Distribution of circulating insulin-like growth factor-I (IGF-I) into tissues

Intravenous infusions of amino terminal methionyl insulin-like growth factor-I (N-Met IGF-I; 8 micrograms/kg body wt x h; 24 h) were performed in lactating sheep and samples of mammary lymph, cerebrospinal fluid, and postinfusion tissues collected to examine distribution of the recombinant analog outside the vascular space. Samples were analyzed using an antibody specific for N-Met IGF-I and a second IGF-I antibody which recognized endogenous IGF-I and the N-Met variant equally. N-Met IGF-I infusion increased total plasma IGF-I immunoreactivity (ir) from 150 to 290 ng/ml. N-Met IGF-I was distributed into mammary lymph, increasing total lymph IGF-I from 60 to 130 ng/ml. By contrast iv N-Met IGF-I had no significant effect on IGF-I ir in cerebrospinal fluid. N-Met IGF-I was distributed on plasma and lymph IGF binding protein as endogenous IGF-I with binding to the 150,000 mol wt species predominant in plasma and the 40,000-50,000 mol wt pool of proteins predominant in lymph. N-Met IGF-I was also distributed into extra-vascular tissue accounting for 36% (kidney) to 62% (spleen) of total tissue IGF-I ir at the end of the infusion. The IGF-I antibodies were also used for the autoradiographical localization of IGF-I in postinfusion muscle and mammary tissue. No significant difference in antibody binding was observed to muscle fiber and mammary epithelium, but in marked contrast binding of the N-Met specific antibody to connective tissue of muscle and mammary was significantly less than the total IGF-I antibody (P less than 0.001; N-Met/total, 0.12). The data suggest that the contribution of blood-derived N-Met to total IGF-I varies markedly between tissues and provides evidence that blood-borne IGF-I may fill specific endocrine functions in selected tissues.