Sex differences in the photoperiodic regulation of RF‐Amide related peptide (RFRP) and its receptor GPR147 in the syrian hamster

Abstract

RF-(Arg-Phe) related peptides (RFRP-1 and -3) are considered to play a role in the seasonal regulation of reproduction; however, the effect of the peptides depends on species and gender. This study aimed at comparing the RFRP system in male and female Syrian hamsters over long and short photoperiods to investigate the neuroanatomical basis of these differential effects. The neuroanatomical distribution of RFRP neurons and fibers, revealed using an antiserum recognizing RFRP-1 and -3, as well as GPR147 mRNA, are similar in male and female Syrian hamsters. RFRP neurons are mainly found in the medial hypothalamus, whereas RFRP projections and GPR147 mRNA are observed in the preoptic area, anteroventral-periventricular nucleus, suprachiasmatic nucleus, paraventricular nucleus, bed nucleus of the stria terminalis, ventromedial hypothalamus, habenular nucleus, and arcuate nucleus. The number of RFRP neurons is higher in females than in males, and in both sexes, the number of RFRP neurons is reduced in short photoperiods. GPR147 mRNA levels are higher in females than in males and are downregulated in short photoperiods, particularly in females. Interestingly, the number of RFRP-positive fibers in the anteroventral-periventricular nucleus is higher only in females adjusted to a short photoperiod. Our results suggest that the RFRP system, which is strongly regulated by photoperiod in both male and female Syrian hamsters, is particularly important in females, with a distinct role in the anteroventral-periventricular nucleus, possibly in the regulation of the preovulatory luteinizing hormone surge via kisspeptin neurons.

Kisspeptin and RFRP-3 differentially regulate food intake and metabolic neuropeptides in the female desert jerboa

“…Our finding of an orexigenic role of RFRP-3 in the jerboa is in agreement with previous results obtained in rats, mice, sheep and non-human primates21222324, but our data are the first to demonstrate that this metabolic effect might involve an increase in Npy and decrease in Pomc gene regulation. This finding is supported by earlier reports of the presence of the RFRP receptor and RFRP fiber terminals in the ARC of rodents84249 with some studies showing that RFRP terminals are in close apposition to NPY3050 and POMC30 neurons. However, studies investigating the effect of RFRP-3/GnIH on POMC and NPY neuronal activity reported paradoxical results since the peptide increased FOS protein in both NPY and POMC neurons in the sheep23, inhibited the firing rate of both POMC and NPY neurons in mice50 and increased Npy but not Pomc gene expression in the rat23 suggesting species-dependent hypothalamic targets of RFRP-3.…”

“…In the female jerboa, our study demonstrates that RFRP-3 induces activation of NPY and inhibition of POMC neurons resulting in a robust orexigenic effect. Even though Rfrp expression is inhibited by short days in seasonal species, including the jerboa14161931, and RFRP receptor expression is reduced in the ARC of short-day adapted hamsters42, we observed no difference in the effect of RFRP-3 on food intake in spring compared to autumn.…”

“…In order to further investigate the hypothalamic sites underlying the anorexigenic effect of Kp10 in fasted jerboas, we measured the expression level of genes coding for peptides well known to regulate food intake, NPY and POMC, as well as RFRP-3 because this later peptide displays marked sex-42 and season-1618193143 dependent variations in seasonal mammals, including the jerboa. In fasted females, central Kp increased Pomc mRNA, with a stronger effect in spring as compared to autumn, which is in agreement with the observed anorexigenic effect of the Kp10 injection.…”

Dynamic expressions of hypothalamic genes regulate seasonal breeding in a natural rodent population

“…Previous studies claimed that Rfrp‐3 expression is inhibited by SP conditions and melatonin in hamsters (Henningsen, Poirel, et al, ; Rasri‐Klosen et al, ; Revel et al, ; Ubuka et al, ). Similarly, we also found a strong correlation between Rfrp‐3 and day length: a significant increase in Rfrp‐3 expression with increasing day length (from April to August) and a decline in Rfrp‐3 expression with the decreasing phase of day length (from August in October).…”

Gonadotrophin‐inhibitory hormone and its mammalian orthologue RFamide‐related peptide‐3: Discovery and functional implications for reproduction and stress

“…In mammals, this neuropeptide precursor cDNA encodes three peptides (also known as RFamide‐related peptides [RFRPs]), RFRP‐1, ‐2 and ‐3, in bovine and human (RFRP‐1 and ‐3 are LPXRFamide peptides, whereas RFRP‐2 is not). RFRP‐3 is now considered to be the mammalian orthologue of avian GnIH, although effects of RFRP‐1 on central and peripheral reproductive functioning have been reported, requiring further investigation to clarify the specific role of neuropeptide …”