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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Neurosci. | doi: 10.3389/fncel.2019.00371

Secretin regulates excitatory GABAergic neurotransmission to GnRH neurons via retrograde NO signaling pathway in mice

  • 1Institute of Experimental Medicine (MTA), Hungary
  • 2Roska Tamás Doctoral School of Sciences and Technology, Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Hungary
  • 3Department of Neuroscience, Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Hungary
  • 4Laboratory of Reproductive Neurobiology, Institute of Experimental Medicine (MTA), Hungary

In mammals, reproduction is regulated by a wide range of metabolic hormones that maintain the proper energy balance. In addition to regulating feeding and energy expenditure, these metabolic messengers also modulate the functional performance of the hypothalamo-pituitary-gonadal (HPG) axis. Secretin, a member of the secretin-glucagon-vasoactive intestinal peptide hormone family, has been shown to alter reproduction centrally, although the underlying mechanisms have not been explored yet. In order to elucidate its central action in the neuroendocrine regulation of reproduction, in vitro electrophysiological slice experiments were carried out on GnRH-GFP neurons in male mice. Bath application of secretin (100 nM) significantly increased the frequency of the spontaneous postsynaptic currents (sPSCs) to 118.0 ± 2.64% compared to the control, and that of the GABAergic miniature postsynaptic currents (mPSCs) to 147.6 ± 19.19 %. Resting membrane potential became depolarized by 12.74 ± 4.539 mV after secretin treatment. Frequency of evoked action potentials also increased to 144.3 ± 10.8 %. The secretin-triggered elevation of the frequency of mPSCs was prevented by using either a secretin receptor antagonist (3 µM) or intracellularly applied G-protein-coupled receptor blocker (GDP-β-S; 2 mM) supporting the involvement of secretin receptor in the process. Regarding the actions downstream to secretin receptor, intracellular blockade of protein kinase A (PKA) with KT-5720 (2 µM) or intracellular inhibition of the neuronal nitric oxide synthase (nNOS) by NPLA (1 µM) abolished the stimulatory effect of secretin on mPSCs. These data suggest that secretin acts on GnRH neurons via secretin receptors whose activation triggers the cAMP/PKA/nNOS signaling pathway resulting in nitric oxide release and in the presynaptic terminals this retrograde NO machinery regulates the GABAergic input to GnRH neurons.

Keywords: GnRH neuron, Secretin, GABA, retrograde signaling, Nitric o×ide, Reproduction, Metabolism

Received: 22 May 2019; Accepted: 30 Jul 2019.

Copyright: © 2019 Csillag, Vastagh, Liposits and Farkas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Imre Farkas, Institute of Experimental Medicine (MTA), Laboratory of Reproductive Neurobiology, Budapest, Hungary,