Does the activation of sea bass GnIH receptor modulate GnRH receptor signaling?

Previous studies have revealed the stimulatory and inhibitory actions of gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH) on the control of reproduction in European sea bass (Dicentrarchus labrax) and other vertebrates, respectively. However, information on the possible interactions between GnRH and GnIH on cell signaling is sparse in vertebrates. In the current study, we investigated if activation of sea bass GnIH receptor (GnIHR) can interfere with GnRH receptor II-1a (GnRHR-II-1a) involving the PKA pathway. Our results showed that GnIH and GnRH functioned via their cognate receptors, respectively. However, it appears that neither GnIH1 nor GnIH2 can block GnRH/GnRHR-II-1a-induced PKA signaling in sea bass. This is the first study to examine the potential interactions of GnIH with GnRH receptor signaling in teleosts. Further research seems necessary to shed light on unknown interactions in other signaling pathways and other GnIH/GnRH receptors involved in the physiological functions of these two relevant neuropeptides, not only in sea bass but also in other species.

Signaling pathways activated by sea bass gonadotropin-inhibitory hormone peptides in COS-7 cells transfected with their cognate receptor.

Results of previous studies provided evidence for the existence of a functional gonadotropin-inhibitory hormone (GnIH) system in the European sea bass, Dicentrarchus labrax, which exerted an inhibitory action on the brain-pituitary-gonadal axis of this species. Herein, we further elucidated the intracellular signaling pathways mediating in sea bass GnIH actions and the potential interactions with sea bass kisspeptin (Kiss) signaling. Although GnIH1 and GnIH2 had no effect on basal CRE-luc activity, they significantly decreased forskolin-elicited CRE-luc activity in COS-7 cells transfected with their cognate receptor GnIHR. Moreover, an evident increase in SRE-luc activity was noticed when COS-7 cells expressing GnIHR were challenged with both GnIH peptides, and this stimulatory action was significantly reduced by two inhibitors of the PKC pathway. Notably, GnIH2 antagonized Kiss2-evoked CRE-luc activity in COS-7 cells expressing GnIHR and Kiss2 receptor (Kiss2R). However, GnIH peptides did not alter NFAT-RE-luc activity and ERK phosphorylation levels. These data indicate that sea bass GnIHR signals can be transduced through the PKA and PKC pathways, and GnIH can interfere with kisspeptin actions by reducing its signaling. Our results provide additional evidence for the understanding of signaling pathways activated by GnIH peptides in teleosts, and represent a starting point for the study of interactions with multiple neuroendocrine factors on cell signaling.