The roles of RFRP in the central control of reproduction: photoperiodic and sex-specific differences. Rôle du RFRP dans le contrôle central de la reproduction saisonnière en fonction du sexe et de la photopériode.
Résumé
Hypothalamic RF (Arg-Phe) amide-related peptides (RFRP-1 and -3) are considered to play a role in the (seasonal) regulation of reproduction, however the effects of the peptides depend on sex and species. Here, we aimed at providing a better neuroanatomical description of the RFRP system in the Syrian hamster, with a specific focus on potential sex- and photoperiod-dependent differences. Keeping in mind possible sex-dependent differences in the effects of RFRP-3, we moreover aimed at investigating the role of RFRP in daily and seasonal control of reproductive activity in female Syrian hamsters, by studying the RFRP system along the oestrus cycle, as well as the effects of acute and chronic administration of RFRP-3 at different reproductive stages.
The present work has provided a much better characterization of the RFRP system and its role in regulating reproductive activity in a seasonal model, the Syrian hamster. We show that besides being strongly regulated by annual changes in day/night cycles, the RFRP system is differently regulated in males and females, and is more strongly expressed in females than in males. In line with these observations we here unveil that RFRP has multiple and distinct roles in regulating female reproductive activity. We found that the activity of RFRP neurons is specifically decreased in the afternoon of proestrus and diestrus, which in proestrus coincides with the dramatic increase in AVPV/MPN kisspeptin activation and LH release from the pituitary, whereas intracerebroventricular injections of RFRP-3, just prior to or in the beginning of the LH-surge, causes a significant inhibition of LH released at the surge. Altogether, these findings point towards a specific daily regulation in RFRP activity, which likely serves to down-regulate the inhibitory RFRP signal, thus allowing a full LH-surge to take place. Chronic infusion of RFRP-3 in sexually inactive females, with an endogenous low level of RFRP expression, reactivates the reproductive axis and clearly describe an essential role of RFRP in the central regulation of seasonal reproduction, and point towards RFRP neurons being a key intermediate through which the melatonin-dependent seasonal signal reaches and thereby regulates the reproductive axis.
Taken together, these findings demonstrate that RFRP acts as a key component in the seasonal control of reproduction while at the same time being an important regulator of cyclic events controlling the pre-ovulatory LH-surge in females, which can help to explain both sex- and species-dependent differences in the RFRP system and its effects on the reproductive axis.
Présentée le 18 mai 2016
Laboratoire où a été préparée la thèse : Neurobiologie des Rythmes, Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212 Université de Strasbourg
Nom du directeur de thèse : François Gauer
