Regulation of growth hormone secretagogue receptor gene expression in the arcuate nuclei of the rat by leptin and ghrelin

R Nogueiras, S Tovar, Sharon Elizabeth Mitchell, D V Rayner, Z A Archer, C Dieguez, Lynda Williams

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

The anorexigenic and orexigenic hormones leptin and ghrelin act in opposition to one another. When leptin signaling is reduced, as in the Zucker fatty rat, or when circulating ghrelin is increased during fasting, the effect of ghrelin becomes more dominant, indicating an influence of both hormones on ghrelin action. This effect could be mediated via the level of expression of ghrelin receptor (growth hormone secretagogue receptor [GHS-R]). For testing this, GHS-R expression was measured using in situ hybridization in Zucker fatty versus lean rats; in fed versus fasted (48 h) rats, treated with either ghrelin or leptin; and in GH-deficient, dwarf versus control rats. In the arcuate nuclei of the Zucker fatty rat and in fasted rats, GHS-R expression is significantly increased. A single leptin intracerebroventricular injection attenuated the fasting-induced increase in GHS-R but had no effect in fed rats 2 h after injection, whereas leptin infusion for 24 h or longer significantly decreased GHS-R expression in fed rats. Ghrelin significantly increased GHS-R expression but not in dwarf rats. These results show that the level of GHS-R expression in the ARC is reduced by leptin and increased by ghrelin and that the effect of ghrelin may be GH dependent.

Original languageEnglish
Pages (from-to)2552-2558
Number of pages7
JournalDiabetes
Volume53
Issue number10
DOIs
Publication statusPublished - Oct 2004

Keywords

  • agouti-related protein
  • messenger-RNA
  • neuropeptide-Y
  • body-weight
  • responsive neurons
  • energy homeostasis
  • mouse hypothalamus
  • peptide ghrelin
  • food-intake
  • brain
  • AgRP, agouti gene–related protein
  • ARC, arcuate nuclei
  • CART, cocaine- and amphetamine-regulated transcript
  • ICV, intracerebroventricular
  • NPY, neuropeptide Y
  • POMC, proopiomelanocortin
  • VMN, ventromedial nuclei

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