Figure 2. In the fetus (insert) IGF-I increases with gestational age toward birth. Endocrine circulating IGF-I is strongly nutritionally dependent and correlated with birth size. Pituitary GH control of IGF-I production is not fully established during the first year of human life. The ability of serum IGF-I levels to increase during childhood is dependent on the shift from binary complexes of IGF-I with short half-life to a complete dominance of IGF-I bound in a stable ternary complex with the GH dependent proteins IGFBP-3 and ALS. Both these proteins increase, when pituitary GH control of the axis is established. During pubertal development, sex steroids change the set-point of negative IGF-I feedback and allow a peak of IGF-I in mid-puberty. Total IGF-I levels decline to low levels in senescence. Serum IGF-I reference values based on Juul (50).