Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIF) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyse effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (ELISA) and mRNA levels (quantitative RT PCR) of growth factors in plasma and brain between normoxic and hypoxic mice (8% O2, 6 h; postnatal day 7, P7) at P14. Exposure to hypoxia led to reduced body weight (p<0.001) and length (p<0.04) compared to controls, and was associated with significantly reduced plasma levels of mouse GH (p<0.01) and IGF-1 (p<0.01). RhGH abrogated these hypoxia-induced changes of the GH/IGF-1 axis associated with normalization of weight and length gain until P14 compared to controls. In addition, rhGH treatment increased cerebral IGF-1, IGF-2, IGFBP-2, and EPO mRNA levels, resulting in significantly reduced apoptotic cell death in the hypoxic, developing mouse brain. These data indicate that rhGH may (i) functionally restore hypoxia-induced systemic dysregulation of the GH/IGF-1 axis, and (ii) induce up-regulation of neuroprotective, HIF-dependent growth factors in the hypoxic developing brain.
- growth hormone
- insulin-like growth factors
- somatotrophic axis
- Copyright © 2017, American Journal of Physiology-Regulatory, Integrative and Comparative Physiology