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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.

Original publication

DOI

10.1210/en.141.11.4321

Type

Journal article

Journal

Endocrinology

Publication Date

11/2000

Volume

141

Pages

4321 - 4324

Addresses

Department of Physiology and Pharmacology and Institute for Molecular Biology, University of Queensland, Brisbane, Australia.

Keywords

Liver, Animals, Rats, Rats, Mutant Strains, DNA Damage, Growth Hormone, DNA-(Apurinic or Apyrimidinic Site) Lyase, Deoxyribonuclease IV (Phage T4-Induced), Metalloendopeptidases, Carbon-Oxygen Lyases, Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, Intracellular Signaling Peptides and Proteins, Proteins, Fibrinogen, Carrier Proteins, Monocarboxylic Acid Transporters, DNA-Binding Proteins, Trans-Activators, Receptors, Interleukin-6, DNA, Complementary, RNA, Messenger, Signal Transduction, DNA Repair, Gene Expression, Kinetics, STAT3 Transcription Factor, Matrix Metalloproteinases, Membrane-Associated