Organ distribution and biliary excretion of intravenously injected insulin-like growth factor-I in suckling rats

The organ distribution of intravenously injected 125I-IGF-I at a dose of 2-4 x 10(6) cpm or 5-10 ng/animal was studied in 10- to 12-day-old Sprague-Dawley rats at 5 and 30 min after injection. Results of the study suggest that, although the main portion of intravenous IGF-I remains in the circulation, significant amounts are also found in the carcass, liver and kidney. Blood radioactivity fell by 50% 30 min after injection, but concentrations in the carcass, liver, kidney and skin either remained stable or increased. Gel chromatography demonstrated that significant portions of radioactivity recovered from serum, liver and kidney coeluted in a position identical to the injected IGF-I. In addition, the extracted peptide bound competitively to a membrane IGF-I receptor preparation. Studies performed on liver and kidney from these animals 5 min after injection showed that on a per gram wet weight basis, these organs contained equivalent amounts of 125I-IGF-I. However, although by 30 min, 65% of the intact labelled IGF-I has been removed from the liver, the amount remaining in kidney tissue was equal to that noted 5 min after injection. Bile was collected over a 2-hour period and contained approximately 2% of the injected radioactivity and a significant portion (30%) of this radioactivity coeluted with native IGF-I. This material also bound competitively in a radioreceptor assay, suggesting 'intactness' of this peptide. From this study, we conclude that (a) IGF-I, when administered intravenously, remains for at least 30 min in a receptor-active form in blood and several organs; (b) IGF-I derived from the circulation is cleared from the liver more quickly than from the kidney of suckling rats, and (c) that IGF-I is transferred from blood to bile.