Differences In Insulin-like Growth Factor-1 Research Articles

Endocrine Responses to Heated Resistance Exercise in Men and Women.

Pryor, JL, Sweet, DK, Rosbrook, P, Qiao, J, Looney, DP, Mahmood, S, and Rideout, T. Endocrine responses to heated resistance exercise in men and women. J Strength Cond Res XX(X): 000-000, 2024-We examined the endocrine responses of 16 (female = 8) resistance trained volunteers to a single bout of whole-body high-volume load resistance exercise in hot (HOT; 40° C) and temperate (TEMP; 20° C) environmental conditions. Thermoregulatory and heart rate (HR) data were recorded, and venous blood was acquired before and after resistance exercise to assess serum anabolic and catabolic hormones. In men, testosterone increased after resistance exercise in HOT and TEMP (p < 0.01), but postexercise testosterone was not different between condition (p = 0.51). In women, human growth hormone was different between condition at pre-exercise (p = 0.02) and postexercise (p = 0.03). After controlling for pre-exercise values, the between-condition postexercise difference was abolished (p = 0.16). There were no differences in insulin-like growth factor-1 for either sex (p ≥ 0.06). In women, cortisol increased from pre-exercise to postexercise in HOT (p = 0.04) but not TEMP (p = 0.19), generating a between-condition difference at postexercise (p < 0.01). In men, cortisol increased from pre-exercise to postexercise in HOT only (p < 0.01). Rectal temperature increased to a greater extent in HOT compared with TEMP in both men (p = 0.01) and women (p = 0.02). Heart rate increased after exercise under both conditions in men and women (p = 0.01), but only women experience greater postexercise HR in HOT vs. TEMP (p = 0.04). The addition of heat stress to resistance exercise session did not overtly shift the endocrine response toward an anabolic or catabolic response. When acute program variables are prescribed to increase postresistance exercise anabolic hormones, adding heat stress is not synergistic but does increase physiologic strain (i.e., elevated HR and rectal temperature).

Perbedaan Kadar Insulin-Like Growth Factor-1 dan Tumor Necrosis Factor-α Serum pada Berbagai Derajat Sarkopenia Pasien Lanjut Usia: Studi Potong Lintang

Introduction. Sarcopenia is a phenomenon of progressive decline in muscle function that occurs due to the aging process. Insulin-like growth factor-1 (IGF-1) and tumor necrosis factor-α (TNF-α) have an important role in the occurrence of sarcopenia as a positive and negative regulator of muscle mass. Research shows differences in IGF-1 and TNF-α levels between sarcopenia and non-sarcopenia groups, but research on differences in severity of sarcopenia remains unclear. The purpose of this study was to determine the difference in levels of IGF-1 and TNF-α in various degrees of sarcopenia in elderly patients. Methods. This was an analytical observational study with a cross-sectional approach involving 45 subjects of elderly patients who came to the internal outpatient clinic of RSUP dr. M. Djamil Padang and met the criteria for inclusion and exclusion. Subjects were grouped into possible sarcopenia, sarcopenia, and severe sarcopenia. Then, serum IGF-1 and TNF-α examinations were performed using the enzyme linked immunosorbent assay (ELISA) method. Data was analyzed using SPSS 26.0. Results. Median of serum IGF-1 levels in the total sample were 41.36 ng/mL. The highest levels of IGF-1 were found in the possible sarcopenia group (55.28 ng/mL), while the lowest level was in the severe sarcopenia group (31 ng/mL). Median of serum TNF-α levels in the total sample were 157.63 ng/L with the lowest was found in the possible sarcopenia group (111.41 ng/L) and the highest was in the severe sarcopenia group (241.1 ng/L). There was a significant difference in serum levels of IGF-1 and TNF-α in the three sarcopenia groups (p= 0.001). IGF-1 levels decreased according to the severity of sarcopenia, while TNF-α levels increased according to the severity of sarcopenia. Conclusions. There are differences in serum levels of IGF-1 and TNF-α between possible sarcopenia, sarcopenia, and severe elderly sarcopenia.

The IGF1/FSH Ratio Correlates with Sperm Count and Testicular Volume

BACKGROUND. Several studies have already investigated the relationship between IGF1 and semen parameters. However, clinical studies rarely concluded on the existence of a relationship between IGF1 and the sperm number, and whether the IGF1 serum levels have a practical value in the diagnostic work-up of patients with oligozoospermia is still unclear. OBJECTIVE. Molecular evidence reported that IGF1 and FSH belongs to the same molecular pathway. The aim of this study is to assess whether insulin-like growth factor-1 (IGF1)/follicle-stimulating hormone (FSH) ratio has an impact on testicular function and, specifically, on sperm number and testicular volume in a cohort of unselected men. METHODS. This is a cross-sectional study on 59 patients who attended the Seminology laboratory of the Division of Endocrinology of the University of Catania (Catania, Italy) for semen analysis. Data were analyzed to evaluate the relationships between IGF1 or IGF1/FSH ratio and sperm concentration, total sperm count (TSC), and testicular volume (TV). We also evaluated the occurrence of any difference in IGF1 and FSH serum levels and the IGF1/FSH ratio in patients with oligozoospermia and those with a TSC &gt; 39 million/ejaculate. MAIN RESULTS AND ROLE OF CHANGE. Patients had a mean age of 31.0 ± 8.5 years. The mean FSH and IGF1 levels were 3.95 ± 2.55 mIU/mL and 232.59 ± 65.13 ng/mL, respectively. IGF1 serum levels did not correlate with sperm concentration, TSC, and TV. The IGF1/FSH ratio showed a positive correlation with sperm concentration (r = 0.408; p = 0.004), TSC (r = 0.468; p = 0.001), and TV (0.463; p = 0.002). Patients with oligozoospermia (Group 1, 23.7%, n = 14) had a significant lower IGF1/FSH ratio (57.9 ± 9.5 vs. 94.1 ± 8.7; p = 0.03) compared to those with TSC &gt; 39 million/ejaculate (Group 2, 76.3%, n = 45). They did not differ significantly for neither IGF1 nor FSH serum levels. CONCLUSION. We found a positive correlation between the IGF1/FSH ratio and sperm concentration, TSC and TV. Furthermore, patients with oligozoospermia showed a significantly lower ratio compared to those with a normal TSC, while neither IGF1 nor FSH differed significantly in the two groups. Our results may reflect the existence of a molecular pathway to which IGF1 and FSH belongs. However, further studies are needed.

High Prevalence of Vertebral Fractures Associated With Preoperative GH Levels in Patients With Recent Diagnosis of Acromegaly.

Osteopathy and morphometric vertebral fractures (VFs) are emerging complications in acromegaly. However, the prediction of VFs in this clinical setting is still a matter of uncertainty, and it is debated whether they are an early event in the natural history of the disease. We aimed to evaluate the prevalence and determinants of morphometric VFs in patients with recently diagnosed acromegaly. We enrolled 92 patients (43 men/49 women) on admission to the neurosurgery unit before transsphenoidal surgery, and compared them with control individuals without secondary forms of osteoporosis and pituitary disorders. We performed a VF assessment on preoperative chest x-ray images and collected biochemical, demographic, and clinical data. We detected a significantly higher prevalence of VFs (33.7%) in patients with acromegaly than in controls (P = .001). Among the patients with acromegaly and VFs, 12 (38.7%) showed multiple VFs, and 5 (16.1%) showed moderate/severe VFs. Patients with VFs had higher random serum growth hormone (GH) levels than those with no VFs (P = .03), but there was no difference in insulin-like growth factor-1 (IGF-1) (P = .07) and IGF-1/Upper Normal Limit ratio (P = .08). Free 3,5,3'-triiodothyronine was slightly lower in patients with acromegaly and VFs than in those without VFs (P = .05). In multiple logistic analysis, GH was independently associated with risk for VFs (P = .003). The preoperative serum GH cutoff value that predicted VFs was 12 ng/mL. For the first time, high prevalence of radiological VFs is reported in patients with recent diagnosis of acromegaly. Therefore, we can hypothesize that VFs are an early phenomenon of acromegaly and related to GH levels. VF assessment should be included in the workup at the diagnosis of acromegaly.

Postnatal Serum Insulin-Like Growth Factor I and Retinopathy of Prematurity in Latin American Infants

ABSTRACT Purpose Identifying at-risk infants for retinopathy of prematurity (ROP) is complex in countries with emerging economies as infants that lack conventional risk factors, such as low birth weight (BW) and young gestational age (GA), still go on to develop severe ROP. Potential biomarkers, like serum insulin-like growth factor 1 (IGF-1) and slow postnatal weight gain, have been identified as good predictors for ROP in developed countries. We sought to determine the relationship between IGF-1 levels and ROP in two Latin American countries where the burden of disease is still significant. Methods Prospective cohort study of infants in Guadalajara, Mexico and La Plata, Argentina. Filter-paper bloodspot IGF-1 assays were performed weekly from birth until hospital discharge or 40 weeks’ postmenstrual age (PMA). Results 112 infants were studied with a median BW of 1412 g (range 620 g-2390 g) and a median GA of 33 weeks (range 25–37). There was no significant difference in IGF-1 between infants who developed ROP and those who did not. Conclusion Low IGF-1 was not associated with ROP in these infants. The lack of an association between ROP and IGF-1 in Latin America supports the observation that growth-based predictive models do not perform as well in this setting where more mature babies still develop severe ROP.

Effect of -202 A/C IGFBP-3 polymorphisms on growth responses in children with idiopathic short stature.

PurposeThis study evaluated the -202 A/C insulin-like growth factor binding protein 3 (IGFBP-3) promoter polymorphism as a predictor of serum IGFBP-3 concentration and growth velocity after recombinant growth hormone (rhGH) therapy in patients with idiopathic short stature (ISS).MethodsGenotyping and serial measurement of clinical parameters were performed in 69 children with a confirmed diagnosis of ISS. Restriction fragment length polymorphism analysis was performed to determine the genotype at the -202 IGFBP-3 locus. Serum insulin-like growth factor 1 (IGF-1) and IGFBP-3 levels were measured at baseline and after 1 year of rhGH treatment, as were height standard deviation score and growth velocity.ResultsThe -202 A/C IGFBP-3 genotype comprised 69.6% AA, 24.6% AC, and 5.8% CC. One year of treatment did not produce a meaningful difference in IGF-1 or IGFBP-3 levels between children in the AA group and those with at least one copy of the C allele (AC/CC group). Comparing the 2 groups after one year also revealed no significant difference in growth velocity (ΔHeight: 9.061±1.612 cm/yr in the AA group, 9.421±1.864 in the AC/CC group, P=0.419).ConclusionsrhGH treatment was effective and there were no significant differences in IGF-1, IGFBP-3, or growth velocity according to genotype. Thus, -202 IGFBP-3 genotype may not be a major factor affecting individual growth responses in Korean children with ISS.

C-reactive protein and insulin-like growth factor-1 in differential diagnosis of ascites.

Insulin-like growth factor-1 (IGF-1) and C-reactive protein (CRP) are produced mainly by the liver; the output of these markers in response to inflammatory processes may be affected in patients with hepatic dysfunction. This may explain the differences in IGF-1 and CRP values in patients with non-portal and portal hypertension ascites. We aimed to evaluate serum and ascitic fluid IGF-1 and CRP as diagnostic markers in the differential diagnosis of benign and malignant ascites. In this prospective study, 398 consecutive patients with ascites were included. Serum and ascitic fluid levels of IGF-1 and CRP were measured using an enzyme-linked immunosorbent assay. Patients were divided into group 1, due to benign ascites (n = 324), and group 2, due to malignant ascites (n = 74). Serum and ascitic IGF-1 were significantly increased in malignant ascites than benign ascites group [305 ± 65.7 ng/mL vs 95 ± 53.8 ng/mL; P < 0.001 and 288 ± 54.7 ng/mL vs 83.2 ± 36.7 ng/mL; P < 0.001], respectively. Serum and ascitic CRP were significantly higher in malignant ascites than benign ascites patients [12.8 ± 6.3 mg/mL vs 6.1 ± 4.9 mg/mL; P < 0.001 and 5.1 ± 2.2 mg/mL vs 1.6 ± 1.3 mg/mL; P < 0.001], respectively. At a cutoff value of 309.4 ng/mL and 7.8 mg/mL, serum IGF-1 and CRP had (95.1%, 81%) sensitivity and (88.6%, 75.5%) specificity for detecting malignant ascites [area under the curve: 0.932, 0.845], respectively. At a cutoff value of 291.6 ng/mL and 2.6 mg/mL, ascitic IGF-1 and CRP had (94.6%, 84%) sensitivity and (83.2%, 80.3%) specificity for detecting malignant ascites (area under the curve: 0.911, 0.893) correspondingly. Elevated serum and ascitic fluid IGF-1 and CRP levels were associated with malignant ascites.

Different Effects of Intraperitoneal and Subcutaneous Insulin Administration on the GH-IGF-1 Axis in Type 1 Diabetes.

In type 1 diabetes mellitus, low levels of insulin-like growth factor -1 (IGF-1) and IGF binding protein-3 (IGFBP-3) and high levels of GH and IGFBP-1 are present, probably due to portal vein insulinopenia. To test the hypothesis that continuous ip insulin infusion (CIPII) has a more pronounced effect than sc insulin therapy on regulation of the GH-IGF-1 axis. This was a prospective, observational case-control study. Measurements were performed twice at a 26-week interval. Two secondary care hospitals in the Netherlands participated in the study. There were a total of 184 patients, age- and gender-matched, of which 39 used CIPII and 145 sc insulin therapy for the past 4 years. Primary endpoint included differences in IGF-1. Secondary outcomes were differences in GH, IGFBP-1, and IGFBP-3. IGF-1 was higher with CIPII as compared to SC insulin therapy: 124 μg/liter (95% confidence interval [CI], 111-138) vs 108 μg/liter (95% CI 102-115) (P = .035). Additionally, IGFBP-3 concentrations were higher and IGFBP-1 and GH concentrations were lower with CIPII as compared to SC insulin therapy: 3.78 mg/liter (95% CI, 3.49-4.10) vs 3.31 mg/liter (95% CI, 3.17-3.47) for IGFBP-3, 50.9 μg/liter (95% CI, 37.9-68.2) vs 102.6 μg/liter (95% CI, 87.8-119.8) for IGFBP-1 and 0.68 μg/liter (95% CI, 0.44-1.06) vs 1.21 μg/liter (95% CI, 0.95-1.54) for GH, respectively. In multivariate analysis, IGF-1 had no significant association with HbA1c. The GH-IGF-1 axis may be affected by the route of insulin administration with CIPII counteracting dysregulation of the GH-IGF1 axis present during sc insulin therapy.

Abstract 15552: Insulin-Like Growth Factor-1 is Lower in Acute Stroke but is Not Related to Recovery

Purpose: Insulin-like growth factor 1 (IGF1) sampled within ten days of stroke has resulted in inconsistent findings. When compared to control participants, one study found elevated levels of IGF1 while another reported lower values. Despite these reported differences, there is evidence to suggest that IGF1 may have a neuroprotective effect and may be related to admitting stroke severity and functional independence at one month post-stroke. The possibility exists that a large sampling window and no consideration for insulin-like growth factor binding protein 3 (IGFBP3), may account for the differing results. The purpose of this study was to: 1) determine the difference in IGF1, IGFBP3, and IGF1 ratio in individuals with acute stroke and controls; and 2) determine the relationship of IGF1, IGFBP3, and IGF1 ratio to admission stroke severity and functional independence at one month post stroke. Methods: Blood was collected from 12 individuals with a diagnosis of acute stroke (4 males; 63.9 + 8.4 years) between 7:30 and 9:00 am, after an overnight fast, and within 72 hours of hospital admission. Blood was obtained from 12 age and gender matched healthy controls (4 males; 64.8 + 9.8 years) after an overnight fast during similar hours. Plasma was obtained from blood samples, aliquoted, and frozen within 1 hour of collection. IGF1 and IGFBP3 were quantified using standard procedure ELISAs (Alpco, Salem, NH). Admission NIH Stroke Scale and the modified Rankin Scale (mRS) at one month post stroke was obtained from the electronic medical record. Results: IGF1 (stroke: 113 ng/mL; control: 123 ng/mL, p = .59) and IGFBP3 (stroke: 2350 ng/mL; control: 2593 ng/mL, p = .33) were lower in the acute stroke patients, but not significantly. IGF1 ratio was not different (stroke: .06; control: 05; p = .55) in acute stroke compared to controls. There were no significant relationships between any IGF marker and stroke severity (p &gt; 0.50), nor mRS (p &gt; 0.50). Conclusion: We report that IGF1 and IGFBP3 is lower in acute stroke patients. A single time point of IGF1 and IGFBP3 during acute stroke may not demonstrate a neuroprotective relationship to stroke recovery. Future work should examine percent change in the IGF family to determine whether this may be a more valuable biomarker of stroke recovery.

Reduced utility of serum IGF-1 levels in predicting retinopathy of prematurity reflects maternal ethnicity

AimsTo validate known risk factors and identify a threshold level for serum insulin-like growth factor 1 (IGF-1) in the development of severe retinopathy of prematurity (ROP) in an ethnically diverse...

Insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 concentrations in children with obstructive sleep apnea-hypopnea syndrome.

The aim of this study was to assess insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) concentrations in children with obstructive sleep apnea-hypopnea syndrome (OSAHS) and to compare the results according to disease severity and duration. Fifty-one children with OSAHS underwent polysomnography and were classified as having mild, moderate, or severe disease. All children underwent bilateral tonsillectomy/adenoidectomy or adenoidectomy. IGF-1 and IGFBP-3 concentrations were assessed before surgery and 3 and 6 months after surgery. Before surgery, IGF-1 and IGFBP-3 concentrations were significantly higher (P < .05) in the < 5-y group (125.20 ± 42.38 μg/L and 2.00 ± 0.54 mg/L) compared with the ≥ 5-y group (61.92 ± 19.07 μg/L and 1.20 ± 0.37 mg/L). After surgery, concentrations significantly increased (P < .05) in both groups, but remained lower in the ≥ 5-y group. Before surgery, there were no significant differences in IGF-1 (mild: 93.82 ± 37.52 mg/L; moderate: 109.06 ± 58.42 mg/L; severe: 73.88 ± 28.51 mg/L) and IGFBP-3 (mild: 1.76 ± 0.57 mg/L; moderate: 1.67 ± 0.72 mg/L; severe: 1.33 ± 0.45 mg/L) concentrations by severity. After surgery, concentrations significantly increased (P < .05) in both groups, but did not differ by severity. After adjusting for time after surgery, disease duration, apnea-hypopnea index, time spent at SpO2 < 90%, and body mass index Z score, IGF-1 and IGFBP-3 concentrations significantly decreased with every year of age. These results suggest that disease duration, but not severity, affects the concentrations of 2 important mediators of growth/development (IGF-1 and IGFBP-3) in children with OSAHS before and after surgery.

Effects of intravascular low-level laser therapy during coronary intervention on selected growth factors levels.

The objective of this study was to evaluate the effect of intravascular low-level laser therapy (LLLT) on selected growth factor levels in subjects undergoing percutaneous coronary interventions (PCI). Restenosis remains the main problem with the long-term efficacy of PCI, and growth factors are postulated to play a crucial role in the restenosis cascade. In a randomized prospective study, an 808 nm LLLT (100 mW/cm2, continuous wave laser, 9 J/cm2, illuminated area 1.6-2.5 cm2) was delivered intracoronarily to patients during PCI. Fifty-two patients underwent irradiation with laser light, and 49 constituted the control group. In all individuals, serum levels of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and fibroblast growth factor-2 (FGF-2) were measured before angioplasty, then 6 and 12 h and 1 month after the procedure. In all patients, a control angiography was performed 6 months later. There were no significant differences in IGF-1 and VEGF levels between the groups. While evaluating FGF-2, we observed its significantly lower levels in the irradiated patients during each examination. There was a significant increase in TGF-β1 level in control group after 12 h of observation. In the irradiated individuals, control angiography revealed smaller late lumen loss and smaller late lumen loss index as compared with the control group. The restenosis rate was 15.0% in the treated group, and 32.4% in the control group, respectively. LLLT decreases levels of TGF-β1 and FGF-2 in patients undergoing coronary intervention, which may explain smaller neointima formation.

Regional and inter-annual trends in marine growth of juvenile salmon in coastal pelagic ecosystems of British Columbia, Canada

We measured insulin-like growth factor 1 (IGF1) concentrations (a proxy for growth) from juvenile coho Oncorhynchus kisutch, sockeye O. nerka, chum O. keta, and Chinook salmon O. tshawytscha collected in 8 regions of British Columbian coastal waters, in June of 2009, 2010, and 2011. We found annual differences in IGF1 for all 4 species, as well as species- specific regional differences in IGF1 concentrations in coho, chum, and sockeye salmon. Sockeye and chum salmon had consistently higher levels in the northern regions of the Dixon Entrance, Haida Gwaii, Hecate Strait, and lower levels in Queen Charlotte Strait. Regional differences in coho, chum, and sockeye salmon were highly correlated (R 2 = 0.61-0.75). These results demonstrate that salmon growth responds to local environmental variability on a scale of several hundred kilo- meters. Thus, IGF1 measures should generate insight into fish production on relatively local regional and temporal scales, and these same measures may allow the assessment of how habitats vary on these same scales.

Reference values for serum levels of insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) in the West Black Sea region of Turkey

Objectives. The aim of this study was to determine the normal values of serum IGF-1 and IGFBP-3 in Turkish children and adults (1–79 years). Material and methods. The study included 571 healthy children and 625 healthy adults from the West Black Sea region of Turkey. Serum IGF-1 and IGFBP-3 concentrations were determined using a chemiluminescent immunometric assay on an Immulite 1000 analyzer. Results. IGF-1 and IGFBP-3 levels tended to be higher in girls compared to boys among the children. The differences were statistically significant in puberty from age 12–14 years for IGF-1 and prepubertally from age 9–10 years for IGFBP-3. Peaks of serum IGF-1 levels were observed 2 years earlier in girls (14 years) than boys (16 years). The general pattern of IGFBP-3 was similar to IGF-1 during puberty. In adults, IGF-1 and IGFBP-3 levels decreased by age. There was no significant difference in IGF-1 and IGFBP3 values between men and women in any age group. Conclusions. This study established age- and sex-specific reference values for serum IGF-1 and IGFBP-3 in healthy Turkish children and adults.

Determination of insulin-like growth factor-1 and bovine insulin in raw milk and its casein and whey fractions after microfiltration and ultrafiltration

Insulin-like growth-factor 1 (IGF-1) and insulin were analysed from bovine milk during microfiltration (MF) and ultrafiltration (UF) processes using immunochemical methods. IGF-1 was found in the MF retentate and in the UF retentate. A very small fraction of IGF-1 was in the UF permeate. The results indicated that IGF-1 was present in milk as a complex molecule or bound to milk proteins. Insulin showed similar behaviour, but more insulin was found in the MF retentate than in the UF retentate. No insulin was found in the UF permeate. There were no differences in IGF-1 or insulin distribution between pasteurised or non-pasteurised milk. The stability of bovine insulin to heat treatments was also determined. The molecule was stable during pasteurisation at 65 and 72 °C, but lost some of its immunochemical activity at 90 and 135 °C.

Suitability of Insulin‐Like Growth Factor 1 (IGF1) as a Measure of Relative Growth Rates in Lingcod

AbstractThe effectiveness of spatial management strategies is typically evaluated through traditional biological measurements of size, density, biomass, and the diversity of species inside and outside management boundaries. However, there have been relatively few attempts to evaluate the processes underlying these biological patterns. In this study, we take the first step toward developing a relative index of body growth for lingcod Ophiodon elongatus using plasma insulin‐like growth factor 1 (IGF1) with the ultimate goal of measuring spatial differences in relative growth rates. Insulin‐like growth factor 1 is one of the principal hormones that stimulates growth at the cellular level in all vertebrates and shows significant relationships with body growth in many fishes. In the laboratory, we found that the level of IGF1 was related to the instantaneous growth of juvenile lingcod. In the field, we measured size, condition, and plasma IGF1 level in 149 lingcod from eight locations inside and outside marine protected areas in the San Juan Islands, Washington. The IGF1 levels in wild lingcod were highly variable from site to site for both genders, and we were able to detect differences in IGF1 across space in males. Multivariate analyses showed that the spatial patterns of IGF1 differed from those of traditional biological measurements. More work is needed to validate the relationship between IGF1 and growth in larger individuals, but our research shows the potential for IGF1 to be used as an ecological indicator.

Abstract PR-1: Genetic African ancestry and race differences in blood insulin-like growth factor 1 (IGF-1), IGF-2, and IGF binding protein 3 (IGFBP-3)

Abstract Purpose: We have previously reported that African American women have significantly higher IGF-1 levels, and lower IGF-2 and IGFBP-3, compared to white women. This investigation aims to determine if genetic African ancestry is associated with these racial differences in blood IGF levels. Methods: The Southern Community Cohort Study (SCCS) is a prospective cohort study of 86,000 men and women, with two-thirds African American recruitment, designed to investigate racial disparities in cancer. We randomly selected 1000 African American and 1000 non-Hispanic white female participants to support focused investigations of racial differences in biomarkers possibly related to breast cancer. Serum IGF-1, IGF-2, and IGFBP-3 levels were measured by ELISA. We estimated African and European admixture using a panel of 276 ancestry informative genetic markers. Final analyses included 821 African American women and 816 white women after excluding women taking hormone replacement therapy or insulin for diabetes. White women had a low African ancestry (median = 0.4%, range=0.1 % to 17.1 %) and thus were considered as a single ancestry category. For African Americans, cutpoints of &amp;lt;85% (n=149), 85%-95% (n=230), and ≥95% (n=442) defined “low,” “medium,” and “high” African ancestry. Using multivariable linear regression, we estimated differences in IGF levels across ancestry categories while adjusting for age, body mass index (BMI), height, menopausal status, and BMI at age 21 years. Results: African American women having 85% African ancestry. For example, IGF-2 levels among white women and African American women with &amp;lt;85%, 85%-95%, and ≥95% African ancestry were 1771.9 ng/ml, 1713.5 ng/ml, 1620.3 ng/ml, and 1620.6 ng/ml, respectively. African American women with &amp;lt; 85% African ancestry had IGF-2 levels that were about 5.8% higher than African American women with 85%-95% (p=0.03) or ≥95% (p=0.01) ancestry. IGF-1 levels among white women and African American women with &amp;lt;85%, 85%-95%, and ≥95% African ancestry were 134.7 ng/ml, 143.8 ng/ml, 147.8 ng/ml, and 147.4 ng/ml, respectively, while IGFBP-3 levels were 3871.8 ng/ml, 3816.9 ng/ml, 3629.0 ng/ml, and 3693.9 ng/ml, respectively. African American women with 85% African ancestry, but these differences in IGF-1 and IGFBP-3 levels between African American ancestry groups were not statistically significant. We also calculated the molar ratio of IGF-1 to IGFBP-3 as an index of biologically available or free IGF-1. Differences in free IGF-1 among white women and African American women with &amp;lt;85%, 85%-95%, and ≥95% African ancestry were 0.126,0.137,0.148, and 0.145, respectively. Free IGF-1 levels were significantly lower among African American women with &amp;lt;85% compared to women with 85%-95% (p=0.02) or ≥95% (p=0.05) ancestry. Conclusion: Estimates of African ancestry are significantly associated with IGF-2 and free IGF-1, and suggest inherited genetic traits associated with African ancestry contribute to racial differences in IGF levels. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):PR-1.

Lack of Polymorphism in Partial Insulin Like Growth Factor 1 (IGF1) and Insulin Like Growth Factor Binding Protein 3 (IGFBP3) Genes of Mithun

Panigrahi, M., Kumar, S., Deb, S.M., Mitra, A., Sharma, A. and Bujarbaruah, K.M. 2009. Lack of polymorphism in partial insulin like growth factor 1 (IGF1) and insulin like growth factor binding protein 3 (IGFBP3) genes of mithun. J. Appl. Anim. Res., 36: 41–44. A 396 bp fragment encompassing exon 5 of Insulin like growth factor 1 (IGF1) gene and 652 bp fragment encompassing exon 2–3 of Insulin like growth factor binding protein 3 (IGFBP3) gene were digested by HindIII and NlaIII restriction enzymes, respectively, in 90 mithun (Bos frontalis). The PCR-RFLP analysis showed the absence of polymorphism in these fragments in the animals screened. HindIII restriction enzyme produced two fragments of 269 and 127 bp in exon-5 of IGF 1. Similarly NlaIII restriction enzyme produced two fragments of 551 and 101 bp in exon 2–3 ofIGFBP3 gene. Two single nucleotide differences in IGF1 while six such differences in IGFBP3 gene existed in mithun sequences when compared to cattle. The sequence of the amplicons, which were the first reports on these genes in mithun, were submitted to GenBank (Accession numbers EF686016 and EF686017, respectively).

Exercise Effects on Tumorigenesis in a p53-Deficient Mouse Model of Breast Cancer

Physically active women have a reduced risk of breast cancer, but the dose of activity necessary and the role of energy balance and other potential mechanisms have not been fully explored in animal models. We examined treadmill and wheel running effects on mammary tumorigenesis and biomarkers in p53-deficient (p53(+/-)):MMTV-Wnt-1 transgenic mice. Female mice (9 wk old) were randomly assigned to the following groups in experiment 1: treadmill exercise 5 d x wk(-1), 45 min x d(-1), 5% grade at 20 m x min(-1), approximately 0.90 km x d(-1) (TREX1, n = 20) or at 24 m x min(-1), approximately 1.08 km x d(-1) (TREX2, n = 21); or a nonexercise control (CON-TREX, n = 22). In experiment 2, mice were randomly assigned to voluntary wheel running (WHL, n = 21, 2.46 +/- 1.11 km x d(-1) (mean +/- SD)) or to a nonexercise control (CON-WHL, n = 22). Body composition was measured at approximately 9 wk and serum insulin-like growth factor 1 (IGF-1) at two to three monthly time points beginning at approximately 9 wk on study. Mice were sacrificed when tumors reached 1.5 cm, mice became moribund, or there was only one mouse per treatment group remaining. TREX1 (24 wk) and TREX2 (21 wk) had shorter median survival times than CON-TREX (34 wk; P < 0.01), whereas those of WHL and CON-WHL were similar (23 vs 24 wk; P = 0.32). TREX2 had increased multiplicity of mammary gland carcinomas compared with CON-TREX; WHL had a higher tumor incidence than CON-WHL. All exercising animals were lighter than their respective controls, and WHL had lower body fat than CON-WHL (P < 0.01). There was no difference in IGF-1 between groups (P > 0.05). Despite beneficial or no effects on body weight, body fat, or IGF-1, exercise had detrimental effects on tumorigenesis in this p53-deficient mouse model of spontaneous mammary cancer.

Social Differences in Insulin-like Growth Factor-1: Findings from a British Birth Cohort

Insulin-like growth factor-1 (IGF-1) is related to factors that are socially patterned and may play a role in social differences in the development of morbidities including disability. Our aim is to examine whether there are social differences in IGF-1 in a cohort of participants between 44 and 45 years of age. We examine the association of IGF-1 with social position measured by father's or own occupational class at three time points in childhood and adulthood, in a cohort of individuals born in one month in 1958 (N = 3,374 men and 3,302 women). Lower IGF-1 levels were associated with lower social position measured with father's occupational class at birth (p < 0.0001) and own occupational class aged 42 years (p < 0.001). Adult social position was associated with IGF-1 independently of social position at birth (p < 0.001) or any covariates examined. IGF-1 secretion is associated with social position such that low social position is associated with lower levels of IGF-1. This biomarker may play a role in the development of social differences in morbidities associated with aging, such as the development of disability.