Improved estimates of clearance of 131I-labelled insulin-like growth factor-I carrier protein complexes from blood plasma of sheep.
Clearance of protein-bound forms of insulin-like growth factor-I (IGF-I) from the circulation of sheep was determined using single injections of 131I-labelled ovine or [Thr59]-human IGF-I, in the 'free' form or prebound to 50 or 150 kDa plasma binding protein fractions. The half-life of circulating protein-bound forms of IGF-I was determined by size-exclusion chromatography of plasma samples taken over a 24- to 26-h experimental period. IGF-I bound to lower molecular weight binding protein(s) (approximately 50 kDa) showed a half-life of 26-40 min (mean 34 min; n = 6), while the half-life of a high molecular weight fraction (150 kDa) was considerably longer (range 398-603 min; mean 545 min; n = 8). Metabolic clearance of IGF-I following administration of free tracer ranged from 3.0 to 5.3 ml/min in sheep (n = 4) weighing 26.0-28.5 kg. Tracer distribution volume was 59 ml/kg liveweight (n = 4). Tracer degradation products were first detected in plasma 8 h after i.v. administration. No differences in stability of the purified ovine and recombinant human IGF-I tracer preparations were observed. However, a fraction of the [Thr59]-IGF-I tracer did not possess binding activity and this was associated with excretion of a greater proportion of administered radioactivity (over 22 h) in urine in animals receiving [Thr59]-IGF-I tracer (18.4-19.3%) compared with ovine IGF-I (7.1-11.0%).(ABSTRACT TRUNCATED AT 250 WORDS)
Davis
S R
SR
Ruakura Agricultural Centre, Ministry of Agriculture & Fisheries, Hamilton, New Zealand.
Hodgkinson
S C
SC
Moore
L G
LG
Gluckman
P D
PD
D000818:Animals; D002352:Carrier Proteins / Q000097:blood / Q000493:pharmacokinetics*; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D012756:Sheep / Q000378:metabolism*; D013002:Somatomedins / Q000493:pharmacokinetics*
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I