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Updated: Jul 15, 2026

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Membrane-initiated signaling of estrogen in the brain
Oline K Rønnekleiv1, Anna Malyala, Martin J Kelly
1Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon 97239-3098, USA. ronnekle@ohsu.edu
Abstract:
It is well known that many of the actions of estrogen in the central nervous system are mediated via intracellular receptor/transcription factors that interact with steroid response elements on target genes. However, there now exists compelling evidence for membrane steroid receptors for estrogen in hypothalamic and other brain neurons. It is not well understood how estrogen signals via membrane receptors, and how these signals influence not only membrane excitability but also gene transcription in neurons. Indeed, it has been known for some time that estrogen can rapidly alter neuronal activity within seconds, indicating that some cellular effects can occur via membrane-delimited events. In addition, estrogen can affect second messenger systems including calcium mobilization and a plethora of kinases to alter cell signaling. Therefore, this review considers our current knowledge of rapid membrane-initiated and intracellular signaling by estrogen in the brain, and the nature of receptors involved and how they contribute to homeostatic functions.
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