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Endocrine Reviews 20 (3): 279-307
Copyright © 1999 by The Endocrine Society

Estrogen Actions in the Central Nervous System1

Bruce S. McEwen and Stephen E. Alves

Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10021

I. Introduction
II. Mechanisms of Estrogen Action
A. "Genomic" and "nongenomic" mechanisms
B. Steroid hormone actions on gene expression
C. Subtypes of estrogen receptors
D. Steroid hormone actions on putative receptors on membranes
E. Rapid actions of steroids on neuronal excitability
F. Steroid hormone actions via second messengers
G. Neuroprotective effects of estrogens
H. Summary
III. Areas of the Brain Affected Outside of the Hypothalamus
A. Studies of hypothalamic and extrahypothalamic actions of estrogens
B. Estrogens and the cholinergic system
C. Estrogens and the serotonergic system
D. Catecholaminergic neurons
E. Spinal cord
F. Hippocampus
G. Glial cells, endothelial cells, and the blood-brain barrier
H. Summary
IV. Effects of Estrogens on Learning and Memory
V. Estrogens, Neuroprotection, and Alzheimer’s Disease
VI. Conclusions




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Endocr. Rev., October 1, 2003; 24(5): 668 - 693.
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EndocrinologyHome page
A. M. Etgen and M. Acosta-Martinez
Participation of Growth Factor Signal Transduction Pathways in Estradiol Facilitation of Female Reproductive Behavior
Endocrinology, September 1, 2003; 144(9): 3828 - 3835.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
T. R. Chakraborty, L. Ng, and A. C. Gore
Age-Related Changes in Estrogen Receptor {beta} in Rat Hypothalamus: A Quantitative Analysis
Endocrinology, September 1, 2003; 144(9): 4164 - 4171.
[Abstract] [Full Text] [PDF]


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NeurologyHome page
C. L. Harden
Menopause and bone density issues for women with epilepsy
Neurology, September 1, 2003; 61(90062): S16 - 22.
[Abstract] [Full Text]


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J. Neurosci.Home page
I. M. Abraham, S.-K. Han, M. G. Todman, K. S. Korach, and A. E. Herbison
Estrogen Receptor {beta} Mediates Rapid Estrogen Actions on Gonadotropin-Releasing Hormone Neurons In Vivo
J. Neurosci., July 2, 2003; 23(13): 5771 - 5777.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
H. L. Rincavage, D. P. McDonnell, and C. M. Kuhn
Expression of Functional Estrogen Receptor {beta} in Locus Coeruleus-Derived Cath.a Cells
Endocrinology, July 1, 2003; 144(7): 2829 - 2835.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
S. W. Mitra, E. Hoskin, J. Yudkovitz, L. Pear, H. A. Wilkinson, S. Hayashi, D. W. Pfaff, S. Ogawa, S. P. Rohrer, J. M. Schaeffer, et al.
Immunolocalization of Estrogen Receptor {beta} in the Mouse Brain: Comparison with Estrogen Receptor {alpha}
Endocrinology, May 1, 2003; 144(5): 2055 - 2067.
[Abstract] [Full Text] [PDF]


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J. Neuropsychiatry Clin. Neurosi.Home page
R. N. McLay, P. M. Maki, and C. G. Lyketsos
Nulliparity and Late Menopause Are Associated With Decreased Cognitive Decline
J Neuropsychiatry Clin Neurosci, May 1, 2003; 15(2): 161 - 167.
[Abstract] [Full Text] [PDF]


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Endocr. Rev.Home page
B. B. Sherwin
Estrogen and Cognitive Functioning in Women
Endocr. Rev., April 1, 2003; 24(2): 133 - 151.
[Abstract] [Full Text] [PDF]


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J. Appl. Physiol.Home page
P. M. Schmitt and M. P. Kaufman
High concentrations of 17beta -estradiol attenuate the exercise pressor reflex in male cats
J Appl Physiol, April 1, 2003; 94(4): 1431 - 1436.
[Abstract] [Full Text] [PDF]


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J. Physiol.Home page
H. Widmer, M. Ludwig, F. Bancel, G. Leng, and G. Dayanithi
Neurosteroid regulation of oxytocin and vasopressin release from the rat supraoptic nucleus
J. Physiol., April 1, 2003; 548(1): 233 - 244.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
K. T. Akama and B. S. McEwen
Estrogen Stimulates Postsynaptic Density-95 Rapid Protein Synthesis via the Akt/Protein Kinase B Pathway
J. Neurosci., March 15, 2003; 23(6): 2333 - 2339.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
J. Nilsen and R. D. Brinton
Mechanism of estrogen-mediated neuroprotection: Regulation of mitochondrial calcium and Bcl-2 expression
PNAS, March 4, 2003; 100(5): 2842 - 2847.
[Abstract] [Full Text] [PDF]


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J. Neurophysiol.Home page
K. Okamoto, H. Hirata, S. Takeshita, and D. A. Bereiter
Response Properties of TMJ Units in Superficial Laminae at the Spinomedullary Junction of Female Rats Vary Over the Estrous Cycle
J Neurophysiol, March 1, 2003; 89(3): 1467 - 1477.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
C. S. Nunemaker, M. Straume, R. A. DeFazio, and S. M. Moenter
Gonadotropin-Releasing Hormone Neurons Generate Interacting Rhythms in Multiple Time Domains
Endocrinology, March 1, 2003; 144(3): 823 - 831.
[Abstract] [Full Text] [PDF]


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NEJMHome page
B. L. Riggs and L. C. Hartmann
Selective Estrogen-Receptor Modulators -- Mechanisms of Action and Application to Clinical Practice
N. Engl. J. Med., February 13, 2003; 348(7): 618 - 629.
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Mol. Endocrinol.Home page
J. Sun, J. Baudry, J. A. Katzenellenbogen, and B. S. Katzenellenbogen
Molecular Basis for the Subtype Discrimination of the Estrogen Receptor-{beta}-Selective Ligand, Diarylpropionitrile
Mol. Endocrinol., February 1, 2003; 17(2): 247 - 258.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
L. Wang, S. Andersson, M. Warner, and J.-A. Gustafsson
Estrogen receptor (ER)beta knockout mice reveal a role for ERbeta in migration of cortical neurons in the developing brain
PNAS, January 21, 2003; 100(2): 703 - 708.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
H. A. Harris, J. A. Katzenellenbogen, and B. S. Katzenellenbogen
Characterization of the Biological Roles of the Estrogen Receptors, ER{alpha} and ER{beta}, in Estrogen Target Tissues in Vivo through the Use of an ER{alpha}-Selective Ligand
Endocrinology, November 1, 2002; 143(11): 4172 - 4177.
[Abstract] [Full Text] [PDF]


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ScienceHome page
S. Kousteni, J.-R. Chen, T. Bellido, L. Han, A. A. Ali, C. A. O'Brien, L. Plotkin, Q. Fu, A. T. Mancino, Y. Wen, et al.
Reversal of Bone Loss in Mice by Nongenotropic Signaling of Sex Steroids
Science, October 25, 2002; 298(5594): 843 - 846.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
S. K. Amateau and M. M. McCarthy
A Novel Mechanism of Dendritic Spine Plasticity Involving Estradiol Induction of Prostaglandin-E2
J. Neurosci., October 1, 2002; 22(19): 8586 - 8596.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
R. A. DeFazio and S. M. Moenter
Estradiol Feedback Alters Potassium Currents and Firing Properties of Gonadotropin-Releasing Hormone Neurons
Mol. Endocrinol., October 1, 2002; 16(10): 2255 - 2265.
[Abstract] [Full Text] [PDF]


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Mol. Biol. CellHome page
M. Marino, F. Acconcia, F. Bresciani, A. Weisz, and A. Trentalance
Distinct Nongenomic Signal Transduction Pathways Controlled by 17beta -Estradiol Regulate DNA Synthesis and Cyclin D1 Gene Transcription in HepG2 Cells
Mol. Biol. Cell, October 1, 2002; 13(10): 3720 - 3729.
[Abstract] [Full Text] [PDF]


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Arch Gen PsychiatryHome page
C. N. Epperson, K. Haga, G. F. Mason, E. Sellers, R. Gueorguieva, W. Zhang, E. Weiss, D. L. Rothman, and J. H. Krystal
Cortical {gamma}-Aminobutyric Acid Levels Across the Menstrual Cycle in Healthy Women and Those With Premenstrual Dysphoric Disorder: A Proton Magnetic Resonance Spectroscopy Study
Arch Gen Psychiatry, September 1, 2002; 59(9): 851 - 858.
[Abstract] [Full Text] [PDF]


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J. Neurosci.Home page
I. Kadish and T. van Groen
Low Levels of Estrogen Significantly Diminish Axonal Sprouting after Entorhinal Cortex Lesions in the Mouse
J. Neurosci., May 15, 2002; 22(10): 4095 - 4102.
[Abstract] [Full Text] [PDF]


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Am. J. PsychiatryHome page
J. R. Stevens
Schizophrenia: Reproductive Hormones and the Brain
Am J Psychiatry, May 1, 2002; 159(5): 713 - 719.
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J. Biol. Chem.Home page
J. P. Greenfield, L. W. Leung, D. Cai, K. Kaasik, R. S. Gross, E. Rodriguez-Boulan, P. Greengard, and H. Xu
Estrogen Lowers Alzheimer beta -Amyloid Generation by Stimulating trans-Golgi Network Vesicle Biogenesis
J. Biol. Chem., March 29, 2002; 277(14): 12128 - 12136.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
H. Brady, S. Desai, L. M. Gayo-Fung, S. Khammungkhune, J. A. McKie, E. O'Leary, L. Pascasio, M. K. Sutherland, D. W. Anderson, S. S. Bhagwat, et al.
Effects of SP500263, a Novel, Potent Antiestrogen, on Breast Cancer Cells and in Xenograft Models
Cancer Res., March 1, 2002; 62(5): 1439 - 1442.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
C. Orikasa, Y. Kondo, S. Hayashi, B. S. McEwen, and Y. Sakuma
Sexually dimorphic expression of estrogen receptor beta in the anteroventral periventricular nucleus of the rat preoptic area: Implication in luteinizing hormone surge
PNAS, February 14, 2002; (2002) 52707299.
[Abstract] [Full Text] [PDF]


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Recent Prog Horm ResHome page
B. McEwen
Estrogen Actions Throughout the Brain
Recent Prog. Horm. Res., January 1, 2002; 57(1): 357 - 384.
[Abstract] [Full Text] [PDF]




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