@inbook{e6b7317055e64999bafe5516530b6651,
title = "Membrane-initiated effects of estrogen in the central nervous system",
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. But, it is not well understood how estrogen signals 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 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 chapter considers our current knowledge of rapid membrane-initiated and intracellular signaling by estrogen in the brain, the nature of receptors involved, and how they contribute to homeostatic functions.",
keywords = "ERα, ERβ, GIRK channels, GPCR, GnRH, MAPK, MER, PCREB, PI3K, PKA, PKC, POMC, μ-Opioid receptor",
author = "Rnnekleiv, {O. K.} and Kelly, {M. J.}",
note = "Funding Information: ERα and ERβ Estrogen receptors α and β are the classical estrogen receptors/transcription factors. GPCRs G-protein-coupled receptors are metabotropic receptors that have traditionally been associated with neurotransmitters. However, GPR30 is an orphan GPCR that binds 17β-estradiol. There are other membrane estrogen receptors that appear to be G-protein coupled. membrane-initiated steroid signaling Terminology adopted (vs. nongenomic) by the FASEB steroid signaling workshop to designate the activation of signaling cascades originating at the membrane. nuclear-initiated steroid signaling Terminology adopted by the FASEB steroid signaling workshop to designate the direct activation of genes by steroid receptors through nuclear events. Dr. R{\o}nnekleiv is a professor in the Department of Physiology and Pharmacology, professor in the Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University (OHSU), and a senior scientist in the Division of Neuroscience, Oregon National Primate Research Center (ONPRC). She earned her PhD in physiology under the guidance of Dr. SM McCann from the University of Texas Southwestern Medical School in 1974. After postdoctoral research at the Max Planck Institute for Biophysical Chemistry in G{\"o}ttingen, Germany, as an Alexander von Humboldt fellow, Dr. R{\o}nnekleiv joined the Department of Psychiatry, University of Pittsburgh School of Medicine as an assistant professor in 1979. She moved to Portland, Oregon in 1982 with joint appointments at OHSU and ONPRC. Dr. R{\o}nnekleiv was promoted to associate professor in 1987 and to professor in 1998. Dr. R{\o}nnekleiv has been continually funded from NIH since 1981, and her research has focused on the actions of estrogen in the brain to control motivated behavior such as eating, drinking, and reproduction. She discovered in primates that GnRH neurons originate in the nose, and has had a particular interest in the mechanism by which these neurons are regulated by estrogen. Recently, Dr. R{\o}nnekleiv, as part of a Program Project Grant on Sex Steroids and Neuroprotection, has embarked on studies to understand the mechanism by which estrogen protects neurons. Martin J. Kelly received his PhD in physiology in 1976 from the University of Texas Southwestern Medical School at Dallas. He did his graduate work on the rapid effects of estrogen on hypothalamic neuronal activity under the guidance of Dr. Robert L. Moss (1940–99). He spent 3 years (1976–79) as a postdoctoral fellow in Germany in the Department of Neurobiology at the Max Planck Institute for Biophysical Chemistry. There he developed the hypothalamic slice preparation, which laid the ground work for doing voltage-clamp studies of small neurons and studying ion channels associated with rapid estrogen signaling. In 1979, Dr. Kelly moved to the University of Pittsburgh where he joined the Department of Physiology as an assistant professor. There he received his first NIH funding (R01) to continue the slice work investigating the membrane-initiated signaling of estrogen. He moved to Oregon Health and Science University in 1981 to continue his work and was a founding member of the neurosciences graduate program at OHSU. Dr. Kelly was promoted to associate professor in 1987 and full professor in 1992. During this period, Dr. Kelly has received two NIH Research Career Development Awards to work on novel estrogen signaling in the brain. ",
year = "2009",
doi = "10.1016/B978-008088783-8.00032-2",
language = "English (US)",
isbn = "9780080887838",
pages = "1099--1122",
booktitle = "Hormones, Brain and Behavior Online",
publisher = "Elsevier Inc.",
}