PLASMA-CLEARANCE AND TISSUE DISTRIBUTION OF LABELED CHICKEN AND HUMANIGF-I AND IGF-II IN THE CHICKEN

The metabolic clearance of chicken IGF-I (cIGF-I), cIGF-II, human IGF- I (hIGF-I), and hIGF-II was examined in the chicken using I-125-labell ed growth factors. Superose-12 chromatography of plasma collected at 7 .5 min post-infusion revealed peaks of radioactivity corresponding to 150 and 43 kDa and unbound tracer. Statistical analysis of trichloroac etic acid (TCA)-precipitable radioactivity in sequential plasma sample s as well as following chromatography of the same samples revealed tha t clearance of the radiolabelled peptides followed an apparent triphas ic pattern. The close similarity of the individual chromatographically defined pools in their clearance rate compared with the three compone nts described by TCA precipitation strongly suggested their identity. Both free I-125-labelled cIGF-II (3.11 min) and hIGF-II (3.01 min) wer e cleared at a greater rate than their IGF-I counterparts. Unbound hIG F-I was cleared at a greater rate than cIGF-I (4.45 vs 5.66 min respec tively). A similar pattern for clearance was evident in the radiolabel led growth factors associated with the 43 kDa component, although at a longer half-life. There was no difference in the apparent clearance o f the radiolabelled growth factors associated with the 150 kDa compone nt between IGF-I or -II or between species. Analysis of the chromatogr aphic profiles of radioactive IGF-I peptides complexed to serum protei ns versus those bound to labelled IGF-II peptides revealed the presenc e of a large molecular mass binding protein in vivo. Ligand blotting o f chicken serum determined that a binding protein with a mass of 70 kD a was detectable with I-125-IGF-II probes only, and was not present in pig serum. In addition, tissue uptake of I-I25-cIGF-I and -II was eva luated. Similar patterns of tissue distribution and uptake were observ ed for I-125-cIGF-I and -II, except that cIGF-II uptake by the liver e xceeded that of I-125-cIGF-I at 15 min post-infusion. The rank order o f tissue distribution was as follows: kidney>testis>heart>liver>pancre as>small intestine>cartilage>bursa>gizzard>leg muscle>breast muscle>br ain. We conclude from these studies that the clearance of IGFs from th e compartments identified in blood and the potential target tissues is dependent on their interactions with IGF-binding proteins and recepto rs.