Serum Insulin-like Growth factor-I Concentrations Research Articles

Endocrine and metabolic profile in Holstein and red Holstein heifers during peripartal period

The aim of this stady was to examine the relationship between triiodothyronine (T3), thyroxin (T4), insulin-like growth factor-I (IGF-I) and blood serum liver function biomarkers concentrations in Holstein and Red Holstein heifers during the peripartal period. In the first experimental group (I) were heifers of Holstein Friesian breed (n=10), and in the second experimental group (II) were Red Holstein heifers (n=10). Blood samples were taken from the vena coccygea three times during the short peripartal period (5 days before delivery, at delivery and 5 days after delivery), and blood serum samples were separated after spontaneous coagulation. Blood serum T3, T4 and IGF-I concentrations were determinated using radioimmunoassay (RIA). Blood serum concentrations of glucose (G), total protein (TP), albumin, (Alb), urea, total bilirubin (tBil) and aspartate aminotrasferase (AST) were determined using commercial ELISA kits. The statistical significance between means was determined using Student t-test. Blood serum T3 concentration in Group II was significantly lower after delivery, and T4 concentration was significantly higher before delivery (p<0.05), compared to Group I. Mean blood serum IGF-I concentrations between the two experimental groups were not significantly different at all time intervals. Relationships between the determined hormones showed a median positive correlation between T3, and T4 (r=0.74) in Group I and highly positive correlation in Group II (r=0.81). Blood serum thyroid gland hormones and IGF-I concentrations in healthy heifers during peripartal period vary considerably, the lowest values being determined immediately after calving in both experimental groups. Blood serum G, TP, Alb and urea concentrations were significantly higher in Group I at all investigated time intervals. Blood serum tBil concentration was significantly higher after partus in Group I (11.02 ± 3.33 : 8.49 ± 3.35 μmol/L, Group I vs. II, respectively), and AST activity was not significantly different at all intervals.

Muscle Protein Metabolism during Compensatory Growth with Changing Dietary Lysine Levels from Deficient to Sufficient in Growing Rats

Livestock and laboratory animals show compensatory growth when they are fed ad libitum following a period of restriction feeding. Lysine is a major limiting essential amino acid in the diets both for humans and animals. We hypothesized that changing dietary lysine levels from deficient to sufficient induced compensatory growth in young rats. We elucidated the effect of lysine sufficiency on the dynamics of hormones, relevant to muscle protein synthesis and degradation, insulin-like growth factor-I (IGF-I) and corticosterone, and on the expression of proteolytic-related genes in skeletal muscle during compensatory growth. Lysine sufficiency where the dietary lysine level was increased from 0.46% to 1.30% after 2 wk of subjecting the rats to the lower lysine level induced 80% enhancement of growth rate of rats. During compensatory growth with the lysine sufficiency, fractional muscle protein synthesis rates were higher whereas fractional muscle protein degradation rates were lower than those of the control group (p<0.05). After lysine sufficiency, the expression of atrogin-1/MAFbx mRNA was decreased in gastrocnemius muscle (p<0.05). With the lysine sufficiency, serum IGF-I concentration increased (p<0.05) whereas serum corticosterone decreased (p<0.05). These findings suggest that compensatory growth with lysine sufficiency is due to a change of hormone levels before and after changing diets, resulting in incrementation of protein synthesis and suppression of protein degradation of skeletal muscle.

Yetişkin Sağlıklı Bir Türk Toplum Örnekleminde İnsülin-Benzeri Büyüme Faktörü-I ve IGF-Bağlayıcı Protein-3 Seviyeleri

Amaç: İnsülin benzeri büyüme faktörü-I (IGF-I) ve IGF-bağlayıcı protein-3 (IGFBP 3) seviyeleri büyüme hormonu (GH) ilişkili hastalıkların tanısında önemli belirteçlerdir. Normal IGF-I ve IGFBP- 3 seviyeleri farklı etnik gruplar arasında değişkenlik göstermektedir ve farklı populasyonlara göre belirlenenen referanslar bazı tanı, tedavi ve izlemde bazen yanlış yönlenmeye neden olabilmektedir. Biz bu amaçla sağlıklı yetişkin Türk toplum örnekleminde IGF-I ve IGFBP-3 düzeylerini inceledik. Gereç ve Yöntemler: Sekiz yüz otuz üç olgu (512 kadın, 321 erkek) çalışmaya alındı. Serum IGF-I ve IGFBP-3 seviyeleri tüm olgularda bir immünoradyometrik tetkikle ölçüldü. Çalışma populasyonu yaş grupları (18-20, 21-23, 24-25, 26-30, 31-40, 41-50, >50 yaş) ve cinsiyet gruplarına (<30 yaş populasyon kadın ve erkekler olarak ayrılırken >30 yaş grubunda birlikte) ayrıldı ve sonuçlar üretici firmanın referans bir toplumu temsil eden referans değerleri ile karşılaştırıldı. Bulgular: Serum IGF-I değerleri ≤30 yaştaki bütün kadın yaş gruplarında referans seviyelerinden istatistiksel olarak anlamlı düzeyde daha yüksekti (p< 0.05). Erkeklerde sadece 26-30 yaş arası grupta IGF-I seviyeleri istatistiksel olarak anlamlı düzeyde daha yüksekti (p< 0.05). Otuz yaş üstündeki cinsiyet yönünden birlikte ele alınan gruplarda IGF-I seviyeleri referans seviyelerinden istatistiksel olarak daha yüksekti (p< 0.05). Serum IGFBP-3 seviyeleri 24-25 yaş arası grupta her iki cinsiyette, 18-20 yaş arası grupta ise erkeklerde referans değerlerinden daha düşüktü (p< 0.05). Serum IGFBP-3 seviyeleri 26-30 yaş arası grupta erkeklerde ve >30 yaş üstünde cinsiyet yönünden birleşik gruplarda istatistiksel açıdan anlamlı derecede daha yüksekti (p< 0.05). Sonuç: Çalışma populasyonumuzdaki serum IGF-I konsantrasyonları ticari kitin referans değerlerinden genelde daha yüksekti. GH'la ilişkili bozukluklarla ilgilenen merkezlerin tanı ve izlemde olası hatalardan kaçınabilmek amacıyla kendi populasyonlarının normal IGF-I ve IGFBP-3 değerlerini belirlemeleri yararlı olabilecektir.

The relationship between serum ghrelin levels and hair zinc concentrations in children

Background: Zinc (Zn) plays a central role in the activation of numerous enzyme systems that synthesize and degrade bioactive peptides. Some of these bioactive peptides, also called neuropeptides, are involved in the regulation of food intake.Objective: In this study we aimed to demonstrate the relationship between serum ghrelin and hair Zn concentrations in children. Methods: Prepubertal children brought to our outpatient clinics by their parents because of signs and symptoms of pica, poor appetite, poor growth, and other complaints were included in the study. The children were divided into two groups according to Zn hair concentrations. Group 1 consisted of children with low (< 70 μg/g) hair Zn levels, and group 2 of children with normal ( ≥ 70 μg/g) hair Zn levels. Hair Zn concentrations, serum ghrelin, insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) levels were measured in all children.Results: There were 10 children with low hair Zn levels (group 1) and 15 with normal levels (group 2). Serum IGF-I, IGFBP-3 and ghrelin concentrations of group 1 (103.1 ± 71.8 ng/mL, 1412.8 ± 615.7 ng/mL and 0.96 ± 0.22 ng/mL, respectively) were lower than in group 2(164.9 ± 40.5 ng/mL, 2398.5 ± 295.5 ng/mL and 1.21 ± 0.23 ng/mL, respectively). In univariate analysis, Zn hair concentration was positively associated with serum IGF-I (r=0.424, p=0.035) and IGFBP-3 (r=0.671, p < 0.001) concentrations. The correlation between ghrelin and hair Zn concentrations was not significant (r=0.202, p=0.333).Conclusion: Serum ghrelin concentrations might be affected by low hair Zn concentrations in children.Conflict of interest:None declared.

Assessment of IGF-I as a factor influencing postpartum reproductive performance and ovarian condition in dairy cattle

This study was carried out to assess insulin-like growth factor-I (IGF-I) influence and the concentration of additional metabolites in different groups of Holstein–Friesian dairy cows based on different ovarian function and reproductive performance after parturition. Eighty-seven lactating Holstein cows, fed the same diet as total mixed ration were incorporated into the study. Blood samples were collected every 2 weeks from 2 weeks before until 6 weeks after calving for IGF-I, non-esterified fatty acids, β-hydroxybutyrate, and glucose analysis. Palpation of the reproductive tract was performed 2, 4, and 6 weeks after calving. Dominant palpable ovarian structures including corpus luteum (CL) and follicle or no palpable structures were recorded. Ultrasonographic assessment of the uterus and ovaries using a rectal linear probe was also performed and ovarian structures (follicle, CL) were scanned and measured using calipers. Cows detected in oestrus after the voluntary waiting period (50 days after calving) were artificially inseminated (AI). Pregnancy diagnosis was performed by ultrasound examination 25–35 days after AI. Calving and AI dates and the results of pregnancy tests were recorded. Serum IGF-I concentration (especially prepartum IGF-I) was significantly higher in cows that received their first AI before 100 days postpartum than cows who received it after that time. Multiparous cows that did not ovulate until 45 days after calving had significantly lower concentration of IGF-I. But when all parity groups were evaluated together, no significant difference were identified in concentration of the plasma metabolites between different groups of cows with different times of luteal activity commencement. Among all metabolites that were measured, IGF-I concentration was the main factor associated with earlier resumption of cyclic activity after calving. In conclusion, high IGF-I concentration was the main factor that was associated with better reproductive performance after calving.

Effect of dietary methionine on growth performance and insulin-like growth factor-I mRNA expression of growing meat rabbits

An experiment was conducted to determine the effects of different amounts of dietary methionine on growth performance, serum protein, growth hormone (GH), insulin-like growth factor-I (IGF-I) concentrations and IGF-I mRNA expression of growing meat rabbits. One hundred weaned growing meat rabbits were allocated to individual cages and randomly divided into five groups. The methionine addition concentrations of the five groups were 0, 2, 4, 6 and 8 g/kg diet (as-fed basis) and sulphur amino acids (SAA) concentrations ranging from 3.8 to 11.6 g/kg diet, respectively. The results obtained were as follows: the average daily gain of 2, 4 and 6 g/kg diet groups was higher than that of 0 g/kg diet group (p < 0.01). The feed gain ratio of the 4 g/kg diet group was lower than those of 0 and 8 g/kg diet group (p < 0.01). Methionine concentrations did not affect serum urea nitrogen, total protein, insulin and IGF-I concentration (p > 0.05). The quadratic effects of methionine on the serum concentration of albumin (Alb) and GH were obtained (p = 0.013, p = 0.018). The quadratic effect of methionine amount on IGF-I mRNA expression was obtained (p = 0.045). The serum concentration of Alb of the 4 g/kg diet group was higher than those of 0 and 8 g/kg diet group (p < 0.01). The serum concentration of GH of 8 g/kg diet group was higher than that of the 0 g/kg diet group (p < 0.05). The liver IGF-I mRNA expression of 4 g/kg diet group was higher than those of the 0 and 8 g/kg diet group (p < 0.05). Providing a diet mainly consisted of corn, wheat bran and peanut vine, the optimum dietary methionine addition concentration and SAA concentration for a weaner to 2-month-old growing meat rabbits were shown to be 2 and 5.7 g/kg diet respectively.

Association of circulating IGF-I and IGFBP-3 concentrations and exercise capacity in healthy volunteers: Results of the Study of Health in Pomerania

Background Insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) are central mediators of endocrine effects of growth hormone and there is increasing evidence for an association with muscle strength and exercise capacity. The aim of the present study was to clarify the possible association of circulating IGF-I and IGFBP-3 concentrations and exercise capacity in a general adult population. Materials and methods From the Study of Health in Pomerania (SHIP) 1332 subjects aged 25 to 85 years participated in a standardised symptom limited cardiopulmonary exercise test on a bicycle. Exercise capacity was characterized by oxygen uptake at anaerobic threshold (VO 2@AT), peak exercise (peakVO 2), oxygen pulse and maximum power output at peak exertion. Multivariable linear regression analyses adjusted for age, sex, body mass index, physical activity and smoking were performed. Results At peak exercise performance, in women IGF-I showed significant associations to peakVO 2 and maximum power output, IGF-I/IGFBP-3 ratio was associated with maximum power output. In men, this association was not consistently reproducible. Neither IGF-I nor IGFBP-3 did reveal any association to VO 2@AT in both genders. Conclusion Serum IGF-I concentrations are associated with peak exercise capacity in healthy women, but not in men over a wide range in ages, body sizes and activity scores.

Maternal serum insulin‐like growth factor‐I at 11–13 weeks in preeclampsia

To investigate the maternal serum concentration of insulin-like growth factor-I (IGF-I) in the first trimester of pregnancies that subsequently develop preeclampsia (PE) and to examine the possible association with uterine artery pulsatility index (PI). The maternal serum concentration of IGF-I and uterine artery PI at 11-13 weeks were measured in 53 cases that developed PE, including 18 that required delivery before 34 weeks (early-PE) and 106 unaffected controls. The measured IGF-I concentration and uterine artery PI were converted into a multiple of the expected median (MoM) in unaffected pregnancies, and median MoM values were compared in the outcome groups. The significance of association of IGF-I MoM with uterine artery PI MoM was determined by regression analysis. In the early-PE and late-PE groups, compared to the unaffected controls, the median IGF-I decreased (0.53 and 0.55 MoM, respectively) and uterine artery PI increased (1.55 and 1.21 MoM, respectively). In the group that developed PE, there was no significant association between serum IGF-I and uterine artery PI (p = 0.632). In pregnancies destined to develop PE, the circulating levels of IGF-I decrease from the first trimester of pregnancy suggesting that IGF-I may be implicated in the pathogenesis of the disease.

A cross-sectional analysis of the associations between adult height, BMI and serum concentrations of IGF-I and IGFBP-1 -2 and -3 in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Background: Height and BMI are risk factors for several types of cancer and may be related to circulating concentrations of insulin-like growth factor-I (IGF-I), a peptide associated with increased cancer risk.Aim: To assess the associations between height, BMI and serum concentrations of IGF-I and IGF binding protein (IGFBP)-1, -2 and -3.Subjects and methods: This cross-sectional analysis included 1142 men and 3589 women aged 32–77 years from the multi-centre study, the European Prospective Investigation of Cancer and Nutrition (EPIC).Results: In men, there was a positive association between height and IGF-I; each 10 cm increment in height was associated with an increase in IGF-I concentrations of 4.3% (95% confidence interval (CI): 1.3–7.5%, p for trend = 0.005), but this association was not statistically significant for women (0.9%, 95% CI: − 0.7 to 2.6%, p for trend = 0.264). In both men and women, the association between IGF-I and BMI was non-linear and those with a BMI of 26–27 kg/m2 had the highest IGF-I concentration. BMI was strongly inversely related to concentrations of IGFBP-1 and IGFBP-2 in men and in women (p for trend for all < 0.001).Conclusion: Height and BMI are associated with IGF-I and its binding proteins, which may be mechanisms through which body size contributes to increased risk of several cancers.

Relationships between insulin-like growth factor-I, milk yield, body condition score, and postpartum luteal activity in high-producing dairy cows

The relations between body condition score (BCS), milk yield, serum insulin-like growth factor-I (IGF-I) profile, and luteal activity were investigated in postpartum dairy cows. Seventy-one healthy high-producing multiparous Holstein cows were subjected to transrectal ultrasound scanning twice weekly from the first to the eighth week postpartum. Blood samples were collected twice weekly to measure serum progesterone (P4) and every 2weeks to detect serum IGF-I concentrations. BCS was monitored weekly after calving. Cows with serum P4 concentrations ≥1ng/ml on at least two consecutive samplings were considered to have commenced luteal activity. Commencement of luteal activity (C-LA) was observed earlier than 45days postpartum in 71.8% of cows while 28.2% showed C-LA later than 45days. Prolonged luteal phase was the most common abnormal pattern of luteal activity observed. Cows with a C-LA earlier than 45days postpartum had higher (P ≤ 0.05) mean serum concentrations of IGF-I than those with later C-LA. In addition, cows which showed C-LA earlier than 45days postpartum had more optimal productive indices including shorter calving to conception interval and calving to first service interval (P ≤ 0.05), and fewer services per conception (P = 0.07). C-LA was significantly later in cows that lost more than 0.5 BCS units within 3weeks postpartum than in those that lost less than 0.5 units BCS during the same interval (P = 0.02). We conclude that high-producing dairy cows with higher postpartum serum IGF-I concentrations have earlier commencement and normal luteal activity, and better reproductive performance. Severity and duration of BCS loss adversely affect commencement of luteal activity.

Bone mineral density in partially recovered early onset anorexic patients - a follow-up investigation

Background and aimsThere still is a lack of prospective studies on bone mineral development in patients with a history of early onset Anorexia nervosa (AN). Therefore we assessed associations between bone mass accrual and clinical outcomes in a former clinical sample. In addition to an expected influence of regular physical activity and hormone replacement therapy, we explored correlations with nutritionally dependent hormones.Methods3-9 years (mean 5.2 ± 1.7) after hospital discharge, we re-investigated 52 female subjects with a history of early onset AN. By means of a standardized approach, we evaluated the general outcome of AN. Moreover, bone mineral content (BMC) and bone mineral density (BMD) as well as lean and fat mass were measured by dual-energy x-ray absorptiometry (DXA). In a substudy, we measured the serum concentrations of leptin and insulin-like growth factor-I (IGF-I).ResultsThe general outcome of anorexia nervosa was good in 50% of the subjects (BMI ≥ 17.5 kg/m2, resumption of menses). Clinical improvement was correlated with BMC and BMD accrual (χ2 = 5.62/χ2 = 6.65, p = 0.06 / p = 0.036). The duration of amenorrhea had a negative correlation with BMD (r = -.362; p < 0.01), but not with BMC. Regular physical activity tended to show a positive effect on bone recovery, but the effect of hormone replacement therapy was not significant. Using age-related standards, the post-discharge sample for the substudy presented IGF-I levels below the 5th percentile. IGF-I serum concentrations corresponded to the general outcome of AN. By contrast, leptin serum concentrations showed great variability. They correlated with BMC and current body composition parameters.ConclusionsOur results from the main study indicate a certain adaptability of bone mineral accrual which is dependent on a speedy and ongoing recovery. While leptin levels in the substudy tended to respond immediately to current nutritional status, IGF-I serum concentrations corresponded to the individual's age and general outcome of AN.

Effects of Dietary Lysine on Growth Performance, Serum Concentrations of Insulin-Like Growth Factor-I (IGF-I) and IGF-I mRNA Expression in Growing Rabbits

The effects of dietary lysine on production performance, serum concentrations of metabolites, growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-I mRNA expression in growing rabbits were examined. One hundred weaned New Zealand rabbits were allocated to individual cages and randomly offered a diet containing 5.5 (L1), 6.5 (L2), 7.5 (L3), 8.5 (L4), or 9.5 g (L5) lysine per kg diet. The results showed that the average daily gain (ADG) of the rabbits from L3, L4 or L5 was higher than those from L1 or L2 ( P < 0.05). The feed gain ratio (F/G) in the rabbits from L4 or L5 was lower than those from L1 or L2 ( P < 0.05). Dietary lysine did not affect serum concentrations of total protein (TP), glucose, insulin (INS), and growth hormone (GH) ( P > 0.05). The quadratic effects of lysine on the serum urea nitrogen (SUN) concentration was detected ( P = 0.035). Serum IGF-I concentrations had a trend to increase quadratically with the increasing dietary lysine ( P = 0.07). A significant correlation was found between serum IGF-I concentrations ( x, ng mL −1) and ADG ( y, g kg −1): y = −0.017 x 2 + 1.984 x + 20.87 ( R 2 = 0.8982, P = 0.003). The relative abundance of hepatic and muscular IGF-I mRNA tended to increase with increasing dietary lysine levels ( P = 0.053 and 0.082, respectively). Providing the diets mainly consisted of corn, wheat bran and peanut vine, the most appropriate dietary lysine level for growing meat rabbits from weaning to 70 d old was found to be 8.5 g kg −1, and IGF-I may be an important factor controlling growth of weaned rabbits.

Abstract 4830: Insulin-like growth factors and kidney cancer risk in men

Abstract Context: Causes of kidney cancer are not fully understood. Incidence is highest in those ages 50 to 70, and almost twice as high in men as in women. Smokers are twice as likely as non-smokers to develop renal cell carcinoma and about four times as likely to develop cancer of the renal pelvis. Insulin-like growth factor-I (IGF-I) has been shown to increase kidney microvascular growth and glomerular filtration rate, and its administration increases renal function in animal models of chronic renal failure, and has been proposed as a possible therapeutic agent (Hirschberg et al, 1998). However, the possible roles of IGF in the development of kidney cancer have not been well-studied. Objective: To examine the relation of serum levels of IGF-I and insulin-like growth factor binding protein 3 (IGFBP-3) to kidney cancer risk. Methods: We conducted a case-cohort study nested within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of 29,133 Finnish male smokers who were 50-69 years of age and not diagnosed with cancer at study entry. Serum concentrations of IGF-I, IGFBP-3 were measured in blood samples collected in 1985 to 1988. One hundred men were identified who had a diagnosis of kidney cancer &amp;gt;5 years after blood collection through the end of 1997. Self-reported information on lifestyle and medical history was collected and weight and height were measured at baseline. Multivariable logistic regression models were used to estimate the relative risk of kidney cancer associated with IGF levels. Results: A history of hypertension (known to be increased in those who are older, overweight, or heavier smokers) was more common among cases than among noncases. Men with IGF-I levels &amp;gt;108 ng/mL were 63% less likely to develop kidney cancer than men with IGF-I levels ≤108 ng/mL (OR=0.37; 95% CI=0.20-0.69). IGFBP-3 levels did not alter the association between IGF-I and kidney cancer risk. Further, no association was observed between IGFBP-3 levels and the development of kidney cancer. Conclusions: Low serum IGF-I levels in this cohort of older middle-aged male smokers are associated with increased kidney cancer risk, independent of IGFBP-3, age, anthropometry, lifestyle and medical history. Further research is needed to confirm the findings and examine the association in women and non-smokers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4830.

Association between serum lipoprotein lipase mass concentration and subcutaneous fat accumulation during neonatal period

Subcutaneous adipose tissue grows rapidly during the first months of life. Lipoprotein lipase (LPL) has a quantitatively important function in adipose tissue fat accumulation and insulin-like growth factor-I (IGF-I) is a determinant of neonatal growth. Recent studies showed that LPL mass in non-heparinized serum (LPLm) was an index of LPL-mediated lipolysis of plasma triacylglycerol (TG). The objective was to know the influence of serum LPL and IGF-I on neonatal subcutaneous fat growth, especially on catch-up growth in low birth weight infants. We included 47 healthy neonates (30 males, 17 females), including 7 small for gestational age. We measured serum LPLm and IGF-I concentrations at birth and 1 month, and analyzed those associations with subcutaneous fat accumulation. Serum LPLm and IGF-I concentrations increased markedly during the first month, and positively correlated with the sum of skinfold thicknesses both at birth (r=0.573, P=0.0001; r=0.457, P=0.0035) and at 1 month (r=0.614, P<0.0001; r=0.787, P<0.0001, respectively). In addition, serum LPLm concentrations correlated inversely to very low-density lipoprotein (VLDL)-TG levels (r=-0.692, P<0.0001 at birth; r=-0.429, P=0.0052 at 1 month). Moreover, the birth weight Z-score had an inverse association with the postnatal changes in individual serum LPLm concentrations (r=-0.639, P<0.0001). Both serum LPLm and IGF-I concentrations were the determinants of subcutaneous fat accumulation during the fetal and neonatal periods. During this time, LPL-mediated lipolysis of VLDL-TG may be one of the major mechanisms of rapid growth in subcutaneous fat tissue. Moreover, LPL, as well as IGF-I, may contribute to catch-up growth in smaller neonates.

Androgens, growth factors, and risk of prostate cancer: The Multiethnic Cohort

Androgens and growth factors are thought to be associated with prostate cancer risk, although past research has produced mixed results. We conducted a nested case-control study of biomarkers of prostate cancer risk within the Multiethnic Cohort. We compared prediagnostic levels of testosterone, dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG), 3alpha-androstanediol glucuronide (3alpha-diol G), insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein 1 (IGFBP-1), and IGFBP-3 in serum from 467 incident prostate cancer cases and 934 cancer-free controls. Controls were matched to the cases on geographic site (HI, LA), ethnicity, age at specimen collection (+/-1 year), date (+/-1 month) and time of day (+/-2 hr) of sample collection, and fasting status (<6, 6-7, 8-9, >10 hr). Multivariate conditional logistic regression models were used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Serum concentrations of testosterone, DHT, SHBG, 3alpha-diol G, IGF-I, IGF-II, IGFBP-1, and IGFBP-3 were not associated with risk of prostate cancer. Tests for trend of quartiles of serum concentrations also did not show any association. Results were relatively unchanged for men with advanced prostate cancer and their matched controls. However, the follow-up period was relatively short (mean of 1.9 years). Analysis by ethnic group showed an increased risk for Latino men in the second (OR = 3.67, 95% CI: 1.63-8.24) and third (OR = 2.96, 95% CI: 1.19-7.40) tertiles of IGF-I serum levels compared with the first tertile. The suggested increased risk for IGF-I in Latino men merits further study, with greater statistical power.

Serum levels of IGF‐I, IGFBP‐3 and colorectal cancer risk: results from the EPIC cohort, plus a meta‐analysis of prospective studies

Several prospective studies have shown a moderate positive association between increasing circulating insulin-like growth factor-I (IGF-I) levels and colorectal cancer risk. However, the associations were often statistically nonsignificant, and the relationship of cancer risk with IGF-I's major binding protein, IGFBP-3, showed major discrepancies between studies. We investigated the association of colorectal cancer risk with serum IGF-I, total and intact IGFBP-3, in a case-control study nested within the EPIC cohort (1,121 cases of colorectal cancer and 1,121 matched controls). Conditional logistic regression was used to adjust for possible confounders. Our present study results were combined in a meta-analysis with those from 9 previous prospective studies to examine the overall evidence for a relationship of prediagnostic serum IGF-I with colorectal cancer risk. In the EPIC study, serum concentrations of IGF-I and IGFBP-3 showed no associations with risk of colorectal cancer overall. Only in subgroup analyses did our study show moderate positive associations of IGF-I levels with risk, either among younger participants only (and only for colon cancer) or among participants whose milk intakes were in the lowest tertile of the population distribution (RR for an increase of 100 ng/ml = 1.43 [95% CI = 1.13-1.93]). Nevertheless, in the meta-analysis a modest positive association remained between serum IGF-I and colorectal cancer risk overall (RR = 1.07 [1.01-1.14] for 1 standard deviation increase in IGF-I). Overall, data from our present study and previous prospective studies combined indicate a relatively modest association of colorectal cancer risk with serum IGF-I.

Insulin like growth factor-I in acute subarachnoid hemorrhage: a prospective cohort study

IntroductionNeuroendocrine deficiencies may affect recovery after aneurysmal subarachnoid hemorrhage (aSAH). Insulin like growth factor-I (IGF-I) regulates neuronal growth and apoptosis in ischemic stroke. Our study was designed to a) characterize the behavior of serum IGF-I and growth hormone (GH) in the acute and late phases after aSAH reflecting possible pituitary gland function and b) evaluate the association between IGF-I and morbidity assessed by Glasgow outcome scale (GOS) and health related quality of life (HRQoL) in patients with aSAH.MethodsIn this prospective cohort study, patients with aSAH (n = 30) were compared to patients who underwent elective aneurysm surgery (n = 16). Serum GH and IGF-I concentrations were measured daily for five (controls) or seven (aSAH) days and at three months. GOS and 15d HRQoL was measured at three months. A mixed models method was used for testing between the groups. For factors possibly affecting HRQoL in aSAH patients, we constructed a Bayesian predicting model using a P-course Bayesian classifier.ResultsThe mean IGF-I concentrations for days one to five were 8.1 ± 3.5 nmol/l in patients with aSAH and 11.2 ± 3.1 in the control group (P = 0.01). No corresponding difference was found at three months. Serum GH concentrations were similar in both patient groups. Severity of the aSAH did not affect serum IGF-I concentrations. Patients with GOS ≤ 4 had lower IGF-I concentrations and lower HRQoL than patients with GOS 5 (P = 0.02 and 0.003 respectively). The 15d HRQoL was 0.81 ± 0.16 in patients with aSAH and 0.86 ± 0.09 in control patients (P = 0.24). In the Bayesian model, the use of statins prior to aSAH, hyponatremia, high maximal sequential organ specific score (SOFAmax), and low cumulative IGF-I concentrations on days one to seven were associated with poor HRQoL (accuracy 89%, sensitivity 86%, and specificity 93%).ConclusionsIGF-I concentrations are low during acute aSAH, which may have an impact on morbidity.Trial registrationClinicalTrials.gov Identifier NCT00614887

Exercise and the Growth Hormone-Insulin-Like Growth Factor Axis

Exercise is a robust physiological stimulator of the pituitary secretion of growth hormone (GH), and within approximately 15 min after the onset of exercise, plasma GH starts to increase. GH and its primary downstream mediator, insulin-like growth factor I (IGF-I), play a critical role in formation, maintenance, and regeneration of skeletal muscles. Consequently, it seems logical to link the exercise-induced stimulation of GH with the hypertrophy observed in exercising muscles. GH stimulates circulating (endocrine) as well as locally produced (peripheral) IGF-I, which acts through autocrine/paracrine mechanisms. However, it remains to be clarified whether skeletal muscle hypertrophy after exercise is stimulated primarily by endocrine or paracrine/autocrine IGF-I. Early cross-sectional studies have observed positive correlations between circulating IGF-I levels and GH secretion, respectively, and indices of fitness. However, longitudinal exercise studies have shown that it is possible to increase muscle strength, performance, and VO2max without concomitant and robust changes in circulating IGF-I, indicating that the effect of exercise on skeletal muscles is mediated via paracrine/autocrine IGF-I rather than endocrine IGF-I. So far, most exercise studies have investigated the concentration of immunoreactive IGF-I in serum or plasma, obtained after extraction of the IGF-binding proteins (i.e., total IGF-I). However, several of the newer exercise studies have included measurement of free IGF-I as well as bioactive IGF-I. The aim of this review was to discuss whether measurement of free and/or bioactive IGF-I have increased our knowledge on the processes that link exercise, muscle hypertrophy, and GH/IGF-I axis. Thus, the current review will discuss (i) the different IGF-I assay methodologies and (ii) the current literature on free, bioactive, and immunoreactive (total) IGF-I in exercising subjects.

The endocrine tumor summit 2008: appraising therapeutic approaches for acromegaly and carcinoid syndrome

The Endocrine Tumor Summit convened in December 2008 to address 6 statements prepared by panel members that reflect important questions in the treatment of acromegaly and carcinoid syndrome. Data pertinent to each of the statements were identified through review of pertinent literature by one of the 9-member panel, enabling a critical evaluation of the statements and the evidence supporting or refuting them. Three statements addressed the validity of serum growth hormone (GH) and insulin-like growth factor-I (IGF-I) concentrations as indicators or predictors of disease in acromegaly. Statements regarding the effects of preoperative somatostatin analog use on pituitary surgical outcomes, their effects on hormone and symptom control in carcinoid syndrome, and the efficacy of extended dosing intervals were reviewed. Panel opinions, based on the level of available scientific evidence, were polled. Finally, their views were compared with those of surveyed community-based endocrinologists and neurosurgeons.

Age- and gender-specific reference ranges for serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 concentrations on the Immulite 2500: results of the Study of Health in Pomerania (SHIP)

The objective of the present study was to calculate age- and gender-specific reference ranges for serum insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) concentrations using quantile regression. From the Study of Health in Pomerania (SHIP), 1798 men and women aged 25-85 years were recruited. Serum IGF-I and IGFBP-3 concentrations were determined using a chemiluminescent immunometric assay on an Immulite 2500 analyzer. Quantile regressions were performed to calculate the 2.5th and 97.5th percentiles. The reference ranges identified 43 (4.6%) women and 41 (4.8%) men with serum IGF-I concentrations, and 47 (5.0%) women and 42 (5.0%) men with serum IGFBP-3 concentrations outside the reference range. The use of quantile regression results in accurate calculation of age- and gender-specific reference ranges for serum IGF-I and IGFBP-3.