Ghrelin and truncated ghrelin variant plasmid vectors administration into skeletal muscle augments long-term growth in rats

Domest Anim Endocrinol. 2004 Aug;27(2):155-64. doi: 10.1016/j.domaniend.2004.03.005.

Abstract

Ghrelin is an acylated peptide recently identified as an endogenous ligand for the growth hormone (GH) secretagogues (GHSs) receptor (GHS-R) and is involved in a novel system for regulating GH release. To study the biological activities of ghrelin using plasmid vector administration, we constructed myogenic expression vectors containing the full length cDNA of swine ghrelin-28 (pGEM-wt-sGhln) and truncated variant (pGEM-tmt-sGhln) consisting of the first seven residues of ghrelin (including Ser3 substituted with Trp3) with addition of a basic amino acid, Lys (K) at the C-terminus. After intramuscular injection of pGEM-wt-sGhln and pGEM-tmt-sGhln, RT-PCR analysis demonstrated that the ectopic expressions of ghrelin and its variant were observed 30 days post-injection. The level of GH increased in rat serum, and was significantly higher than that of the control group 20 days post-injection with pGEM-tmt-sGhln (P < 0.05). Administration of 150 microg of pGEM-wt-sGhln and pGEM-tmt-sGhln enhanced growth in rats over 30 days and great stimulatory responses were observed at day 10 and 20 post-injection respectively, whose body weight gains were on average 15% (P < 0.05) and 21% P < 0.033 significantly heavier than controls. These results suggested that skeletal muscle might have the potential to perform post-translational acylation for ghrelin, and short ghrelin variant might have the biological effects as wild type ghrelin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Amino Acid Sequence
  • Animals
  • Gene Expression
  • Genetic Vectors*
  • Ghrelin
  • Growth Hormone / blood
  • Injections, Intramuscular
  • Male
  • Molecular Sequence Data
  • Muscle, Skeletal / metabolism*
  • Peptide Fragments
  • Peptide Hormones / chemistry
  • Peptide Hormones / genetics*
  • Peptide Hormones / physiology*
  • Plasmids / genetics*
  • Protein Processing, Post-Translational
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Swine / genetics
  • Weight Gain*

Substances

  • Ghrelin
  • Peptide Fragments
  • Peptide Hormones
  • Growth Hormone