KINETICS OF INSULIN-LIKE-GROWTH-FACTOR (IGF) AND IGF-BINDING PROTEIN RESPONSES TO A SINGLE-DOSE OF GROWTH-HORMONE

The in vivo physiological relationships among GH, the insulin-like gro wth factors (IGFs), and the IGF-binding proteins (IGFBPs) are not comp letely defined, and single random measurements of these serum proteins do not completely reveal their dynamic relationships. We report the k inetic responses of the IGFs and IGF-binding proteins to exogenous GH in 23 subjects with untreated GH deficiency [5 women and 18 men; age, 15.0 +/- 6.2 yr (+/- SD), height z-score = -4.4 +/- 2.2 (+/- SD); body mass index = 19.3 +/- 2.4 kg/m(2)]. After an overnight fast, subjects were given a sc dose of recombinant human GH (2.85 IU/m(2)), and bloo d was sampled from an indwelling peripheral venous catheter 0, 1, 2, 3 , 4, 5, 6, 8, 10, 12, 14, and 24 h after the injection. Subjects were then treated with recombinant human GH (2.85 IU/m(2) day); fasting sam ples were obtained at 3 months (n = 22), and timed sampling was repeat ed at 6 months (n = 21). Fasting levels of IGF-I, free IGF-I, IGF-II, IGFBP-3, and insulin increased significantly within 3 months of GH tre atment, whereas IGFBP-1, IGFBP-2, and IGFBP-6 showed no change. In the timed sampling studies at 0 and 6 months, GH levels peaked 3 h after treatment; the degree of rise and the rate of decline were both greate r at 6 months. IGF-I levels increased beginning at 4 h, continuing thr oughout the 24-h period at month 0, whereas a plateau was observed aft er 6-8 h during the 6-month study. Free IGF-I paralleled total IGF-I e xcept during fasting, when it varied inversely with IGFBP-1. IGFBP-3 a nd IGF-II both showed late (> 20 h) responses to a dose of GH, whereas IGFBP-2 and IGFBP-6 showed minimal changes. IGFBP-1 varied inversely with insulin, which, in turn, varied with meal intake. Comparative stu dies in 2 subjects with GH receptor deficiency showed no response to e xogenous GH. However, both IGFBP-1 and IGFBP-2 were several fold eleva ted, and IGFBP-1 varied inversely with the low insulin levels. Our dat a are the first to examine multiple elements of the serum IGF system i n response to GH in both GH-deficient and replete states. The relation ships of the different response patterns provide insight into the phys iology of this system and may guide future studies.