IGF-binding Protein-3 Concentrations Research Articles

Novel Relationships of Age, Visceral Adiposity, Insulin-Like Growth Factor (IGF)-I and IGF Binding Protein Concentrations to Growth Hormone (GH) Releasing-Hormone and GH Releasing-Peptide Efficacies in Men during Experimental Hypogonadal Clamp

Sex steroids influence GH secretion in complex ways. Analyses in a low sex-steroid milieu will help unveil the effects of age and other nonsteroidal regulators on GH secretion. The study was conducted in a tertiary medical center. The study group included 13 healthy young men and 12 healthy older men. We used GnRH agonist-induced down-regulation of testosterone and estradiol secretion, followed by consecutive infusion of l-arginine and GHRH or GHRP-2, to test secretagogue efficacies. We measured basal and pulsatile GH secretion. During experimental testosterone/estradiol deprivation, older (57 +/- 1.7 yr) men maintained: 1) 6.8-fold less pulsatile GH secretion (P < 0.001); and 2) 2-fold lower maximal GH responses to GHRH (P = 0.0065) and GHRP-2 (P = 0.022) than young (23 +/- 1.1 yr old) individuals. Stepwise forward-selection regression analyses identified: 1) abdominal visceral fat as a dominant negative predictor of both GHRH (R(2) = 0.49; P = 0.001) and GHRP-2 (R(2) = 0.38; P = 0.005) efficacies; and 2) fasting IGF-I concentration as a major positive correlate of GHRH (R(2) = 0.52; P < 0.001) and GHRP-2 (R(2) = 0.31; P = 0.018) efficacies. Unstimulated pulsatile GH secretion was jointly correlated with IGF-I and IGFBP-3 (P = 0.039). Measures of body composition (abdominal visceral fat) and pulsatile GH action (IGF-I) explain up to one half of interindividual variability in the efficacies of GHRH and GHRP-2 in sex steroid-depleted men. Accordingly, normative ranges for maximal single peptide-stimulated GH secretion in short-term hypogonadal states should incorporate the influence of these determinants as well as age.

Influence of Gender on Serum Growth Hormone, Insulin-Like Growth Factor-I and Its Binding Protein-3 during Aging

PurposeThe serum concentrations of insulin-like growth factors-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and growth hormone (GH) are related to body composition, function and metabolism, and are influenced by the aging process. This study was to investigate the influence of gender on serum concentrations of IGF-I, IGFBP-3 and GH in middle and old age subjects.Materials and MethodsSixty healthy volunteers (male 35, female 25, 36-70 years) were divided into ≤ 50 and > 50 years groups, based on gender. Women > 50 years were post-menopause. IGF-I, IGFBP-3, and GH were determined by immunoradiometric assay.ResultsIGF-I was shown to be negatively correlated with age (women r = -0.62, p < 0.001; men r = -0.38, p < 0.05), whereas there was no correlation between IGF-I and GH values. Women > 50 years showed a significant reduction in IGF-I values than women ≤ 50 years (p < 0.01). Women > 50 years showed smaller IGF-I/IGFBP-3 molar ratios (0.177998 ± 0.039404) than men of same age group (0.228326 ± 0.050979, p < 0.01) and women ≤ 50 years (0.247667 ± 0.069411, p < 0.01). Age was shown to positively correlate with GH/IGF-I (r = 0.49, p < 0.05) and GH/IGFBP-3 ratios (r = 0.40, p < 0.05) in women.ConclusionsThe influence of aging on serum concentrations of IGF-I is more remarkable in women than in men. Menopause causes reduction of IGF-I/IGFBP-3 molar ratio. Women have the trend of progressive hypoactivity of GH to stimulate IGF-I and IGFBP-3 secretions with age.

Growth hormone/insulin-like growth factor axis in patients with subclinical thyroid dysfunction

Objective Our aim was to evaluate serum concentrations of GH, IGF-I, and insulin-like growth factor-binding protein-3 (IGFBP-3) in patients with subclinical thyroid dysfunction before and after normalization of thyroid function. Design and methods The study included 51 patients (mean age 42.2 ± 1.8 years) with subclinical hypothyroidism and 30 patients (mean age 44.3 ± 2.4 years) with subclinical hyperthyroidism. A group of 37 euthyroid healthy subjects were studied as controls. Serum concentrations of TSH, FT4, FT3, GH, insulin, IGF-I, and IGFBP-3 were measured in all patients before starting therapy and after normalization of thyroid function. The dosage of levothyroxine (LT4) and antithyroid drugs was adjusted in attempt to keep the serum-free thyroxine (FT4) and thyrotropin (TSH) concentrations within the normal range. Main outcome Baseline growth hormone levels were similar with hypothyroid group and hyperthyroid group in relation to euthyroid control subjects. Fasting serum IGF-I levels were significantly lower in the subclinical hypothyroid group compared with the control group. On the other hand, IGF-I levels of subclinical hyperthyroid patients and control group were similar. After normalization of thyroid function tests, IGF-I concentrations were increased in subclinical hypothyroid subjects, but unchanged in subclinical hyperthyroid subjects. Patients with subclinical hyperthyroidism showed slightly lower mean serum IGFBP-3 concentrations than those found in control group, but the difference was not statistically significant. Serum GH and IGFBP-3 levels were unaltered by treatment. Conclusions In this study, it was shown that GH–IGF axis was not affected in patients with subclinical hyperthyroidism, while it was affected in patients with subclinical hypothyroidism. That is, investigation of the axis in subclinical hyperthyroidism would not bring any extra advantages, but LT4 replacement therapy could prevent abnormalities related to GH–IGF axis in patients with subclinical hypothyroidism.

Factors affecting decidual IGFBP‐1 levels in the vagina and cervix in the first and mid‐second trimester of pregnancy

The aim of this study was to determine the concentrations of and factors associated with decidual insulin-like growth factor-binding protein-1 (IGFBP-1) in the lower genital tract in early- and mid-gestation in singleton pregnancies. Prospective population-based cohort study. Maternity Clinic, Department of Obstetrics and Gynaecology, University Central Hospital, Helsinki, Finland. A total of 1702 unselected pregnant women undergoing the first- and the second-trimester ultrasound screening between April 2005 and December 2006. The vaginal and cervical swab samples for assay of decidual IGFBP-1 and vaginal pH measurement were taken before transvaginal ultrasonography in the first trimester and in the mid-second trimester. Use of antibiotics, history of vaginal bleeding, and the history of sexual intercourse were questioned on both occasions. The concentration of IGFBP-1 was measured by a quantitative immunoenzymometric assay, which detects the decidual phosphoisoforms of IGFBP-1 (phIGFBP-1). The concentration of 10 micrograms/l was used as a cutoff when factors influencing phIGFBP-1 levels were analysed. The phIGFBP-1 concentrations in the vagina and the cervix and associations between the levels of > or =10 micrograms/l and selected factors. In the first trimester, the median (range) concentrations of phIGFBP-1 in vaginal and cervical samples were <0.3 micrograms/l (<0.3-176 micrograms/l) and 4.8 micrograms/l (<0.3-174 micrograms/l), respectively. During the second trimester, the corresponding values were <0.3 micrograms/l (<0.3-55 micrograms/l) in the vagina and 3.6 micrograms/l (<0.3-126 micrograms/l) in the cervix. In the vaginal samples, the frequency of phIGFBP-1 concentrations > or =10 micrograms/l was 5.8% in the first trimester and 1.5% in the second trimester (P < 0.001). In the cervical samples, the corresponding rates were 34.3 and 28.4%, respectively (P < 0.001). Of the factors studied, nulliparity (P < 0.001) and history of vaginal bleeding (P < 0.001) were independently associated with cervical phIGFBP-1 concentrations > or =10 micrograms/l during both trimesters. In addition, short cervical length (<30 mm) was associated with phIGFBP-1 concentration > or =10 micrograms/l in both vaginal and cervical samples in the second trimester in multivariate analysis. The rate of phIGFBP-1 concentrations > or =10 micrograms/l, both in the vagina and in the cervix, was significantly lower during the second trimester compared with the first trimester. The low rate of levels > or =10 micrograms/l in vaginal samples compared with cervical samples during both trimesters indicates that the exact site of sampling is important when phIGFBP-1 is used as a decidual marker. Nulliparity and history of vaginal bleeding were independently associated with phIGFBP-1 concentrations > or =10 micrograms/l in cervical samples during both trimesters.

Sugar and Bone: A Not-So Sweet Story

I predict that most readers of the article by Moyer-Mileur and colleagues in this month’s Journal of Bone and Mineral Research will be challenged not just by the results of their study, but also by the long term implications of their findings. In this relatively small, but well done CRU (Clinical Research Unit) investigation, several indices of the growth hormone- IGF-I axis in adolescent girls with at least 5 years of Type I diabetes mellitus (TIDM), were compared to appropriately age and tanner staged- matched controls (1). These parameters were then regressed against measures of skeletal size and content using areal and volumetric bone mass measurements. On first inspection, the results are not surprising, and are consistent with earlier studies from this group and others; i.e. adolescent girls with long standing TIDM have lower serum IGF-I, higher IGFBP-1, and greater growth hormone concentrations than their age-matched controls. Moreover, those girls with poor metabolic control had the lowest circulating IGF-I and highest IGFBP-1 concentrations. In respect to skeletal structure, increased urinary magnesium in the diabetic girls predicted a smaller, lighter skeleton, and overall disease duration accounted for the greatest variability in bone mineral content and cross sectional area. Higher blood glucoses and greater urinary magnesium were also associated with measures of increased bone resorption. Low serum IGF-I was a major predictor of tibial bone strength, as determined by pQCT.

Plasma Insulinlike Growth Factor 1 and Binding-Protein 3 and Risk of Myocardial Infarction in Women: A Prospective Study

The aim of this study was to prospectively evaluate relationships between plasma concentrations of insulinlike growth factor 1 (IGF1) and insulinlike growth factor binding protein 3 (IGFBP3) and subsequent myocardial infarction (MI) in women. We used case-control sampling to select study participants from women who had already been selected for inclusion in the prospective Nurses' Health Study cohort. Blood samples were collected from 32 826 women in 1989-1990. During the follow-up period from sample collection through June 1998, MI (fatal and nonfatal) was diagnosed in 245 women. Cases were matched to controls 1:2 by age, cigarette-smoking status, and month and fasting status at the time of blood collection. Conditional logistic regression was used to adjust for potential confounders (menopausal status, parental history of MI, postmenopausal hormone use, diabetes mellitus, hypertension, hypercholesterolemia, aspirin use, alcohol use, body mass index, and physical activity). Multivariable adjusted analyses did not reveal a statistically significant linear relationship between IGF1 or IGFBP3 concentrations or their molar ratio and risk of MI. Women in the highest IGF1 quartile had a multivariable-adjusted rate ratio of 1.46 (95% CI 0.79, 2.72; P for trend = 0.46) for MI, compared with those in the lowest. The corresponding rate ratios (95% CI) for IGFBP3 and the IGF1:IGFBP3 mol/L ratio were 1.24 (0.71, 2.17) and 1.29 (0.70, 2.37), respectively. We did not observe a monotonic relationship between IGF1 or IGFBP3 and MI among predominantly postmenopausal women. Future studies are warranted to evaluate these relationships in other demographic groups including younger women.

Insulin-Like Growth Factor Binding Protein 1 as a Novel Specific Marker of Hepatic Insulin Sensitivity

The liver is the main source and insulin the main regulator of IGF binding protein 1 (IGFBP-1) in humans. Here we examined how serum IGFBP-1 concentrations are related to directly measured hepatic insulin sensitivity and liver fat content in humans. We measured fasting serum (fS) IGFBP-1 concentrations and liver fat content by proton magnetic resonance spectroscopy in 113 nondiabetic subjects. In addition, hepatic insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp (insulin 0.3 mU/kg.min) technique in combination with the infusion of [3-(3)H]glucose in 78 subjects. fS-IGFBP-1 concentrations were inversely related to liver fat content (r = -0.38, P < 0.0001). Of circulating parameters, fS-IGFBP-1 was better correlated to hepatic insulin sensitivity (r = 0.48, P < 0.0001) than fS-insulin (r = -0.42, P = 0.0001), fS-C-peptide (r = -0.41, P = 0.0002), fS-triglyceride (r = -0.33, P = 0.003), or fS-high-density lipoprotein cholesterol (r = 0.30, P = 0.007). In multiple linear regression analyses, body mass index (P < 0.0001) and fS-IGFBP-1 (P = 0.008), but neither age nor gender, were independently associated with hepatic insulin sensitivity (P < 0.0001 for ANOVA). Neither fS-insulin nor fS-C-peptide were independent determinants of hepatic insulin sensitivity after adjusting for age, gender, and body mass index. fS-IGFBP-1 is inversely correlated with liver fat and is an obesity-independent and liver-specific circulating marker of hepatic insulin sensitivity.

Differential lipid profile and hormonal response in type 2 diabetes by exogenous insulin aspart versus the insulin secretagogue repaglinide, at the same glycemic control

Our aim was to study, at the same glycemic control, how treatment with either the insulin secretagogue repaglinide or exogenous insulin aspart affects endogenous insulin secretion, plasma insulin and IAPP (islet amyloid polypeptide) levels, GH-IGF (growth hormone-insulin-like growth factor) axis and plasma lipoprotein concentrations in patients with type 2 diabetes. Five patients, age 65.0+/-4.1 years (mean+/-SE), body weight 82.5+/-5.0 kg, BMI (body mass index) 27.7+/-1.5 kg/m(2) were treated for 10 weeks with repaglinide or insulin aspart in a randomized, cross-over study. At the end of each treatment a 24-h metabolic profile was performed. Blood glucose, C-peptide, free human insulin, free total (human and analogue) insulin, proinsulin, IAPP, IGF-I, IGFBP-1 (IGF binding protein-1), GHBP (growth hormone binding protein) and plasma lipoprotein concentrations were measured. Similar 24-h blood glucose profiles were obtained with repaglinide and insulin aspart treatment. During the repaglinide treatment, the meal related peaks of C-peptide and free human insulin were about twofold higher than during treatment with insulin aspart. Proinsulin, GHBP were higher and IAPP levels tended to be higher during repaglinide compared to insulin aspart. Postprandial plasma total cholesterol, triglycerides and apolipoprotein B concentrations were higher on repaglinide than on insulin aspart treatment. Our results show that, at the same glycemic control, treatment with exogenous insulin aspart in comparison with the insulin secretagogue repaglinide result in a lower endogenous insulin secretion, and a tendency towards a less atherogenic postprandial lipid profile.

Comparison of the Somatotropic Axis in Free-ranging and Rehabilitated Harbor Seal Pups (Phoca vitulina)

The somatotropic axis, including growth hormone (GH), insulin-like growth factor (IGF)-I, and IGF binding proteins (IGFBP), is a bridge between growth physiology, developmental age, and nutritional status in domestic animals. However, the importance of the somatotropic axis in nutrition, growth, and development of harbor seals has not been previously explored. Given the difficulty of conducting longitudinal studies in free-ranging harbor seals, this study focused on the potential use of harbor seals in rehabilitation facilities as a model for free-ranging seals. The purpose of this research was to compare concentrations of components of the somatotropic axis in free-ranging versus rehabilitated harbor seal pups. The hypothesis was that measurements of the somatotropic axis will be similar between individuals of comparable age and nutritional status (fasting versus feeding). To investigate this hypothesis, harbor seal pups (n=8) brought to The Marine Mammal Center (Sausalito, California, USA) or Mystic Aquarium (Mystic, Connecticut, U.S.A.) were initially assessed and determined to be healthy but abandoned. All pups were less than 2 wk of age upon arrival at rehabilitation facilities. Standard length was assessed at the time of arrival and again at release. Body mass was measured every week and blood samples were collected from each pup at 0, 4, and 8 wk of rehabilitation. Blood was collected and morphometrics assessed in free-ranging harbor seal pups (n=8) from the Gulf of Maine. Sera were analyzed for GH, IGF-I, and IGFBP concentrations. Concentrations of GH, IGF-I, and IGFBP-2 and -3 in rehabilitated pups were within a similar range compared with free-ranging pups when considered in the context of presumed nutrient intake. These data suggest that rehabilitated harbor seals may provide a useful model to investigate the effects of nutrient intake on growth and development of harbor seals, and will provide insight into phocid endocrinology and metabolism.

Bone mineral density of young boy soccer players at different pubertal stages: Relationships with hormonal concentration

Objectives To examine the effects of soccer in relation with the hormonal concentration, on the bone mass of young Tunisian players at different pubertal stages. Methods Two groups of 152 young boys (age: 13.3 ± 0.9 years) participated in this study: (1) 91 soccer players, and (2) 61 non-athletic boys used as control subjects. The bone mineral density (BMD) and the bone mineral content (BMC) were measured by dual-energy X-ray absorptiometry (DXA). Pubertal stages were assessed, and serum concentrations of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), growth hormone (GH) and the total testosterone were measured. Results The BMD and BMC for whole body, lumbar spine, femoral neck, pelvis and lower limbs were higher in soccer players than in controls ( p < 0.001). In early puberty, the soccer players also exhibited significantly greater BMD and BMC in the whole body and in weight-bearing bones compared with the controls ( p < 0.001). However, there was no intersubject variability due to puberty in either BMD or BMC. The pubescent soccer players had significantly higher hormonal concentrations of IGF-1 and IGFBP-3 than their counterpart controls ( p < 0.05). Moreover, the whole body BMD was significantly ( p < 0.001) correlated with GH, IGF-1 and IGFBP-3 but not with the testosterone concentrations. Conclusion The soccer participation of boys is generally associated with the improvement of their bone mass which is mainly marked at early and late puberty. The relationships between somatotropic axis hormones and BMD of the players may be linked to the parallel development of these two parameters during puberty.

IGFBP-1 Levels in Cervicovaginal Secretions before and after Amniocentesis

Background: To evaluate the levels of insulin-like growth factor-binding protein-1 (IGFBP-1) in cervicovaginal secretions before and after midtrimester amniocentesis and relate to clinical outcome. Methods: 100 consecutive amniocentesis procedures were studied. We measured the IGFBP-1 concentration by radioimmunoassay in a cervicovaginal specimen before and after mid-trimester amniocentesis. The post-amniocentesis occurrence of vaginal loss of fluid or blood and abdominal pain was assessed by questionnaire. Results: In 6 cases there was a 100-fold increase in IGFBP-1 levels after amniocentesis. Loss of fluid per vaginam occurred in 4 (67%) of these pregnancies, compared to 3.2% of pregnancies without significant surge (p < 0.0001). In addition, post-procedural abdominal pain was more common among women with increased IGFBP-1 levels after amniocentesis (50 vs. 14%, p = 0.05). Two (33%) of the 6 patients with increased IGFBP-1 after amniocentesis delivered prior to 37 weeks as a result of spontaneous preterm labor and/or preterm ruptured membranes, compared to 7 (7%) in the group without surge in IGFBP-1 (p = 0.09). Conclusion: Increased post-procedure IGFBP-1 levels are after mid-trimester amniocenteses are related to procedure-related complications like abdominal pain and subsequent amniotic fluid leakage.

Ramadan Fasting and the GH/IGF-1 Axis of Trained Men during Submaximal Exercise

Aims: The aim of this study was to explore possible changes in body composition, blood glucose regulation, plasma growth hormone (GH), insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein-3 (IGFBP-3), and insulin concentrations of trained athletes in response to the intermittent fasting and dehydration of Ramadan observance. Methods: Nine trained male rugby players (age 19 ± 2 years, height 1.78 ± 0.74 m) were tested 3 times: before Ramadan (C), at the end of the first week (R1), and during the fourth week (R2). They performed a progressive cycle ergometer test at each visit. The work rate was increased in 6-min stages corresponding to 20, 30, 40, 50 and 60% of &Wdot; max. Substrate oxidation was evaluated by indirect calorimetry. On each occasion, substrate and plasma hormone concentrations were measured at rest and at the end of the exercise. Results: Ramadan fasting induced a significant decrease in body mass and body fat (R2 vs. C, p < 0.001). Plasma concentrations of glucose, insulin, GH, IGF-1 and IGFBP-3 did not change significantly between C and R2, either at rest or following exercise. Conclusion: Ramadan fasting induces positive changes in body composition without disturbing glucose regulation or activity of the GH/IGF-1 system.

Maternal hormones linking maternal body mass index and dietary intake to birth weight

BackgroundObese women often give birth to large-for-gestational age infants (typically defined as a birth weight greater than the 90th percentile), who are at risk of birth injuries and of developing metabolic syndrome later in life. The mechanisms underlying increased fetal growth remain to be established. ObjectiveWe aimed to identify maternal hormones that can explain the link between dietary intake, body mass index (BMI), and birth weight. DesignPregnant women with BMIs (in kg/m2) ranging from 17 to 44 (n = 49) were recruited in gestational weeks 8–12. Serum hormone concentrations were measured and dietary history interviews were performed in the first and third trimesters. Multiple regression models were produced to identify hormones that correlate with birth weight and are influenced by BMI or dietary factors. ResultsWe found a strong positive correlation between BMI and first- and third-trimester insulin and leptin concentrations and a negative correlation between BMI and first-trimester adiponectin and first- and third-trimester insulin-like growth factor binding protein-1 (IGFBP-1). Maternal total fat intake in the first trimester was positively correlated with maternal leptin and inversely correlated with adiponectin. In addition, third-trimester total fat intake was positively correlated with circulating resistin concentrations. First-trimester maternal serum resistin was positively correlated with birth weight, whereas third-trimester maternal IGFBP-1 was negatively correlated with birth weight. ConclusionsHigh first-trimester maternal serum resistin and low third-trimester IGFBP-1 were correlated with increased birth weight. We propose that low serum concentrations of IGFBP-1 represent a link between high BMI and increased fetal growth by increasing the bioavailability of insulin-like growth factor-I, which up-regulates placental nutrient transport.

Insulin-like growth factor-binding protein-1 in the prediction and development of type 2 diabetes in middle-aged Swedish men

Insulin-like growth factor-binding protein-1 (IGFBP-1) production in the liver is inhibited by insulin, and low circulating levels are associated with the metabolic syndrome. The aim of this study was to evaluate the predictive role and change in IGFBP-1 concentrations during development of abnormal glucose regulation. IGFBP-1 levels were determined at baseline and at 10 years in an incident case-control prospective study of Swedish white men aged 35-56 years. Individuals with normal glucose tolerance at baseline who developed abnormal glucose tolerance during a 10 year period (n = 355) according to WHO criteria were pair-matched to controls for age and family history of diabetes. Fasting IGFBP-1 concentrations were lower in individuals who later developed abnormal glucose regulation and correlated inversely with fasting proinsulin values (r = -0.48; p < 0.0001), and both were significant predictors. Individuals in the highest quartile at baseline for an algorithm incorporating fasting IGFBP-1, blood glucose, proinsulin and waist and height had a 40-fold increased risk of developing type 2 diabetes compared with the lowest quartile (95% CI 7.7-214). IGFBP-1 increased 32% (95% CI 17-49%) during the 10 years in those developing diabetes and was increased in relation to insulin levels, suggesting the emergence of hepatic insulin resistance. Moreover, elevated IGFBP-1 levels at follow-up were associated with higher 2 h glucose values during an OGTT. Low IGFBP-1 predicts the development of abnormal glucose regulation and, as an inhibitor of the insulin-like actions of insulin-like growth factors, elevated levels of IGFBP-1 after the development of diabetes may also play a pathophysiological role.

Insulin-like Growth Factor 1, Insulin-like Growth Factor-Binding Protein 3, and Testicular Germ-Cell Tumor Risk

Studies have consistently shown that taller men are at increased risk of testicular germ-cell tumors. Thus, it is plausible that factors associated with height may also influence risk of these tumors. The authors examined associations between testicular germ-cell tumor risk and circulating concentrations of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) among 517 cases and 790 controls from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) Study (2002-2005). Odds ratios and 95% confidence intervals were estimated using logistic regression models, adjusting for age, race/ethnicity, height, and body mass index. All tests of significance were two-sided. Overall, there were no associations between IGF-1 or IGFBP-3 concentrations and risk of testicular germ-cell tumors (p > 0.05). However, when cases were separated by histologic type, there was a suggestion of a reduction in seminoma risk associated with the highest concentrations of IGF-1 as compared with the lowest concentrations (odds ratio = 0.66, 95% confidence interval: 0.40, 1.09). Although there were no overall associations with insulin-like growth factor, contrary to expectation, there was a suggestion that IGF-1 concentrations may be inversely associated with risk of seminoma.

Reproducibility of Serum Leptin, Insulin-Like Growth Factor-I, and Insulin-Like Growth Factor-Binding Protein-3 Measurements

Background: Many epidemiologic studies examine the effects of single measurements of hormones, including those related to obesity such as insulin-like growth factors (IGFs) or leptin, on disease associations; however, few studies have determined whether these single values accurately reflect measurements over time. Methods: We examined the reproducibility of hormones associated with obesity, specifically leptin, IGF-I, and IGF-binding protein-3 (IGFBP-3). Two fasting blood samples, approximately four months apart, were collected from 38 participants from the Seattle metropolitan area; leptin, IGF-I, and IGFBP-3 concentrations were measured in previously unthawed serum samples. Unadjusted and adjusted intraclass correlation coefficients (ICC) were calculated to assess reproducibility. Results: Adjusting for age and sex, the ICCs for leptin, IGF-I, and IGFBP-3 were 0.73, 0.83 and 0.60, respectively. Weighted kappas yielded similar results. Conclusion: These data suggest that for leptin, IGF-I, and IGFBP-3, a single fasting serum measurement can fairly reliably reflect the hormonal milieu over periods of months.

Three-dimensional power Doppler sonography of the (sub)endometrium and angiogenic cytokine concentrations

The aim of this study was to determine the correlation between three-dimensional power Doppler sonography (3D-PDS) of the (sub)endometrium and concentrations of angiogenic cytokines in patients attending an IVF programme. A total of 42 patients was included in a prospective, non-randomized clinical study. 3D-PDS of the (sub)endometrium was performed on the day of oocyte aspiration, with and without contrast agent. Quantitative assessment included the following 3D Doppler parameters: vascularization index, flow intensity, and vascularization flow index. On the same day, concentrations of oestradiol (serum only), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF) 1, IGF-binding protein 3 (IGFBP-3) and leptin were determined in the serum and in the follicular fluid. All 3D-PDS indices were significantly higher with contrast enhancement ( P < 0.05). Follicular fluid concentrations of VEGF and IGFBP-3, as well as serum concentrations of leptin, showed significant P-values when correlated with (sub)endometrial Doppler indices. A weak linear dependency appeared between flow intensity and VEGF and leptin. Furthermore, weak dependencies were apparent between 3D Doppler parameters and high follicular fluid concentrations of VEGF and IGFBP-3. It is concluded that there is only little evidence for an association between (sub)endometrial Doppler indices as assessed by 3D-PDS and concentrations of angiogenic cytokines.

Insulin-like growth factor-binding protein-1 (IGFBP-1) in cervical secretions as a predictor of preterm delivery

Objective. The objective of this study was to investigate the level of insulin-like growth factor-binding protein-1 (IGFBP-1) in cervical secretions and Bishop score as predictors of preterm delivery in asymptomatic pregnant women.Methods. This was a prospective study at the Clinic for Gynecology and Obstetrics at the University Clinical Center in Tuzla, on a sample of 80 healthy pregnant women at between 24 and 34 gestational weeks. After interview every woman underwent IGFBP-1 concentration measurement by the ‘Actim Partus’ test. The Bishop score was determined by the author (A.L) during vaginal examination. Rates among groups were compared using arithmetic mean and standard deviation, Student's t-test, Mann–Witney U-test, and Spearman–Rank correlation test. Statistical importance was determined at the variation levels of 5% and 1%.Results. Eight (10.00%) women in the study group had a positive Actim Partus test and six (7.50%) of them had a preterm delivery. The positive predictive value was 44.44% and negative predictive value was 98.59%. The specificity of the Bishop score in the study group was 83.78% and the sensitivity was 50.00%. The positive predictive value of the Bishop score in this group was 20.00% and the negative predictive value was 95.36%. There was no correlation between the Bishop score and Actim Partus test (p = 0.15).Conclusions. If the concentration of IGFBP-1 is <10 μg/L (negative Actim Partus test) in asymptomatic pregnant women, the risk of preterm delivery is low. The Actim Partus test could be used as a screening test for preterm delivery in asymptomatic pregnant women.

Serum insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3, leptin concentrations and insulin resistance in benign and malignant epithelial ovarian tumors in postmenopausal women

Aims. The aims of the present study were to determine the serum concentrations of insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and leptin and insulin resistance in benign and malignant epithelial ovarian tumors, and to discuss the use of these markers in benign–malignant tumor differentiation.Methods. Forty-seven postmenopausal women with ovarian tumor and 31 age-matched, postmenopausal, healthy controls were included in this study. Insulin resistance index by homeostasis model assessment (HOMA score) and fasting blood glucose (FBG), serum IGF-I, IGFBP-3, leptin and CA-125 concentrations were determined in all patients preoperatively. The results were evaluated according to postoperative histopathology results.Results. According to postoperative histopathology results, the patients were divided into malignant (n = 23), benign (n = 24) and control (n = 31) groups. There were no differences among the groups in relation to age, body mass index, FBG and HOMA score (p > 0.05). Serum concentrations of CA-125 were elevated in the malignant group compared with the benign ovarian tumor and control groups (p < 0.05). In contrast, serum IGF-I concentrations were significantly decreased in patients with malignant and benign ovarian tumors compared with controls (p < 0.05). Serum IGFBP-3 concentrations were also found to be lower in women with malignant ovarian tumors than in women with benign tumors (p < 0.05). Serum leptin did not differ among patients with malignant–benign tumors and controls (p > 0.05).Conclusion. Serum leptin and HOMA score have not been found to be valid indicators in ovarian tumors. However, the present data suggest that low concentrations of IGF-I and IGFBP-3 could be a reliable marker to differentiate benign from malignant ovarian tumors. Further experimental studies are warranted to understand the impact of the IGF-I system in ovarian carcinogenesis.

Insulin like growth factor‐1 and insulin like growth factor binding proteins in the cerebrospinal fluid and serum from patients with Alzheimer's disease

Insulin like growth factor-1 (IGF-1) is ubiquitously expressed growth factor that has profound effects on the growth and differentiation of many cell types and tissues, including cells of the central nervous system (CNS). IGF-1 is produced by a wide variety of cells and is found in many biological fluids including cerebrospinal fluid (CSF). IGF-1 plays important role during CNS development and repair. IGF-1 has broad range neuroprotective effects and is a therapeutic candidate for Huntington's disease (HD). IGF-1 protects striatal neurons from the toxicity of mutated Huntington in vitro and improves neuronal survival in vivo in a phenotypic model of HD. Alzheimer's disease (AD) is an age-dependent dementia characterized by progressive loss of cognitive functions and by characteristic pathological changes in the brain: the formation of aggregates extracellularly by beta-amyloid (AB) peptide and intracellularly by tau proteins. Since cerebrospinal fluid (CSF) is in contact with the extracellular space of the brain, biochemical brain modifications could be reflected in the CSF. IGFs in circulation and other physiological fluids are associated with a group of high-affinity binding proteins insulin like growth factor binding proteins (IGFBPs) that specifically bind and modulate their bioactivity at the cellular level. The aim of this study was to determine the level of CSF and serum IGF-1 and IGFBPs concentrations in the patients with AD. CSF was obtained by lumbar puncture. The presence of IGF-1 and IGFBPs in the CSF and serum samples was confirmed by Western blot using anti-IGF-1 and IGFBPs antibodies. Using enzyme linked immunosorbent assay (ELISA), it was shown that the concentration of CSF and serum IGF-1 and IGFBPs in the patients with AD is higher than in normal control. The data from this study indicate that IGF-1 is a constant component of human CSF. It is also concluded that high levels of CSF IGF-1 may be partly related to AD pathophysiology.