Growth hormone and insulin-like growth factor I: nutritional pathophysiology and therapeutic potential

The growth hormone--insulin-like growth factor I axis has been appreciated for more than 30 years and the effects of malnutrition on this axis for more than 20 years. Over the last decade, advances in molecular biology have permitted enhanced understanding of feedback regulation between growth hormone and IGF-I at the gene level, including limited information on nutritional influences. Similarly, the availability of recombinant human growth hormone has allowed controlled clinical studies demonstrating its net anabolic actions at hypocaloric dietary energy intake levels and its ability to enhance height velocity in children with various causes of diminished growth. Although investigational use of recombinant IGF-I in humans has been limited, its actions are likely to complement those of growth hormone during periods of profound dietary energy deficit. From the information presented, two hypotheses are developed. First, recombinant IGF-I administration will enhance substrate anabolic events during the acutely malnourished state when dietary intake is severely limited. Second, administration of recombinant human growth hormone will accelerate protein anabolism and catch-up growth during the period of recovery from protein-energy malnutrition. Given current clinical investigational tools and the availability of both recombinantly-produced hormones, these are testable hypotheses.