Ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue receptor acts at a central level to elicit growth hormone release and to regulate food intake. In order to elucidate the neural circuit that exerts its effects, we measured the expression of hypothalamic neuropeptides involved in weight regulation and growth hormone secretion, following ghrelin administration.

Chronic intracerebroventricular cannulae were implanted under ketamine-xylazine anaesthesia into adult male rats, fed or fasted for 72 h, were treated centrally (I.C.V.) with one, single dose of ghrelin (5 mg). After 2, 4 and 6 or 8 h, the animals were humanely killed and agouti-related peptide, melanin-concentrating hormone, neuropeptide Y, prepro-orexin, growth hormone-releasing hormone and somatostatin mRNA levels were measured by in situ hybridization.

We found that ghrelin increased agouti-related peptide (60% vs. control) and neuropeptide Y (80% vs. control) 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 growth hormone-releasing hormone and somatostatin mRNA levels in GH-deficient (dwarf) rats. Our results show, that ghrelin increases somatostatin mRNA levels in the hypothalamus of these rats (increase is 40% vs. control).

Data are expressed as a percentage vs. control. Comparison between the different groups was assessed by ANOVA.

This study furthers our understanding of the molecular basis and mechanisms involved in ghrelin effect on food intake and GH secretion.

This work was supported by Fondo de Investigaciones Sanitarias, Spanish Ministry of Health, Spanish Ministry of Education, DGICYT, and European Union.