The plasma clearance of intravenously injected 125I-labelled insulin-like growth factor I (IGF-I, n = 13) and IGF-II (n = 12) and their transfer into lymph draining the foreleg of 3.5- to 8-week-old British Saanen goats was studied. Both peptides were initially distributed into a volume equivalent to the plasma volume, while the final distribution spaces for IGF-I and IGF-II were 90 +/- 9.8 and 125 +/- 12 ml/kg live weight respectively. There were two phases to the plasma clearance of both IGF-I and IGF-II, with the half-lives of both phases for IGF-I (9.6 +/- 0.9 and 287 +/- 23 min, first and second phase respectively) being significantly (P less than 0.001) longer than those of IGF-II (4.2 +/- 0.6 and 172 +/- 18 min, respectively). The radioactivity transferred into lymph originated from intact IGF-I and IGF-II as well as degraded products of these compounds, as assessed by precipitation with trichloroacetic acid and gel filtration. Levels of undegraded IGF-I in lymph were 50% greater than IGF-II. While more than 90% of either peptide was bound to specific IGF-binding proteins in plasma, in lymph 34 +/- 2% of IGF-I and 23 +/- 3% of IGF-II remained in the free form 60-80 min after injection. The plasma: lymph ratio for free IGF-I was 2:1 and for bound IGF-I, 8:1. The corresponding values for IGF-II were 3:2 and 8:1 respectively. These results provide direct experimental evidence for transfer of undegraded IGF-I and IGF-II from blood into lymph of the foreleg, consistent with the ability of these factors to act in an endocrine role in growing tissues. Differences between plasma clearance and transfer of IGF-II into lymph compared with IGF-I may be due to its greater cellular uptake and/or degradation in vivo.

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