RFRP neurons are critical gatekeepers for the photoperiodic control of reproduction

Valérie Simonneaux,Caroline Ancel

doi:10.3389/fendo.2012.00168

Abstract

Seasonally breeding mammals rely on the photoperiodic signal to restrict their fertility to a certain time of the year. The photoperiodic information is translated in the brain via the pineal hormone melatonin, and it is now well-established that it is the variation in the duration of the nocturnal peak of melatonin which synchronizes reproduction with the seasons. The Syrian hamster is a long day breeder, and sexual activity is therefore promoted by exposure to a long day photoperiod and inhibited by exposure to a short day photoperiod. Interestingly, in this species electrolytic lesion of the mediobasal hypothalamus abolishes the short day-induced gonadal regression. We have shown that the expression of a recently discovered neuronal population, namely RFamide-related peptide (rfrp) neurons, present in the mediobasal hypothalamus, is strongly down-regulated by melatonin in short day conditions, but not altered by circulating levels of sex steroids. The role of rfrp and its product RFRP-3 in the regulation of reproductive activity has been extensively studied in mammals, and our recent findings indicate that this peptide is a potent stimulator of the reproductive axis in the Syrian hamster. It induces a marked increase in GnRH neuron activity and gonadotropin secretion, and it is able to rescue reproductive activity in short day sexually inactive hamsters. Little is known about the localization of the RFRP-3 receptor, GPR147, in the rodent brain. Accumulating evidence suggests that RFRP-3 could be acting via two intermediates, the GnRH neurons in the preoptic area and the Kiss1 neurons in the arcuate nucleus, but future studies should aim at describing the localization of Gpr147 in the Syrian hamster brain. Altogether our data indicate that the rfrp neuronal population within the mediobasal hypothalamus might be a serious candidate in mediating the photoperiodic effects of melatonin on the regulation of the reproductive axis.

Highlights

Breeding mammals rely on the photoperiodic signal to restrict their fertility to a certain time of the year.The photoperiodic information is translated in the brain via the pineal hormone melatonin, and it is well-established that it is the variation in the duration of the nocturnal peak of melatonin which synchronizes reproduction with the seasons
In the Syrian hamster, we demonstrated that the short day (SD) downregulation of rfrp expression is not due to the lower levels of RFRP-3 NEURONS LOCATED IN THE MEDIOBASAL HYPOTHALAMUS ARE STRONGLY REGULATED BY MELATONIN In the Syrian hamster, the dorsal part of the mediobasal hypothalamus appears as a key structure for the photoperiodic regulation of reproductive activity since it contains melatonin binding sites and its ablation by electrolytic lesion prevents the inhibitory effect of melatonin on reproductive activity (Maywood et al, 1996)
We demonstrated that central injection of RFRP-3 to Syrian hamsters induces c-Fos expression in 30% of the GnRH neurons (Figure 2A) suggesting that the effects observed on the reproductive axis are mediated via these neurons (Ancel et al, 2012)

Summary

Introduction

Breeding mammals rely on the photoperiodic signal to restrict their fertility to a certain time of the year.The photoperiodic information is translated in the brain via the pineal hormone melatonin, and it is well-established that it is the variation in the duration of the nocturnal peak of melatonin which synchronizes reproduction with the seasons. In the Syrian hamster, we found that at least 3 weeks of daily melatonin administration is required to induce a significant reduction in the level of rfrp mRNA (Revel et al, 2008) whereas the pineal hormone is much faster to control the expression of other photoperiodically regulated genes like tsh in the pars tuberalis or deiodinase 2 in the tanycytes (Revel et al, 2006a; Yasuo et al, 2007; Dardente, 2012).

Results

Conclusion