PURPOSE: Insulin-like growth factor(IGF-I) and IGF binding protein(IGFBP)-3 is thought to play an important role in fetal erythropoiesis. The objective of this study was to establish a relation between IGF-I, free IGF-I, IGFBP-1, and -3 with hemoglobin level in healthy term, 3-month, and 12-month old infants. METHODS: Healthy term infants(n=20)were enrolled at birth, as well as 3 months1 and -3 were measured by specific immunoradiometric assay(IRMA) kit. RESULTS: The mean level of hemoglobin was 15.6+/-1.4g/dL, IGF-I was 14.5+/-7.0ng/mL and IGFBP-3 was 1205.2+/-292.1ng/mL at birth. Serum IGF-I, IGFBP-3 and hemoglobin concentrations were correlated positively at birth(P<0.01), and a positive correlation was observed between hemoglobin and free IGF-I(P<0.05). The mean level of hemoglobin was 10.7+/-0.8g/dL, IGF-I was 27.3+/-11.1 ng/mL and IGFBP-3 was 1674.1+/-399.1ng/mL at three months of age. No correlation was observed between hemoglobin and IGF-I, IGFBP-3 and free IGF-I. The mean level of hemoglobin was 10.6+/-0.8g/dL, IGF-I was 45.5+/-13.9ng/mL and IGFBP-3 was 2124.5+/-401.8ng/mL at 12 months of age. CONCLUSION: Our results show that blood hemoglobin is positively correlated to serum IGF-I and IGFBP-3 concentrations, indirectly indicating the involvement of mediators of growth hormone on the regulation of physiologic hemoglobin concentration at birth.
Erythropoiesis ; Growth Hormone ; Humans ; Infant* ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Parturition

PURPOSE: It is well known that the linear growth velocity in children with insulin-dependent diabetes mellitus (type 1 DM) is closely related to metabolic control and onset age of the disease. Many studies have demonstrated growth impairment in children with type 1 DM, regardless of the degree of metabolic control, whereas other studies have found no growth retardation. Therefore, we examined the growth status and the level of growth factors in children with type 1 DM, and compared them with healthy children. METHODS: Thirty-six patients with type 1 DM (21 female, 15 male; mean age, 10.8 years : range, 5-15 years)were studied. The mean duration of type 1 DM in these patients was 2.7 years (range, 0.1-7.0 years). Their growth status in height standard deviation score (HTSDS) and levels of insulin-like growth factor (IGF)-I, free IGF-I, IGF-II and IGF-binding protein (IGFBP)-3 were compared with age and sex matched normal children (21 female, 15 male; mean age, 10.3 years; range, 5-15 years). RESULTS: As HTSDS in type 1 DM, children were 0.4 +/- 1.1, no prominent growth impairment was observed in type 1 DM children. IGF-I and IGF-II levels decreased significantly in type 1 DM, but no significant differences in free IGF-I and IGFBP-3 levels compared to normal. Height in type 1 DM children was in direct correlation with free IGF-I (r=0.35, P<0.05) and IGFBP-3 (r= 0.45, P<0.01), respectively. CONCLUSION: This study reveals that the levels of IGF-I and -II are decreased in children with type 1 DM, whereas free IGF-I levels are not. These findings may be related to the decreased IGFBP-3 levels in diabetic children, and may explain no growth impairment, except in cases of extremely poor metabolic control.
Age of Onset ; Child* ; Diabetes Mellitus, Type 1* ; Female ; Humans ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Intercellular Signaling Peptides and Proteins* ; Male

PURPOSE: It is well known that the linear growth velocity in children with insulin-dependent diabetes mellitus (type 1 DM) is closely related to metabolic control and onset age of the disease. Many studies have demonstrated growth impairment in children with type 1 DM, regardless of the degree of metabolic control, whereas other studies have found no growth retardation. Therefore, we examined the growth status and the level of growth factors in children with type 1 DM, and compared them with healthy children. METHODS: Thirty-six patients with type 1 DM (21 female, 15 male; mean age, 10.8 years : range, 5-15 years)were studied. The mean duration of type 1 DM in these patients was 2.7 years (range, 0.1-7.0 years). Their growth status in height standard deviation score (HTSDS) and levels of insulin-like growth factor (IGF)-I, free IGF-I, IGF-II and IGF-binding protein (IGFBP)-3 were compared with age and sex matched normal children (21 female, 15 male; mean age, 10.3 years; range, 5-15 years). RESULTS: As HTSDS in type 1 DM, children were 0.4 +/- 1.1, no prominent growth impairment was observed in type 1 DM children. IGF-I and IGF-II levels decreased significantly in type 1 DM, but no significant differences in free IGF-I and IGFBP-3 levels compared to normal. Height in type 1 DM children was in direct correlation with free IGF-I (r=0.35, P<0.05) and IGFBP-3 (r= 0.45, P<0.01), respectively. CONCLUSION: This study reveals that the levels of IGF-I and -II are decreased in children with type 1 DM, whereas free IGF-I levels are not. These findings may be related to the decreased IGFBP-3 levels in diabetic children, and may explain no growth impairment, except in cases of extremely poor metabolic control.
Age of Onset ; Child* ; Diabetes Mellitus, Type 1* ; Female ; Humans ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Intercellular Signaling Peptides and Proteins* ; Male

Insulin-like growth factor (IGF) is closely associated with cardiovascular diseases. Low IGF-I level and high insulin-like growth factor binding protein-1 (IGFBP-1) level in serum can be used as a marker in predicting the long term morbidity and mortality of acute myocardial infarction (AMI). The article reviews the recent advances in IGFBP-1 in the prognosis of AMI.
Humans ; Insulin-Like Growth Factor Binding Protein 1 ; blood ; Insulin-Like Growth Factor I ; metabolism ; Myocardial Infarction ; blood ; Prognosis

PURPOSE: PTEN/MMAC1, a novel tumor suppressor gene, is mutated in a variety of advanced and metastatic cancers. It acts as a phosphatase, and thereby, regulates the PI-3 kinase/Akt pathway. In this study, we examined to evaluate the new function of anti-tumor effects of PTEN/MMAC1 through the regulation of the IGFs-IGFBPs in gastric cancer cells. METHODS: PTEN/MMAC1 was expressed in an adenovirus-mediated gene delivery system and introduced into gastric cancer cells(SNU-484 & SNU-668) in vitro. The effect of cell growth and the expression of IGFs and IGFBPs after Ad/PTEN infection was analyzed by MTT assay, RT-PCR and Western immunoblot. RESULTS: Ad/PTEN infected cells were inhibited in cell growth compared with moak cells and Ad/ LacZ infected cells. Overexpression of PTEN/MMAC1 induced decrease in expression of IGF-I, -II and IGF-I receptors which are known as growth prompt molecules in a variety of cancers. Of the six IGFBPs, the expressions of IGFBP-4 and IGFBP-6 were decreased in Ad/PTEN infected cells. In contrast, IGFBP-3 expression was markedly increased by up to 3-fold in Ad/PTEN infected cells. Overexpression of PTEN/MMAC1 inhibited the activation of Akt/PKB pathway, but had no effect on the MAPK pathway. CONCLUSION: These findings suggest that the tumor suppressor function of PTEN/MMAC1 is, at least in part, mediated through the down-regulation of IGF-I abd IGF-II, and up-regulation of IGFBP-3 in gastric cancer cells by the inhibition of PI-3 kinase pathway.
Blotting, Western ; Down-Regulation ; Gene Transfer Techniques ; Genes, Tumor Suppressor ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Protein 4 ; Insulin-Like Growth Factor Binding Protein 6 ; Insulin-Like Growth Factor Binding Proteins* ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Phosphatidylinositol 3-Kinase ; Phosphatidylinositol 3-Kinases ; Receptor, IGF Type 1 ; Stomach Neoplasms ; Up-Regulation

The insulin-like growth factor(IGF) system consists of IGFs, their receptor and binding proteins(IGFBPs). The IGFs are important growth factors in the regulation of fetal growth. Since IGFBPs control IGF actions, the IGFBPs themselves may also be important in fetal growth and development. The goals of this study are to investigate the profiles of IGFBPs in cord sera of appropriate-for-gestatinal age(AGA, n=27), small-for-gestatinal age(SGA, n=14), large-for-gestatinal age(LGA, n=10) infants and preterm(PT, n=14) infants and to evaluate the relationship between these IGFBP levels and gestational weeks and birth weight and between total IGFBP levels in cord sera and paired maternal sera(n=65). The IGFBPs were analyzed by Western ligand blot and immunoprecipitation. In cord sera of AGA infants IGFBPs with molecular weight with 37/43 kilocatons(kDa; IGFBP-3), 31 kDa(IGFBP-2), 26 kDa(IGFBP-1), 24 kDa(IGFBP-4) were detected. In cord sera of LGA infants there was a significant increase in IGFBP-3 levels and a reduction of IGFBP-1 and IGFBP-4 levels compared with those in AGA infants. SGA infants had significantly higher IGFBP-1 and IGFBP-2 levels in cord sera than AGA infants. There was a similiar trend in IGFBP-1 levels in cord sera of PT infants. The relative proportion of IGFBP-4 in cord sera of SGA and PT infants was significantly higher than that of AGA infants. There was no significant correlation beween total IGFBP levels in cord sera and paired maternal sera. The ratios of total IGFBP in cord sera to that in maternal sera to that in maternal sera were significantly higher in SGA and PT infants than in AGA infants. The IGFBP-1 and IGFBP-2 levels correlated with birth weight but did not correlate with gestational weeks. These data suggest that there is an unique profile of IGFBPs in cord sera of infants according to their weight, and that IGFBPs may play a major role in the control of fetal growth.
Birth Weight ; Fetal Development ; Gestational Age* ; Humans ; Immunoprecipitation ; Infant* ; Infant, Newborn ; Infant, Premature* ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor Binding Protein 2 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Protein 4 ; Insulin-Like Growth Factor Binding Proteins ; Intercellular Signaling Peptides and Proteins ; Molecular Weight

OBJECTIVE: To investigate the influence of activin and follistatin on the expression of IGF (insulin-like growth factor)-I, II, IGFBP (insulin-like growth factor binding protein)-1, 2, and 3 mRNA in cultured mouse granulosa cells MATERIALS AND METHODS: The granulosa cells were obtained from the mouse and cultured for 6 days with 10 ng/ml of activin, 10 ng/ml of follistatin, and 10 ng/ml of activin with 10 ng/m of follistatin, respectively. The cells not treated with activin or follistatin served as control. Reverse transcription-polymerase chain reaction (RT-PCR) has been used to examine the expression of IGF-I, II, IGFBP-1, 2, and 3 mRNA. Results were analyzed with Kolmogorov-Smirnov test and analysis of variance (ANOVA) and statistical significance was defined as p<0.05. RESULTS: The expression of IGF-I and II mRNA were not different significantly. However, the expression of IGFBP-3 mRNA was significantly increased in the follistatin group compared to the control group (p<0.05) and significantly decreased in the activin with follistatin group compared to the control group (p<0.05). The expression of IGFBP-1 mRNA was seemed to be increased in the activin group and decreased in the follistatin group compared to the control group, respectively (p=0.07, p=0.07). The expression of IGFBP-2 and 3 mRNA were seemed to be decreased in the activin group compared to the control group (p=0.06, p=0.07, respectively). CONCLUSION: Activin and follistatin might play a role as regulators of mouse ovarian physiology by modulating the IGF system, especially IGFBPs.
Activins* ; Animals ; Carrier Proteins* ; Female ; Follistatin* ; Granulosa Cells* ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor Binding Protein 2 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins ; Insulin-Like Growth Factor I ; Mice* ; Physiology ; RNA, Messenger*

Backgrounds: Thyroid hormones play a fundamental role in the initiation and maintenance of somatic growth in mammalian species, and the insulin-like growth factors(IGFs) occupy a position of central importance in the growth of all tissues. To evaluate the changes in serum insulin-like growth factor-I(IGF-I) and insulin-like growth factor binding proteins in hyperthyroid and hypothyroid patients, sera was obtained from 19 hyperthyroid patients, 9 hypothyroid patients, and 10 healthy volunteers. Methods: IGF-I concentration was determined by radioimmunoassay, and changes in IGFBPs were assesed by Western Ligand Blotting. To evaluate the binding pattern of IGF-I & IGFBPs, autoradiographs were obtained. Results & Conclusion: IGF-I levels were increased significantly in hyperthyroid patients(mean ±SE, 267.88±9.80 ng/ml, p<0.05) and decreased significantly in hypothyroid patients(154.81±1.43 ng/ml, p<0.01) compaired to healthy control group(209.45±.60 ng/ml). Autoradiograph of serum IGFBPs from patients with hyperthyroidism and hypothyroidism did not show any change in the intensity of IGFBP-3 bands(40-45 KD) and IGFBP-1 bands, but in hyperthyroid patients, it showed increased intensity of IGFBP-2 band compared to healthy control group and hypothyroid patients.
Equidae ; Healthy Volunteers ; Humans ; Hyperthyroidism ; Hypothyroidism ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor Binding Protein 2 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins ; Insulin-Like Growth Factor I ; Radioimmunoassay ; Thyroid Hormones

PURPOSE: In children with simple obesity, spontaneous and stimulated growth hormone (GH) secretion are diminished, but their heights usually are normal or even taller for their age and sex. The exact mechanism to explain the discrepancy between impaired GH secretion and normal height velocity has not been elucidated. In this study, we aimed to determine the level of serum growth factors, and the degree of insulin-like growth factor binding protein (IGFBP)-3 proteolysis, and to assess the alteration of the IGF system associated with accelerated or normal growth in simple obesity. METHODS: We evaluated serum growth factors, and IGFBP-3 proteolysis in 27 obese, 25 obesity risk group, and 28 age-matched control group. We measured serum levels of insulin-like growth factor (IGF)-I, IGFBP-1, -3, and free IGF-I by immuno-radiometric assay and IGFBP-3 fragment by Western immunoblotting. RESULTS: The height was taller in obese children than in lean control group. The results showed no significant difference in the level of serum total IGF-1 and IGFBP-3 between obese and normal control group. Although there was no significant difference in other components, serum free IGF-I levels were significantly increased (P<0.05) and showed positive correlation with their height in obese children (r=0.25, P<0.05). The degree of IGFBP-3 proteolysis was increased in obesity and obesity risk group compared to control group. The densities of the IGFBP-3 proteolytic fragment approximate 18 kDa also showed positive correlation with levels of free IGF-I (r=0.23, P<0.05) and height (r=0.19, P<0.05). CONCLUSION: These findings may suggest that elevated levels of serum IGFBP-3 proteolytic fragments showing decreased affinity to IGF-I result in the increase of biologically active free IGF-I, thereby maintain normal growth in the obese children.
Blotting, Western ; Carrier Proteins ; Child* ; Growth Hormone ; Humans ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Intercellular Signaling Peptides and Proteins* ; Obesity* ; Proteolysis*

PURPOSE:Most but not all intrauterine growth retardation(IUGR) children has catch-up growth postnatally. However, nothing is known about the predictive parameters on the catch-up growth. The aim of this study was to describe serum IGF-I, free IGF-I, IGFBP-1, and IGFBP-3 levels in IUGR children and to correlate these hormone values with auxologic parameters to investigate their value on the postnatal growth pattern. METHODS:Among children with IUGR born at Ewha Womans University from Jan. 1995 to Aug. 1998, 16 children with IUGR at 3 years of age and 12 age-matched normal controls were studied for auxologic and biologic parameters. We measured height, weight, and serum levels of insulin-like growth factor(IGF)-I, free IGF-I, IGF binding protein(BP)-1, IGFBP-3 using immunoradiometric kits. RESULTS: 1)Among 16 children with IUGR at 3 years of age, 13 children had catch-up growth(81.3%), but 3 children remained short stature(18.7%). The height standard deviation score(SDS) in children with IUGR and control were -0.3+/-0.8 and 0.8+/-0.7, respectively(P<0.05) and weight SDS were -0.7+/-0.9 and 1.1+/-1.1, respectively(P>0.05). 2)Serum IGF-I levels in children with IUGR at 3 years of age and normal control were 90.9+/-35.4ng/mL and 68.4+/-24.4ng/mL, respectively(p>0.05) and free IGF-I were 0.9+/-0.5ng/mL and 0.6+/-0.3ng/mL(p>0.05), IGFBP-1 were 50.5+/-30.5ng/ mL and 52.3+/-23.2ng/mL(p>0.05), IGFBP-3 were 4,116.7+/-1,062.2ng/mL and 4,058.4+/-808.5ng/mL(p>0.05), respectively. 3)In children with IUGR at 3 years of age, height SDS in IUGR children with catch-up growth and those without catch-up growth were 0.002+/-0.6 and -1.5+/-0.7, respectively(P<0.001), but there were no differences in weight SDS, body mass index, IGF-I, free IGF-I, IGFBP-1 and IGFBP-3. 4)There were no significant correlations between height gain and any growth factors. CONCLUSION: The results show that there is no difference in the levels of IGF-I, free IGF-I, IGFBP-1 and IGFBP-3 in IUGR children at 3 years of age compared to age-matched normal control, suggesting that other factors rather than IGF-I, free IGF-I, IGFBP-1, IGFBP-3 may cause short stature in IUGR.
Body Mass Index ; Child* ; Female ; Fetal Growth Retardation* ; Humans ; Insulin-Like Growth Factor Binding Protein 1* ; Insulin-Like Growth Factor Binding Protein 3* ; Insulin-Like Growth Factor I* ; Intercellular Signaling Peptides and Proteins