Rat RFamide-related peptide-3 stimulates GH secretion, inhibits LH secretion, and has variable effects on sex behavior in the adult male rat

A recently described avian neuropeptide, gonadotropin inhibitory hormone (GnIH), has been shown to have seasonal regulatory effects on the hypothalamic-pituitary-gonadotropin axis (HPG) in several avian species. In the bird, GnIH expression is increased during the photorefractory period and has inhibitory effects on the HPG. A recently described mammalian neuropeptide, RF-amide-related peptide-3 (RFRP-3), may be genetically related and functionally similar to this avian neuropeptide. The purposes of this study were to first see if rat RFRP-3 is expressed in the male rat brain and second to determine if ICV injections of RFRP-3 will have effects on feeding and sex behaviors, as well as hormone release from the anterior pituitary. Results confirm other studies in that immunoreactive cell bodies and fibers are observable in areas of the male rat brain known to control the HPG and feeding and sex behaviors. RFRP-3 fibers are also observed in close proximity to GnRH immunoreactive cell bodies. Behavioral tests indicate that high but not low ICV RFRP-3 (500 vs. 100 ng, respectively) significantly (p<0.05) suppressed all facets of male sex behavior while not having any observable effects on their ability to ambulate. Sex behavior was later exhibited when those same male rats received the ICV vehicle. While suppressing sex behavior, ICV RFRP-3 significantly (p<0.05) increased food intake compared to controls. ICV RFRP-3 also significantly reduced plasma levels of luteinizing hormone but increased growth hormone regardless of the time of day; however, at no time did RFRP-3 alter plasma levels of FSH, thyroid hormone, or cortisol. These results indicate that although RFRP-3 has similar effects on LH as observed with GnIH in avian species, in the rat RFRP-3 has additional roles in regulating feeding and growth.