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 Ottem, E. N. Articles by Petersen, S. L. Search for Related Content PubMed PubMed Citation Articles by Ottem, E. N. Articles by Petersen, S. L.

Glutamatergic Signaling through the N-Methyl-D-Aspartate Receptor Directly Activates Medial Subpopulations of Luteinizing Hormone-Releasing Hormone (LHRH) Neurons, But Does Not Appear to Mediate the Effects of Estradiol on LHRH Gene Expression

Department of Biology, Neuroscience and Behavior Program, and Center for Neuroendocrine Studies, University of Massachusetts, Amherst, Massachusetts 01003

Address all correspondence and requests for reprints to: Dr. Sandra L. Petersen, Department of Biology, University of Massachusetts, Amherst, Massachusetts 01003. E-mail: sandyp{at}bio.umass.edu.

Although estradiol (E₂) triggers phasic increases in LH-releasing hormone (LHRH) synthesis and release, the neurocircuitry responsible for these changes is unclear. We used an ovariectomized, E₂-treated animal model to investigate the possibility that glutamate, through N-methyl-D-aspartate (NMDA) receptors (NMDAR), communicates E₂ signals to LHRH neurons. A neuroanatomical analysis of the region containing LHRH neurons revealed that approximately 80% of LHRH neurons in medial, but less than 40% in lateral, nuclei of the preoptic area contained NMDAR1 mRNA. Consistent with this distribution pattern, NMDA doubled LHRH mRNA levels in medial neurons, but increased them by less than 30% in cells of the lateral nuclei. Steroids did not alter NMDAR1 mRNA levels in LHRH neurons or change the percentage of LHRH neurons expressing the gene. Furthermore, in contrast to the regionalized effects of NMDA, E₂ treatment increased LHRH mRNA levels to the same extent in medial and lateral neurons, and MK801 failed to block E₂-induced changes in LHRH gene expression. These results demonstrate that glutamatergic signaling via NMDA receptors is direct and preferentially targets LHRH neurons in medial nuclei of the preoptic area. However, it is unlikely that NMDAR activation mediates E₂-dependent increases in LHRH mRNA levels before the LH surge.

This article has been cited by other articles:

				J. Pielecka-Fortuna, Z. Chu, and S. M. Moenter Kisspeptin Acts Directly and Indirectly to Increase Gonadotropin-Releasing Hormone Neuron Activity and Its Effects Are Modulated by Estradiol Endocrinology, April 1, 2008; 149(4): 1979 - 1986. [Abstract] [Full Text] [PDF]

				W. Yin, J. M. Mendenhall, S. B. Bratton, T. Oung, W. G. M. Janssen, J. H. Morrison, and A. C. Gore Novel Localization of NMDA Receptors Within Neuroendocrine Gonadotropin-Releasing Hormone Terminals Experimental Biology and Medicine, May 1, 2007; 232(5): 662 - 673. [Abstract] [Full Text] [PDF]

				M. El-Etr, Y. Akwa, E.-E. Baulieu, and M. Schumacher The Neuroactive Steroid Pregnenolone Sulfate Stimulates the Release of Gonadotropin-Releasing Hormone from GT1-7 Hypothalamic Neurons, through N-Methyl-D-Aspartate Receptors Endocrinology, June 1, 2006; 147(6): 2737 - 2743. [Abstract] [Full Text] [PDF]

				S. R. Ojeda, A. Lomniczi, C. Mastronardi, S. Heger, C. Roth, A.-S. Parent, V. Matagne, and A. E. Mungenast Minireview: The Neuroendocrine Regulation of Puberty: Is the Time Ripe for a Systems Biology Approach? Endocrinology, March 1, 2006; 147(3): 1166 - 1174. [Abstract] [Full Text] [PDF]

				T. M. Plant, S. Ramaswamy, and M. J. DiPietro Repetitive Activation of Hypothalamic G Protein-Coupled Receptor 54 with Intravenous Pulses of Kisspeptin in the Juvenile Monkey (Macaca mulatta) Elicits a Sustained Train of Gonadotropin-Releasing Hormone Discharges Endocrinology, February 1, 2006; 147(2): 1007 - 1013. [Abstract] [Full Text] [PDF]

				A. Lomniczi, A. Cornea, M. E. Costa, and S. R. Ojeda Hypothalamic Tumor Necrosis Factor-{alpha} Converting Enzyme Mediates Excitatory Amino Acid-Dependent Neuron-to-Glia Signaling in the Neuroendocrine Brain J. Neurosci., January 4, 2006; 26(1): 51 - 62. [Abstract] [Full Text] [PDF]

				G. S. Neal-Perry, G. D. Zeevalk, N. F. Santoro, and A. M. Etgen Attenuation of Preoptic Area Glutamate Release Correlates with Reduced Luteinizing Hormone Secretion in Middle-Aged Female Rats Endocrinology, October 1, 2005; 146(10): 4331 - 4339. [Abstract] [Full Text] [PDF]

				Z. Chu and S. M. Moenter Endogenous Activation of Metabotropic Glutamate Receptors Modulates GABAergic Transmission to Gonadotropin-Releasing Hormone Neurons and Alters Their Firing Rate: A Possible Local Feedback Circuit J. Neurosci., June 15, 2005; 25(24): 5740 - 5749. [Abstract] [Full Text] [PDF]

				E. N. Ottem, J. G. Godwin, S. Krishnan, and S. L. Petersen Dual-Phenotype GABA/Glutamate Neurons in Adult Preoptic Area: Sexual Dimorphism and Function J. Neurosci., September 15, 2004; 24(37): 8097 - 8105. [Abstract] [Full Text] [PDF]

				A. C. Gore Gonadotropin-Releasing Hormone Neurons: Multiple Inputs, Multiple Outputs Endocrinology, September 1, 2004; 145(9): 4016 - 4017. [Full Text] [PDF]

				S. L. Petersen, E. N. Ottem, and C. D. Carpenter Direct and Indirect Regulation of Gonadotropin-Releasing Hormone Neurons by Estradiol Biol Reprod, December 1, 2003; 69(6): 1771 - 1778. [Abstract] [Full Text] [PDF]