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%).
Following administration of free tracer or tracer bound to the 50 kDa protein, the proportion of radioactivity bound to the 150 kDa fraction increased over the first 20-30 min of observation. However, this was not apparent following administration of tracer bound to the 150 kDa protein, indicating that the more rapid turnover of IGF-I bound to the 50 kDa protein was associated, in part, with transfer of IGF-I to the 150 kDa binding protein fraction.
The calculated secretion rates of the IGFs were two- to threefold and twentyfold higher, for IGF-I and -II respectively, relative to that of insulin. These data are evidence supporting roles for IGFs in the regulation of metabolism.
Journal of Endocrinology (1989) 123, 469–475
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