PURPOSE:Insulin-like growth factors, IGF- I and IGF-II, are proteins that promote cellular growth and differentiation of the various organs including the kidney. These peptides circulate in serum bound to specific carrier proteins, called IGF binding proteins(IGFBPs). The IGFs are produced in most organs but liver is believed to be the principal source of circulating IGF-I. We studied the correlation of serum IGF-I and IGFBP-2 pattern with aging. METHODS:Sera were collected from 320 healthy population who were grouped according to age. IGF-I was seperated from IGFBPs by Sephadex G-50 acid chromatography. We measured serum IGF-I and IGFBP-2 by using radioimmuno-assay (RIA) and immunoradiometric assay (IRMA) respectively. RESULTS:Serum IGF-I levels were quite low in early childhood, rising slowly and reaching a peak during puberty and a significant decline(P<00.01) during adulthood. The age-dependent pattern of serum IGFBP-2 levels shows a pattern opposite to that of IGF-I which are high at birth, decline by late puberty and increase again with aging. CONCLUSION: Our results demonstrate the alteration of serum IGF-I and IGFBP- 2 pattern with aging. These data suggests that when these tests are performed in the clinic, their interpretation should be based upon age specific criteria.
Adolescent ; Aging* ; Carrier Proteins ; Chromatography ; Humans ; Immunoradiometric Assay ; Insulin-Like Growth Factor Binding Protein 2 ; Insulin-Like Growth Factor Binding Proteins ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Intercellular Signaling Peptides and Proteins ; Kidney ; Liver ; Parturition ; Peptides ; Puberty

The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis is an essential component of the hypothalamic-pituitary growth hormone axis and plays a crucial role in childhood growth and development. Disruptions and abnormalities in the GH/IGF-1 signaling pathway and its pathways typically manifest as short stature in children. Children with short stature often undergo GH stimulation testing and IGF-1 level measurements to differentiate growth hormone deficiency (GHD) from other causes of growth delay. This article aims to analyze and elucidate the values of GH stimulation testing and IGF-1 measurement, providing reference for the diagnosis of GHD in children.
Child ; Humans ; Growth Hormone/metabolism* ; Insulin-Like Growth Factor I/metabolism* ; Insulin-Like Peptides ; Insulin-Like Growth Factor Binding Protein 3 ; Human Growth Hormone/metabolism* ; Dwarfism, Pituitary/diagnosis*

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

Polypeptide growth factors belong to a class of potent biologic mediators which regulate cell differentiation, proliferation, migration and metabolism. IGF-I is polypeptides secreted by skeletal cells and is considered as regulators of bone formation. The purpose of this study is to evaluate the effects of IGF-I on bone nodule formation and alkaline phosphatase activity of MC3T3-E1 cells. MC3T3-E1 cells were seeded at 1x10(4) cells/well, 1x10(5) cells/well in alpha-modified Eagle medium containing 10% fetal bovine serum, 10 mM beta-glycerophosphate and 50microgram/ml of ascorbic acid. Before 48 hours of indicated time, medium were changed with serum free medium. After 24 hours, 0.1, 1, 10 ng/ml IGF-I were added to the cells and cultured for 3, 7, 14, 21, 28 days. And histochemical analysis was done and ALP activity was measured and was expressed as nmol/min/mg of protein. The bone nodule formation in MC3T3-E1 cells of IGF-I was seen at 21, 28 days, but there were no difference between control group and experimental groups. The ALP activity decreased when it is compare to control 2 group except for 1 ng/ml, 10 ng/ml IGF-I of 21-day-groups and 1 ng/ml IGF-I of 28-day-groups. Dose response effects of IGF-I of ALP activity in MC3T3-E1 cells were seen the highest ALP activity at 1ng/ml until 21days and the highest ALP activity at 10 ng/ml of 28 daygroups. The peak times were seen at 7-day group, 14-day group on control group and experimental group respectively, and 1 ng/ml group was the highest ALP activity. From the above results, IGF-I was not seen notable effect on bone nodule formation and decreased ALP activity of MC3T3-E1 cells but the use of IGF-I to mediate biological stimulation of MC3T3-E1 cells shows promise for future therapeutic application.
Alkaline Phosphatase ; Ascorbic Acid ; Cell Differentiation ; Eagles ; Insulin-Like Growth Factor I* ; Intercellular Signaling Peptides and Proteins ; Metabolism ; Osteogenesis ; Peptides

PURPOSE: Insulin-like growth factors (IGFs) are mitogenic peptides that are essential for fetal and maternal tissue growth during pregnancy. They circulate primarily with serum IGF-binding protein (IGFBP) which regulates the availability of IGFs to their specific target tissue. This study was performed to examine the relationships between birth weight and IGFs, insulin and growth hormone in the sera of cord blood. METHODS: Fetal serum samples were obtained by direct puncture of the umbilical cord and were stored at -20degrees C until assay. Serum IGF-I, insulin and growth hormone were measured by radioimmunoassay. IGF-II and IGFBP-1 were measured by immunoradiometric assay. RESULTS: The values of insulin, growth hormone, and IGFBP-1 in the cord blood did not significantly correlate with birth weight or gestational age. The values of IGF-I significantly correlated with gestational age (P<0.05). The correlation of IGF-I and birth weight was statistically significant (P<0.05). IGF-II in the sera of cord blood did not significantly correlate with birth weight. CONCLUSION: Cord blood IGF-I level strongly correlated with birth weight, which suggests that IGF-I may play an important role in fetal growth.
Birth Weight* ; Fetal Blood* ; Fetal Development ; Gestational Age ; Growth Hormone* ; Humans* ; Immunoradiometric Assay ; Insulin* ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Parturition* ; Peptides ; Pregnancy ; Punctures ; Radioimmunoassay ; Somatomedins* ; Umbilical Cord

PURPOSE: Zinc is an essential nutrient, which is required to maintain the normal structure and/or function of multiple enzymes. Therefore, zinc nutriture has been known to influence the physical growth of young children. This study was desinged to evaluate the relationship between blood zinc levels and growth parameters in children. METHODS: Two hundred eighty three children (150 boys and 133 girls) who visited the Youngdong Severance Hospital as short stature were enrolled in this study. Height standard deviation score (Ht. SDS), weight standard deviation score (Wt. SDS), and pubertal stage were obtained for each children. Blood samples were collected for zinc, alkaline phosphatase (ALP), insulin-like growth factor binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1), and free thyroxine (fT4). The relationship between blood zinc levels and growth status, and growth factors were analyzed. RESULTS: The Ht. SDS and Wt. SDS were -0.16+/-0.99, 0.16+/-0.88 respectively for the low blood zinc level group; the Ht. SDS and Wt. SDS were -0.16+/-0.97, 0.08+/-0.93 respectively for the normal blood zinc level group. Between two groups, Ht. SDS, Wt. SDS, bone age, pubertal stage, ALP, and IGF-1 showed no significant differences, while IGFBP-3 and fT4 showed significant differences (P<0.05). The mean zinc concentrations showed no significant difference between the normal stature group and short stature group (101.60+/-41.11 microgram/dL, 93.72+/-35.38 microgram/dL respectively). The Ht. SDS, Wt. SDS, pubertal stage, ALP, and IGF-1 showed no significant correlation with the zinc levels, while the IGFBP-3 and fT4 showed significant correlation (P<0.05). CONCLUSION: We could not find any significant relationship between blood zinc level and growth status. However, interpretation of our results should be cautious in aspect that the result might come from the subjects with mild zinc deficiency. Further study is required to investigate the severe zinc deficiency patients and zinc replacement study.
Alkaline Phosphatase ; Child* ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Intercellular Signaling Peptides and Proteins ; Thyroxine ; Zinc*

pose:Growth delay in asthmatic children has been reported, but the causes are unclear. In this study, we analyzed growth status in children with mild asthma and measured serum insulin-like growth factor (IGF)-I and insulin-like growth factor binding protein (IGFBP)-3 to evaluate the relationship between the growth status and growth factors. We also evaluated the difference in the relationship of height standard deviation score (HTSDS) according to weight standard deviation score (WTSDS) between children with asthma and controls. METHODS:58 children between the age of 9 months and 12 years, who visited Konkuk University Hospital between July 2002 to June 2003, with wheeze and responded to bronchodilators were enrolled as asthma group. 59 children between the age of 6 months and 14 years without any medical problem were enrolled as controls. Height and weight were measured for both groups and their standard deviation scores were calculated respectively. Blood samples were collected for serum IGF-I, IGFBP-3 levels and IGF-I/IGFBP-3 ratio were calculated from those values. The relationships between each growth status and growth factors were analyzed. RESULTS:The HTSDS and WTSDS were 0.17+/-.00, 0.38+/-.23 respectively for the asthma group; the HTSDS and WTSDS were 0.05+/-.95, 0.08+/-.06 respectively for the controls. IGF-I was 169.6+/-0.7 ng/mL, IGFBP-3 was 2146.0+/-36.5 ng/mL, and IGF-I/IGFBP-3 ratio was 0.08+/-.03 for the asthma group; IGF-I was 422.6+/-70.3 ng/mL, IGFBP-3 was 3409.6+/-61.1 ng/mL, and IGF-I/IGFBP-3 ratio was 0.12+/-.05 for the controls. In both groups, the concentration of IGF-I, IGFBP-3 and IGF-I/ IGFBP-3 ratio showed significant correlation with the age (P<0.01). In both groups, the correlation coefficient for WTSDS and HTSDS were 0.39 and 0.64, which were statistically significant. In the asthma group, the height gain was significantly smaller than the weight gain compared with controls (P<0.05). CONCLUSION: We concluded that in children with mild asthma the increment in HTSDS according to WTSDS is less than that of controls.
Asthma* ; Bronchodilator Agents ; Carrier Proteins ; Child* ; Humans ; Insulin-Like Growth Factor Binding Protein 3* ; Insulin-Like Growth Factor I* ; Intercellular Signaling Peptides and Proteins ; Weight Gain

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*

BACKGROUND: Pregnancy in human and rodents is associated with dramatic matemal metabolic changes. Insulin-like growth factors (IGFs) are mitogenic peptides that are essential for fetal and maternal tissue growth during pregnancy. They circulate complexed primarily with a serum IGF-binding protein (IGFBP-3) which regulates the availability of the IGFs to their specific target tissues. METHODS: To examine the changes of IGFs and IGFB-3 during pregnancy, we measured serum total IGF-I, free IGF-I, IGF-II and IGFBP-3 by using specific radioimmunoassay, immunoradio-metric assay, western ligand blot and western immunoblot. Blood samples were obtained from 88 pregnant women between 6-40 weeks gestation. RESULTS: While serum IGF-I levels increased up to 50% in late pregnancy, serum IGF-II levels remained unchanged. However, serum free IGF-I levels were significantly higher during pregnancy than in nonpregnancy. Western ligand blot analysis revealed that IGFBP-3 in pregnancy serum was significantly decreased at 6 weeks of gestation, continued decreased level until term, and returned to a nonpregnant level by postpartum 10 day. Serum IGFBP-3 profiles in Western immunoblot analysis revealed that 30 kDa fragments of IGFBP-3 were detectable in pregnancy serum but not in nonpregnancy serum. In contrast, serum IGFBP-3 levels using radioimmunoassay was significantly increased in late pregnancy. CONCLUSIONS: 1) serum IGF-I was significantly elevated in late pregnancy 2) serum IGF-II was not significantly changed 3) free IGF-I significantly elevated throughout gestation 4) intact IGFBP-3 was markedly reduced after 6 weeks of gestation.
Blotting, Western ; Female ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Peptides ; Postpartum Period ; Pregnancy* ; Pregnant Women ; Radioimmunoassay ; Rodentia ; Somatomedins