Serum IGF-I Concentrations Research Articles

Elevated serum concentrations of IGF-1 and IGF-1R in patients with thyroid cancers.

The rising incidence of thyroid cancer observed in the last few decades requires an improvement in diagnostic tools and management techniques for patients with thyroid nodules. The aim of this study was to assess serum concentrations of IGF-1 and IGF-1R in patients diagnosed with thyroid cancers. 36 patients diagnosed with papillary thyroid cancer (PTC), 11 subjects with follicular thyroid cancer (FTC), 9 patients with anaplastic thyroid cancer (ATC) and 19 subjects with multinodular nontoxic goiter (MNG) were enrolled to the study. The control group (CG) consisted of 20 healthy volunteers. Blood samples were collected one day before surgery. Serum IGF-1 and IGF-1R concentrations were measured using specific ELISA methods. Significantly higher concentrations of IGF-1 were found in patients with PTC as compared with controls but not that obtained from subjects diagnosed with MNG. The concentration of IGF-1R was significantly elevated in subjects with PTC and ATC as compared with healthy volunteers. Similarly, patients diagnosed with PTC or ATC presented significantly higher serum concentration of IGF-1R in comparison to the MNG group. Our results show that the IGF-1 - IGF-1R axis plays a significant role in the development of PTC and ATC and imply that serum concentrations of both cytokines may be considered as additional markers for the differentiation of malignancies during the preoperative diagnosis of patients with thyroid gland tumors. These results indicate that IGF-1R serum concentrations allow us to differentiate between MNG and PTC or ATC. Moreover IGF-1R serum values appear to be better predictor of PTC and ATC than IGF-1 concentrations.

Sex hormone, insulin, and insulin-like growth factor signaling in recurrence of high stage endometrial cancer: Results from the NRG Oncology/Gynecologic Oncology Group 210 trial.

5509 Background: Sex hormone and insulin/insulin-like growth factor (IGF) axis signaling pathways play an important role in endometrial cancer development but their role in endometrial cancer recurrence is unknown. In this study GOG-8015 we evaluated these pathways in a prospective cohort of patients diagnosed with the most common type of endometrial cancer, endometrioid adenocarcinoma. Methods: Stage II-IV endometrioid endometrial adenocarcinoma patients (N = 816) enrolled in the GOG-210 study with pre-treatment specimens were tested for tumor mRNA and protein expression levels of IGF1, IGF2, IGF binding proteins ( IGFBP) -1and -3, the insulin (IR) and IGF-I receptors (IGF1R), and phosphorylated (activated) IR/IGF1R as well as estrogen (ER) and progesterone receptors (PR) using quantitative PCR and immunohistochemistry (IHC). Serum concentrations of insulin, IGF-I, IGFBP-3, estradiol, estrone and sex hormone binding globulin were measured using ELISAs. Hazard ratios (HR) and 95% confidence intervals (CI) for risk of recurrence were obtained from multivariable Cox proportional hazard’s models with adjustment for age, stage and grade. Results: Recurrence occurred in 280 (34%) cases during a mean of 5.4 years of follow-up. ER-positivity (HR 0.67, 95% CI 0.47-0.95), IR-positivity (HR 0.53, 95% CI 0.29-0.98) and serum IGF-I levels (highest versus lowest quartile, HR 0.66, 95% CI 0.47-0.92) were inversely associated with recurrence risk. Conversely, circulating estradiol (highest versus lowest tertile, HR 1.55, 95% CI 1.02-2.36) and insulin (per 10 uU/ml, HR 1.52, 95% CI 1.12-2.06) and phosphorylated IGF1R/pIR expression (HR 1.40, 95% CI 1.02-1.92) were associated with increased risk of recurrence. Conclusions: We identified novel sex hormone and insulin/IGF axis tissue and circulating biomarkers of recurrence in a prospective study of high stage endometrioid endometrial cancer. Circulating insulin and estradiol, and tissue phosphorylated (activated) IGR1R/IR were independently associated with recurrence. These findings support prioritizing studies to establish their clinical utility as prognostic biomarkers and to investigate new strategies that target these pathways for prevention and treatment of endometrial cancer recurrence.

Effect of moderate and high-intensity endurance and resistance training on serum concentrations of MSTN and IGF-1 in old male Wistar rats.

Background Skeletal muscle is very sensitive to extracellular and intracellular signaling evoked by contractions from endurance and resistance exercise. The aim of this study was to compare the effects of moderate- and high-intensity endurance and resistance training on the serum myostatin (MSTN) and insulin-like growth factor (IGF-1) levels in older rats. Materials and methods Fifty old Wistar male rats (23 months old) were randomly divided into four experimental and one control groups, including moderate-endurance training (MET) (n = 10), high-intensity endurance training (EHT) (n = 10), moderate-intensity resistance training (MRT) (n = 10), high-intensity resistance training (HRT) (n = 10), and control group (C) (n = 10). Seventy-two hours after the last exercise session, euthanasia of the rats were rendered unconscious and direct blood samples were collected. Serum IGF-1 and MSTN concentration were measured using the enzyme-linked immuno sorbent assay (ELISA) method. The statistical analysis was performed using one-way analysis of variance (ANOVA) test with a significance level of p ≤ 0.05. Results There was a significant reduction in MSTN and an increase in IGF-1 concentrations was observed between IGF-I levels in high and moderate resistance and endurance training. However, no significant difference was observed in MSTN levels between groups. Discussion Therefore, it appears that resistance training, especially HRT, is effective to increase growth mediators among older rats.

IGF1 is Developmentally Regulated in the Neonatal Intestine and Protects Neonatal Mice against Necrotizing Enterocolitis by Preserving the VEGF/VEGFR2 Signaling Pathway in an Animal Model

Necrotizing enterocolitis (NEC) is a common gastrointestinal disease affecting premature infants and associated with high morbidity and mortality. Its pathogenesis remains poorly understood. Decreased levels of serum IGF1 has been shown to be associated with a higher incidence of NEC in premature infants. We previously found that neonatal pups are most susceptible to NEC in the first few days of life. Here we hypothesize that IGF‐1 levels are low during the first days of life, and that exogenous IGF1 is protective against NEC via promoting intestinal VEGF/VEGFR2 signaling. To test our hypotheses, we first assessed the developmental expression of IGF1 in the serum and the intestinal tissues in neonatal mice during the first 3 weeks of life, and determined whether exposure to a NEC protocol affects serum and intestinal IGF1 levels. Secondly, we examined whether exogenous IGF1 protects against NEC and affects intestinal VEGF production both in vivo and in vitro. We found that: Serum IGF1 level is low during the first 2 days of life, and gradually increases over 3 weeks. In contrast, IGF1 expression in the intestinal tissue is low at birth, peaks between 3 days and 2 weeks of age, before decreasing to low level by 3 weeks. In pups exposed to a NEC protocol compared to DF controls, serum IGF1concentration was significantly decreased at 12 hours and 24 hours (by 35%, p<0.05; and 59%, p<0.0001 respectively ). Intestinal tissue IGF1 expression decreased as early as 6 hours into NEC, which occurred before the decrease in serum IGF1. Exogenous IGF1 treatment decreased mortality in pups exposed to NEC protocol (41% vs. 68%, p<0.05), decreased the incidence of severe NEC (histological score ≥ 2) (χ2=4.03, p<0.05) and increased intestinal VEGF/VEGFR2 protein expression. Neonatal intestinal endothelial cells treated with IGF1 in vitro had increased VEGF mRNA transcription and protein expression (p<0.05 for both). We conclude that the beneficial effect of IGF1 on experimental NEC may be due to protection of small intestinal microvasculature development through preserving VEGF/VEGFR2 signaling pathway.Support or Funding InformationShireThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Serum and seminal plasma IGF-1 associations with semen variables and effect of IGF-1 supplementation on semen freezing capacity in buffalo bulls

The objective of the study was to establish correlation of seminal and serum IGF-1 with seminal attributes, estimate antioxidant potential of IGF-1 by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays and to study the effect of IGF-1 supplementation on semen cryopreservation. For this study, buffalo bulls were divided into sub-fertile (n = 2) and normal (n = 5) on the basis of sperm mass motility and individual motility. The serum IGF-1 concentration of normal bulls was greater than in sub-fertile bulls, but there was no difference in the seminal IGF-1 concentration among the groups. The values from correlation analyses indicated that serum IGF-1 concentration is positively correlated with semen mass motility and sperm concentration. In the second experiment, IGF-1 did not have antioxidant activities when assessed with DPPH and FRAP assays. In the third experiment, the ejaculates of normal and sub-fertile bulls were cryopreserved using semen extender in which there was IGF-1 supplementation at 0 (control), 50, 100, 150, 200, 250, 350 and 450 ng/mL of extender. Supplementation of IGF-1 at 250 ng/ml resulted in improved sperm motility, longevity and membrane intactness as compared to control after cryopreservation of semen from normal buffalo bulls, but not sub-fertile bulls. In summary, serum IGF-1 concentration was correlated with sperm mass motility and concentration in buffalo bulls and supplementation of IGF-1 protected sperm during the cryopreservation process but effects were not due to direct antioxidant activity.

The Prospective Association Between Plasma Concentrations of Cellular Growth Factors and Risk of Heart Failure Mortality in Japanese Population.

BackgroundLimited evidence is available on the association of insulin-like growth factors (IGFs) and risk of heart failure in population-based samples. We investigated whether serum IGFs concentrations can predict mortality from heart failure.MethodsWe conducted a nested case-control study of 39,242 subjects aged 40–79 years who participated in the JACC study, a large Japanese prospective cohort study; participants provided serum samples and were followed up for 9 years. In heart failure cases and age-, sex-, community-, and year of blood withdrawal-matched controls, we measured serum concentrations of IGF-I, IGF-II, and IGF binding protein 3 (IGFBP3) and transforming growth factor (TGF-β1).ResultsDuring the follow-up, there were 88 heart failure deaths (44 men and 44 women). Each increment of 1 standard deviation [SD] of IGF-II (120.0 ng/mL in women and 143.7 ng/mL in men) was associated with a 47% reduced risk of mortality from heart failure; multivariable odds ratio was 0.53 (95% confidence interval [CI], 0.30–0.94, P-trend = 0.03). The multivariable odds ratio in the highest quartile of IGFBP3 serum concentrations (≥3.29 µg/mL in women and ≥3.31 µg/mL in men) compared with the lowest (<2.11 µg/mL in women and <2.56 µg/mL in men) was 0.24 (95% CI, 0.05–1.11; P-trend = 0.12). No association was found between serum concentrations of IGF-I or TGF-β1 and risk of heart failure.ConclusionsHigher serum concentrations of IGF-II were associated with lower mortality from heart failure, which might suggest a possible role of IGF-II in the occurrence or prognosis of heart failure.

Serum concentrations of IGF-I/IGF-II as biomarkers of alcohol damage during foetal development and diagnostic markers of Foetal Alcohol Syndrome

Foetal Alcohol Syndrome (FAS) is the most deleterious health effect derived from alcohol consumption during pregnancy and is placed at the end of the Foetal Alcohol Spectrum Disorders (FASD). Few studies have proposed potential molecular biomarkers of physical and neurological damage associated with prenatal alcohol exposure. We prospectively recruited 55 children from 8 to 12 years old, with a prenatal assessment for ethanol exposure using meconium analysis of fatty acid ethyl esters (FAEE). The control group was established for FAEE < 2 nmol/g (n = 31) and a Prenatal Ethanol Exposure (PEE) group for FAEEs > 2 nmol/g (n = 33). Moreover, 98 children adopted from Eastern European Countries (EEC) were also recruited to evaluate FASD diagnosis comprising 31 cases with complete FAS, 42 with partial FAS, 6 with ARBD and 5 with ARND. Serum values of IGF-I and IGF-II for all children recruited were determined by immunoassay. Anthropometric and neurocognitive evaluation showed severe impairments in FAS children, moderate effects in PEE and no harmful effects in the control group with no prenatal exposure to alcohol. Analysis of IGF-I and IGF-II serum concentrations revealed that FASD from EEC as well as PEE children showed significantly lower concentrations of both IGF-I and IFG-II than the control group and reference values. Moreover, Spearman correlations showed a significant effect of IGF-I on anthropometric measurements in girls, whereas IGF-II affected the neuropsychological variables in both genders. These findings validate the use of growth factors IGF-I and IGF-II as surrogate biomarkers of damage induced by prenatal exposure to ethanol and could be used in the diagnosis of foetal alcohol spectrum disorders.

GH replacement titrated to serum IGF-1 does not reduce concentrations of myostatin in blood or skeletal muscle

ObjectiveTraditional weight-based regimens of GH replacement are more effective at reversing the loss of skeletal muscle in GH-deficient adults than currently recommended regimens, where the dose of GH is increased to restore serum concentrations of IGF-1. While weight-based regimens increase concentrations of IGF-1 and decrease concentrations of myostatin, it is not known whether the reduced effectiveness of individually titrated GH regimens is due to ongoing hypersecretion of myostatin. Consequently, the aims of this study were to determine whether concentrations of myostatin in blood and skeletal muscle are increased in GH-deficient adults, and whether these concentrations are decreased by GH replacement regimens titrated to restore serum IGF-1. DesignTwenty-six GH deficient adults (18 men and 8 women) were treated with individualised regimens of recombinant human GH aiming to achieve serum concentrations of IGF-1 within one standard deviation of the age- and gender-adjusted mean. Plasma concentrations of myostatin were measured at baseline and after 6 months of treatment were compared to fifteen healthy controls (9 men and 6 women). Skeletal muscle biopsies were performed in 19 of these GH-deficient adults (15 men and 4 women) and 10 of the healthy controls (6 men and 4 women). Expression of IGF-1 and myostatin mRNA was determined by qPCR. ResultsConcentrations of IGF-1 in serum and mRNA in skeletal muscle were reduced, and concentrations of myostatin in plasma and mRNA in skeletal muscle were increased in GH-deficient adults at baseline (P < .05 versus healthy controls). Despite restoring concentrations of IGF-1, GH replacement did not reduce concentrations of myostatin in either blood or skeletal muscle. Concentrations of IGF-1 and myostatin in both blood and skeletal muscle were positively correlated in GH-deficient adults at baseline (P < .05), but not in GH-replete adults. ConclusionsConcentrations of myostatin in blood and skeletal muscle are increased in GH-deficient adults. Despite normalising concentrations of IGF-1, individualised regimens of GH replacement do not reduce concentrations of myostatin in blood or skeletal muscle. Ongoing hypersecretion of myostatin may explain why individually titrated GH replacement regimens are less effective than higher weight-based regimens in increasing skeletal muscle mass.

91 Can propylene glycol modulate insulin and insulin-like growth factor-1 in superovulated dairy heifers?

The aim of this study was to determine the effect of propylene glycol (PPG) on serum concentrations of insulin and insulin-like growth factor (IGF)-1 in superovulated dairy heifers. We hypothesised that administration of PPG would have a positive effect on superovulation results via increased insulin and IGF-1. A total of 20 clinically healthy Holstein heifers with an average age of 12 months were used for this experiment. Superovulation was performed using a standard protocol. Briefly, each heifer received 3mg of oestradiol-17β IM and an intravaginal progesterone-releasing insert (CIDR) containing 1.9g of progesterone at random stages of the oestrous cycle (designated Day 0). From Day 4 to 8, heifers received a total of 200mg of NIH-follicle-stimulating hormone-P1 administered intramuscularly through 9 injections of decreasing doses (from 50 to 10mg) at 12-h intervals. On Day 7, heifers received 2 injections of 500µg of cloprostenol, a PGF2α analogue, at ~6-h intervals, after which intravaginal inserts were removed. Artificial insemination was performed on Day 10, 12h after treatment with 100µg of gonadotropin-releasing hormone IM. Embryos were flushed from the uterus of donor heifers 6 days after AI. The method consisted of simultaneously using 1 catheter per uterine horn. Catheters were maintained in place to perform 2 flushes 1h apart. A total of 1L of flushing medium was used, 700 and 300mL for the first and the second flush, respectively. Embryos were assessed for viability immediately after collection using the IETS classification. Heifers were divided into 2 groups (PPG and control group). From Day 4 to 14 of the superovulation protocol, PPG group received a daily dose of 400mL of a 66.7% propylene glycol solution, whereas the control group received the same amount of water. Two months later, the same experiment was conducted by inverting the groups. At Day 4 and 14, four blood samples were collected to measure insulin and IGF-1 at 25-min intervals. The first sample (0) was taken before heifers received PPG or water. Insulin was analysed using an ELISA kit following manufacturer’s instructions, whereas IGF-1 was determined using a chemiluminescence immunoassay. Embryo associated data were analysed using t-test. Both IGF-1 and insulin data were analysed using a two-way ANOVA, followed by Bonferroni post-hoc test. Treatment with PPG had no effect on the number of transferable embryos (8±5.1v. 7±5.5), degenerated embryos (0.5±0.8v. 1.5±2.4), or unfertilized oocytes (0.3±0.7v. 0.7±1.2) recovered. There was also no effect of PPG on IGF-1 serum concentrations at the beginning (Day 4) or the end (Day 14) of the treatment regimen. However, PPG treatment enhanced (P = 0.02) serum insulin concentrations 50min after administration on Day 4 (10.69 v. 6.88 pmol/L), as well as at 25 (19.58 v. 9.64 pmol/L) and 50min (16.67v. 8.21 pmol/L) on Day 14. It has been suggested that PPG metabolism may stimulate insulin and IGF-1 secretion, which can promote embryo development. However, in the present study, there was no effect of oral doses of PPG on IGF-1. Although higher serum concentrations of insulin were observed after PPG treatment, there was no effect of PPG treatment on the number of transferable embryos recovered following superovulation.

IGF1R Gene Alterations in Children Born Small for Gestitional Age (SGA).

BACKGROUND:Small for gestational age (SGA)-born children are a heterogeneous group with few genetic causes reported. Genetic alterations in the IGF1 receptor (IGF1R) are found in some SGA children.AIM:To investigate whether alterations in IGF1R gene are present in SGA born children.PATIENTS AND METHODS:We analysed 64 children born SGA who stayed short (mean -3.25 ± 0.9 SDS) within the first 4 years of age, and 36 SGA children who caught up growth (0.20 ± 1.1 SDS). PCR products of all coding IGF1R exons were screened by dHPLC followed by direct sequencing of conspicuous fragments to identify small nucleotide variants. The presence of IGF1R gene copy number alterations was determined by Multiplex Ligation-dependent Probe Amplification (MLPA).RESULTS:The cohort of short SGA born children revealed a heterozygous, synonymous variant c.3453C > T in one patient and a novel heterozygous 3 bp in-frame deletion (c.3234_3236delCAT) resulting in one amino acid deletion (p.Ile1078del) in another patient. The first patient had normal serum levels of IGF1. The second patient had unusually low IGF1 serum concentrations (-1.57 SD), which contrasts previously published data where IGF1 levels rarely are found below the age-adjusted mean.CONCLUSIONS:IGF1R gene alterations were present in 2 of 64 short SGA children. The patients did not have any dysmorphic features or developmental delay. It is remarkable that one of them had significantly decreased serum concentrations of IGF1. Growth response to GH treatment in one of the patients was favourable, while the second one discontinued the treatment, but with catch-up growth.

Longitudinally monitoring of P-III-NP, IGF-I, and GH-2000 score increases the probability of detecting two weeks' administration of low-dose recombinant growth hormone compared to GH-2000 decision limit and GH isoform test and micro RNA markers.

To detect doping with growth hormone (GH), GH isoform and biomarkers tests are available. Both methods use population-based decision limits. Future testing in anti-doping is progressing toward individual-based reference ranges, and it is possible that with such an approach the sensitivity to detect GH doping may increase. In addition to monitoring different proteins, the use of miRNAs as future GH biomarkers has been discussed. Here we have longitudinally studied the serum concentrations of IGF-I, P-III-NP and the different GH isoforms in nine healthy men prior to, during and after two weeks' administration with low doses (1 and 4IU/day) of recGH. Moreover, three putative miRNAs were analyzed. The results show that 80% of the participants were identified as atypical findings using the GH isoform test. However, the participants were only positive 1.5-3hours directly after an injection. Only one of the participants reached a GH-2000 score indicative of doping when a population-based decision limit was applied. When IGF-I and P-III-NP were longitudinally monitored, 88% of the participants were identified above an individual upper threshold arbitrarily calculated as three standard deviations above the mean values of four baseline samples. The miRNA levels displayed large intra-subject variations that did not change in relation to recGH administration. Our results show that the GH isoform test is very sensitive in detecting low doses of recGH but with a short detection window. Moreover, longitudinally monitoring of IGF-I and P-III-NP may be a promising future approach to detect GH doping.

Pituitary Pathology and Gene Expression in Acromegalic Cats.

The prevalence of GH-secreting pituitary tumors in domestic cats (Felis catus) is 10-fold greater than in humans. The predominant inhibitory receptors of GH-secreting pituitary tumors are somatostatin receptors (SSTRs) and D2 dopamine receptor (DRD2). The expression of these receptors is associated with the response to somatostatin analog and dopamine agonist treatment in human patients with acromegaly. The aim of this study was to describe pathological features of pituitaries from domestic cats with acromegaly, pituitary receptor expression, and investigate correlates with clinical data, including pituitary volume, time since diagnosis of diabetes, insulin requirement, and serum IGF1 concentration. Loss of reticulin structure was identified in 15 of 21 pituitaries, of which 10 of 15 exhibited acinar hyperplasia. SSTR1, SSTR2, SSTR5, and DRD2 mRNA were identified in the feline pituitary whereas SSTR3 and SSTR4 were not. Expression of SSTR1, SSTR2, and SSTR5 was greater in acromegalic cats compared with controls. A negative correlation was identified between DRD2 mRNA expression and pituitary volume. The loss of DRD2 expression should be investigated as a mechanism allowing the development of larger pituitary tumors.

Biochemical following-up of treated acromegaly. Limitations of the current determinations of IGF-I and perspective.

Acromegaly is a rare disease caused by excess growth hormone (GH) secretion leading to an insulin-like growth factor-1 (IGF-I) which is the major mediator of GH action. Biochemical diagnosis of GH excess is accomplished by the combined measurement of baseline serum IGF-I concentration and the response of GH on an oral glucose tolerance test (OGTT). Several drawbacks regarding the interpretation of biochemical tests that include measurement of GH have been widely described in the literature, including different protocols for obtaining serum samples, great differences in the results obtained by different immunoassays, different cut-off points used to differentiate the normal status of the hypersecretion of GH. Clinical guidelines related to the diagnosis and management of patients with acromegaly state that "normal" IGF-I concentrations, (within an established age- and sex- reference range), excludes the diagnosis of active acromegaly, and mean disease control in patients who have received treatment. But many factors may exert influence over IGF-I measurement or interpretation and limit its value as a biological marker of disease activity. Major drawbacks of IGF-I measurements derive both from its own physiology, to the divergences in results obtained from different biochemical methods used for their quantification, to the heterogeneous ways of expressing the results obtained and to the lack of uniformity of the cut-offs to define treatment effectiveness. All these issues make it difficult to compare the results obtained by different authors. We will focus on the issues regarding the measurement and interpretation of IGF-I concentrations in the management of acromegaly patients.

Diabetes mellitus induced by somatostatin analogue therapy is not permanent in acromegalic patients.

SummaryContextTherapy with somatostatin analogues (SSAs) may have deleterious effects on glucose metabolism in patients with acromegaly, often leading to the development of diabetes mellitus (DM).AimThe aim of the study was to evaluate whether DM, developed during therapy with SSAs, may revert after drug withdrawal and cure of acromegaly with pituitary adenomectomy.DesignRetrospective cohort study, in a tertiary referral centre.PatientsEighteen acromegalic patients without DM at the diagnosis of acromegaly treated with SSAs as a primary therapy, and then cured by pituitary adenomectomy.MethodsEndocrine status and glucose homeostasis were evaluated at diagnosis of acromegaly and at least every 6 months during SSA therapy. At each visit, patients were classified into one of the following classes: normal glucose tolerance, prediabetes, overt diabetes.ResultsMedian follow‐up after starting SSAs therapy was 69 months (IQR 54.75‐132.25). During SSA therapy, all patients had controlled acromegaly defined by normal serum IGF1 concentrations for the age. Of the 13 euglycaemic patients at diagnosis, three developed prediabetes and three diabetes, whereas, of the five prediabetic patients at diagnosis, two worsened to overt diabetes and three remained in the prediabetic range (P = 0.04). After curing acromegaly with pituitary adenomectomy and subsequent SSA withdrawal, prediabetes reverted in five of six patients, and diabetes in all five patients (three reverted to euglycaemia, while two reverted to prediabetes) (P = 0.01).ConclusionsIn acromegalic patients with controlled disease, changes in glycaemic status induced by SSAs are not permanent.

Comparative Study of Different Maternal Zinc Resource Supplementation on Performance and Breast Muscle Development of their Offspring.

Maternal zinc supplementation has a pivotal role in enhancing breast muscle development of the offspring. What is poorly defined is the impact of supplemental zinc from different sources on the offspring. Broiler breeders at 24-week-old were randomly divided into three treatments with six replicates of 40 hens each and respectively fed for 8weeks with supplemental 0-(group Zn/C), 100mg/kg organic-(group Zn/O), and 100mg/kg inorganic-(group Zn/I) zinc. The male offspring from each nutritional treatment were allocated into eight cages of 14 birds each, and a commercial diet supplemented with zinc from ZnSO4 at 20mg/kg was fed to the offsprings. Results showed that eggs from Zn/O group had the highest zinc deposition (P < 0.05). Furthermore, maternal zinc supplementation promoted breast muscle yield; increased serum insulin and IGF-I concentration; upregulated AKT, mTOR, and P70S6K mRNA levels; and improved the phosphorylation of AKT at Serine 473 residue, mTOR at Serine 2448 residue, and FOXO at Serine 256 residue in the breast muscles of the offspring. In contrast, hens' diet supplemented with zinc could result in downregulation of atrogin-1 and MuRF1 mRNA levels in the breast muscle of the offspring. Additionally, no significant effect on breast muscle development post-hatch was observed between organic and inorganic zinc supplementation. In conclusion, maternal organic zinc supplementation improved zinc deposition in egg; however, no significant difference was detected in breast muscle development of the offspring of broiler breeder between organic and inorganic zinc supplementation.

Sequential measurements of IGF-I serum concentrations in adolescents with Laron syndrome treated with recombinant human IGF-I (rhIGF-I).

Background Recombinant human insulin-like growth factor 1 (rhIGF-I) has been approved as an orphan drug for the treatment of growth failure in children and adolescents with severe primary IGF-I deficiency (SPIGFD) with little pharmacokinetic data available. Therefore, sequential measurements of serum IGF-I, glucose, potassium, insulin and cortisol were performed in patients treated with rhIGF-I to evaluate their significance in safety and efficacy. Methods Repetitive blood samples were taken after meals before and 30, 60, 120, 180 and 360 min after rhIGF-I injections in two male patients with Laron syndrome at times of dose adjustments. Results Maximal IGF-I concentrations were observed 2 h after injections (495 ng/mL) and concentrations were still higher 6 h after injections than at baseline (303 ng/mL vs. 137 ng/mL). Thirteen percent of all and 33% of maximum IGF-I concentrations were greater than +2 standard deviation score (SDS) calculated for bone age (BA) (IGF-I SDS BA) rather than chronological age (CA) as BA was significantly delayed to CA by 3.2 years (p=0.0007). Height velocities correlated with individual maximum IGF-I SDS BA (ρ=0.735; p<0.0001). Serum insulin, cortisol and glucose did not correlate with IGF-I concentrations, but serum potassium showed a negative correlation (ρ=-0.364; p<0.0001) with IGF-I concentrations. Conclusions Sequential measurements of serum IGF-I, glucose and potassium in patients with Laron syndrome may aid in optimizing and individualizing rhIGF-I treatment. IGF-I concentrations should be referenced according to BA which better reflects the biological age. The inverse correlation of IGF-I and serum potassium concentrations after injections of rhIGF-I has not been reported before and warrants further consideration.

Abstract A36: Serum insulin-like growth factor (IGF)-I and IGF binding protein-3 in relation to terminal duct lobular unit involution in Caucasian and African American women: The Susan G. Komen Tissue Bank

Abstract Background: Insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 play important roles in carcinogenesis, particularly for breast cancer. However, little is known about whether the IGF system influences histologic characteristics of normal glandular tissue and whether relationships vary by race. Lesser degrees of age-related terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have been associated with higher breast cancer risk. We examined the associations of IGF measures with TDLU involution of normal breast using standardized TDLU measures. Methods: Among 715 Caucasian and 283 African American (AA) women with normal breast tissue samples from the Komen Tissue Bank, serum concentrations of IGF-I and IGFBP-3 were quantified using enzyme-linked immunosorbent assay (ELISA). Hematoxilyn and eosin-stained tissue sections were assessed for numbers of TDLUs (“TDLU count”) and acini/TDLU. Zero-inflated Poisson regression models with a robust variance estimator were used to estimate associations of IGF-I, IGFBP-3, and IGF-I:IGFBP-3 molar ratio (tertiles) with TDLU count by race and menopausal status, adjusting for potential confounders. We also tested for interactions by race using likelihood ratio tests. Results: AA (vs. Caucasian) women had higher age-adjusted mean levels of serum IGF-I (137 vs. 131 ng/mL, p=0.07) and lower levels of IGFBP-3 (4165 vs. 4684 ng/mL, p&amp;lt;0.0001); the differences persisted after adjustment for additional covariates including BMI and parity/age at first birth. Postmenopausal IGFBP-3 was inversely associated with TDLU count among both AA (RR T3vs.T1=0.49, 95% CI=0.28-0.84, p-trend=0.04) and Caucasian (RR T3vs.T1=0.63, 95% CI=0.41-0.99, p-trend=0.04) women. In premenopausal women, higher IGF-I:IGFBP-3 ratios were associated with higher TDLU count in Caucasians (OR T3vs.T1=1.33, 95% CI=1.01-1.31, p-trend=0.04) but not in AA (OR T3vs.T1=0.65, 95% CI=0.42-1.00, p-trend=0.05) women. There was no statistically significant interaction by race (p-interaction≥0.10). Conclusions: Our data suggest the potential role of the IGF system, particularly IGFBP-3, in TDLU involution of the normal breast among both Caucasian and AA women. Citation Format: Hannah OH, Ruth M. Pfeiffer, Roni T. Falk, Hisani N. Horne, Jackie Xiang, Michael Pollak, Louise A. Brinton, Anna Maria V. Storniolo, Mark E. Sherman, Gretchen L. Gierach, Jonine D. Figueroa. Serum insulin-like growth factor (IGF)-I and IGF binding protein-3 in relation to terminal duct lobular unit involution in Caucasian and African American women: The Susan G. Komen Tissue Bank [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A36.

Temporal relationships of GH, IGF-I and fructosamine concentrations in pregnant Spanish Purebred mares: A substantial contribution from the hormonal standpoint

Growth hormone (GH) and insulin-like growth factor (IGF-I) exert essential functions to maintain an adequate metabolic activity for correct placental and fetal development. Although fructosamine (FRUCT) is used in clinical evaluation to assess the glycaemic state, the relationships between GH, IGF-I and FRUCT remain unknown in the mare. Therefore, the objectives of this study were to evaluate the relationships among these parameters in pregnant mares. A total of 30 healthy Spanish Purebred mares, with an age range of 9.33 ± 3.31 years, were studied during the 11 months of gestation. Serum concentrations of GH, IGF-I and FRUCT were analyzed by EIA, competition ELISA and spectrophotometry, respectively. GH showed a biphasic pattern, the first occurred during 4th and 5th month and the second which was higher than the 1st one during the 7th, 8th and 9th month (P < 0.05). Compared to the 1st month, the IGF-I concentrations increased in the 2nd month (P < 0.05), decreased in the 3rd and 4th month and increased to reach the maximum average value in the 5th month (P < 0.05); after slight oscillations between the 6th and 8th month, IGF-I concentrations increased in the 9th month (P < 0.05), decreasing until the end of gestation. FRUCT increased progressively and significantly from the 6th month of gestation, reaching the maximum values in the last month of gestation (P < 0.05). These results suggest that alternative mechanisms other than GH and IGF-I could be involved in the regulation of glycaemic metabolism in pregnant mare.

IGF1R Gene Alterations in Small for Gestational Age (SGA) Children.

BACKGROUND:Small for gestational age children (SGA) is born on term with BW and or BL of -2.0 standard deviation score (SDS). SGA children have an increased risk of being short, developing DM, and cardiovascular and cerebrovascular disease. Often defects of IGF1R are the cause of SGA. Most frequently affected part of the IGF1R gene is the exon 2.AIM:To investigate whether the exon 2 of the IGF1R gene is affected in the SGA children.PATIENTS AND METHODS:A cohort of 100 SGA children born in term was evaluated for alterations in IG1R gene. Their anthropometric parameters, IGF1 serum concentrations and IGF1 SDS values were analysed. The molecular analysis of IGF1R gene was performed by PCR restriction-site analysis and followed by direct sequencing of conspicuous fragments.RESULTS:Within our cohort, 64 SGA children were with short stature (height SDS -3.25 ± 0.90 SDS), and 36 were with normal height for their age and sex, (H SDS was 0.20 ± 1.1 SDS). None of these children had microcephaly (occipitofrontal circumference -0.70 ± 1.01 SDS vs 0.06 ± 0.56 SDS in SGA children with normal height) or dysmorphic features. The IGF1 serum concentrations and IGF1 SDS values of all children were within normal range. Only one child had lower normal serum IGF1 concentration. No alterations in exon 2 of IGF1R gene were detected.CONCLUSIONS:The genetic analysis of the exon 2 of the IGF1R gene did not detect any gene defects in the analysed patients. The putative genetic defect in those children affects other parts of the IGF1R gene or another gene (s), or yet unidentified factors.

Effects of zinc, magnesium and vitamin B6 (ZMA) supplementation on serum IGF-I, IGFBP-3 and Testosterone concentrations in young athletes

Effects of zinc, magnesium and vitamin B6 (ZMA) supplementation on serum IGF-I, IGFBP-3 and Testosterone concentrations in young athletes