Circulating insulin-like growth factor-binding proteins in fetal, neonatal and adult sheep

A specific radioimmunoassay for insulin-like growth factor I (IGF-I) has been used to study the distribution of circulating IGF-I on its carrier proteins in sheep. Serum or plasma samples obtained from fetal, neonatal and adult sheep were chromatographed at neutral pH on Sephadex G-200 columns. IGF-I eluted primarily in the 20 000-100 000 dalton region and to a lesser extent in the 20 000-100 000 dalton region in the adult. In the fetus, IGF-I eluted primarily in the 20 000-50 000 dalton region. Studies in the neonatal lamb showed IGF-I activity to fluctuate between different size binding proteins but by 7 days after birth the pattern was similar to that of the adult. When labelled IGF-I and IGF-II were added to serum which was chromatographed over Sephadex G-200 at a neutral pH, binding was displayed in the 50 000-100 000 dalton region for both adult and fetus. However in the fetus, but not in the adult, binding of 125I-labelled IGF-II was also found at greater than 200 000 daltons. These studies demonstrate that the distribution of IGF-binding proteins varies between the adult and the fetal lamb. The appearance of the 150 000 dalton binding protein is coincidental with the appearance of the somatogenic receptor in the infant liver and is consistent with the GH-dependent nature of this form of binding protein in other species. The marked developmental changes in the circulating form of IGF-I in the perinatal lamb may be of functional significance and lead to altered biological availability of circulating IGF-I.