The GnRH analogues affect novel neuropeptide SMIM20/phoenixin and GPR173 receptor expressions in the female rat hypothalamic-pituitary-gonadal (HPG) axis

The recently discovered peptide phoenixin (PNX) and its receptor GPR173 are novel factors that exhibit a large spectrum of regulatory activity, especially when considered as a central modulator of GnRH-related hormonal control of reproductive processes. It has been already proven that GnRH agonists and antagonists can modulate peptidergic signaling in the HPG axis. Despite these findings, there is so far no information regarding the influence of treatment with GnRH analogues on SMIM20/phoenixin signaling in the hypothalamic-pituitary-gonadal axis. In the current study we measured SMIM20/phoenixin and GPR173 mRNA levels in the hypothalamus, pituitary and ovaries of female rats in the diestrus phase following treatment with GnRH-R agonist (buserelin) and antagonist (cetrorelix) using quantitative Real-Time PCR. The serum PNX concentrations were also estimated with ELISA technique. Results: The hypothalamic, hypophyseal and especially ovarian levels of SMIM20 mRNA were increased after both buserelin and cetrorelix administration. The GPR173 expressions were in turn decreased in the hypothalamus and pituitary. Treatment with the GnRH analogues led to the modulation of SMIM20/phoenixin and GPR173 mRNA expression in the female rat hypothalamic-pituitary-gonadal axis. By identifying buserelin and cetrorelix as novel modulators of phoenixin signalling in the animal HPG axis, these results cast new light on the GnRH analogues mode of action and contribute to a better understanding of the mechanisms responsible for the hormonal control of reproduction.