On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.

Nutritional intake is an important regulator of plasma somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) concentrations in plasma. Concentrations in humans are reduced to the hypopituitary range by fasting for only a few days, and their normalization after fasting depends on the adequacy of energy and protein in the refeeding diet. The changes correlate with changes in nitrogen balance. In rats we have observed a close relationship between change in plasma Sm-C/IGF-I and hepatic GH binding with fasting and refeeding, suggesting that alterations in GH binding might be responsible partly for changes in Sm-C/ IGF-I. When malnourished humans are given nutrient repletion, the increase in Sm-C/ IGF-I is far more dramatic than changes in other nutrient-related serum proteins.

Several studies have shown that insulin-like growth factor-binding proteins (IGF-BPs) modify IGF activity. To investigate their role in regulating growth, the number and size of IGF-BPs in porcine serum and the role of nutritional and endocrine factors in controlling their relative abundance were determined. IGF-BPs were analyzed by ligand blotting; sera were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, then the separated proteins were transferred to nitrocellulose filters and probed with [125I]IGF-I or -II. The band intensities of various forms of IGF-BPs were quantified by scanning densitometry. Fetal and postnatal sera contained six IGF-BPs of 220,000, 43,000, 39,000, 34,000, 29,000, and 24,000 mol wt (Mr). The band intensity of all forms of IGF-BPs increased with advancing gestational age. Specifically, the intensities of the 43,000, 39,000, 34,000, 29,000, and 24,000 Mr IGF-BP bands were 2.8-, 2.7-, 4.3-, 4.4-, and 3.1-fold higher, respectively, in fetal plasma at 110 than at 45 days gestation. In fetal plasma the 34,000 and 29,000 Mr forms predominated, whereas postnatally, the 43,000 and 39,000 Mr IGF-BPs predominated. Fasting of newborn pigs for 24 h reduced the intensity of the 43,000, 39,000, 34,000, and 24,000 Mr forms to 11.5%, 7.2%, 69.8%, and 5.2% of control levels, respectively. However, the 29,000 Mr IGF-BP was 1.8-fold higher in fasted pig serum than in that of fed controls. The band intensities of the 34,000 and 29,000 Mr forms were increased in postnatal animals after hypophysectomy. In contrast, fetal decapitation resulted in a preferential decrease in only the 34,000 Mr form, which was reduced by 30% compared to that in age-matched controls. These studies indicate that porcine serum contains six IGF-BPs that can be detected by ligand blotting. The level of each of these proteins increases with advancing gestational age, although the increases are not uniform, suggesting that the proteins may be regulated differentially. In the postnatal animal both endocrine and nutritional factors modulate the levels of IGF-BPs by distinct controlling mechanisms.