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.
Binding Sites ; Child* ; Chromatography ; Diagnosis ; Growth Hormone* ; Humans ; Insulin* ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Radioimmunoassay ; Somatomedins

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

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*

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

Based on the facts that expression of insulin-like growth factors(IGFs), their receptors, and insulin-like growth factor binding proteins(IGFBPs) have been found in many different types of malignancies including human ovarian cancer and their potent mitogenic effects in vitro, a role for IGFs mediated autocrine loop in oncogenesis and growth regulation of human malignancies was suggested. Since ascites support the biological environment for advanced ovarian cancer, it seemed to be resonable to measure the level of growth factors or cytokines in ascites for understanding precise mechanism of those factors in tumor biology. To investigate their roles and to evaluate prognostic significance in ovarian cancer, the IGFs/IGFBPs system were studied in the ascites, not in sera or cystic fluids, from 22 patients with ovarian cancer, who underwent surgical staging and subsequent cis-platinum based systemic chemotherapyery at the Department of Obstetrics and Gnecology, Hanyang University Hospital from Jan. 1989 through Dec. 1994. Ascites from 7 patients with benign disease were used as the control. IGF-I, II, IGFBP-1, and 3 were measured by immunoradiometric assay. The IGF-I level was significantly higher in ascites with ovarian cancer compared with those of benign disease(63.3-/+11.1 vs 17.9-/+6.2ng/ml, p=0.0098), but the level of IGF-II was not significantly different(70.5-/+13.9 vs 70.8-/+31.5 ng/ml, p=0.2827). IGFBP-1 levels were tend to be lower in ascites of patients with ovarian cancer than that of control(25.2-/+9.5 vs 58.6-/+28.2ng/ml, p=0.0637). However, IGFBP-3 levels had no statistically significant difference between two groups(779.7-/+110.6 vs 674.7-/+175.1ng/ml, p=0.8328). Although growth hormone levels were significantly higher in ascites with metastatic ovarian cancer than those of primary epithelial ovarian cancer, the levels of IGF-I, II, IGFBP-1 and 3 in ascites were not significantly different between two groups. IGF-I levels were correlated with the levels of IGFBP-3 in ascites with ovarian cancer(Y=8.83X-2.0, r=0.745, p=0.0000). High level of IGF-I in ascites of patients with ovarian cancer in this study was suggested that IGF-I had an important role on growth regulation of ovarian cancer. As majority of ascites were obtained from advanced and poorly differentiated ovarian cancer patients, IGF-I in ascites seemed to be related with intraperitoneal metastasis. Further large number of study including data from sera or cystic fluid will be needed to elucidate the role of the IGFs and IGFBPs in ascites of patients with ovarian cancer.
Ascites* ; Biology ; Carcinogenesis ; Cisplatin ; Cytokines ; Growth Hormone ; Humans ; Immunoradiometric Assay ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins* ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Intercellular Signaling Peptides and Proteins ; Neoplasm Metastasis ; Obstetrics ; Ovarian Neoplasms* ; Somatomedins*

OBJECTIVES: We examined the effects of neurotrophins and insulin-like growth factors on cell death induced by haloperidol, a typical anti-psychotic agent. METHOD: Neocortices from 14- or 15-daysold fetal mice for neuron-glia co-cultures were used for this experiment. RESULT: Twenty-four hours treatment of mouse cortical cell cultures with 30 M haloperidol-induced wide spread neuronal apoptosis characterized by cell body shrinkage, DNA fragmentation and condensation. Concurrent treatment with growth factors, BDNF, NT4/5, IGF-I and IGF-II, protect the neurons from the haloperidol-induced neuronal apoptosis(HINA) in a dose dependent manner(10-100ng/ml). CONCLUSION: The present study suggests the possibility that haloperidol toxicity can be hampered with growth factors. Further study about the mechanism underlying the protective capacity of the growth factors on HINA may lead to the development of the new protective strategy for tardive dyskinesia.
Animals ; Apoptosis* ; Brain-Derived Neurotrophic Factor ; Cell Culture Techniques* ; Cell Death ; Coculture Techniques ; DNA Fragmentation ; Haloperidol ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Intercellular Signaling Peptides and Proteins ; Mice* ; Movement Disorders ; Neocortex ; Nerve Growth Factors* ; Neurons* ; Somatomedins

PURPOSE: Insulin-like growth factors (IGFs) regulate a wide range of biological functions including cell proliferation, differentiation, and apoptosis through paracrine and autocrine mechanisms. Accordingly, the present study analyzed polymorphisms of IGF genes and their impact on the prognosis for patients with gastrointestinal stromal tumors (GISTs). METHODS: Two hundred-thirteen consecutive patients with GISTs who underwent curative surgery from 5 medical centers were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tumor tissue, and four IGF-1 (+2995C/A, +533C/T, IVS2-16540A/G, Ex4-177G/C) and one IGF-2 (IVS1+1280A/G) gene polymorphisms were determined using a Sequenom MassARRAY system. RESULTS: With a median follow-up of 18.4 months, the estimated 5-year relapse-free survival and overall survival rates were 69.9% and 86.7%, respectively. In a multivariate analysis including age, gender, primary site of disease, pathology, and risk stratification, no significant association was observed between the polymorphism of the IGF-1 and IGF-2 genes and survival. CONCLUSION: None of the five IGF-1 and IGF-2 gene polymorphisms investigated in this study was found to be an independent prognostic marker for Korean patients with surgically resected GIST. However, further studies on a larger scale are warranted to clarify the role of IGF-1 and IGF-2 gene polymorphisms as a prognostic biomarker for GIST patients.
Apoptosis ; Cell Proliferation ; DNA ; Follow-Up Studies ; Gastrointestinal Stromal Tumors ; Humans ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Multivariate Analysis ; Polymorphism, Single Nucleotide ; Prognosis ; Somatomedins ; Survival Rate

No abstract available.
Somatomedins*

No abstract available.
Child* ; Humans ; Insulin-Like Growth Factor I* ; Plasma* ; Somatomedins*

OBJECTIVE: The involvement of IGF system in hyperandrogenism and abnormal follicular development is controversial. This study is to assess whether IGF system contribute to it in the women with polycystic ovary(PCO). METHODS: Baseline serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), testosterone (T), androstenedione (ADD), prolactin, thyroid stimulating hormone (TSH), free insulin-like growth factor(IGF)-I, free IGF-II, insulin-like growth factor binding protein(IGFBP)-1, and IGFBP-3 were measured in twelve healthy regularly cycling volunteers and forty-two women with PCO then, the changes of baseline serum levels were evaluated after laparoscopic ovarian electrocauterization in nine PCO patients. In addition, the expression pattern of IGF-I and IGF-II was examined in the ovary of control and PCO group. RESULTS: Baseline levels of LH, ADD, free IGF-II, and IGFBP-3 were significantly higher in PCO group. However, there were no significant differences in the levels of free IGF-I and IGFBP-1, although free IGF-I showed decreasing tendency in PCO group. And there was a significant positive correlation between the LH and free IGF-II level in the PCO(P=0.011, r2=0.3899), but not in the control. After ovarian electrocauterization, LH, T, and ADD levels decreased, and free IGF-I and IGFBP-3 level increased. While free IGF-II and IGFBP-1 level showed no significant changes. In the ovary, expression of both IGFs showed similar pattern in normal and PCO ovaries. CONCLUSIONS: The elevated IGFBP-3 level may alter the bioavailability of IGF(s) in the PCO. The change in IGF-I level and resumption of ovulation after electrocauterization, suggest a possible role of IGF system in the impairment of follicular development in the PCO.
Androstenedione ; Biological Availability ; Carrier Proteins* ; Estradiol ; Female ; Follicle Stimulating Hormone ; Humans ; Hyperandrogenism ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Insulin-Like Growth Factor II ; Luteinizing Hormone ; Ovary* ; Ovulation ; Prolactin ; Somatomedins* ; Testosterone ; Thyrotropin ; Volunteers