Estradiol suppresses glutamatergic transmission to gonadotropin-releasing hormone neurons in a model of negative feedback in mice

Catherine A. Christian, Justyna Pielecka-Fortuna, Suzanne M. Moenter

Research output: Contribution to journalArticlepeer-review

Abstract

A surge of gonadotropin-releasing hormone (GnRH) release from the brain triggers the luteinizing hormone (LH) surge that causes ovulation. The GnRH surge is initiated by a switch in estradiol action from negative to positive feedback. Estradiol signals critical for the surge are likely transmitted to GnRH neurons at least in part via estradiol-sensitive afferents. Using an ovariectomized estradiol-treated (OVX+E) mouse model that exhibits daily LH surges, we examined changes in glutamate transmission to GnRH neurons during negative feedback and positive feedback. Spontaneous glutamatergic excitatory post-synaptic currents (EPSCs) mediated by alpha-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid/kainate receptors (AMPA/KA Rs) or N-methyl-D-aspartate receptors (NMDARs) were recorded in GnRH neurons from OVX+E and OVX mice. There were no diurnal changes in the percentage of GnRH neurons from OVX mice exhibiting EPSCs. In cells from OVX+E mice, the profile of AMPA/KA R-mediated and NMDAR-mediated EPSCs showed changes dependent on time of day. Comparison of AMPA/KA R-mediated EPSC frequency in OVX+E and OVX cells showed that estradiol suppressed transmission during negative feedback but had no effect during positive feedback. Tetrodotoxin treatment to block action potential firing did not affect AMPA/KA R-mediated EPSC frequency in OVX cells during negative feedback or in OVX+E cells during positive feedback, suggesting that estradiol-induced suppression of glutamate transmission may be primarily due to activity-independent changes. The diurnal removal of estradiol-induced suppression of AMPA/KA R-mediated glutamate transmission to GnRH neurons during positive feedback suggests that the primary role for estradiol-induced changes in glutamate transmission may be in mediating negative feedback.

Original languageEnglish (US)
Pages (from-to)1128-1135
Number of pages8
JournalBiology of reproduction
Volume80
Issue number6
DOIs
StatePublished - Jun 2009
Externally publishedYes

Keywords

  • AMPA
  • Estradiol
  • Glutamate
  • Gonadotropin-releasing hormone
  • NMDA
  • Neuroendocrinology

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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