Serum somatomedin binding proteins: physiologic significance and interference in radioligand assay

Mammalian sera contain binding proteins that specifically complex with somatomedins (insulin-like growth factor I and II) so that there are no detectable free somatomedins. There is immunologic evidence of two distinct types of serum binding proteins. The major binding protein complex (150,000 Mr) is growth hormone dependent. Binding proteins protect somatomedins from proteolytic degradation, retard plasma clearance, and decrease the availability to tissue receptors. The presence of serum binding proteins interferes with radioimmunoassays and radioreceptor assays for somatomedins. Proposed strategies to neutralize the interference from binding proteins without their elimination do not achieve this goal. Extraction of somatomedins by acid ethanol, hydrophobic absorption on C18 silicates (SepPak), and acid gel filtration are effective with human serum, but only acid gel filtration is satisfactory with rat serum. Failure to eliminate binding proteins from assays can lead to serious artifacts in conditions where abnormalities of binding proteins exist.