This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McEwen, B. S. Articles by Weiland, N. G. Search for Related Content PubMed PubMed Citation Articles by McEwen, B. S. Articles by Weiland, N. G.

Inhibition of Dendritic Spine Induction on Hippocampal CA1 Pyramidal Neurons by a Nonsteroidal Estrogen Antagonist in Female Rats¹

Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10021; and the Department of Psychology, Princeton University (P.T.), Princeton, New Jersey 08540

Address all correspondence and requests for reprints to: Bruce S. McEwen, Ph.D., Rockefeller University, Box 165, 1230 York Avenue, New York, New York 10021. E-mail: mcewen{at}rockvax.rockefeller.edu

Estrogens regulate the formation of excitatory synaptic connections in the hippocampus of female rats. Because the adult hippocampus has a very low concentration of intracellular estrogen receptors, it is unclear whether a conventional genomic mechanism is involved. Nonsteroidal estrogen antagonists are useful tools to study estrogen action because they can provide pharmacological data in favor of a particular pathway of estrogen action and evidence against other pathways. To investigate the role of intracellular estrogen receptors in the estrogen induction of synapse formation, we took advantage of previous studies in which we had shown that an estrogen antagonist, CI-628, enters the brain and blocks estrogen induction of progestin receptors to study whether the same antagonist would either mimic or block effects of estradiol to induce excitatory spine synapses. Using silver impregnation of neurons by the single section Golgi technique and morphometric analysis, we found that CI-628 effectively prevented estrogen induction of spines on CA1 pyramidal neurons, without having any agonist effects of its own. This result is consistent with an action of estradiol via intracellular estrogen receptors that are known to be expressed by interneurons within the hippocampus.

This article has been cited by other articles:

				R. N. Pechnick, S. Zonis, K. Wawrowsky, J. Pourmorady, and V. Chesnokova p21Cip1 restricts neuronal proliferation in the subgranular zone of the dentate gyrus of the hippocampus PNAS, January 29, 2008; 105(4): 1358 - 1363. [Abstract] [Full Text] [PDF]

				K. B. Jelks, R. Wylie, C. L. Floyd, A. K. McAllister, and P. Wise Estradiol Targets Synaptic Proteins to Induce Glutamatergic Synapse Formation in Cultured Hippocampal Neurons: Critical Role of Estrogen Receptor-{alpha} J. Neurosci., June 27, 2007; 27(26): 6903 - 6913. [Abstract] [Full Text] [PDF]

				K. Ito, Y. Hirooka, Y. Kimura, Y. Sagara, and K. Sunagawa Ovariectomy Augments Hypertension Through Rho-Kinase Activation in the Brain Stem in Female Spontaneously Hypertensive Rats Hypertension, October 1, 2006; 48(4): 651 - 657. [Abstract] [Full Text] [PDF]

				R. D. Romeo, D. Staub, A. M. Jasnow, I. N. Karatsoreos, J. E. Thornton, and B. S. McEwen Dihydrotestosterone Increases Hippocampal N-Methyl-D-Aspartate Binding But Does Not Affect Choline Acetyltransferase Cell Number in the Forebrain or Choline Transporter Levels in the CA1 Region of Adult Male Rats Endocrinology, April 1, 2005; 146(4): 2091 - 2097. [Abstract] [Full Text] [PDF]

				C. N. Rudick and C. S. Woolley Selective Estrogen Receptor Modulators Regulate Phasic Activation of Hippocampal CA1 Pyramidal Cells by Estrogen Endocrinology, January 1, 2003; 144(1): 179 - 187. [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]

				B. S. McEwen Genome and Hormones: Gender Differences in Physiology: Invited Review: Estrogens effects on the brain: multiple sites and molecular mechanisms J Appl Physiol, December 1, 2001; 91(6): 2785 - 2801. [Abstract] [Full Text] [PDF]

				C. N. Rudick and C. S. Woolley Estrogen Regulates Functional Inhibition of Hippocampal CA1 Pyramidal Cells in the Adult Female Rat J. Neurosci., September 1, 2001; 21(17): 6532 - 6543. [Abstract] [Full Text] [PDF]

				R. H. Price Jr., C. A. Butler, P. Webb, R. Uht, P. Kushner, and R. J. Handa A Splice Variant of Estrogen Receptor {beta} Missing Exon 3 Displays Altered Subnuclear Localization and Capacity for Transcriptional Activation Endocrinology, May 1, 2001; 142(5): 2039 - 2049. [Abstract] [Full Text]

				W. G. Brake, S. E. Alves, J. C. Dunlop, S. J. Lee, K. Bulloch, P. B. Allen, P. Greengard, and B. S. McEwen Novel Target Sites for Estrogen Action in the Dorsal Hippocampus: An Examination of Synaptic Proteins Endocrinology, March 1, 2001; 142(3): 1284 - 1289. [Abstract] [Full Text] [PDF]

				D. B. Dubal, H. Zhu, J. Yu, S. W. Rau, P. J. Shughrue, I. Merchenthaler, M. S. Kindy, and P. M. Wise Estrogen receptor alpha , not beta , is a critical link in estradiol-mediated protection against brain injury PNAS, February 1, 2001; (2001) 41483198. [Abstract] [Full Text]

				B. S. McEwen and S. E. Alves Estrogen Actions in the Central Nervous System Endocr. Rev., June 1, 1999; 20(3): 279 - 307. [Abstract] [Full Text]

				B. S. McEwen The Molecular and Neuroanatomical Basis for Estrogen Effects in the Central Nervous System J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 1790 - 1797. [Full Text]

				D. B. Dubal, H. Zhu, J. Yu, S. W. Rau, P. J. Shughrue, I. Merchenthaler, M. S. Kindy, and P. M. Wise Estrogen receptor alpha , not beta , is a critical link in estradiol-mediated protection against brain injury PNAS, February 13, 2001; 98(4): 1952 - 1957. [Abstract] [Full Text] [PDF]