Growth Hormone (GH) and GH-Releasing Peptide-6 Increase Brain Insulin-Like Growth Factor-I Expression and Activate Intracellular Signaling Pathways Involved in Neuroprotection

Beneficial effects of GH on memory, mental alertness, and motivation have been documented. Many actions of GH are mediated through IGF-I; hence, we investigated whether systemic administration of GH or GH-releasing peptide (GHRP)-6 modulates the brain IGF system. Treatment of adult male rats with GH...

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Published in:Endocrinology (Philadelphia) 2002-10, Vol.143 (10), p.4113-4122
Main Authors: Frago, Laura M, Pañeda, Covadonga, Dickson, Suzanne L, Hewson, Adrian K, Argente, Jesús, Chowen, Julie A
Format: Article
Language:English
Subjects:
Animals
Brain - drug effects
Brain - metabolism
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Cell Death
Cytoprotection - physiology
Enzyme Activation
Glycogen Synthase Kinases
Growth Hormone - pharmacology
Insulin-Like Growth Factor Binding Protein 2 - metabolism
Insulin-Like Growth Factor Binding Protein 5 - metabolism
Insulin-Like Growth Factor I - genetics
Insulin-Like Growth Factor I - metabolism
Intracellular Membranes - physiology
Male
Oligopeptides - pharmacology
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation
Proto-Oncogene Proteins - metabolism
Rats
Rats, Wistar
Receptors, Somatomedin - metabolism
RNA, Messenger - metabolism
Signal Transduction - physiology
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Summary:Beneficial effects of GH on memory, mental alertness, and motivation have been documented. Many actions of GH are mediated through IGF-I; hence, we investigated whether systemic administration of GH or GH-releasing peptide (GHRP)-6 modulates the brain IGF system. Treatment of adult male rats with GHRP-6 or GH for 1 wk significantly increased IGF-I mRNA levels in the hypothalamus, cerebellum, and hippocampus, with no effect in cerebral cortex. Expression of the IGF receptor and IGF-binding protein (IGFBP)-2 were not affected. Phosphorylation of Akt and Bad was stimulated in areas where IGF-I was increased, with no change in MAPK or glycogen synthase kinase-3β. This suggests that GH and GHRP-6 activate phosphatidylinositol kinase intracellular pathways involved in cell survival in response to growth factors. Indeed, the antiapoptotic protein Bcl-2 was augmented in these same areas, with no change in the proapoptotic protein Bax. IGFBP-5, also reported to be involved in neuron survival processes, was increased mainly in the hypothalamus, suggesting a possible neuroendocrine role. In conclusion, GH and GHRP-6 modulate IGF-I expression in the central nervous system in an anatomically specific manner. This is coincident with activation of intracellular signaling pathways used by IGF-I and increased expression of proteins involved in cell survival or neuroprotection.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2002-220261