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Estrogen Actions in the Central Nervous System¹

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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				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				J. R. Stevens Schizophrenia: Reproductive Hormones and the Brain Am J Psychiatry, May 1, 2002; 159(5): 713 - 719. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

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