A Radioimmunoassay for Insulin-like Growth Factor II Specific for the C-Peptide Region*

Publisher Website
Google Scholar
Abstract
Insulin-like growth factor II (IGF-II) is a human plasma peptide whose sequence is homologous to both insulinlike growth factor I/somatomedin C (IGF-I/SM-C) and human proinsulin in the A and B regions. However, there is no obvious homology in the C (connecting peptide) region. The synthetic 8- amino acid C-peptide segment of IGF-II (Ser-Arg-Val-Ser-Arg- Arg-Ser-Arg) was covalently linked to thyroglobulin to render it more antigenic. Antiserum against the IGF-II C-peptide was generated which had a titer of 1:2000 determined with [125I]IGFII C-peptide. Half-maximum displacement was by 350 pg/ml IGF-II C-peptide or 80 ng/ml IGF-II. There was no displacement by IGF-I/SM-C, insulin, or a wide variety of peptides. There was also a high degree of species specificity of this antisera. Isoelectric focusing studies of immunoreactive IGF-II showed an apparent pi of 6–6.5. The mean (±SEM) level of IGF-II after acid chromatography of 28 normal adult males was 687.0 ± 31.9 ng/ml. The mean of 8 acromegalics was 600.5 ± 57.4 ng/ml, indistinguishable from normal. The IGF-II levels of 21 hypopituitary children were significantly lower (231.5 ± 32.3 ng/ml). Thus, GH action appears to be necessary for normal levels of IGF-II, but excess GH does not cause an elevation above normal of IGF-II, unlike what is seen with IGF-I/SM-C. These structurally related IGF peptides have different control mechanisms and ultimately may play different functional roles. The availability of specific RIAs for the measurement of IGF-II will help to clarify its role in human physiology and disease states.