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Table of Contents
Vol. 16, No. 2-3, 2008
Issue release date: February 2008
Section title: Paper
Neurosignals 2008;16:140–153
(DOI:10.1159/000111559)

Rapid Estrogen Signaling in the Brain

Raz L.a · Khan M.M.a · Mahesh V.B.a · Vadlamudi R.K.b · Brann D.W.a
aInstitute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Ga., and bDepartment of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, San Antonio, Tex., USA
email Corresponding Author

Abstract

Estrogen has multiple actions in the brain to modulate homeostasis, synaptic plasticity/cognition and neuroprotection. While many of these actions undoubtedly involve mediation via the classical genomic mechanism of regulation of transcription of genes via estrogen nuclear receptors, there has been growing interest in the rapid nongenomic effects of estrogen and the role they may play in the neural actions of estrogen. In this review, we will focus on these rapid nongenomic actions of estrogen in the brain and discuss the potential physiological significance of these actions. The evidence for rapid estrogen regulation of cell signaling pathways, including calcium, ion channel and kinase signaling pathways in the brain will be reviewed, as will evidence derived from plasma-membrane impermeable estrogen-peptide conjugates in the regulation of these cell signaling pathways. Evidence supporting classical and nonclassical estrogen receptor localization to the plasma membrane of neurons will also be reviewed, including the putative new membrane estrogen G-protein-coupled receptor, GPR30. Precisely how membrane estrogen receptors couple to kinase signaling pathways is unclear, but we will discuss the latest findings on estrogen receptor-interacting scaffold proteins, such as MNAR/PELP1, striatin and p130Cas, which are capable of linking estrogen receptors and kinases such as Src and PI3K, to potentially mediate estrogen-induced kinase signaling. Finally, we will review the growing evidence that rapid membrane-mediated effects of estrogen play an important physiological role in the neural actions of estrogen in the brain, including estrogen feedback control and modulation of homeostasis, regulation of synaptic plasticity/cognition, and estrogen-mediated neuroprotection.

© 2008 S. Karger AG, Basel


  

Key Words

  • Estradiol, nongenomic
  • Membrane
  • Estrogen receptor
  • Neuron
  • Kinase
  • GPR30 synapse

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Author Contacts

Darrell W. Brann, PhD
Regents’ Professor and Director of the Graduate Program in Neuroscience
Institute of Molecular Medicine and Genetics, Medical College of Georgia
1120 15th Street, Augusta, GA 30912 (USA)
Tel. +1 706 721 7779, Fax +1 706 721 8685, E-Mail dbrann@mcg.edu

  

Article Information

Published online: February 5, 2008
Number of Print Pages : 14
Number of Figures : 3, Number of Tables : 0, Number of References : 129

  

Publication Details

Neurosignals

Vol. 16, No. 2-3, Year 2008 (Cover Date: February 2008)

Journal Editor: Ip, N.Y. (Hong Kong)
ISSN: 1424–862X (Print), eISSN: 1424–8638 (Online)

For additional information: http://www.karger.com/NSG


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Estrogen has multiple actions in the brain to modulate homeostasis, synaptic plasticity/cognition and neuroprotection. While many of these actions undoubtedly involve mediation via the classical genomic mechanism of regulation of transcription of genes via estrogen nuclear receptors, there has been growing interest in the rapid nongenomic effects of estrogen and the role they may play in the neural actions of estrogen. In this review, we will focus on these rapid nongenomic actions of estrogen in the brain and discuss the potential physiological significance of these actions. The evidence for rapid estrogen regulation of cell signaling pathways, including calcium, ion channel and kinase signaling pathways in the brain will be reviewed, as will evidence derived from plasma-membrane impermeable estrogen-peptide conjugates in the regulation of these cell signaling pathways. Evidence supporting classical and nonclassical estrogen receptor localization to the plasma membrane of neurons will also be reviewed, including the putative new membrane estrogen G-protein-coupled receptor, GPR30. Precisely how membrane estrogen receptors couple to kinase signaling pathways is unclear, but we will discuss the latest findings on estrogen receptor-interacting scaffold proteins, such as MNAR/PELP1, striatin and p130Cas, which are capable of linking estrogen receptors and kinases such as Src and PI3K, to potentially mediate estrogen-induced kinase signaling. Finally, we will review the growing evidence that rapid membrane-mediated effects of estrogen play an important physiological role in the neural actions of estrogen in the brain, including estrogen feedback control and modulation of homeostasis, regulation of synaptic plasticity/cognition, and estrogen-mediated neuroprotection.

© 2008 S. Karger AG, Basel


  

Author Contacts

Darrell W. Brann, PhD
Regents’ Professor and Director of the Graduate Program in Neuroscience
Institute of Molecular Medicine and Genetics, Medical College of Georgia
1120 15th Street, Augusta, GA 30912 (USA)
Tel. +1 706 721 7779, Fax +1 706 721 8685, E-Mail dbrann@mcg.edu

  

Article Information

Published online: February 5, 2008
Number of Print Pages : 14
Number of Figures : 3, Number of Tables : 0, Number of References : 129

  

Publication Details

Neurosignals

Vol. 16, No. 2-3, Year 2008 (Cover Date: February 2008)

Journal Editor: Ip, N.Y. (Hong Kong)
ISSN: 1424–862X (Print), eISSN: 1424–8638 (Online)

For additional information: http://www.karger.com/NSG


Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: 2/5/2008
Issue release date: February 2008

Number of Print Pages: 14
Number of Figures: 3
Number of Tables: 0

ISSN: 1424-862X (Print)
eISSN: 1424-8638 (Online)

For additional information: http://www.karger.com/NSG


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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