The Two Faces of Estradiol: Effects on the Developing Brain

Abstract

Estradiol is a potent steroid of both gonadal and neuronal origin that exerts profound and enduring effects on the brain as it develops. Differences in estradiol production in males and females underlie the establishment of many sexually dimorphic brain characteristics. Two paradigm shifts in the understanding of estradiol and its actions have expanded the view from one of slow narrowly controlled nuclear transcription to include rapid effects initiated at the membrane and inducible by locally synthesized steroid. A survey of estradiol actions reveals regional specificity underlying opposing effects such that estradiol induces cell death in one region but prevents it in another or promotes synaptogenesis in one region but retards it in the other. Similarly, estradiol is neuroprotective or neurodamaging and enhances excitation or dampens excitation, depending on the model and neurotransmitter under study. Understanding the diverse actions of estradiol in different brain regions under differing conditions is essential to harnessing the tremendous therapeutic potential of this endogenous naturally occurring and efficacious neural modulator.