Free insulin-like growth factor (IGF) in disorders of IGF binding protein 3 complex formation.

Abstract

The concentration of free IGF-I and -II in normal human serum is less than 0.5% of the total concentration of the IGF (1). Despite the fact that this component is critical in the feedback regulation of pituitary GH secretion and is important in the endocrine action of IGF-I on target tissues, its measurement has been little used in clinical practice. This is because the small concentrations of this entity are technically difficult to measure accurately and concentrations are subject to rapid change, depending on the fluctuations of the concentration of IGF binding protein 1 (IGFBP1) in fasting and metabolic disorders such as diabetes mellitus. For this reason, measurement of total serum IGF-I has been the accepted clinical method of evaluating IGF-I activity in patients. About 80% of what is being measured is IGF-I that is bound to the ternary complexes of IGF-I-IGFBP3-acid labile subunit (ALS) (2) and to a lesser extent to the ternary complex of IGF-IGFBP5-ALS. The remainder is in loose binary association with IGFBP1, -2, and -4. Measurement of serum IGFBP3 as an index of GH action, therefore, is a surrogate measure of the total IGF-I and IGF-II in serum. However, in conditions when the formation of the IGFBP3 ternary complex is impaired, total serum IGF no longer reflects free IGF. Two different examples by which this might occur are considered.