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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

Journal of the Korean Pediatric Society 1996;39(6):846-855.
Published online June 15, 1996.
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
Woo Yeong Chung1, Dae-Yeol Lee2
1Department of Pediatrics, Pusan Paik Hospital, College of Medicine, Inje University, Pusan, Korea
2Department of Pediatrics, Chonbuk National University, Medical School, Chonju, Korea
성장호르몬 결핍증 환아에서 혈청 IGF-I, IGFBP-3 농도 및 성장호르몬 치료 후의 변화
정우영1, 이대열2
1인제대학교 의과대학 부산백병원 소아과학교실
2전북대학교 의과대학 소아과학교실
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 adiagnostic 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¡¾40.1 ng/ml vs 147.5¡¾37.9 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¡¾49.2 ng/ml vs 78.7¡¾23.4 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.
Key Words: Serum IGF-I, Serum IGFBP-3, 150 kDa complex, Radioimmunoassay, Western Ligand Blot, Growth Hormone Deficiency, Growth Hormone Treatment


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