are not directly involved in reproductive processes. Estrogens are now known to influence a wide variety of functions in the mammalian brain ranging from regulation of various aspects of neurotransmitter function and modulation of behaviour to the stimulation of differentiation and plasticity of distinct neuronal populations and circuits. Acting via both genomic and nongenomic mechanisms estrogens can influence higher cognitive functions, pain mechanisms, fine motor skills, mood, susceptibility to. seizures, and also appear to have important neuroprotective function in relation to stroke damage and neurodegenerative disorders. This review focuses on new advancements from clinical and basic studies on estrogen action in the central nervous system especially illustrating the brain regions and cell types in which estrogens produce their effects, emphasizing new knowledge regarding estrogen actions outside the hypothalamus and pituitary gland. Current therapeutic strategies to develop suitable estrogen receptor modulators with a selective spectrum of action in the brain and priorities for future research are also briefly discussed.