Growth Hormone‐Releasing Peptide‐6 Increases Insulin‐Like Growth Factor‐I mRNA Levels and Activates Akt in RCA‐6 Cells as a Model of Neuropeptide Y Neurones

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Abstract
Chronic systemic administration of growth hormone (GH)‐releasing peptide‐6 (GHRP‐6), an agonist for the ghrelin receptor, to normal adult rats increases insulin‐like growth factor (IGF)‐I mRNA and phosphorylated Akt (pAkt) levels in various brain regions, including the hypothalamus. Because neuropeptide Y (NPY) neurones of the arcuate nucleus express receptors for ghrelin, we investigated whether these neurones increase their IGF‐I and p‐Akt levels in response to this agonist. In control rats, immunoreactive pAkt was practically undetectable; however, GHRP‐6 increased p‐Akt immunoreactivity in the arcuate nucleus, with a subset of neurones also being immunoreactive for NPY. Immunoreactivity for IGF‐I was detected in NPY neurones in both experimental groups. To determine if activation of this intracellular pathway is involved in modulation of NPY synthesis RCA‐6 cells, an embryonic rat hypothalamic neuronal cell line that expresses NPY was used. We found that GHRP‐6 stimulates NPY and IGF‐I mRNA synthesis and activates Akt in this cell line. Furthermore, inhibition of Akt activation by LY294002 treatment did not inhibit GHRP‐6 induction of NPY or IGF‐I synthesis. These results suggest that some of the effects of GHRP‐6 may involve stimulation of local IGF‐I production and Akt activation in NPY neurones in the arcuate nucleus. However, GHRP‐6 stimulation of NPY production does not involve this second messenger pathway.