Agouti-related peptide, neuropeptide Y, and somatostatin-producing neurons are targets for ghrelin actions in the rat hypothalamus

Endocrinology. 2003 Feb;144(2):544-51. doi: 10.1210/en.2002-220795.


Ghrelin, the endogenous ligand of the GH secretagogue receptor, acts at central level to elicit GH release and regulate food intake. To elucidate the neural circuit that exerts its effects, we measured the expression of hypothalamic neuropeptides involved in weight regulation and GH secretion after ghrelin administration. Adult male rats, fed or fasted for 72 h, were treated centrally (intracerebroventicularly) with a single dose of ghrelin (5 micro g). After 2, 4, and 6 or 8 h, agouti-related peptide, melanin-concentrating hormone, neuropeptide Y, prepro-orexin, GHRH, and somatostatin mRNA levels were measured by in situ hybridization. We found that ghrelin increased agouti-related peptide and neuropeptide Y expression in the arcuate nucleus of the hypothalamus of fed and fasted rats. In contrast, no change was demonstrated in the mRNA levels of the other neuropeptides studied at any time evaluated. Finally, we examined the effect of ghrelin on GHRH and somatostatin mRNA levels in GH-deficient (dwarf) rats. Our results show that ghrelin increases somatostatin mRNA levels in the hypothalamus of these rats. This study furthers our understanding of the molecular basis and mechanisms involved in the effect of ghrelin on food intake and GH secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti-Related Protein
  • Animals
  • Arcuate Nucleus of Hypothalamus / cytology*
  • Arcuate Nucleus of Hypothalamus / physiology
  • Eating / physiology
  • Fasting / physiology
  • Gene Expression / drug effects
  • Ghrelin
  • Growth Hormone / blood
  • Growth Hormone / genetics
  • Growth Hormone-Releasing Hormone / genetics
  • Growth Hormone-Releasing Hormone / metabolism
  • Injections, Intraventricular
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Neurons / metabolism*
  • Neuropeptide Y / genetics*
  • Neuropeptide Y / metabolism
  • Paraventricular Hypothalamic Nucleus / cytology*
  • Paraventricular Hypothalamic Nucleus / physiology
  • Peptide Hormones / pharmacology*
  • Proteins / genetics
  • Proteins / metabolism
  • RNA, Messenger / analysis
  • Rats
  • Rats, Inbred Lew
  • Rats, Mutant Strains
  • Rats, Sprague-Dawley
  • Somatostatin / genetics*
  • Somatostatin / metabolism


  • Agouti-Related Protein
  • Ghrelin
  • Intercellular Signaling Peptides and Proteins
  • Neuropeptide Y
  • Peptide Hormones
  • Proteins
  • RNA, Messenger
  • Somatostatin
  • Growth Hormone
  • Growth Hormone-Releasing Hormone