It is well-established that gonadotropin-inhibitory hormone (GnIH) and its mammalian orthologues (RFRP: RF-amid related peptides) can decrease gonadotrophin secretion. Moreover, substance P (SP) is another modulator of the secretion of gonadotropins in a species-dependent manner. This study aimed to find out the impacts of concomitant infusion of RFRP-3 and SP on luteinizing hormone (LH) concentration. Methods: Forty-two rats were arbitrarily assigned to 7 groups (n=6 per group). Animals in the

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... experimental groups were intracerebroventricularly injected with saline +DMSO, SP, RFRP-3, SP + RFRP-3, SP + RF9 (RFRP-3 receptor antagonist), SP + P234 (kisspeptin receptor antagonist) + RFRP-3 and SP + CP-96,345 (SP receptor antagonist) + RFRP-3 in a final volume of 3 µL. Blood samples were collected at 30-minute intervals after injections, and serum was used to measure the LH concentration by radioimmunoassay. Results: According to the results, injections led to the elevation of LH serum concentration at 30-minute post injection (P<0.05) in the SP and SP+RF9 groups. Moreover, administration of either RFRP-3 or SP + RFRP-3 + SP receptor antagonist strikingly decreased the LH mean serum concentration at 30-minute after injections (P<0.05). On the contrary, the infusion of SP+RFRP-3 and SP+RFRP-3+P234 caused no dramatic changes in the LH mean serum concentration. Conclusion: In general, the data showed that SP suppresses the impacts of RFRP-3 on the serum levels of LH.