title: Mechanisms for luteinizing hormone induction of growth hormone gene transcription in fish model: crosstalk of the cAMP/PKA pathway with MAPK-and PI3K-dependent cascades.
abstract: In our previous studies in grass carp pituitary cells, local production of luteinizing hormone (LH) was shown to induce growth hormone (GH) production and gene expression, which constitutes a major component of the "intrapituitary feedback loop" regulating GH secretion and synthesis via autocrine/paracrine interactions between gonadotrophs and somatotrophs in the carp pituitary. To further investigate the signaling mechanisms mediating LH action at the transcriptional level, promoter studies were performed in GH3 cells co-transfected with the expression vector for carp LH receptor and luciferase-expressing reporter constructs with grass carp GH promoter. In this cell model, treatment with human chorionic gonadotropin (hCG) was effective in increasing GH promoter activity and the responsive sequence was mapped to position -616 and -572 of the grass carp GH promoter. GH promoter activation induced by hCG occurred with concurrent rise in cAMP production, CREB phosphorylation, and could be inhibited by inactivation of adenylate cyclase (AC), PKA, MEK1/2, P(38) MAPK, PI3K and mTOR. AC activation, presumably via cAMP production, could mimic hCG-induced CREB phosphorylation and GH promoter activity, and these stimulatory effects were also sensitive to the blockade of PKA-, MAPK- and PI3K- dependent cascades. These results, as a whole, suggest that LH receptor activation in the carp pituitary may trigger GH gene transcription through CREB phosphorylation as a result of the functional crosstalk of the cAMP/PKA pathway with MAPK-and PI3K-dependent cascades.
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Hong Kong, China; State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals and Guangdong Provincial Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China. Electronic address: suncyhku@gmail.com.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Sun
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
authors.forename: Mulan
authors.initials: M
authors.lastname: He
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
authors.forename: Wendy K W
authors.initials: WK
authors.lastname: Ko
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Hong Kong, China. Electronic address: olwong@hku.hk.
authors.forename: Anderson O L
authors.initials: AO
authors.lastname: Wong
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002347:Carps / Q000502:physiology; D045744:Cell Line, Tumor; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D007986:Luteinizing Hormone / Q000235:genetics* / Q000378:metabolism; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D006063:Chorionic Gonadotropin; D017362:Cyclic AMP Response Element-Binding Protein; D011974:Receptors, LH; D007986:Luteinizing Hormone; D013006:Growth Hormone; D000242:Cyclic AMP; D008156:Luciferases; D019869:Phosphatidylinositol 3-Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482127:Map2k1 protein, mouse; D000262:Adenylyl Cyclases
keywords: CA; CREB; DN; GH; GH3 cell; Gene transcription; Grass carp; Growth hormone; LHR; Luteinizing hormone receptor; MAPK; PI3 K; PKA; Signal transduction pathway; constitutively active mutant; cyclic AMP response element binding protein; dominant negative mutant; growth hormone; hCG; human chorionic gonadotropin; luteinizing hormone receptor; mitogen-activated protein kinase; phosphoinositide 3-kinase; protein kinase A