GHRP-2, a GHS-R agonist, directly acts on myocytes to attenuate the dexamethasone-induced expressions of muscle-specific ubiquitin ligases, Atrogin-1 and MuRF1

Life Sci. 2008 Feb 27;82(9-10):460-6. doi: 10.1016/j.lfs.2007.11.019. Epub 2007 Dec 5.


Recent reports suggest that Atrogin-1 and MuRF1, E3 ubiquitin ligases, play a pivotal role in muscle atrophy. In the present study, effect of Growth Hormone Releasing Peptide-2 (GHRP-2), a GH secretagogue receptor (GHS-R) agonist, on the expressions of Atrogin-1 and MuRF1 in vivo rat muscles was examined. Dexamethasone administration increased Atrogin-1 mRNA level in rat soleus muscle. The increased mRNA level of Atrogin-1 was significantly attenuated by GHRP-2. In addition, GHRP-2 decreased MuRF1 mRNA level irrespective of the presence of dexamethasone. Although IGF-I is a well-known protective factor for muscle atrophy, GHRP-2 did not influence plasma IGF-I levels and IGF-I mRNA levels in muscles. To clarify a direct effect of GHRP-2, differentiated C2C12 myocytes were used. Ten micrometer dexamethasone increased both Atrogin-1 and MuRF1 mRNA levels in C2C12 cells. GHRP-2 attenuated dexamethasone-induced expression of them dose-dependently and decreased the basal level of MuRF1 mRNA. The suppressive effect on the expressions of Atrogin-1 and MuRF1 by GHRP-2 was blocked by [D-Lys(3)]-GHRP-6, a GHS-R1a blocker, suggesting the effect of GHRP-2 was mediated through GHS-R1a. Taken together, GHRP-2 directly attenuates Atrogin-1 and MuRF1 mRNA levels through ghrelin receptors in myocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Dexamethasone / pharmacology*
  • Dose-Response Relationship, Drug
  • Gene Expression / drug effects
  • Glucocorticoids / pharmacology
  • Male
  • Mice
  • Muscle Cells / cytology
  • Muscle Cells / drug effects*
  • Muscle Cells / metabolism
  • Muscle Proteins / genetics*
  • Oligopeptides / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Ghrelin / agonists
  • Receptors, Ghrelin / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • SKP Cullin F-Box Protein Ligases / genetics
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / genetics*


  • Glucocorticoids
  • Muscle Proteins
  • Oligopeptides
  • RNA, Messenger
  • Receptors, Ghrelin
  • Tripartite Motif Proteins
  • Dexamethasone
  • growth hormone-releasing peptide-2
  • Fbxo32 protein, mouse
  • Fbxo32 protein, rat
  • SKP Cullin F-Box Protein Ligases
  • Trim63 protein, mouse
  • Trim63 protein, rat
  • Ubiquitin-Protein Ligases