Estrogens: neuroprotective or neurotoxic?

The present paper reviews the major modes of action of estrogen on the molecular, cellular, tissue, and neurobehavioral levels of mammalian physiology, with an emphasis on the brain as an estrogen target tissue. We draw a distinction between receptor- and nonreceptor-mediated actions, as well as delineate the range of different signal transduction pathways that might be available within a given tissue to mediate estrogenic effects. We consider species differences relevant to understanding the predictability of effects in humans from data obtained in rats or monkeys. Finally, we emphasize the importance of developmental stage in determining whether estrogenic effects are beneficial or harmful; "neuroprotective" or "neurotoxic."