Child ; Child, Preschool ; Female ; Growth Disorders ; blood ; diagnosis ; Human Growth Hormone ; deficiency ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Male

OBJECTIVEIntrauterine growth retardation (IUGR) may contribute to the disorder of development of fetal brains. L-arginine has been known to be effective in blood vessel distension and improving the blood circulation of placentas. Recent studies have shown that L-arginine can ameliorate the placental hypoxia and improve the development of fetus. This study aimed to explore the effects of L-arginine on the expression of insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein-3(IGFBP3)and IGF-I mRNA in brains of IUGR rats and the possible mechanisms of L-arginine.

METHODSThirty-six pregnant rats were randomly assigned into four groups: Control, Model, Low dose L-arginine (100 mg/kg) and High-dose L-arginine (200 mg/kg L-arginine) groups (n=9 each). IUGR was induced by passive smoking in rats from the last three groups. L-arginine was administered for the last two groups between days 8 and 20 of gestation. On day 21 of gestation, the pup rats were delivered by cesarean section. The levels of IGF-I, IGF-II and IGFBP3 in the brains of pup rats were measured by enzyme-linked immunoadsordent assay (ELISA) and the expression of IGF-I mRNA was detected by fluorescence quantitative PCR (FQ-PCR).

RESULTSThe levels of IGF-I, IGF-II and IGF-I mRNA expression in the Model group were significantly lower than in the Control group, with the IGF-I levels of 0.789 +/- 0.062 ng/mg vs 0.947 +/- 0.042 ng/mg, the IGF-II levels of 0.270 +/- 0.020 ng/mg vs 0.374 +/- 0.015 ng/mg and the IGF-I mRNA expression of (13.12 +/- 1.39) x 10(4) cps/mug RNA vs (21.28 +/- 3.54) x 10(4) cps/mug RNA (P < 0.01). In contrast, the IGFBP3 levels in the Model group were significantly higher than in the Control group (0.253 +/- 0.011 ng/mg vs 0.089 +/- 0.015 ng/mg; P < 0.01). Low or high dose L-arginine treatment increased significantly the IGF-I levels from 0.789 +/- 0.062 ng/mg (Model group) to 0.937 +/- 0.067 ng/mg (low dose group) or 0.858 +/- 0.077 ng/mg (high dose group), the IGF-II levels from 0.270 +/- 0.020 ng/mg (Model group) to 0.318 +/- 0.018 ng/mg (low dose group) or 0.354 +/- 0.021 ng/mg (high dose group) and the IGF-I mRNA expression from (13.12 +/- 1.39) x 10(4) cps/mug RNA (Model group) to (19.24 +/- 2.48) x 10(4) cps/mug RNA (low dose group) or (17.35 +/- 2.30) x 10(4) cps/mug RNA (high dose group) (P < 0.01). The IGFBP3 levels were significantly reduced after low or high dose L-arginine treatment (0.132 +/- 0.006 ng/mg or 0.146 +/- 0.009 ng/mg) compared with those of the Model group (0.253 +/- 0.011 ng/mg) ( P < 0.01).

CONCLUSIONSL-arginine can increase the levels of IGF-I and IGF-II and the IGF-I mRNA expression, and decrease the IGFBP3 level in the brain of rats with IUGR induced by passive smoking, thereby offering protective effects against IUGR.

Animals ; Arginine ; pharmacology ; therapeutic use ; Female ; Fetal Growth Retardation ; metabolism ; prevention & control ; Insulin-Like Growth Factor Binding Protein 3 ; analysis ; Insulin-Like Growth Factor I ; analysis ; genetics ; Insulin-Like Growth Factor II ; analysis ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar

Cows with different Insulin-like Growth Factor-I (IGF-I) concentrations showed comparable expression levels of hepatic growth hormone receptor (GHR). Suppressor of cytokine signaling 2 (SOCS2), could be responsible for additional inhibition of the GHR signal cascade. The aims were to monitor cows with high or low antepartal IGF-I concentrations (IGF-I(high) or IGF-I(low)), evaluate the interrelationships of endocrine endpoints, and measure hepatic SOCS2 expression. Dairy cows (n = 20) were selected (240 to 254 days after artificial insemination (AI)). Blood samples were drawn daily (day -17 until calving) and IGF-I, GH, insulin, thyroid hormones, estradiol, and progesterone concentrations were measured. Liver biopsies were taken (day 264 +/- 1 after AI and postpartum) to measure mRNA expression (IGF-I, IGFBP-2, IGFBP-3, IGFBP-4, acid labile subunit (ALS), SOCS2, deiodinase1, GHR1A). IGF-I concentrations in the two groups were different (p < 0.0001). However, GH concentrations and GHR1A mRNA expression were comparable (p > 0.05). Thyroxine levels and ALS expression were higher in the IGF-I(high) cows compared to IGF-I(low) cows. Estradiol concentration tended to be greater in the IGF-I(low) group (p = 0.06). It was hypothesized that low IGF-I levels are associated with enhanced SOCS2 expression although this could not be decisively confirmed by the present study.
Animals ; Cattle ; Estradiol/blood ; Female ; Growth Hormone/blood ; Insulin/blood ; Insulin-Like Growth Factor Binding Protein 2/analysis ; Insulin-Like Growth Factor Binding Protein 3/analysis ; Insulin-Like Growth Factor Binding Protein 4/analysis ; Insulin-Like Growth Factor I/*analysis/physiology ; Liver/chemistry ; Pregnancy/metabolism/physiology ; Pregnancy, Animal/*metabolism/physiology ; Progesterone/blood ; Suppressor of Cytokine Signaling Proteins/analysis ; Thyroid Hormones/blood

OBJECTIVETo study the clinical significance of serum levels of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) in children with Henoch-Schonlein purpura (HSP) or Henoch-Schonlein purpura nephritis (HSPN).

METHODSThirty-one children with HSP were selected as the HSP group, and 28 children with HSPN were selected as the HSPN group. Another 31 healthy children were selected as the control group. ELISA was used to measure serum levels of IGF-1 and IGFBP-3 in each group. Measurement of 24-hour urinary protein excretion was performed using an automatic biochemical analyzer in the HSPN group. Serum immunoglobulin (Ig) levels, complement C3 level and complete blood counts in each group were determined, and urine analysis was also performed.

RESULTSSerum levels of IGF-1 and IGFBP-3 in the HSP group were significantly higher than in the control group (P<0.05), and serum levels of IGF-1 and IGFBP-3 in the HSPN group were significantly higher than in the HSP and control groups (P<0.05). Among 12 children who underwent renal puncture biopsy, patients with higher pathological grades had higher serum levels of IGF-1 and IGFBP-3. In children with HSPN, those with proteinuria had significantly higher serum levels of IGF-1 and IGFBP-3 than those without proteinuria (P<0.05). Levels of white cells, red cells, platelet count, complement C3, IgG, and IgA and IgA/C3 ratio were significantly higher in the HSP and HSPN groups than in the control group (P<0.05).

CONCLUSIONSIncreased serum levels of IGF-1 and IGFBP-3 are observed in the acute onset period of HSP, which may be related to the degree of proteinuria and renal damage. Serum levels of IGF-1 and IGFBP-3 may be indicators of renal involvement.

Child ; Child, Preschool ; Female ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Nephritis ; blood ; pathology ; Purpura, Schoenlein-Henoch ; blood ; pathology

OBJECTIVESTo determine changes of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) in serum samples from benign prostatic hyperplasia (BPH) patients and to evaluate the value of these molecules as possible etiologic factors for BPH.

METHODSThe serum IGF-1 and IGFBP-3 levels were measured with immunoradiometric assay(IRMA) in 64 cases of BPH and in 30 healthy subjects as controls. The cases of BPH were divided into 3 groups according to the prostate volume(PV). There were 18 cases(PV < or = 30 ml) in group A, 24 cases(PV31 approximately 50 ml) in group B, 22 cases(PV > or = 50 ml) in group C.

RESULTSThere were no statistical differences between the levels of Both IGF-1 and IGFBP-3 in BPH groups and healthy groups (both P > 0.05), but there were statistical differences among three groups of BPH. Both IGF-1 and IGFBP-3 levels in group C of BPH were significantly higher than those in group A (both P < 0.05). A positive correlation between the serum levels of IGF-1 and PV displayed(r = 0.58), as well as IGFBP-3 (r = 0.48).

CONCLUSIONSTogether these observations implicate IGF-1 and IGFBP-3 as important factors during the progression of BPH. It shows the value of non-operation treatment for this disease.

Aged ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Prostatic Hyperplasia ; blood ; Radioimmunoassay

OBJECTIVETo study serum levels and clinical significance of insulin-like growth factor-1 (IGF-1) and growth factor binding protein 3 (IGFBP-3) in children with acute lymphocytic leukemia (ALL).

METHODSSerum samples were obtained from 36 children with ALL before treatment and 6 months after complete remission. Thirty children with surgical diseases severed as the control group. Serum IGF-1 levels were measured using radioimmunoassay (RIA). Serum IGFBP-3 levels were measured using immunoradioassays (IRMA).

RESULTSSerum levels of IGF-1 and IGFBP-3 in the ALL group were 19±4 ng/mL and 1216±132 ng/mL, respectively before treatment, which were lower than those in the control group (32±3 ng/mL and 2104±191 ng/mL respectively) (P<0.01). Serum levels of IGF-1 and IGFBP-3 in the ALL group increased to 30±3 ng/mL and 1941±164 ng/mL respectively 6 months after complete remission, which were significantly higher than those before treatment (P<0.01) and were similar to the levels of the control group.

CONCLUSIONSSerum levels of IGF-1 and IGFBP-3 are reduced in children with ALL, but increase significantly after complete remission, suggesting that IGF-1 and IGFBP-3 might serve as useful markers for the diagnosis and evaluation of therapeutic effects of childhood ALL.

Adolescent ; Biomarkers, Tumor ; blood ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; diagnosis

AIMTo investigate the relationships of serum testosterone, insulin-like growth factor (IGF)-1 and IGF-binding protein (IGFBP)-3 levels with prostate cancer risk and also with known prognostic parameters of prostate cancer in Korean men who received radical retropubic prostatectomy (RRP) for clinically-localized prostate cancer.

METHODSSerum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 were determined in 592 patients who subsequently received prostate biopsy. Results were compared between patients who eventually received RRP for prostate cancer (n=159) and those who were not diagnosed with prostate cancer from biopsy (control group, n=433). Among the prostate cancer only patients, serum hormonal levels obtained were analyzed in relation to serum prostate specific antigen (PSA), pathological T stage and pathological Gleason score.

RESULTSProstate cancer patients and the control group demonstrated no significant differences regarding serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 across the different age groups. Among the cancer only patients, no significant associations were observed for serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 levels with pathological T stage, pathological Gleason score and preoperative PSA.

CONCLUSIONOur data indicate that simple quantifications of serum testosterone and IGF-1 along with IGFBP-3 levels might not provide useful clinical information in the diagnosis of clinically localized prostate cancer in Korean men. Also, our results suggest that serum levels of testosterone, IGF-1 and IGFBP-3 might not be significantly associated with known prognostic factors of clinically localized prostate cancer in Korean men.

Aged ; Biomarkers, Tumor ; blood ; Biopsy, Needle ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins ; blood ; Insulin-Like Growth Factor I ; analysis ; Korea ; Male ; Middle Aged ; Prognosis ; Prostatic Neoplasms ; blood ; pathology ; Testosterone ; blood

OBJECTIVETo investigate the efficacy and safety of different doses of recombinant human growth hormone (rhGH) in the treatment of short stature in children born small for gestational age (SGA).

METHODSA total of 37 children with short stature born SGA were enrolled, and based on the dose of rhGH treatment, they were divided into low-dose rhGH group (0.1-0.15 IU/kg daily) and high-dose rhGH group (0.16-0.2 IU/kg daily). The changes in height standard deviation score (ΔHtSDS), height velocity (HV), serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3), and fasting blood glucose at 3, 6, 9, 12, and 24 months after treatment were compared between the two groups.

RESULTSΔHtSDS and HV both increased after the treatment with high- and low-dose rhGH, but ΔHtSDS and HV in the high-dose rhGH group were significantly higher than in the low-dose rhGH group 9, 12 and 24 months after treatment (P<0.05). Both high- and low-dose rhGH treatment increased serum levels of IGF-1 and IGFBP-3. Serum levels of IGF-1 and IGFBP-3 were positively correlated with HtSDS in both groups. One child each in the high- and low-dose rhGH groups experienced transient slight increase in fasting blood glucose (6.1 mmol/L). There were no cases of abnormal thyroid function.

CONCLUSIONSrhGH has good efficacy in the treatment of short stature in children born SGA, with few adverse events, and high-dose rhGH has some advantages over low-dose rhGH.

Body Height ; Child ; Child, Preschool ; Female ; Growth Disorders ; blood ; drug therapy ; Human Growth Hormone ; therapeutic use ; Humans ; Infant, Small for Gestational Age ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Recombinant Proteins ; therapeutic use

OBJECTIVETo study the effects of maternal folate deficiency on fetal growth and development and the methylation profiles of insulin-like growth factor system in the offspring rats.

METHODSTwenty-two Sprague-Dawley female rats were randomly assigned to two groups: a folate deficient group (n=12) and a control group (n=10). They were fed with folate deficient and normal diet respectively. Dams were mated after 2 weeks of feeding. Eight female rats from each group were pregnant. On the 20th day of gestation, the fetuses were delivered by caesarean section. Thirty-two fetal rats from each group were randomly selected and the body length and weight were measured. Eight fetal rats from each group were randomly selected and ELISA was used to measure the level of folate content, IGF-1 and IGFBP-3 in the fetal brain and liver. Three fetal rats from each group were randomly selected and methylated DNA immunoprecipitation sequencing (MeDIP-Seq) was used to detect the methylation level of insulin-like growth factor system in the fetal brain and liver. ELISA was used to measure the level of IGF-1 and IGFBP-3 in the maternal serum from both groups.

RESULTSThe mean fetal length and weight were lower in the folate deficient group than in the control group (P<0.05). The levels of IGF-1 and IGFBP-3 in the maternal serum, as well as folate content and IGFBP-3 in the fetal brain and liver were significantly lower in the folate deficient group than in the control group (P<0.05). The methylation levels of IGF-1R, IGF-2R, IGFBP-2, IGFBP-5, IGFBP-6 and IGFBP-7 in the fetal brain were higher in the folate deficient group than in the control group (P<0.05). The methylation levels of IGF-1R, IGF-2R, IGFBP-3 and IGFBP-5 in the fetal liver were higher in the folate deficient group than in the control group. The methylation of IGF-2 gene showed a significant reduction in the folate deficient group (P<0.05).

CONCLUSIONSMaternal folate deficiency may cause retardation of growth and development of the offspring, which is possibly associated with the changes of methylation profiles of insulin-like growth factors.

Animals ; Brain ; metabolism ; DNA Methylation ; Female ; Fetal Development ; Fetus ; metabolism ; Folic Acid Deficiency ; metabolism ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Liver ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate changes in serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) and their significance in children with left-to-right shunt congenital heart disease (CHD) associated with heart failure (HF).

METHODSTwenty healthy children (control group), 20 children with HF, without basic heart disease (HF group), 20 children with left-to-right shunt CHD, without HF (CHD group), and 30 children with left-to-right shunt CHD associated with HF (CHD+HF group) were included in the study. These groups were compared in terms of serum IGF-1 and IGFBP-3 levels. According to the New York Heart Association (NYHA) Functional Classification, the CHD+HF group was further divided into NYHA-II, NYHA-III and NYHA-IV subgroups and the subgroups were compared in terms of serum IGF-1, IGFBP-3, and cardiac troponin I (cTnI) levels. The correlation of serum IGF-1 and IGFBP-3 levels with serum cTnI level in the CHD+HF group was analyzed.

RESULTSThe CHD group showed decreased serum IGF-1 and IGFBP-3 levels compared with the control group (P<0.01). The CHD+HF group showed a significantly decreased serum IGF-1 level compared with the control group (P<0.01) and CHD group (P<0.05). The HF group had significantly increased serum IGF-1 and IGFBP-3 levels compared with other groups (P<0.01). The NYHA-II subgroup had the highest serum IGF-1 level and the NYHA-IV subgroup had the lowest serum IGF-1 level (P<0.01). In the CHD+HF group, serum IGF-1 and IGFBP-3 levels were negatively correlated with serum cTnI level (r=-0.692, P<0.05; r=-0.530, P<0.05).

CONCLUSIONSSerum IGF-1 level can be used as an objective condition evaluation indicator for CHD, and low serum IGF-1 level is a risk factor for HF. This also provides a clinical basis for treatment of HF using exogenous IGF-1.

Child, Preschool ; Female ; Heart Defects, Congenital ; blood ; Heart Failure ; blood ; Humans ; Infant ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Troponin I ; blood