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

Abstract

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.

Seasonal effects of GnIH on basal and GnRH-induced goldfish somatotrope functions

“…These results indicate that gGnIH can reduce GH release, at least in part, by direct actions on basal GH secretion and by inhibition of GnRHstimulated GH release at the level of the pituitary cells. These results differ from those observed for amphibians and male rats, where the GnIH homolog (fGRP and RFRP3 respectively) stimulates GH secretion in vivo (Koda et al 2002, Johnson et al 2007. Whether the inhibitory effects of i.p.…”

“…In frogs, a GnIH ortholog (termed frog growth hormone-releasing peptide (fGRP)) stimulates GH release in vitro and in vivo (Koda et al 2002, Ukena et al 2003. Similarly, the rat GnIH ortholog RFRP3 increases the levels of GH in plasma (Johnson et al 2007). In teleosts, gGnIH and the other two putative RFamide peptides stimulate the release of GH from cultured pituitary cells from male sockeye salmon (Amano et al 2006).…”

Recent advances in reproductive neuroendocrinology: a role for RFamide peptides in seasonal reproduction?

“…leptin; Castellano et al 2005Castellano et al , 2006bSmith et al 2006;Luque et al 2007). Recent evidence suggests that GnIH may interact with the ingestive system in chickens and rats, with injections of GnIH leading to a significant increase in feeding behaviour (Tachibana et al 2005;Johnson et al 2007). Thus, it is likely that seasonal breeders respond not only to photoperiodic cues, but also to supplementary cues that allow for adjustments of the kisspeptin and GnIH systems in response to real-time changes in energy availability.…”

“…Kisspeptin, the peptide encoded by the KiSS-1 gene, plays an important role in the development and upregulation of the reproductive system (de Roux et al 2003;Funes et al 2003;Seminara et al 2003), whereas GnIH has been reported to play an important role in regulating reproduction by downregulating release of pituitary gonadotropins via actions on the HPG axis ( Tsutsui et al 2000;Ciccone et al 2004;Osugi et al 2004;Bentley et al 2006b;Kriegsfeld et al 2006;Ubuka et al 2006;Johnson et al 2007). The distinct opposing roles played by these two peptides, along with associated changes in the predicted direction following photoperiodic manipulations (described below), suggest that these peptides may provide key modulatory input necessary for precise control of reproductive activity in seasonal breeders.…”

The roles of kisspeptin and gonadotropin inhibitory hormone in stress-induced reproductive disorders

“…1). The central administration of GnIH/ RFRP-3 decreased sexual behavior in male rats [90], and it reduced sexual motivation in female hamsters [71,91]. GnIH/RFRP-3 affects neuronal activity in some hypothalamic nuclei (the POA, medial amygdala, and the bed nucleus of the stria terminalis) that are related to female sexual behavior [91].…”