It is well known that many of the actions of estrogens in the central nervous system are mediated via intracellular receptor/transcription factors that interact with steroid response elements on target genes. But there is also a compelling evidence for the involvement of membrane estrogen receptors in hypothalamic and other CNS functions. However, it is not well understood how estrogens signal via membrane receptors, and how these signals impact not only membrane excitability but also gene transcription in neurons. Indeed, it has been known for sometime that estrogens can rapidly alter neuronal activity within seconds, indicating that some cellular effects can occur via membrane delimited events. In addition, estrogens can affect second messenger systems including calcium mobilization and a plethora of kinases within neurons to alter cellular functions. Therefore, this brief review will summarize our current understanding of rapid membrane-initiated and intracellular signaling by estrogens in the hypothalamus, the nature of receptors involved and how these receptors contribute to maintenance of homeostatic functions, many of which go awry in menopausal states. This article is part of a Special Issue entitled Hormone Therapy.
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