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.
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.
Ottem
Erich N
EN
Department of Biology, Neuroscience and Behavior Program, and Center for Neuroendocrine Studies, University of Massachusetts, Amherst, Massachusetts 01003, USA.
Godwin
Jonathan G
JG
Petersen
Sandra L
SL
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005973:Glutamine / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D010052:Ovariectomy; D011301:Preoptic Area / Q000166:cytology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014018:Tissue Distribution
D016291:Dizocilpine Maleate; D004958:Estradiol; D018691:Excitatory Amino Acid Antagonists; D005973:Glutamine; D007987:Gonadotropin-Releasing Hormone; D016202:N-Methylaspartate; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate