Central Injection of Substance P Antagonizes the RF Amide-Related Peptide-3 Impacts on Hypothalamic KISS-1 and GnRH Gene Expressions in Male Wistar Rats

Gonadotropin-inhibitory hormone and its mammalian orthologues (RFRP: RF amid related peptide) are known to inhibit the secretion of gonadotropins. In addition, substance P (SP) a member of tachykinin’s family is demonstrated that can increase the firing rate of kisspeptin/neurokinin B/dynorphin (KNDy) neurons and provokes the of secretion gonadotropins. In this experimental study we investigated the effects of co-administration of RFRP-3 and SP on the expression of KISS-1 and GnRH genes in male rats. forty-two mature Wistar rats were randomly allocated in 7 groups (n=6 in each group). Animals in each group intracerebroventricularly received either saline+DMSO, 1nmol SP, 5 nmol RFRP-3, 1nmol SP plus 5 nmol RFRP-3, 1 nmol SP plus10 nmol RF9 (RFRP-3 receptor antagonist), 1 nmol SP plus 1 nmol P234 (kisspeptin receptor antagonist) plus 5 nmol RFRP-3 or 1 nmol SP plus 5 nmol CP-96,345 (SP receptor antagonist) plus 5 nmol RFRP-3 in final volume of 3 µl. After two hours following injections hypothalamic samples were collected for evaluating the expression of target genes by real-time PCR technique. Injections in SP and SP plus RF9 groups increase the expression of the both GnRH and KISS-1 genes (P<0.05). Injections in RFRP-3 group and SP plus RFRP-3 plus SP antagonist group significantly decrease the expression of both GnRH and KISS-1 genes (P<0.05). Injections of SP plus RFRP-3 group and SP plus RFRP-3 plus P234 group did not significantly change the expression of GnRH and KISS-1 genes. The results indicate that SP antagonizes the effects of RFRP-3 on the expression of Hypothalamic KISS-1 and GnRH genes.