Rfamide-related peptide-3 suppresses the substance P-induced promotion of the reproductive performance in female rats mo

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RESEARCH ARTICLE

Rfamide‑related peptide‑3 suppresses the substance P‑induced promotion of the reproductive performance in female rats modulating hypothalamic Kisspeptin expression Parastoo Rahdar1 · Homayoun Khazali1  Received: 6 April 2020 / Accepted: 22 June 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract RFamide-related peptide-3 (RFRP-3) has been postulated as the suppressor of the reproductive axis at hypothalamic, pituitary and gonadal levels. Considering the hypothalamic level, RFRP-3 can suppress the activity of gonadotropin-releasing hormone (GnRH) neurons and their upstream neuronal stimulator, namely; the kisspeptin neurons. The effects of the RFRP-3 on the other regulators of GnRH neurons, however, are not completely investigated. Furthermore, substance P (SP) has been known as one of the coordinators of GnRH/ luteinizing hormone (LH) and the kisspeptin/G protein-coupled receptor 54 (GPR54) systems. The present study was aimed at investigating the impacts of RFRP-3 on the effects of SP on the reproductive performance in ovariectomized female rats. After intracerebroventricular (ICV) cannulation, the rats were subjected to the ICV injection of either SP or RFRP-3 and simultaneous injection of them and their selective antagonists. Blood and hypothalamic samplings and also sexual behavioral test were carried out on two main groups of rats. The analyses of the results of LH radioimmunoassay, gene expression assay for hypothalamic Gnrh1, Kisspeptin and Gpr54 accompanied by sexual behavioral examination revealed that the SP administration promotes reproductive behavior and GnRH/LH system and upregulates Kisspeptin expression. The RFRP-3 administration suppressed reproductive behavior, GnRH / LH system and Kisspeptin expression; however, the simultaneous injection of SP and RFRP-3 was devoid of significant alterations in the assessed parameters. The results showed that RFRP-3 can modulates the impacts of SP on the reproductive performance in ovariectomized female rats in part through adjusting Kisspeptin expression. Keywords  Gonadotropin-inhibitory hormone · Tachykinins · Gonadotropin-releasing hormone · Luteinizing hormone · Sexual behavior

Introduction The reproductive process is a complicated process with its behavioral and hormonal aspects being influenced by many internal and environmental factors. Input signals that directly or indirectly affect the reproductive axis are integrated at the hypothalamic level and are translated into gonadotropin releasing hormone (GnRH) pulses which are the last reproductive axis gatekeeper at the hypothalamic level Communicated by Sreedharan Sajikumar. * Homayoun Khazali [email protected] 1



Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

(Bédécarrats 2015). The function of many regulators and neurotransmitters that affect the secretion of GnRH is mediated by interneurons such as kisspeptin (KP) neurons that are deemed to be the upstream regulators o