The Concentration of Insulin Like Growth Factor-I(IGF-I) and IGF-Binding Protein-3 (IGFBP-3) in the Serum of Children with Growth Hormone Deficiency and the Alterations after Growth Hormone Treatment

Chung, Woo Yeong; Lee, Dae Yeol

Abstract

PURPOSE
The insulin like growth factors (IGFs) circulate complexed to IGF-binding proteins(IGFBPs). IGFBP-3 is the major circulating IGFBP and is found primarily as a 150 kDa complex which contains an acid labile subunit(ALS), IGFBP-3, and IGF-I or IGF-II and is considered to be growth hormone(GH) dependent. In this study, we measured serum IGF-I, IGFBP-3 and 150 kDa levels in sera of growth hormone deficient children(GHD) before and after GH treatment respectively to clarify the utility of these factors as a diagnostic marker for GHD and to observe the alterations of these factors according to GH treatment.
METHODS
Measurement of serum IGF-I, IGFBP-3 and 150 kDa complex were performed in 10 children with complete growth hormonr deficiency(cGHD), in 6 children with partial growth hormone deficiency(pGHD) and in 10 normal healthy subjects. Serum IGF-I was measured by radioimmunoassay (RIA). IGF-I was seperated from IGFBPs by Sephadex G-50 acid chromatography. Serum IGFBP-3 was assessed by Western ligand blot(WLB) analysis as described by Hossenlopp with minor modifications. To evaluate alterations of different molecular size classes of IGF-BP complexes according to GH treatment, WLB was done after neutral size-exclusion chromatography using Sephacryl S-200.
RESULTS
1) The serum IGF-I level in children with GHD was significantly lower than that of control subjects(96.2+/-40.1 ng/ml vs 147.5+/-37.9 ng/ml)(p<0.01). 2) The serum IGF-I level in children with cGHD was significantly lower than that of normal subjects (p<0.01). But four of the 10 children with cGHD the IGF-I levels were distributed within the range of -2 S.D.. The serum IGF-I level in children with pGHD was also lower than that of normal subjects but there was no statistical significance between two groups(P>0.05). 3) The serum IGFBP-3 level is markedly decreased in 9 of 10 children with cGHD, but only in 2 of 6 children with pGHD which was measured by WLB method. 4) The serum IGF-I level after GH treatment was increased significantly in children with GHD(138.7+/-49.2 ng/ml vs 78.7+/-23.4 ng/ml)(p<0.01). The serum IGFBP-3 level was also increased after GH treatment as similar pattern. 5) The marked decrement of serum IGFBP-3 level in children with cGHD was explained as the result of decline in the 150 kDa IGFBP complex, and after GH treatment 150 kDa complex was increased; in the 150 kDa IGFBP complex, free IGF-I binding sites were increased.
CONCLUSIONS
The serum levels of IGF-I, IGFBP-3 and 150 kDa complex in children with cGHD were decreased significantly, but in children with pGHD these changes were not observed as prominant as cGHD. These findings suggest that the measurments of serum IGF-I, IGFBP-3 level may be useful not only in the diagnosis of GHD but also differentiate cGHD from pGHD and the serum IGFBP-3 level may be more sensitive for diagnosing GHD even though each test by itself has a limited diagnostic accuracy as a single test.