title: Gonadotropin releasing hormone (GnRH) enhances annexin A5 mRNA expression through mitogen activated protein kinase (MAPK) in LbetaT2 pituitary gonadotrope cells.
abstract: The mechanism by which GnRH stimulates annexin A5 expression was examined with LbetaT2 gonadotrope cells. Continuous stimulation with GnRH analog (GnRHa, Des-Gly10 [Pro9]-GnRH ethylamide) transiently elevated LHbeta mRNA expression while maintaining annexin A5 mRNA at high levels for 24 h. GnRH antagonist blocked the effect of GnRHa on annexin A5. While 12-O-tetradecanoyl-phorbol-13 acetate, a protein kinase C activator, increased the expression of annexin A5 mRNA, bisindolylmaleimide, an inhibitor of protein kinase C, suppressed GnRHa-stimulated expression of annexin A5 and LHbeta mRNA. GnRHa stimulation of LHbeta mRNA was inhibited to a greater extent than annexin A5 by a calcium chelator BAPTA/AM. Although a calcium ionophore ionomycin stimulated the expression of both genes, only LHbeta was down-regulated. The MAPK kinase inhibitor PD98059 inhibited GnRHa induction of annexin A5 but not LHbeta mRNA. EGF stimulated the expression of annexin A5 mRNA but caused only a transient effect on LHbeta mRNA expression. These results indicate that GnRH stimulation of signaling pathway for annexin A5 mRNA expression is distinct from that of LHbeta mRNA and dependent more on MAPK.
authors.affiliation: Laboratory of Veterinary Physiology, School of Veterinary Medicine, Kitasato University, Towada, Aomori, Japan.
authors.forename: Mitsumori
authors.initials: M
authors.lastname: Kawaminami
authors.forename: Natsuko
authors.initials: N
authors.lastname: Uematsu
authors.forename: Kaoru
authors.initials: K
authors.lastname: Funahashi
authors.forename: Ryo
authors.initials: R
authors.lastname: Kokubun
authors.forename: Shiro
authors.initials: S
authors.lastname: Kurusu
mesh_terms: D017304:Annexin A5 / Q000235:genetics* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D052681:Gonadotrophs / Q000187:drug effects* / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D017304:Annexin A5; D002614:Chelating Agents; D006727:Hormone Antagonists; D007476:Ionophores; D037101:Luteinizing Hormone, beta Subunit; D012333:RNA, Messenger; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D007987:Gonadotropin-Releasing Hormone; D004533:Egtazic Acid; D015759:Ionomycin; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; C062876:cetrorelix; D002118:Calcium