Hormonal therapies during recovery from neonatal malnutrition in rats
Malnutrition leads growth stunting and low serum insulin-like growth factor-I (IGF-I) concentration in humans and animals. Nutritional repletion alone does not support the full body wt recovery or normalize serum IGF-I concentrations. As growth-promoters and anabolic agents, growth hormone (GH) and IGF-I have been successfully used to treat GH-deficient patients and patients in catabolic conditions. However, no studies have been done to determine the effects of GH and IGF-I on recovery from neonatal malnutrition. Herein, a series of experiments have been designed using an animal model of neonatal malnutrition (1) to investigate whether short-term (4 d) GH and IGF-I or an analog of IGF-I (des-IGF-I) treatment with refeeding would enhance recovery from malnutrition in neonatal rats; (2) to compare the combination GH and IGF-I with each agent given alone in a longer-term treatment (24 d) on growth during recovery from malnutrition; and (3) to determine the underlying mechanism of enhanced lean body mass accretion by GH treatment. Malnutrition of neonatal pups was induced by maternal food restriction (60% of control intake). A subset of restricted pups were refed between d 16-39 and received GH, IGF-I, GH+IGF-I or des-IGF-I, and saline. The results demonstrated that short-term treatment with hIGF-I and des-IGF significantly increased spleen and kidney growth, but had no effect on overall body wt gain. In contrast, hGH was moderately effective at increasing body wt gain and muscle growth during recovery. Longer-term treatment showed that the combined GH+IGF-I therapy was most efficacious at promoting rapid and complete body wt recovery and at increasing body protein accretion. This increased body protein accretion by GH was associated with enhanced muscle protein growth rate and decreased muscle protein degradation rate. Furthermore, the results suggested that the actions of exogenous GH and IGF-I involved in regulation of serum and tissue IGF-I and IGFBP levels and probably IGF receptor expression. Further studies using this animal model to investigate muscle IGF-I and IGFBP mRNA expressions and the tissue distribution of GH receptor are needed.
Biology, Animal Physiology, Health Sciences, Nutrition
University of Illinois - Urbana-Champaign
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University of Illinois at Urbana-Champaign