Inhibitory action of tongue sole LPXRFa, the piscine ortholog of gonadotropin-inhibitory hormone, on the signaling pathway induced by tongue sole kisspeptin in COS-7 cells transfected with their cognate receptors

Peptides. 2017 Sep:95:62-67. doi: 10.1016/j.peptides.2017.07.014. Epub 2017 Jul 25.

Abstract

Kisspeptin (Kiss) acts as a positive regulator of reproduction by acting on gonadotropes and gonadotropin-releasing hormone (GnRH) neurons. Despite its functional significance, the intricate web of intracellular signal transduction pathways in response to Kiss is still far from being fully understood in teleosts. Accordingly, we investigated the molecular mechanism of Kiss action and its possible interaction with LPXRFa signaling in this study. In vitro functional analysis revealed that synthetic tongue sole Kiss2 decapeptide increased the cAMP responsive element-dependent luciferase (CRE-luc) activity in COS-7 cells transfected with its cognate receptor, while this stimulatory effect was markedly reduced by two inhibitors of the adenylate cyclase (AC)/protein kinase A (PKA) pathway. Similarly, Kiss2 also significantly stimulated serum responsive element-dependent luciferase (SRE-luc) activity, whereas this stimulatory effect was evidently attenuated by two inhibitors of the phospholipase C (PLC)/protein kinase C (PKC) pathway. In addition, LPXRFa-2 suppressed Kiss2-elicited CRE-luc activity in a dose-dependent manner. Taken together, Kiss2 utilizes both AC/PKA and PLC/PKC pathways to exert its functions via its cognate receptor and LPXRFa may antagonize the action of Kiss2 by inhibiting kisspeptin signaling. As far as we know, this study is the first to characterize the half-smooth tongue sole kisspeptin and LPXRFa signaling pathway in COS-7 cells transfected with their cognate receptors and provides novel information on the interaction between LPXRFa system and kisspeptin system in teleosts.

Keywords: Cynoglossus semilaevis; GnIH; Kisspeptin; LPXRFa; Signaling pathway.

MeSH terms

  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / metabolism
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Fishes / genetics
  • Gene Expression Regulation / genetics
  • Gonadotrophs / chemistry
  • Gonadotrophs / metabolism
  • Gonadotropin-Releasing Hormone / chemistry
  • Gonadotropin-Releasing Hormone / genetics
  • Gonadotropins / genetics*
  • Gonadotropins / metabolism
  • Kisspeptins / genetics*
  • Kisspeptins / metabolism
  • Neurons / metabolism
  • Neurons / physiology*
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Reproduction / genetics*
  • Reproduction / physiology
  • Signal Transduction / genetics
  • Transfection
  • Type C Phospholipases / genetics
  • Type C Phospholipases / metabolism

Substances

  • Gonadotropins
  • Kisspeptins
  • Gonadotropin-Releasing Hormone
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Type C Phospholipases
  • Adenylyl Cyclases