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

Abstract

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.

Differential activation of neuropeptide FF receptors by gonadotropin-inhibitory hormone peptides in the European sea bass

“…Our recent studies showed that sea bass GnIHR signals are transduced through the PKA and PKC pathways, and GnIH2 antagonized Kiss2/Kiss2R-stimulated PKA signaling via its cognate receptor GnIHR (Wang et al, 2022b). However, neither GnIH1 nor GnIH2 reduced Kiss1/Kiss1R-, Kiss1/Kiss2R-, or Kiss2/ Kiss1R-induced PKA signaling (Wang et al, 2022b). It is of note that both NPFF and NPAF could activate sea bass GnIHR coupling to G ai protein (Wang et al, 2022b), and two NPFFR2 genes (npffr2-1 and npffr2-2) have been predicted by automated computational analysis derived from genomic sequence whole genome shotgun sequencing project (GenBank Accession No.…”

“…We previously identified the European sea bass (Dicentrarchus labrax) gnih gene, whose precursor polypeptide encompassed two RFamide peptides, GnIH1 and GnIH2, that inhibited the reproductive axis of this species (Paullada-Salmeron et al, 2016a;Paullada-Salmeron et al, 2016b;Paullada-Salmeron et al, 2016c). Our recent studies showed that sea bass GnIHR signals are transduced through the PKA and PKC pathways, and GnIH2 antagonized Kiss2/Kiss2R-stimulated PKA signaling via its cognate receptor GnIHR (Wang et al, 2022b). However, neither GnIH1 nor GnIH2 reduced Kiss1/Kiss1R-, Kiss1/Kiss2R-, or Kiss2/ Kiss1R-induced PKA signaling (Wang et al, 2022b).…”

“…However, neither GnIH1 nor GnIH2 reduced Kiss1/Kiss1R-, Kiss1/Kiss2R-, or Kiss2/ Kiss1R-induced PKA signaling (Wang et al, 2022b). It is of note that both NPFF and NPAF could activate sea bass GnIHR coupling to G ai protein (Wang et al, 2022b), and two NPFFR2 genes (npffr2-1 and npffr2-2) have been predicted by automated computational analysis derived from genomic sequence whole genome shotgun sequencing project (GenBank Accession No. XM_051412533 and XM_051421705).…”

Food deprivation differentially modulates gene expression of LPXRFa and kisspeptin systems in the brain-pituitary axis of half-smooth tongue sole (Cynoglossus semilaevis)

“…Three different GPR147 types are found in some Cypriniform species, but only one exists in other vertebrates investigated so far (4). The molecular mechanisms of GnIH actions have been investigated in mammals (9)(10)(11)(12), chicken (13), Nile tilapia (14), orange-spotted grouper (15), zebrafish (16), half-smooth tongue sole (17), chub mackerel (18), and European sea bass (19). It is of note that activation of GnIH receptor can interfere with signaling pathways induced by other neuroendocrine factors (9-13, 16, 19-21).…”

Gonadotropin inhibitory-hormone modulates neurosteroids-synthesizing enzymes expression and aggressive behavior in male sea bass, Dicentrarchus labrax

“…The European sea bass (Dicentrarchus labrax) is one of the most important species for European aquaculture and has been commonly used in our laboratory as model species for neuroanatomical, neuroendocrinological, physiological, cellular, molecular and behavioral studies (Cerda-Reverter et al, 2001a;Cerda ́-Reverter et al, 2001b;Gonzaĺez-Martıńez et al, 2001;Gonzaĺez-Martıńez et al, 2002;Cerda-Reverter et al, 2008;Servili et al, 2009;Servili et al, 2010;Sańchez-Vaźquez and Muñoz-Cueto, 2014;Paullada-Salmeroń et al, 2016a;Paullada-Salmeroń et al, 2016b;Paullada-Salmerón et al, 2016c;Cowan et al, 2017;Paullada-Salmeroń et al, 2017;Paullada-Salmeroń et al, 2019;Wang et al, 2022;Paullada-Salmeroń et al, 2023). Recently, we identified a sea bass gnih gene encoding a precursor with two different RFamide peptides, named as sbGnih-1 and sbGnih-2, and elucidated the immunohistochemical localization of Gnih neurons and their projections in the brain and pituitary by using specific antibodies against both peptides (Paullada-Salmeroń et al, 2016a).…”