Time dependent impact of perinatal hypoxia on growth hormone, insulin-like growth factor 1 and insulin-like growth factor binding protein-3
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Hypoxic-ischemia (HI) is a widely used animal model to mimic the preterm or perinatal sublethal hypoxia, including hypoxic-ischemic encephalopathy. It causes diffuse neurodegeneration in the brain and results in mental retardation, hyperactivity, cerebral palsy, epilepsy and neuroendocrine disturbances. Herein, we examined acute and subacute correlations between neuronal degeneration and serum growth factor changes, including growth hormone (GH), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after hypoxic-ischemia (HI) in neonatal rats. In the acute phase of hypoxia, brain volume was increased significantly as compared with control animals, which was associated with reduced GH and IGF-1 secretions. Reduced neuronal survival and increased DNA fragmentation were also noticed in these animals. However, in the subacute phase of hypoxia, neuronal survival and brain volume were significantly decreased, accompanied by increased apoptotic cell death in the hippocampus and cortex. Serum GH, IGF-1, and IGFBP-3 levels were significantly reduced in the subacute phase of HI. Significant retardation in the brain and body development were noted in the subacute phase of hypoxia. Here, we provide evidence that serum levels of growth-hormone and factors were decreased in the acute and subacute phase of hypoxia, which was associated with increased DNA fragmentation and decreased neuronal survival.
KeywordsPerinatal hypoxia Brain injury Apoptosis Serum GH IGF-1 IGFBP-3 levels
This work was supported by EMBO (European Molecular Biology Organization) installation Grant and The Turkish Academy of Sciences (TUBA).
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Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Brywe KG, Leverin AL, Gustavsson M, Mallard C, Granata R, Destefanis S, Volante M, Hagberg H, Ghigo E, Isgaard J (2005) Growth hormone-releasing peptide hexarelin reduces neonatal brain injury and alters Akt/glycogen synthase kinase-3beta phosphorylation. Endocrinology 146:4665–4672CrossRefPubMedGoogle Scholar
- Ciccone MM, Scicchitano P, Zito A, Gesualdo M, Sassara M, Calderoni G, Di Mauro F, Ladisa G, Di Mauro A, Laforgia N (2011) Different functional cardiac characteristics observed in term/preterm neonates by echocardiography and tissue doppler imaging. Early Hum Dev 87:555–558CrossRefPubMedGoogle Scholar
- Cohen P, Rosenfeld RG, Griffin JE, Ojeda SR (2002) Growth regulation. Textbook of endocrine physiology, 4th edn. Oxford University Press, Oxford, pp. 286–302Google Scholar
- Goodman CS, Tessier-Lavigne M (1997) Molecular mechanisms in axon guidance and targeted recognition. In: Cowan WM, Jessell TM, Zipursky SL (eds) Molecular and cellular approaches to neural development. Oxford University Press, New York, pp. 108–178Google Scholar
- Higgins RD, Raju T, Edwards AD, Azzopardi DV, Bose CL, Clark RH, Ferriero DM, Guillet R, Gunn AJ, Hagberg H, Hirtz D, Inder TE, Jacobs SE, Jenkins D, Juul S, Laptook AR, Lucey JF, Maze M, Palmer C, Papile L, Pfister RH, Robertson NJ, Rutherford M, Shankaran S, Silverstein FS, Soll RF, Thoresen M, Walsh WF, Eunice Kennedy Shriver National Institute of Child Health and Human Development Hypothermia Workshop Speakers and Moderators (2011) Hypothermia and other treatment options for neonatal encephalopathy: an executive summary of the Eunice Kennedy Shriver NICHD workshop. J Pediatr 159:851–858CrossRefPubMedPubMedCentralGoogle Scholar
- Kilic E, Reitmeir R, Kilic Ü, Caglayan AB, Beker MC, Kelestemur T, Ethemoglu MS, Ozturk G, Hermann DM (2014) HMG-CoA reductase inhibition promotes neurological recovery, peri-lesional tissue remodeling, and contralesional pyramidal tract plasticity after focal cerebral ischemia. Front Cell Neurosci 8:422CrossRefPubMedPubMedCentralGoogle Scholar
- Macglilivray MH, Felig P, Frohman LA (2001) Disorders of growth and development. Endocrinology and Metabolism. 4th ed. pp.1265–1316. MacGrawHillGoogle Scholar
- Scheepens A, Williams CE, Breier BH, Guan J, Gluckman PD (2000) A role for the somatotropic axis in neural development, injury and disease. J Ped Endoc Metabol 13:1483–1491Google Scholar
- Wilson JD, Foster DW, Kronenberg HM (1998) Williams textbook of endocrinology. 9th ed. pp. 249–326. W.B. Saunders CompanyGoogle Scholar
- Zhang GY, Lu XM, Sun RP, Wang SZ (2006) Serum growth hormone and prolactin levels in neonates with hypoxic-ischemic encephalopathy. Chin J Contemp Pediatr 8:450–452Google Scholar