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GnRH episodic secretion is altered by pharmacological blockade of Gap junctions: Possible involvement of glial cells

Abstract : Episodic release of GnRH is essential for reproductive function. In vitro studies have established that this episodic release is an endogenous property of GnRH neurons and that GnRH secretory pulses are associated with synchronization of GnRH neuron activity. The cellular mechanisms by which GnRH neurons synchronize remain largely unknown. There is no clear evidence of physical coupling of GnRH neurons through gap junctions to explain episodic synchronization. However, coupling of glial cells through gap junctions has been shown to regulate neuron activity in their microenvironment. The present study investigated whether glial cell communication through gap junctions plays a role in GnRH neuron activity and secretion in the mouse. Our findings show that Glial Fibrillary Acidic Protein-expressing glial cells located in the median eminence in close vicinity to GnRH fibers expressed Gja1 encoding connexin-43. To study the impact of glial-gap junction coupling on GnRH neuron activity, an in vitro model of primary cultures from mouse embryo nasal placodes was used. In this model, GnRH neurons possess a glial microenvironment and were able to release GnRH in an episodic manner. Our findings show that in vitro glial cells forming the microenvironment of GnRH neurons expressed connexin-43 and displayed functional gap junctions. Pharmacological blockade of the gap junctions with 50 mu M 18-alpha-glycyrrhetinic acid decreased GnRH secretion by reducing pulse frequency and amplitude, suppressed neuronal synchronization and drastically reduced spontaneous electrical activity, all these effects were reversed upon 18-alpha-glycyrrhetinic acid washout.
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Submitted on : Thursday, March 4, 2021 - 2:42:34 PM
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Caroline Pinet-Charvet, Sarah Geller, Elodie Desroziers, Monique Ottogalli, Didier Lomet, et al.. GnRH episodic secretion is altered by pharmacological blockade of Gap junctions: Possible involvement of glial cells. Endocrinology, Endocrine Society, 2016, 157 (1), pp.304-322. ⟨10.1210/en.2015-1437⟩. ⟨hal-03159322⟩



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