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. 2019 Apr 10;10:183. doi: 10.3389/fendo.2019.00183

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Copyright © 2019 Angelopoulou, Quignon, Kriegsfeld and Simonneaux.

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.

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Working model illustrating the contribution of RFRP-3 neurons in the central control of the daily gating of the preovulatory LH surge in female rodents. Neurons of the suprachiasmatic nuclei (SCN) synthesizing vasopressin (AVP) and vasoactive interstinal peptide (VIP) exhibit daily variation controlled by an intrinsic circadian clock and the daily change in light input. The SCN VIP output time GnRH neurons activity either directly or via the RFRP3 neurons located in the dorsomedial hypothalamus (DMH) which further inhibit GnRH neurons at the light/dark transition. The SCN AVP output activates GnRH neurons through the stimulation of neurons located in the anteroventral periventricular nuclei (AVPV) and releasing the potent stimulatory peptide kisspeptin. Additionally kisspeptin neurons receive a positive estradiol (E2) feedback on the day of proestrus while the effect of E2 on RFRP3 neurons is still unclear. This coordinated pathway is proposed to trigger a preovulatory GnRH/LH surge at the light/dark transition of the proestrus stage [LH data adapted from (105)].