Insulin-like growth factors I and II in healthy man. Estimations of half-lives and production rates.
IGF-I and -II share specific serum carrier proteins which elute on neutral Sephadex G-200 gel permeation chromatography at apparent molecular masses of 50 and 200 kD. The half-lives of free and carrier protein-bound 125I-IGF-I and -II were determined after bolus injections of the tracers into two normal adults. Labelled IGF-I and -II migrated first with the 50-kD and later with the 200-kD complex. In these complexes their apparent half-lives were 20-30 min and 12-15 h, respectively. The apparent half-life a free 125I-IGF-I and -II was 10-12 min. In a second set of experiments, recombinant human insulin-like growth factor I was infused during 6 days in two healthy adults at a dose of 20 micrograms.kg-1.h-1 (corresponding to around 30 mg/day). Serum obtained before and during the infusion was subjected to neutral Sephadex G-200 gel permeation chromatography and fractions were pooled according to the apparent molecular masses at which the carrier protein complexes elute. IGF-I and -II in these pools were determined by RIA. Before the IGF-I infusion, 92 and 272 micrograms/l of IGF-I and -II were found in the 200-kD complex, 45 and 91 micrograms/l in the 50-kD complex, and 15 and 5 micrograms/l were present in the free form. Corresponding figures during the IGF-I infusion were 389 and 18 micrograms/l for the 200-Kd complex, 201 and 54 micrograms/l for the 50-kD complex, and 80 and less than 1 microgram/l for free IGF-I and -II. Using the half-lives of the tracer studies and the levels of the different molecular weight forms of IGF in serum, the production rates for IGF-I and -II were calculated to be 10 mg and 13 mg per day.