Differential effects of central administration of relaxin-3 on food intake and hypothalamic neuropeptides in male and female rats

Relaxin-3 (RLN3) is an orexigenic neuropeptide that produces sex-specific effects on food intake by stronger stimulation of feeding in female compared with male rats. This study determined which hypothalamic nuclei and associated neuropeptides may be involved in the sex-specific orexigenic effects of RLN3. Relaxin-3 (800pmol) or vehicle was injected into the lateral ventricle of female and male rats. Food and water intake were measured after the first injection, and rats were euthanized after the second injection to determine the mRNA expression of the hypothalamic neuropeptides. Food but not water intake showed sex-specific effects of RLN3. Stimulation of food intake by RLN3 was significantly higher in female than in male rats. No effect of RLN3 injection was found on c-fosmRNA expression in the arcuate, dorsomedial and ventromedial hypothalamic nuclei. Increased c-fosmRNA expression was observed in the paraventricular hypothalamic nucleus (PVN) in both sexes and in the lateral hypothalamic area (LHA) in female rats. Relaxin-3 injections led to a sex-nonspecific increase in the expression of oxytocin mRNA in the magnocellular PVN. Conversely, RLN3-induced expression of anorexigenic neuropeptide arginine vasopressin (AVP) was significantly higher in the parvocellular PVN in male compared with female rats. Finally, RLN3 administration significantly increased the expression of orexin (ORX) mRNA in the LHA in female but not in male rats. Stronger expression of anorexigenic AVP in the PVN in male rats and increased expression of ORX in the LHA in female rats may contribute to stronger orexigenic effects of RLN3 in female rats compared with male rats.