Hypophysiotropic role of RFamide-related peptide-3 in the inhibition of LH secretion in female rats

Gonadotropin-inhibitory homone (GnIH), a newly discovered hypothalamic kFamide peptide, inhibits reproductive activity by decreasing gonadotropin synthesis and release in birds. The gene of the mammalian R'Famide-related peptides (R-FRP) is orthologous to the GnIH gene. This 1 Rfrp gene gives rise to the two biologically active peptides R-FRP-l (NPSF) and R-FRP-3 (NPVF),and i.c.v. injections of RFRP-3 suppress LH secretion in several mammalian species. In this study, we show whether RFRP-3 affects LH secretion at the pituitarylevel and/or via the release of GnRH at the hypothalamus in mammals. To investigate the suppressive effects of R-FRP-3 oil the mean level of LH secretion and the frequency of pulsatile LH secretion fit vivo, ovariectomized (OVX) mature rats were administered RFRP-3 using either i.c.v. or i.v. injections. Furthermore, the effect of RFRP-3 on LH secretion was also investigated using cultured female rat pituitary cells. With i.v. adiministrations, RFRP-3 significantly reduced plasma LH concentrations when compared with the physiological saline group. However, after i.c.v. RFRP-3 injections, neither the mean level of LH concentrations nor the frequency of the pulsatile LH secretion was affected. When using cultured pituitary cells, in the absence of GnRH, the suppressive effect of RFRP-3 oil LH secretion was not clear, but when GnKH was present, RFRP-3 significantly suppressed LH secretion. These results suggest that RFRY-3 does not affect LH secretion via the release of GnRH, and that RFRP-3 directly acts upon the pituitary to suppress GnRH-stimulated LH secretion in female rats.