Insulin-Like Growth Factor Binding Protein 3 (IGFBP-3)

IGFBP-3 is the most abundant of the six high-affinity insulin-like growth factor binding proteins, a glycoprotein of roughly 40 to 45 kilodaltons that carries the great majority of circulating IGF-1 and IGF-2. Bound to the acid-labile subunit, it forms a ternary complex near 150 kilodaltons that cannot leave the vasculature. Its synthesis is itself growth hormone-dependent, so the carrier and its cargo tend to move together. Limited proteolysis of IGFBP-3 in tissue lowers its affinity and is one mechanism by which IGF-1 is delivered where it is needed.

The complex is what makes IGF-1 a plasma hormone rather than a purely local factor. Free IGF-1 is cleared within minutes; sequestered in the ternary complex it persists for hours, and the reservoir is large enough that unbound concentrations stay very low. That buffering also limits acute hypoglycaemia from insulin-receptor cross-reactivity, which is a real risk when recombinant IGF-1 is given without its binding partner.

As a test, IGFBP-3 adds most in children, where it is less age-labile than IGF-1 and stays measurable at the low end, and in confirming complete axis failure, where IGF-1, IGFBP-3 and the acid-labile subunit are all low together. In adults it discriminates poorly and rarely changes management on its own. Nutritional status lowers it, as it does IGF-1.

The recurring misinterpretation concerns bioavailability. A high IGFBP-3 is sometimes read as neutralising IGF-1 and a low one as liberating it, but the binding protein is a reservoir as much as a brake, and total IGF-1 with a normal carrier remains the interpretable pair. Calculated free IGF-1 derived from the two totals is a model output, not a measurement, and should not be treated as one.