Prostaglandin E2 release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation.

Jerome Clasadonte 1 Pierre Poulain 1 Naresh Hanchate 1 Gabriel Corfas 2 Sergio Ojeda 3, * Vincent Prevot 1, *
* Auteur correspondant
1 Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer
2 F.M. Kirby Neurobiology Center
3 Division of Neuroscience
Abstract : Astrocytes in the hypothalamus release prostaglandin E(2) (PGE(2)) in response to cell-cell signaling initiated by neurons and glial cells. Upon release, PGE(2) stimulates the secretion of gonadotropin-releasing hormone (GnRH), the neuropeptide that controls reproduction, from hypothalamic neuroendocrine neurons. Whether this effect on GnRH secretion is accompanied by changes in the firing behavior of these neurons is unknown. Using patch-clamp recording we demonstrate that PGE(2) exerts a dose-dependent postsynaptic excitatory effect on GnRH neurons. These effects are mimicked by an EP2 receptor agonist and attenuated by protein kinase A (PKA) inhibitors. The acute blockade of prostaglandin synthesis by indomethacin (INDO) or the selective inhibition of astrocyte metabolism by fluoroacetate (FA) suppresses the spontaneous firing activity of GnRH neurons in brain slices. Similarly, GnRH neuronal activity is reduced in mice with impaired astrocytic PGE(2) release due to defective erbB signaling in astrocytes. These results indicate that astrocyte-to-neuron communication in the hypothalamus is essential for the activity of GnRH neurons and suggest that PGE(2) acts as a gliotransmitter within the GnRH neurosecretory system.
Keywords : LHRH glia-to-neuron signaling gliotransmission cyclooxygenase hypothalamus
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Article dans une revue
Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2011, 108 (38), pp.16104-9. 〈10.1073/pnas.1107533108〉
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Jerome Clasadonte, Pierre Poulain, Naresh Hanchate, Gabriel Corfas, Sergio Ojeda, et al.. Prostaglandin E2 release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation.. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2011, 108 (38), pp.16104-9. 〈10.1073/pnas.1107533108〉. 〈inserm-00626467〉

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