Identification of genes induced by growth hormone in rat liver using cDNA arrays.
Growth hormone (GH) is a pleiotropic cytokine that acts upon its target cells to regulate their growth, differentiation and metabolism. GH is thought to act by altering gene expression in target cells, but few GH-regulated genes are known. In this study, we used cDNA array analysis to identify genes rapidly induced in the liver of GH-deficient dwarf rats following a single systemic injection of GH. Eight genes were found to upregulate their mRNA expression within 1-3 hours of GH administration, results which were confirmed by northern analysis. The identity of these genes suggests GH may influence a diversity of cellular processes. A role for GH in regulating cytokine and growth factor signalling is suggested by upregulation of mRNAs encoding three signal transducers: a subunit of the receptor for IL-6-type cytokines (gp130), STAT3 (signal transducer and activator of transcription) and p38MAPK (mitogen activated protein kinase). Two genes involved in DNA repair and cell cycle control, APEN (apurinic endonuclease) and GADD45 (growth arrest and DNA damage 45) were upregulated. Other induced genes include those encoding a lactate transporter (MCT-1), an extracellular matrix remodelling enzyme, MTI-MMP (membrane type 1 matrix metalloproteinase) and an acute phase protein (fibrinogen beta). In summary, this work is the first to apply cDNA arrays to the study of peptide hormone action in vivo and has identified 8 novel GH target genes.
Thompson
B J
BJ
Department of Physiology and Pharmacology and Institute for Molecular Biology, University of Queensland, Brisbane, Australia.
Shang
C A
CA
Waters
M J
MJ
D000818:Animals; D019757:Carbon-Oxygen Lyases / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair; D018076:DNA, Complementary / Q000032:analysis*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004268:DNA-Binding Proteins / Q000235:genetics; D043223:Deoxyribonuclease IV (Phage T4-Induced); D005340:Fibrinogen / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D013006:Growth Hormone / Q000172:deficiency / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D027501:Monocarboxylic Acid Transporters; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011922:Rats, Mutant Strains; D019947:Receptors, Interleukin-6 / Q000235:genetics; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases; D000097642:GADD45 Proteins
D019757:Carbon-Oxygen Lyases; D002352:Carrier Proteins; D018076:DNA, Complementary; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004268:DNA-Binding Proteins; D043223:Deoxyribonuclease IV (Phage T4-Induced); D005340:Fibrinogen; D013006:Growth Hormone; D047908:Intracellular Signaling Peptides and Proteins; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020928:Mitogen-Activated Protein Kinases; D027501:Monocarboxylic Acid Transporters; D011506:Proteins; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D048051:p38 Mitogen-Activated Protein Kinases; D000097642:GADD45 Proteins; C494088:Stat3 protein, rat