Kisspeptins and RFRP-3 Act in Concert to Synchronize Rodent Reproduction with Seasons

Valérie Simonneaux,Caroline Ancel,François Gauer,Vincent Joseph Poirel

doi:10.3389/fnins.2013.00022

Abstract

Seasonal mammals use the photoperiodic variation in the nocturnal production of the pineal hormone melatonin to synchronize their reproductive activity with seasons. In rodents, the (SD) short day profile of melatonin secretion has long been proven to inhibit reproductive activity. Lately, we demonstrated that melatonin regulates the expression of the hypothalamic peptides kisspeptins (Kp) and RFamide-related peptide-3 (RFRP-3), recently discovered as potent regulators of gonadotropin-releasing hormone (GnRH) neuron activity. In the male Syrian hamster, Kp expression in the arcuate nucleus is down-regulated by melatonin independently of the inhibitory feedback of testosterone. A central or peripheral administration of Kp induces an increase in pituitary gonadotropins and gonadal hormone secretion, but most importantly a chronic infusion of the peptide reactivates the photo-inhibited reproductive axis of Syrian hamsters kept in SD conditions. RFRP-3 expression in the dorsomedial hypothalamus is also strongly inhibited by melatonin in a SD photoperiod. Although RFRP-3 is usually considered as an inhibitory component of the gonadotropic axis, a central acute administration of RFRP-3 in the male Syrian hamster induces a marked increase in gonadotropin secretion and testosterone production. Furthermore, a chronic central infusion of RFRP-3 in SD-adapted hamsters reactivates the reproductive axis, in the same manner as Kp. Both Kp and RFRP-3 neurons project onto GnRH neurons and both neuropeptides regulate GnRH neuron activity. In addition, central RFRP-3 infusion was associated with a significant increase in arcuate Kp expression. However, the actual sites of action of both peptides in the Syrian hamster brain are still unknown. Altogether our findings indicate that Kp and RFRP neurons are pivotal relays for the seasonal regulation of reproduction, and also suggest that RFRP neurons might be the primary target of the melatoninergic message.

Highlights

Seasonal mammals use the photoperiodic variation in the nocturnal production of the pineal hormone melatonin to synchronize their reproductive activity with seasons
We reported that Kiss1 mRNA and Kp-ir in the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV) are significantly down-regulated when male Syrian hamsters are kept for 8–10 weeks in SD, in parallel to the expected important reduction in testis size and circulating levels of testosterone, as compared to long day (LD) conditions (Revel et al, 2006)
In an attempt to evaluate whether the photoperiodic variation in RFRP expression is critical for the seasonal timing of reproductive activity, we tested the effect of chronic RFamide-related peptide-3 (RFRP-3) administration in SD-adapted male Syrian hamsters

Summary

Introduction

Seasonal mammals use the photoperiodic variation in the nocturnal production of the pineal hormone melatonin to synchronize their reproductive activity with seasons. Using the male Syrian hamster as a model for the study of seasonal reproduction, we tested the hypothesis that photoperiod/melatonin could regulate this function via an action on Kp neurons (Revel et al, 2006, 2007; Ansel et al, 2010, 2011). We reported that Kiss1 mRNA and Kp-ir in the ARC and AVPV are significantly down-regulated when male Syrian hamsters are kept for 8–10 weeks in SD, in parallel to the expected important reduction in testis size and circulating levels of testosterone, as compared to LD conditions (Revel et al, 2006).

Results

Conclusion