ORGAN DISTRIBUTION AND BILIARY-EXCRETION OF INTRAVENOUSLY INJECTED INSULIN-LIKE GROWTH-FACTOR-I IN SUCKLING RATS

The organ distribution of intravenously injected I-125-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 st udy suggest that, although the main portion of intravenous IGF-I remai ns in the circulation, significant amounts are also found in the carca ss, liver and kidney. Blood radioactivity fell by 50% 30 min after inj ection, but concentrations in the carcass, liver, kidney and skin eith er 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 addi tion, the extracted peptide bound competitively to a membrane IGF-I re ceptor preparation. Studies performed on liver and kidney from these a nimals 5 min after injection showed that on a per gram wet weight basi s, these organs contained equivalent amounts of I-125-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 tha t noted 5 min after injection. Bile was collected over a 2-hour period and contained approximately 2% of the injected radioactivity and a si gnificant portion (30%) of this radioactivity coeluted with native IGF -I. This material also bound competitively in a radioreceptor assay, s uggesting 'intactness' of this peptide. From this study, we conclude t hat (a) IGF-I, when administered intravenously, remains for at least 3 0 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 t han from the kidney of suckling rats, and (c) that IGF-I is transferre d from blood to bile.