Opposing Metabolic Effects of Growth Hormone and IGF-I: Review and Clinical Implications

The growth hormone (GH)/insulin-like growth factor I (IGF-I) endocrine system has a central role in metabolism and growth. The Somatomedin Hypothesis, postulated in the mid-1950s, claimed that the biological activities of pituitary GH are mediated by a liver-produced peptide termed somatomedin or IGF-I. In spite of the fact that this theory has been modified several times throughout the years to accommodate new developments in the field, it is still regarded as the main conceptual framework in the area of GH and IGF-I biology. Regardless of the unifying view that emanates from the Somatomedin Hypothesis, several opposing activities of GH and IGF-I have been described over the years. The present review addresses some of these metabolic activities, including diverging effects of these hormones on serum lipoprotein(a), sex hormone-binding globulin, insulin secretion, and adiponectin/leptin biology. In addition, we propose a number of potential mechanisms that can probably provide a cellular and biochemical basis for these divergent actions. Understanding the complex interactions between the GH and IGF-I signaling pathways might improve our understanding of basic molecular endocrine processes and result in potential clinical applications.