Context: The somatomedin/insulin-like growth factor (IGF) hypothesis was based on the observation that growth hormone (GH) was inactive when added to an in vitro incubation system but required a GH-dependent substance in the circulation to mediate its activity. Newer experimental evidence has led to several modifications of the hypothesis but none of the proposed modifications accounts for all of the integrated actions of GH and IGF-I. In this paper we propose an augmentative/counteractive modification of the existing hypothesis that takes into account all the actions of the GH-IGF system.

Evidence Acquisition: The modification is based on experimental evidence published since the hypothesis was originally developed.

Evidence Synthesis: The modification is based on an integration of the results of published experimental evidence regarding the actions of GH and the IGF complex.

Conclusion: We propose a new augmentative/counteractive modification of the hypothesis that the actions of the GH-IGF system provide a distinct evolutionary advantage to the organism by augmenting the anabolic actions of GH while countering its potentially deleterious effects of hyperglycemia and depletion of lipid stores.