Central Injection of Substance P Antagonizes the RF AmideRelated Peptide3 Impacts on Hypothalamic KISS1 and GnRH Gene Expressions in Male Wistar Rats

Introduction: Gonadotropininhibitory hormone (GnIH) and its mammalian orthologue RF amiderelated peptide (RFRP) are known to inhibit the secretion of gonadotropins. In addition, substance P (SP), a member of tachykinin’s family, can increase the firing rate of kisspeptin/ neurokinin B/dynorphin (KNDy) neurons and provoke the secretion of gonadotropins. In this experimental study, we investigated the effects of coadministration of RFRP3 and SP on the expression of KISS1 and GnRH genes, as gonadotropin regulator genes, in male rats. Methods: Fortytwo mature Wistar rats were randomly allocated into 7 groups (n=6 in each group). Animals in each group intracerebroventricularly received either saline+DMSO, SP (1nmol), RFRP3 (5 nmol), SP (1nmol) + RFRP3 (5 nmol), SP (1 nmol) + RF9 (RFRP3 receptor antagonist, 10 nmol), SP (1 nmol) + P234 (kisspeptin receptor antagonist, 1 nmol) + RFRP3 (5 nmol), or SP (1 nmol) + CP96,345 (SP receptor antagonist, 5 nmol) + RFRP3 (5 nmol). Two hours after injections, hypothalamic samples were collected to evaluate the expression of target genes by realtime PCR. Results: Injections in SP and SP + RF9 groups increased the expression of both GnRH and KISS1 genes (P lt;0.05). Injections in RFRP3 and SP + RFRP3 + CP96,345 groups significantly decreased the expression of GnRH and KISS1 genes (P lt;0.05). However, injections of SP + RFRP3 and SP + RFRP3 + P234 did not significantly change the expression of GnRH and KISS1 genes. Conclusion: The results of our study indicated that SP antagonized the effects of RFRP3 in the expression of hypothalamic KISS1 and GnRH genes.