Estrogen signaling in the hypothalamus

Estrogen has multifaceted effects on the hypothalamus that regulate a number of homeostatic functions including reproduction, temperature, energy balance, stress, and motivated behaviors. Estrogen targets all of the major hypothalamic neuroendocrine and autonomic cellular groups to activate multiple signaling pathways. Originally it was thought that all of these actions of estrogen could be ascribed to its binding to its "classical" intracellular receptor and to alterations in gene transcription. However, we now know that this steroid hormone activates multiple signaling pathways to affect neuronal excitability and gene transcription. Although the "classical" genomic signaling pathway has been recognized for almost half a century, until recently little attention has been paid to the rapid membrane-initiated signaling by estrogen in neurons. It has been known since the 1970s that estrogen can rapidly alter neuronal firing within seconds, indicating that some cellular effects of estrogen could occur via rapid, non-transcriptional mechanisms. Therefore, this chapter reviews the current status of estrogen signaling in the hypothalamus via membrane-initiated and nuclear-mediated events that affect the excitability of hypothalamic neurons and, ultimately, neuroendocrine and autonomic functions.