Circulating IGF-1 Concentrations Research Articles

Dairy Intake and Incidence of Common Cancers in Prospective Studies: A Narrative Review

Dairy products are commonly consumed and sometimes recommended by governmental authorities; however, significant evidence indicates that dairy consumption modifies cancer risk. Prospective studies examining the relationship between dairy intake and cancer of the prostate, breast, ovary, and colorectum were reviewed. These studies indicate that dairy consumption is associated with prostate cancer risk, possibly as a consequence of dairy-induced increases in circulating IGF-1 concentrations and the calcium and estrogen content of dairy products. Evidence also suggests a positive association between dairy intake and ovarian cancer. Findings on breast cancer have been mixed; however, recent studies of populations with a wide range of dairy intakes have shown clear associations between dairy intake and breast cancer risk. In contrast, there is a negative association between dairy products and colorectal cancer, which is likely driven by the protective effect of calcium. Current evidence suggests that dairy intake is associated with increased risk of prostate, ovarian, and possibly breast cancer, and reduced risk of colorectal cancer.

Associations between Circulating IGF-1 Concentrations, Disease Status and the Leukocyte Transcriptome in Early Lactation Dairy Cows

Peripartum dairy cows commonly experience negative energy balance (EB) and immunosuppression together with high incidences of infectious and metabolic disease. This study investigated mechanisms linking EB status with immune defense in early lactation. Data were collected from multiparous Holstein cows from six herds and leukocyte transcriptomes were analyzed using RNA sequencing. Global gene expression was related to circulating IGF-1 (as a biomarker for EB) by subdividing animals into three groups, defined as IGF-1 LOW (<35 ng/mL, n = 35), MODERATE (35–100 ng/mL, n = 92) or HIGH (>100 ng/mL, n = 43) at 14 ± 4 days in milk (DIM). Differentially expressed genes between groups were identified using CLC Genomics Workbench V21, followed by cluster and KEGG pathway analysis, focusing on the comparison between LOW and HIGH IGF-1 cows. LOW cows were older and had significantly lower dry matter intakes and EB values, whereas HIGH cows produced more milk. During the first 35 DIM, 63% of LOW cows had more than one health problem vs. 26% HIGH cows, including more with clinical mastitis and uterine infections. Gene expression analysis indicated that leukocytes in LOW cows switched energy metabolism from oxidative phosphorylation to aerobic glycolysis (PGM, LDH, and PDK4). Many antimicrobial peptides were up-regulated in LOW cows (e.g., PTX3, DMBT1, S100A8, and S100A9) together with genes associated with inflammation, platelet activation and the complement cascade. HIGH cows had greater expression of genes regulating T and B cell function and the cytoskeleton. Overall, results suggested an ongoing cycle of poor EB and higher infection rates in LOW IGF-1 cows which was reflected in altered leukocyte functionality and reduced milk production.

PSII-B-25 Age-related changes in growth hormone-insulin like growth factor 1 axis-regulating factors and metabolic hormones in Korean cattle steer

Abstract Meat yield is important for beef industry for maximum profits. Enhancing muscle growth by promoting hypertrophy of muscle fiber is required for increasing meat yield. Growth hormone (GH)-insulin like growth factor 1 (IGF1) axis and metabolic hormones have a central role for regulating hypertrophy of muscle fiber. We investigated age-related changes in GH-IGF1 axis-regulating factors and metabolic hormones in beef cattle. Ten Korean cattle steers were used. The longissimus thoracis (LT) samples were biopsied between the 11th and 12th rib at 12, 18, and 24 months of age. Steers were slaughtered at 34 month of age and the LT samples were collected. The LT samples were used for histological observation of muscle fiber size and detection of mRNA levels by real-time PCR analysis. Blood was collected at 12, 18, 24, and 34 months of age and used for hormone analyses. The mean muscle fiber size increased (P < 0.01) from 12 to 24 months, and remained unchanged at 34 months. Plasma GH concentrations were unchanged with age, whereas circulating IGF-1 concentrations decreased (P < 0.001) with age. Testosterone and insulin concentrations increased from 12 to 24 months and remained unchanged at 34 months. Leptin concentrations were unchanged from 12 to 24 months and increased at 34 months. The mRNA levels of growth hormone receptor (GHR) and signal transducer and activator of transcription 5a/b (STAT5a/b) decreased (P < 0.01) from 12 to 24 months, whereas mRNA levels of IGF-1 gene increased (P < 0.001) with age. Results indicate that the increased muscle fiber size in LT from 12 to 24 months are characterized with increasing concentrations of circulating testosterone and insulin. Age-dependent changes in muscle fiber hypertrophy were also related with changes in GHR, STAT5a/b, IGF-1 mRNA levels in the LT.

The effect of HMB ingestion on the IGF-I and IGF binding protein response to high intensity military training

ObjectiveInsulin-like growth factor-I (IGF-I) is a metabolic and anabolic biomarker that has been proposed to reflect physiological adaptations resulting from multistressor environments. The bioactivity of IGF-I is regulated by seven different insulin-like growth factor binding proteins (IGFBPs) which act not only as carriers of IGF-1, but also function as a modulator of IGF-I availability and activity. Supplementing with β-hydroxy-β-methylbutyrate (HMB) has been shown to enhance physiological outcomes associated with intense training, and has been reported to augment the IGF-1 response. The purpose of this study was to examine the effect of 23days of HMB supplementation on circulating levels of IGF-I and IGFBPs in combat soldiers during highly intense military training. MethodsThirteen male soldiers from an elite infantry unit volunteered to participate in this double-blind, parallel design study. Soldiers were provided 3g·day−1 of either HMB (n=6) or placebo (PL; n=7). During the study soldiers performed advanced military training with periods of restricted sleep and severe environmental stressors. Blood samples were obtained prior to (PRE) and approximately 18h following the final supplement consumption (POST). ResultsNo significant differences were observed for circulating IGF-1 concentrations between HMB and PL (p=0.568). In addition, no differences were seen between the groups for IGFBP-1 (p=1.000), IGFBP-2 (p=0.855), IGFBP-3 (p=0.520), IGFBP-4 (p=0.103), IGFBP-5 (p=0.886), or IGFBP-6 (p=0.775). A significant difference was noted between HMB (169.9±23.0ng·ml−1) and PL (207.2±28.0ng·ml−1) for IGFBP-7 at POST (p=0.042). ConclusionsAlthough the results of this study do not support the influence of HMB supplementation on circulating concentrations of IGF-1 or IGFBPs1–6 during high intensity military training, it does present initial evidence that it may lower circulating IGFBP-7 concentrations. This may provide some indication of a reduced stress response, but further investigation on the physiological role of IGFBP-7 and military training is needed.

The role of insulin-like growth factor 1 and its receptor in the formation and development of colorectal carcinoma

To investigate the role of insulin-like growth factor (IGF)-1 and its receptor (IGF1R) in the formation and development of colorectal carcinoma. Colorectal tissue and matching serum samples were collected from patients with adenomatous polyps or carcinoma and healthy control subjects. IGF1R mRNA levels were determined via quantitative real-time reverse transcription-polymerase chain reaction. Serum IGF1 was quantified using enzyme-linked immunosorbent assay. Serum IGF1 concentrations and mucosal IGF1R mRNA levels were significantly higher in patients with adenomatous polyps (n = 24) or carcinoma (n = 13) compared with healthy control subjects (n = 13). There was a significant positive correlation between serum IGF1 and mucosal IGF1R mRNA in patients with adenomatous polyps. High circulating IGF1 concentrations and mucosal IGF1R expression may play important roles in both the formation and development of colorectal carcinoma. IGF1 and its receptor may be activated before carcinogenesis, and may promote the growth and malignant transformation of adenomatous polyps. IGF1 and IGF1R may be useful biomarkers for evaluating the stage and risk of carcinogenesis.

Light at Night Activates IGF-1R/PDK1 Signaling and Accelerates Tumor Growth in Human Breast Cancer Xenografts

Regulation of diurnal and circadian rhythms and cell proliferation are coupled in all mammals, including humans. However, the molecular mechanisms by which diurnal and circadian rhythms regulate cell proliferation are relatively poorly understood. In this study, we report that tumor growth in nude rats bearing human steroid receptor-negative MCF-7 breast tumors can be significantly accelerated by exposing the rats to light at night (LAN). Under normal conditions of an alternating light/dark cycle, proliferating cell nuclear antigen (PCNA) levels in tumors were maximal in the early light phase but remained at very low levels throughout the daily 24-hour cycle period monitored. Surprisingly, PCNA was expressed in tumors continually at a high level throughout the entire 24-hour period in LAN-exposed nude rats. Daily fluctuations of Akt and mitogen activated protein kinase activation in tumors were also disrupted by LAN. These fluctuations did not track with PCNA changes, but we found that activation of the Akt stimulatory kinase phosphoinositide-dependent protein kinase 1 (PDK1) directly correlated with PCNA levels. Expression of insulin-like growth factor 1 receptor (IGF-1R), an upstream signaling molecule for PDK1, also correlated with fluctuations of PDK1/PCNA in the LAN group. In addition, circulating IGF-1 concentrations were elevated in LAN-exposed tumor-bearing nude rats. Finally, RNAi-mediated knockdown of PDK1 led to a reduction in PCNA expression and cell proliferation in vitro and tumor growth in vivo, indicating that PDK1 regulates breast cancer growth in a manner correlated with PCNA expression. Taken together, our findings demonstrate that LAN exposure can accelerate tumor growth in vivo, in part through continuous activation of IGF-1R/PDK1 signaling.

The association between bladder cancer and a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) gene

Insulin-like growth factors (IGF) regulate growth and development and enhance cellular proliferation. IGF-binding protein-3 (IGFBP-3) inhibits IGF action by competitively binding IGFs that prevents their binding to the IGF cell surface receptor. Altered expression and serum levels of IGFBP-3 are associated with a number of malignancies. Study addressing the effect of IGFBP-3 gene polymorphism on bladder cancer is lacking. The aim of this study was to examine the effect of -202 A/C polymorphism of IGFBP-3 gene on development of bladder transitional cell carcinoma (TCC) and its correlation with serum concentration of IGF-1 and IGFBP-3 and with clinicopathological characteristics. One single nucleotide polymorphism (rs2854744) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP) technique. One hundred and sixty-two bladder cancer patients were genotyped for this SNP. The genotypes were compared with those of a random sample of 324 age-matched controls of the general population. Serum levels of IGF-I and IGFBP-3 were also determined. We found statistically significant differences in the genotypic distribution between the cases and the control subject (χ(2)=6.43, df=2.0, P=0.028). Using CC genotype as a reference, the odds ratio for the subjects with AC genotype was 1.76 (95% CI: 1.27-2.84; P=0.038). We detected a significantly decreased risk of bladder cancer associated with the AA genotype (adjusted OR=0.48; 95% CI=0.24-0.64; P=0.001) compared with the CC genotype. This decreased risk was more pronounced for invasive bladder cancer. Age-adjusted mean serum IGFBP-3 levels were lowest in the individuals with the CC genotype. We found a positive correlation between age-adjusted serum IGFBP-3 levels and circulating IGF-1 concentrations (16% difference in IGFBP-3 in top vs. bottom tertiles of IGF-1, P for trend=0.001), which was comparable across genotypes at the -202 IGFBP-3 locus (interaction term, F=0.10, P=0.87). Genetic polymorphism of the IGFBP-3 gene may be involved in the etiology of bladder TCC, and our results need further confirmation by larger studies.

Reproductive and metabolic endocrinology of Romney rams selected for high or low circulating IGF-I concentrations

The objectives of this study were to characterise reproductive and metabolic endocrinology parameters in Romney rams from lines selected since 1986, for high or low circulating IGF-1 concentrations. Seasonal changes were recorded in the patterns of IGF-1, insulin and the response of serum testosterone to hCG administration. Serum testosterone concentrations, adjusted for covariance with IGF-1 concentrations, were higher in both strains ( P < 0.05) in the autumn (March), compared to other times of year. The response of serum testosterone to hCG increased ( P < 0.01) between mid-winter (July) and the following autumn. Serum testosterone concentrations were higher ( P < 0.05) in high, compared to low-IGF rams in July and September (spring), but not in March (autumn). The serum IGF-1 concentrations were higher ( P < 0.01) throughout the entire experiment in the high- versus the low-IGF rams, although the concentrations in the high-IGF rams declined between July and March. Insulin concentrations were also higher in the high-IGF line. The difference between the two lines was greatest in July, but not significant in March. Samples of liver and testes tissue were collected from 4 animals in each line for the polymerase chain reaction (PCR) determinations of mRNA expression for IGF-1, Type 1 IGF receptor (IGF-1R) and IGF-binding proteins (IGFBP's). Genes for IGF-1, IGF-1R and the IGFBP-2, -3, -4, -5 and -6 were expressed in the testis. Expression of IGF-1R and IGFBP-3 in the testis and that of IGF-1 in the liver, was greater in the high- than the low-IGF line rams. These studies suggest circulating concentrations IGF-1 to be associated with basal, but not gonadotrophin-stimulated steroidogenesis. The differences in IGF-1 status between lines are modulated by the differential expression of mRNA for IGF-1R and the IGFBP's and by differences between lines in the negative feedback of IGF-1.

Abstract 1047: Circadian disruption induced by light at night upregulates PCNA expression in tissue-isolated human breast cancer xenografts in nude rats

Abstract The circadian system and the cell cycle are two global regulatory systems in animals and humans. Previous studies have shown that disruption of either the circadian system or the cell cycle increases the risk of cancer in humans. However, the molecular mechanisms of circadian-mediated cell cycle dysregulation are not completely understood. Because proliferating cell nuclear antigen (PCNA) plays an essential role in DNA replication and cell cycle regulation, we studied the circadian regulation and disruption of PCNA in an in vivo animal model of human breast cancer. In tissue-isolated ER- MCF-7 human breast cancer xenografts grown in female nude rats exposed to a normal 12L:12D circadian condition, PCNA protein levels were maximal in the morning (2 h after lights on) but remained at very low levels throughout the rest of the 24 h period. To determine whether circadian disruption alters PCNA protein expression, xenograft-bearing nude rats were exposed to low intensity of light at night (LAN) (0.08 μW/cm2). PCNA protein was continuously expressed at a high level throughout the 24 h period in breast cancer xenografts growing in nude rats exposed to the LAN. Exposure of tumor-bearing rats to LAN also resulted in significantly accelerated growth of these xenografts. Moreover, several signaling cascades related to cell growth were examined. Daily rhythms of Akt and MAPK activation in the human breast cancer tumors were disrupted by LAN but did not track the changes in PCNA expression; however, PDK1 activation directly correlated with PCNA expression. Expression of PKCδ and PKCα, downstream targets of PDK1, was differentially elevated by LAN in xenografts in a manner consistent with their reported roles in cell proliferation. In contrast, LAN did not disrupt the rhythmic expression of either PCNA, PKCδ, or PKCα in the liver of the tumor-bearing rats. Expression of insulin-like growth factor 1 receptor (IGF-1R) protein, an upstream signaling molecule for PDK1, also correlated with the expression pattern of PDK1/PKC/PCNA in tumor-bearing rats exposed to LAN. Exposure of tumor-bearing rats to LAN disrupted the circadian rhythm of IGF-1R protein levels in the liver. Finally, circulating IGF-1 concentrations showed circadian disruption in LAN-exposed tumor-bearing nude rats. Thus, interruption of the IGF-1 signaling pathway may constitute a novel molecular mechanism of circadian regulated tumor growth. Taken together, our results suggest that LAN-induced disruption of circadian rhythms in cell signaling cascades accelerates tumor growth in vivo through continuous up-regulation of PCNA. 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 1047.

Abstract 2853: Genetic variation in IGF1, GHR, and IGFBP1 is associated with colorectal cancer

Abstract Background The insulin-like growth factor (IGF-1)/growth hormone (GH) pathway has been implicated in the development of colorectal cancer. Circulating IGF-1 increases cell proliferation and inhibits apoptosis. Genetic variation in the IGF pathway genes has been shown to alter circulating IGF-1 concentrations and has been associated with colorectal cancer. This risk may differ by anatomic location. Methods We used a principal components approach to evaluate the relationship between genetic variation in six IGF pathway genes (IGF1, IGF2, IGFBP1, IGFBP3, GHR, and GH1) and colorectal cancer in a family-based case-control study from the Colon Cancer Family Registry (CCFR). Cases were recruited from both high-risk clinics and population-based registries. Controls had no previous diagnosis of colorectal cancer and were full biologic siblings of the cases. Clinic-based (cases = 268, controls = 475) and population-based (cases = 1,802, controls = 2,874) data were analyzed separately and all models were adjusted for age and sex. Results There was no overall association between genetic variation in the IGF pathway genes and colorectal cancer. However, when the data were analyzed by colorectal cancer anatomic location, GH1 was associated with distal colon cancer (p=0.05) in the population-based families and IGF1 was associated with rectal cancer (p=0.004) in the clinic-based families. Furthermore, when the data were stratified by MSI-status, IGFBP1 was associated with MSI-low/stable tumors (p=0.017) in the clinic-based families. Conclusion In this family-based case-control study, genetic variation in IGF1, GHR, and IGFBP1 was associated with colorectal cancer differentially by anatomic location, population source, and tumor type. The clinic-based data represent families with high genetic risk in contrast to the population-based data which represent families of moderate to average genetic risk. These results replicate prior case-only analyses that suggest IGF1 is a modifier of colorectal cancer risk in high-risk families. Single SNP analyses and exploration of SNP x SNP interactions may further elucidate the significance of IGF pathway genes on colorectal cancer risk. 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 2853.

Inhibition of Dipeptidyl-Peptidase IV Does Not Increase Circulating IGF-1 Concentrations in Growing Pigs

The enzyme dipeptidyl peptidase-IV (DPP-IV) inactivates a variety of bioactive peptides, including glucagon-like peptide-1 (GLP-1) and growth hormone releasing hormone (GHRH). Inhibiting DPP-IV in order to increase circulating GLP-1 is of interest as a treatment for Type II diabetes. Inactivation of DPP-IV may also increase circulating GHRH, potentially enhancing growth in domestic animals. To test the hypothesis that inhibition of DPP-IV activity will influence the growth hormone/ IGF-1 axis, growing pigs (Sus scrofa domesticus, 78 kg) were treated with a DPP-IV inhibitor (Compound 1, the 2,5-difluor-ophenyl analog of the triazolopiperazine MK0431, sitagliptin), and plasma concentrations of IGF-1 were monitored. Pigs were administered either sterile saline (0.11 ml/kg followed by a continuous infusion at 2 ml/hr for 72 hrs, controls, n = 2), Compound 1 (2.78 mg/kg followed by a continuous infusion at 0.327 mg/kg x hr for 72 hrs, n = 4) or GHRH (0.11 ml/kg sterile saline, followed by a continuous infusion of GHRH at 2.5 microg/ kg x hr for 48 hrs, n = 4). Plasma concentrations of Compound 1 were maintained at 1 microM, which resulted in a 90% inhibition of circulating DPP-IV activity. Relative to the predose 24-hr period, area under the IGF-1 concentration curve (AUC) tended to be lower (P = 0.062) with Compound 1 (.79 +/- 130 ng/ml x hr) than controls (543 +/- 330 ng/ml x hr). GHRH treatment increased the IGF-1 AUC (1210 +/- 160 ng/ml x hr, P = 0.049 vs. controls and P = 0.001 vs. Compound 1). We conclude that inhibition of DPP-IV does not alter the circulating levels of IGF-1 in the growing pig.

The Influence of Nutrition on IGF-1 in Tube-Fed Profoundly Retarded Adults

Objective: This study was conducted to determine whether IGF-1 concentrations are low in nonambulant profoundly retarded adults and to identify associated nutritional factors.Methods: Serum IGF-1, albumin, pre-albumin, creatinine, zinc (Zn) and plasma amino acids were measured before and after a four-week 25% increase in formula in 25 individuals, divided into those fed by day (Group A) or by night (Group B).Results: Circulating IGF-1 was low in nine of the 22 subjects (40.9%) included in the analysis. Mean IGF-1 increased 10.4% (p=0.004). Despite high intakes of essential amino acids and Zn, initial mean plasma tryptophan and phenylalanine were low, and serum Zn was low in 40.9% of subjects. Plasma tryptophan was low at both samplings and correlated with circulating IGF-1 concentrations (p=0.02) at the beginning of the study. Serum IGF-1 and Zn also correlated (p=0.02) initially.Conclusions: IGF-1 is commonly low in this population and is associated with low plasma amino acid and Zn concentrations, despite high intakes of these nutrients. The causes and clinical implications of these abnormalities need further study.

Glucose regulation of growth hormone secretion in lactating sheep.

Exogenous growth hormone stimulates milk secretion in all breeds of dairy animal [ I ] Thus an understanding of the mechanisms which regulating growth hormone secretion is vital if endocrine manipulation of dairy animals to improve milk production and composition are to become viable techniques in agriculture. The regulation of growth hormone secretion during lactation appears to differ markedly from that prevailing in the non-pregnant, non-lactating animal Growth hormone concentrations are elevated despite the high circulating concentrations of non-esterified fatty acids, which normally inhibit growth hormone secretion [2] In addition the normal positive correlation between growth hormone and IGF-I concentrations is no longer apparent [3] The elevated growth hormone concentrations do not appear to stimulate IGF1 secretion to the normal extent. A similar abnormal regulation of growth hormone secretion is observed in insulin-dependent diabetes [4,5] Here, too, the high circulating concentrations of non-esterifed fatty acids do not inhibit growth hormone secretion and circulating IGF-1 concentrations are low in view of the high growth hormone levels. In the diabetic subject hyperglycaemia and/or hyperinsulinaemia has been shown to stimulate growth hormone secretion by an, as yet, unidentified mechanism [5]. A similar stimulation of growth hormone secretion by glucose and elevated insulin has also been described in the sheep but these were of limited duration [6] Data are reported here which show the effects of longer infusions of glucose on plasma concentrations of insulin and growth hormone in lactating sheep which have been fed normally or undernourished by 24h starvation. Sheep at about 20 days postpartum (peak lactation) were infused vici a jugular catheter with sterile glucose at a rate of 12pmol/kg/min for 6h in fed sheep and 5h in 24h starved animals. Blood samples were taken via a second jugular catheter at regular intervals before, during and after inhsion Heparinised blood was centrifuged immediately and plasma stored at -20°C before analysis for glucose [6]and growth hormone [7]. Some blood was left to clot at room temperature and serum collected and stored at -20 C before analysis for insulin [6]. Plasma glucose concentrations rose significantly (p<O 00 1) by about 1.5 to 2 mM during glucose infusion in both groups of animals and remained elevated for the duration of the infusion (Fig I ) . Serum insulin concentrations rose significantly during the early stages of the infusions (p<O.OI and p<O 05 for fed and starved animals respectively) but started to return to basal values after about 2h (Fig 1) Plasma growth hormone concentrations increased rapidly and significantly (p<O 0 1) during the early stages of the infusion but then declined to return to basal values by about 2h. This response was significantly greater (p<O.OI) in the 24h starved compared with the fed group. The data reported here demonstrate that glucose inhsion results in a stimulation of growth hormone secretion as has been shown previously [8] However, this growth hormone response to glucose is relatively short-lived and is not maintained for the duration of the inhsion In this respect it mirrors the changes in serum insulin concentrations rather than those of glucose itself Thus the increase in growth hormone secretion may be better attributed to hyperinsulinaemia rather than hyperglycaemia. It is also apparent that changing insulin concentrations alone are not the sole regulator. Other factors are at work as the response is greatly accentuated in the 24h starved group compared with those on a normal feeding regime even though the increase in insulin is much reduced in this group. Thus energy balance also has a major role to play in regulating growth 24

Effects of Thyroxine Supplement on Serum Insulin-Like Growth Factor-Binding Activity in Propylthiouracil Induced Hypothyroid Cockerels

In propylthiouracil (PTU)-fed (g/kg feed) hypothyroid cockerels, serum levels of growth hormone (GH), but not insulin-like growth factor (IGF)-1, tended to rise and those of IGF-binding activity to fall. Thyroxine (T4) supplement (200 micrograms/kg/day) to PTU-fed cockerels for 8 days produced a hyperthyroid state and reversed these serum parameters. A chromatographic analysis of serum proteins revealed that T4 supplement markedly enhanced the IGF-binding activity of a 30 kDa protein and slightly lowered that of a 150 kDa protein, suggesting that T4 increases unsaturated IGF-binding proteins by reducing circulating IGF-1 concentrations.