PURPOSE: We performed this study to evaluate the mean serum levels of insulin-like growth factor (IGF)-I, insulin-like growth factor binding protein(IGFBP)-2 and IGFBP-3 in healthy Korean children according to age and sex. METHODS: Ninety two healthy children, consisting of 42 boys and 50 girls, were classified into five groups according to age:neonate; infancy; early childhood; late childhood; and adolescence. We measured serum levels of IGF-I, IGFBP-2 and IGFBP-3 by enzyme-linked immunosorbent assay(ELISA) and analysed the serum levels according to sex and age group. RESULTS: For boys, the mean serum levels of IGF-I(ng/mL) in neonate, infancy, early childhood, late childhood and adolescence were 41.1+/-3.6, 70.9+/-33.7, 103.5+/-97.2, 89.8+/-46.5 and 51.4+/-27.8, respectively. Those of IGFBP-2(ng/mL) were 8.2+/-3.4, 5.8+/-0.4, 9.3+/-4.0, 9.5+/-1.1 and 7.0+/-0.5, respectively. Those of IGFBP-3(ng/mL) were 559.2+/-215.2, 1,333.3+/-692.5, 2,254.6+/-1,513.8, 2,447.1+/-1,464.2, 1,533.6+/-807.4, respectively. For girls, the mean serum levels of IGF-I(ng/mL) according to five age groups were 53.3+/-9.5, 99.3+/-45.8, 69.6+/-51.1, 106.2+/-67.0 and 145.1+/-127.8, respectively. Those of IGFBP-2 (ng/mL) were 9.1+/-7.4, 5.3+/-0.9, 6.9+/-2.0, 10.5+/-3.0 and 7.9+/-1.3, respectively. Those of IGFBP-3(ng/ mL) were 858.2+/-433.4, 1,834.8+/-851.3, 1,404.3+/-570.2, 2,203.5+/-899.4 and 2,029.3+/-1,316.7, respectively. There were significant positive correlations observed between IGF-I and IGFBP-3 levels(r=0.589, P= 0.000). CONCLUSION: IGF-I and IGFBP-3 levels increased as children get older. The peak level of IGFBP-3 was observed in late childhood for both boys and girls, suggesting a current trend of children reaching peak growth velocity before adolescence. The IGFBP-2 level was higher in neonates compare to infancy, suggesting that IGFBP-2 is an important substance for fetal growth.
Adolescent ; Child* ; Female ; Fetal Development ; Humans ; Infant, Newborn ; Insulin-Like Growth Factor Binding Protein 2 ; Insulin-Like Growth Factor Binding Protein 3* ; Insulin-Like Growth Factor I

BACKGROUND: Sex steroid hormones are believed to play an important role in the genesis and growth of uterine myoma. Several studies suggest a possible role of insulin-like growth factor(IGF) as a mediator of estradiol in uterine myama. We have recently demonstrated that some IGF binding proteins(IGFRPs) messenger ribonucleic acid(mRNA) expressions in myoma are dependent on the in vivo esttogen status. The purposes of this study are to evaluate the in vitro effects of sex steroid hormones including estrogen on the IGFBPs gene expression in tissues from uterine myoma and adjacent normal myometrium. METHODS: Tissues from myoma and adjacent normal myometrium of patients with uterine myoma during early proliferative phase of menstrual cycle were cultured in the absence(control) and presence of 17b-estradiol(10M/L) or/and progesterone(10M/L) for 3 days. The IGFBPs mRNA expressions in these explants were analyzed by Nothern blot using specific human complementary deoxyribonucleic acid(cDNA) probes. RESULTS: The addition of 17b-estradiol, progesterone alone and in combination to conditioned media of explants from myoma and adjacent normal myornetrium did not result in any changes in the expression of IGFBP-2, IGFBP-4, IGFBP-5, and IGFBP-6 mRNA. With progesterone addtion, lGFBP-3 rnRNA expression was significantly reduced in myoma explant but not in adjacent ncemal myometrium explant. There was no significant change in the IGFBP-3 mRNA expression with 17b-estradiol and with the combination of both 17b-estradiol and progesterone. CONCLUSION: 17b-estradiol does not affect IGFBPs gene expression in the myoma and adjacent normal myometrium explant regardless of the presence of progesterone in vitro. However progesterone alone induces a decrease in IGFBP-3 synthesis in myoma explant.
Animals ; Culture Media, Conditioned ; Estradiol ; Estrogens ; Female ; Gene Expression ; Gonadal Steroid Hormones ; Humans* ; 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 Protein 5 ; Insulin-Like Growth Factor Binding Protein 6 ; Insulin-Like Growth Factor Binding Proteins ; Leiomyoma* ; Menstrual Cycle ; Mice ; Myoma ; Myometrium* ; Progesterone ; RNA, Messenger*

BACKGROUND: Uterine leiomyoma is the most common pelvic tumor, occurring in 20-25% of women in reproductive age. Gonadotropin releasing hormone agonist (GnRHa) has been reognized as a temporary medical management for this disorder. The etiology of these tumors is unknown but it has been shown that the insulin-like growth factors (IGF-I, IGF-II) are promoters of growth in nongynecologic tumors. Several recent studies have suggested the possible role of IGFs in human leiomyoma growth. The IGF binding proteins (IGFBPs) are believed to modulate actions of IGF and to have IGF-independent actions. The purpose of this study was to evaluate the type of IGF and IGFBP which may be involved in leiomyoma growth and to investigate a possible IGF related mechanism of action of GnRHa. METHOD: The IGFs and IGFBPs were measured by double antibody radioimmunoassay, western ligand blot and immunoprecipitation in the tissue cytosols of normal uterine myometria (n=15), nontumorous myometria adjacent to a leiomyoma and leiomyoma from patients nontreated (n=15) and treated (n=10) with GnRHa. RESULTS: The mean IGF-I and IGF-II level were significantly higher in leiomyoma from untreated patients than in the adjacent myometrium and normal myometrium but no significant differences in these IGF levels between normal myometrium and adjacent myometrium were noted. The IGFBP-2, IGFBP-3 and 26kDa IGFBP were detected variably but IGFBP-4 was consistently present in all tissues. There were no significant differences in the relative intensity for IGFBP-4 and the frequency of IGFBPs between leiomyoma, adjacent myometrium and normal myometrium from untreated patients. The IGF-I, IGF-II levels and the relative intensity of IGFBP-4 in leiomyoma from GnRHa-treated patients were significantly lower than those in untreated patients, but these levels in the adjacent myometrium were comparable. The frequency of each IGFBP in leiomyoma and the adjacent myornetrium from GnRHa-treated patients did not significantly differ from untreated patients. CONCLUSION: Both IGF-I and IGF-II are involved in the growth of leiomyoma and GnRHa may in part act to decrease size of leiomyoma by regulating the local levels of IGF-I, IGF-II and IGFBP-4.
Animals ; Cytosol ; Female ; Gonadotropin-Releasing Hormone ; Humans ; Immunoprecipitation ; 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 ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Leiomyoma* ; Mice ; Myometrium ; Radioimmunoassay ; Somatomedins*

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 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

PURPOSE: The purpose of this study was to demonstrate the hypothesis that tussue IGFBP-2,-3, and -4 levels would differ between colon cancer tissue and adjacent normal tissue and to determine whether these factors could affect the clinicopathologic characteristics such as age, tumor stage, differentiation, serosal invasion, and CEA in patients with colon cancer. METHODS: This study group consisted of 102 patients with colorectal cancer who under went operations between January 2004 and December 2006. Postoperative colon cancer specimens and adjacent normal colon tissues were obtained immediately. Histopathologic examinations were made by on pathologist for each specimen. The gene expressions of IGFBP-2,-3,-4 in cancer and normal tissues were measured using a reverse transcriptase-polymerase chain reaction (RT-PCR). In additional, the various clinic-opathologic factors were evaluated for both tissues by comparing the IGFBP-2, -3, -4 expression densities. RESULTS: No significant difference was found in the expression of IGFBP-3, -4 between colon cancer and normal colon tissues. A statistically significant expression of IGFBP-2 was detected in the cancer specimens compared with the normal colon tissues. IGFBP-3 was significantly associated with pathologic N stage. CONCLUSIONS: This is a rare report comparing colon cancer with normal colon tissue for IGFBP expression by means of a systemical evaluation of colon cancer patients. Our data suggest that IGFBP-2 may be intimately associated with malignant phenotypes, and may confer some growth advantage on tumor cells, which means that IGFBP-2 shows a high sensitivity for colorectal cancer. Interestingly, IGFBP-3 was strongly associated with the pathologic N stage. We think further studies are needed to understand this phenomenon.
Colon ; Colonic Neoplasms ; Colorectal Neoplasms ; Gene Expression ; Humans ; Imidazoles ; Insulin-Like Growth Factor Binding Protein 2 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins ; Nitro Compounds ; Phenotype

Angiotensin I ; Hepatic Stellate Cells ; Insulin-Like Growth Factor Binding Protein 2 ; Peptide Fragments ; Peptidyl-Dipeptidase A

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*

PURPOSE: Insulin-like growth factor (IGF)-I and II are potent mitogens, postulated to exert autocrine and paracrine effects on growth regulation in human gastric cancer. In this study, we evaluated the expression of IGF-I, -II and IGFBPs in a panel of human gastric cancer cell lines. We also evaluated whether high expression of IGFBP-3 in human gastric cancer cells may increase the sensitivity to the anti-proliferative agents. MATERIALS AND METHODS: 10 human korean gastric cancer ceIl lines and 1 Caucacian gastric adenocarcinoma cell line were used for this study. IGF and IGFBP expressions were evaluated by RT-PCR. IGFBP proteins in conditioned media were detected by Western Ligand Blot. Cell survival after treatment of anti-proliferative agents was assessed by MTT assay. RESULTS: IGF-I and II were expressed in all gastric cancer cell lines. In addition, IGF-I and II stimulated the proliferation of gastric cancer cells. The expression of IGFBP-2 was found in all gastric cancer cell lines. IGFBP-4 was expressed in the most of cell lines. IGFBP-3, -4 and -6 were expressed in about 50% of cell lines. The growth inhibition of IGFBP-3 expressing cells by anti- proliferative agents was more significant than that of IGFBP-3 nonexpressing cells. Cell growth inhibition with treatment of these agents was accompanied by increased IGFBP-3 mRNA level. CONCLUSION: These data confirm that IGF-I, -II, and certain IGFBPs were expressed in gastric cancer cells, and gastric cancer cells show the differential growth inhibition by anti-proliferative agents. The differential growth inhibitory effect of anti-proliferative agents is, at least in part, mediated through up-regulation of IGFBP-3 expression.
Adenocarcinoma ; Carrier Proteins* ; Cell Line* ; Cell Survival ; Culture Media, Conditioned ; Humans ; 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 ; Insulin-Like Growth Factor I ; Mitogens ; RNA, Messenger ; Stomach Neoplasms* ; Up-Regulation

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