How much insulin-like growth factor-I (IGF-I) circulates?: impact of standardization on IGF-I assay accuracy

Insulin-like growth factor-I (IGF-I, somatomedin-C) is a peptide hormone which plays an important role in growth regulation. Accurate measurements of circulating IGF-I levels in plasma samples are an important part of many studies on growth and development, and therefore many assays have been developed for this purpose. We have found that assay standardization has a major impact on IGF-I quantification. Most IGF-I assays are calibrated against the World Health Organization (WHO) International Reference Reagent (IRR) for IGF-I Immunoassays (87/518). The protein content assigned to WHO IRR 87/518 was a consensus value from a multicentre WHO collaborative study. Here we present physico-chemical data showing that WHO IRR 87/518 is Met(-1) IGF-I of low purity (44%), and that the assigned protein content is somewhat higher than the <> value determined by quantitative amino acid analysis. We show that assays calibrated against WHO IRR 87/518 report total IGF-I concentrations that are in excess of actual values by approximately two-fold. For this reason much of the IGF-I concentration data in the literature, which are based on assays calibrated against WHO IRR 87/518, are of questionable accuracy.