title: Inhibitory action of gonadotropin-inhibitory hormone on the signaling pathways induced by kisspeptin and vasoactive intestinal polypeptide in GnRH neuronal cell line, GT1-7.
abstract: Gonadotropin-inhibitory hormone (GnIH) acts as a negative regulator of reproduction by acting on gonadotropes and gonadotropin-releasing hormone (GnRH) neurons. Despite its functional significance, the molecular mechanism of GnIH action in the target cells has not been fully elucidated. To expand our previous study on GnIH actions in gonadotropes, we investigated the potential signal transduction pathway that conveys the inhibitory action of GnIH in GnRH neurons by using the GnRH neuronal cell line, GT1-7. We examined whether GnIH inhibits the action of kisspeptin and vasoactive intestinal polypeptide (VIP), positive regulators of GnRH neurons. Although GnIH significantly suppressed the stimulatory effect of kisspeptin on GnRH release in hypothalamic culture, GnIH had no inhibitory effect on kisspeptin stimulation of serum response element and nuclear factor of activated T-cell response element activities and ERK phosphorylation, indicating that GnIH may not directly inhibit kisspeptin signaling in GnRH neurons. On the contrary, GnIH effectively eliminated the stimulatory effect of VIP on p38 and ERK phosphorylation, c-Fos mRNA expression, and GnRH release. The use of pharmacological modulators strongly demonstrated the specific inhibitory action of GnIH on the adenylate cyclase/cAMP/protein kinase A pathway, suggesting a common inhibitory mechanism of GnIH action in GnRH neurons and gonadotropes.-Son, Y. L., Ubuka, T., Soga, T., Yamamoto, K., Bentley, G. E., Tsutsui, K. Inhibitory action of gonadotropin-inhibitory hormone on the signaling pathways induced by kisspeptin and vasoactive intestinal polypeptide in GnRH neuronal cell line, GT1-7.
authors.affiliation: Laboratory of Integrative Brain Sciences, Department of Biology, Center for Medical Life Science of Waseda University, Tokyo, Japan;
authors.forename: You Lee
authors.initials: YL
authors.lastname: Son
authors.affiliation: Laboratory of Integrative Brain Sciences, Department of Biology, Center for Medical Life Science of Waseda University, Tokyo, Japan; Brain Research Institute, School of Medicine and Health Sciences, Monash University, Sunway, Malaysia; and.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ubuka
authors.affiliation: Brain Research Institute, School of Medicine and Health Sciences, Monash University, Sunway, Malaysia; and.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Soga
authors.affiliation: Laboratory of Integrative Brain Sciences, Department of Biology, Center for Medical Life Science of Waseda University, Tokyo, Japan;
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Integrative Biology and Helen Wills Neuroscience Institute, University of California, Berkley, Berkeley, California, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Bentley
authors.affiliation: Laboratory of Integrative Brain Sciences, Department of Biology, Center for Medical Life Science of Waseda University, Tokyo, Japan; k-tsutsui@waseda.jp.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Tsutsui
mesh_terms: D000818:Animals; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D016762:Genes, fos; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology; D059648:Kisspeptins / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D000074502:Receptors, Kisspeptin-1; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C492248:Kiss1r protein, mouse; D059648:Kisspeptins; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D007987:Gonadotropin-Releasing Hormone; D014660:Vasoactive Intestinal Peptide; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: GPCR; GnIH receptor signaling; RFamide-related peptide