Effects of alcohol on insulin-like growth factor I and insulin-like growth factor binding protein 3 in postmenopausal women

BACKGROUND: Increased circulating insulin-like growth factor I (IGF-I) concentrations, frequently adjusted for IGF binding protein 3 (IGFBP-3), have been associated with increased risk of several types of cancer, including colon, prostate, and breast. Studies have suggested that alcohol may affect IGF-I or IGFBP-3; however, controlled feeding studies to assess alcohol's effects on IGF-I or IGFBP-3 have not been conducted. OBJECTIVE: To determine whether chronic, moderate alcohol intake affects serum IGF-I or IGFBP-3 concentrations, we performed a controlled, crossover feeding study. DESIGN: Fifty-three postmenopausal women were randomly assigned to consume 0 g (control), 15 g (one drink), or 30 g (2 drinks) alcohol daily for 8 wk and were rotated through the other 2 intake levels in random order. All foods and beverages were provided during the intervention. Individuals were monitored and calories adjusted to maintain constant weight, and serum was collected at the end of each diet period. RESULTS: Compared with the effects of 0 g alcohol/d, IGF-I concentrations were nearly unchanged by 15 g alcohol/d (0.8%; 95% CI: -3.2%, 3.5%) but decreased significantly by 4.9% (95% CI: -8.0%, -1.6%) with 30 g alcohol/d. IGFBP-3 concentrations significantly increased by 3.0% (95% CI: 0.4%, 5.6%) with 15 g alcohol/d but did not increase significantly with 30 g/d (1.8%; 95% CI: -0.9%, 4.5%). CONCLUSIONS: To our knowledge, this is the first published controlled diet study to find that in postmenopausal women, when weight is kept constant, alcohol consumption reduces the amount of serum IGF-I potentially available for receptor binding. These findings suggest that the effect of alcohol intake should be considered in studies of IGF-I, IGFBP-3, and cancer in postmenopausal women.     

Insulin-like growth factor I,insulin-like growth factor binding protein 3, and urologic measures of benign prostatic hyperplasia

Laboratory studies suggest that insulin-like growth factor I (IGF-I) promotes prostatic growth. The authors evaluated the association between benign prostatic hyperplasia and IGF-I and its binding protein IGFBP-3 in community-dwelling men to determine whether this laboratory finding is manifest at the population level. Participants (n = 471) were Olmsted County, Minnesota, Caucasian males aged 40-79 years in 1990. Urologic measures were assessed from the International Prostate Symptom Score, peak urinary flow rates, prostate volume, and serum prostate-specific antigen (PSA), and serum IGF-I and IGFBP-3 levels were measured. After adjustment for age, the relative odds (odds ratios) of an abnormal urologic measure in men with high versus low serum IGF-I levels were 0.98 (95% confidence interval (CI): 0.66, 1.45) for a symptom score of >7, 1.14 (95% CI: 0.72, 1.80) for a peak urinary flow rate of <12 ml/second, 1.11 (95% CI: 0.72, 1.72) for a prostate volume of >30 ml, and 0.71 (95% CI: 0.46, 1.09) for a PSA level of >1.4 ng/ml. A low IGFBP-3 level was associated with an enlarged prostate (odds ratio = 1.72, 95% CI: 1.05, 2.82), after simultaneous adjustment for IGF-I and age, but not with other urologic measures. These data do not provide evidence for an association between benign prostatic hyperplasia and serum IGF-I.     

Body size in early life and adult levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3

Body size in early life has been associated with breast cancer risk. This may be partly mediated through the insulin-like growth factor (IGF) pathway. The authors assessed whether birth weight, body fatness at ages 5 and 10 years, and body mass index (BMI; weight (kg)/height (m)(2)) at age 18 years were associated with plasma concentrations of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 in 6,520 women aged 32-70 years at blood draw from the Nurses' Health Study (1990-2006) and Nurses' Health Study II (1997-2005). Birth weight, body fatness in childhood, and BMI at age 18 years were inversely associated with adult IGF-1 levels. For example, IGF-1 levels were 11.9% lower in women who reported being heaviest at age 10 years than in those who were leanest at age 10 (P-trend < 0.0001). Further, women who reported their birth weight as ≥10 pounds (≥4.5 kg) (vs. <5.5 pounds (<2.5 kg)) had 7.9% lower IGF-1 levels (P-trend = 0.002). Women whose BMI at age 18 years was ≥30 (vs. <20) had 14.1% lower IGF-1 levels (P-trend < 0.0001). Similar inverse associations were observed for insulin-like growth factor binding protein 3. These observations did not vary by adult BMI or menopausal status at blood draw. These findings suggest that altered IGF-1 levels in adulthood may be a mechanism through which early-life body size influences subsequent breast cancer risk.     

Anthropometric and behavioral correlates of insulin-like growth factor I and insulin-like growth factor binding protein 3 in middle-aged Japanese men

High levels of plasma insulin-like growth factor I (IGF-I) and low levels of insulin-like growth factor binding protein 3 (IGFBP-3) have been related to increased risk of several cancers. Little is known about the behavioral determinants of these biologic markers. The authors examined the relation of anthropometric and behavioral factors to plasma concentrations of IGF-I and IGFBP-3 in a cross-sectional study of 616 Japanese men aged 45-55 years in 1995-1996. In univariate analyses, body mass index was strongly, positively associated with both IGF-I and IGFBP-3. The waist/hip ratio was also linearly related to IGF-I and IGFBP-3 up to the third quartile level. Height was weakly, positively associated with IGF-I and IGFBP-3. Smoking was inversely associated with IGF-I and IGFBP-3. Alcohol use was associated inversely with IGF-I and positively with IGFBP-3. Neither IGF-I nor IGFBP-3 was related to physical activity. Results of the multivariate analysis were essentially the same as those of the univariate analyses. The findings regarding body mass index are in contrast to those of previous studies showing null or inverse associations, and they suggest that the relation of body mass index to IGF-I or IGFBP-3 may vary among populations. The study also indicates that smoking and alcohol use might affect plasma IGF-I and IGFBP-3.     

Maternal concentrations of insulin-like growth factor I and insulin-like growth factor binding protein 1 during pregnancy and birth weight of offspring

Maternal concentrations of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 1 (IGFBP-1) may influence fetal growth. Offspring birth weight related to maternal IGF-I and IGFBP-1 measured in pregnancy was studied in 368 randomly selected women without preeclampsia who delivered a singleton liveborn child in Norway between 1992 and 1994. Maternal IGF-I concentrations were not consistently associated with birth weight, but a 1-standard deviation stronger increase in IGF-I from the first to second trimester was associated with an 82-g (95% confidence interval (CI): 11, 153) higher birth weight. IGFBP-1 concentrations were inversely associated with birth weight: Birth weight was 71 g (95% CI: 14, 128) lower per 1-standard deviation higher IGFBP-1 in the second trimester, and an increase in IGFBP-1 from the first (below median) to second (above median) trimester was associated with a 342-g (95% CI: 124, 560) lower birth weight, compared with having low IGFBP-1 (below median) in both trimesters. Conversely, low IGFBP-1 in both trimesters was associated with a 200-350-g higher birth weight compared with other combinations of IGFBP-1. In conclusion, persistently low IGFBP-1 in pregnancy is associated with relatively higher birth weight. Maternal insulin resistance may provide a link between IGFBP-1 and offspring birth weight.     

Markers of fetal growth and serum levels of insulin-like growth factor (IGF) I, -II and IGF binding protein 3 in adults

Fetal growth has been linked with increased risk of cancer and cardiovascular disease later in life. The insulin-like growth factor (IGF) axis has recently been proposed as a predictor of risk of subsequent cancer and cardiovascular disease. However, only few data are available on the possible association between fetal growth and levels of IGFs later in life. We examined the association between markers of fetal growth, i.e. birth weight, birth length and Ponderal Index, from birth records and serum IGF-I, IGF-II, and IGF binding protein 3 (IGFBP-3) levels in 545 middle-aged Danish men and women. We fitted separate multivariate models including birth weight, birth length, Ponderal Index and serum IGF-I, IGF-II, and IGFBP-3, respectively. After adjustment for age, alcohol intake, smoking, diabetes mellitus, systolic and diastolic blood pressure, serum total cholesterol and current height and weight, we found negative associations between birth weight and Ponderal Index, respectively, and serum IGF-II in men, i.e. the mean regression coefficients were -49.41 (95% CI: -87.06-11.77) (microg/l)/kg and -3.49 (95% CI: -6.73-0.25) (microg/l)/(kg/m3), respectively. Furthermore, in men birth weight was negatively associated with the (IGF-I + IGF-II)/IGFBP-3 and IGF-II/IGFBP-3 ratios, which are believed to be indicators of bioavailable IGF and IGF-II, respectively. However, no other associations were found in any of the models. Between 1 and 16% of the variance in serum IGF-I, IGF-II, and IGFBP-3, respectively, could be explained by the statistical models used in the analyses. We found very little support to the hypothesis of an association between fetal growth and the IGF axis throughout life.     

Serum insulin-like growth factor I and subsequent risk of colorectal cancer among Japanese-American men

Recent reports suggest that colorectal cancer is positively related to insulin-like growth factor I (IGF-I) and inversely related to insulin-like growth factor binding protein 3 (IGFBP-3). To evaluate these associations further and separately for colon and rectal cancer, the authors conducted a nested case-control study in a cohort of 9,345 Japanese-American men examined in Hawaii in 1971-1977. A total of 177 incident colon cancer cases and 105 incident rectal cancer cases were identified from 1972 to 1996. These patients' stored sera and those of 282 age-matched controls were measured for IGF-I and IGFBP-3. The adjusted mean level of IGF-I was higher in colon cancer cases than in controls (154.7 ng/ml vs. 144.4 ng/ml; p = 0.01). However, the multivariate odds ratio for the highest quartile compared with the lowest was just 1.8 (95% confidence interval: 0.8, 4.3). Adjusted mean IGF-I levels were similar between rectal cancer cases and their controls. For IGFBP-3, adjusted mean levels were lower for both colon and rectal cancer cases than for their matched controls, but the differences were not significant. The IGF-I results weakly support findings from other studies and suggest that there are differences in IGF-I findings between colon and rectal cancer cases. It is possible that IGF-related risk is confounded by other factors that may vary among different cohorts. Further research is needed to clarify these relations.     

Levels of plasma insulin-like growth factor I (IGF I), IGF II,IGF binding proteins,type 1 IGF receptor and growth hormone binding protein in community-dwelling elderly subjects with no malnutrition and no inflammation

Plasma samples from community-dwelling subjects aged 65 to 92 presenting no malnutrition and no inflammation (as assessed by albumin, transthyretin, CRP, and orosomucoid levels and BMI) were compared to those of healthy controls aged 20 to 65 to determine the effect of aging on the IGF system. Concentrations of IGF I, IGF II and IGFBP3 significantly decreased, and those of GHBP slightly increased with age from 20 to 92 years (n=327 r=-0.64 p<0.0001; n=45 r=-0.44 p<0.003; n=91 r=-0.23 p<0.03 and n=61 r=0.26; p<0.05 respectively). Western immunoblotting showed that the proteolysis of IGFBP3 was not significantly different in elderly and younger subjects. The affinity of the IGF type 1 receptor for IGF I was moderately lower (Ki=0.56 0.2 vs 0.33 0.1, nM respectively; p<0.005) and the number of binding sites was moderately higher (10.4 1.5 vs 8.1 1.9 binding sites/cell, respectively; p<0.03) in the elderly than in the younger adults. Our results suggest that the age-related decline in plasma levels of IGF I, IGF II and IGFBP3 occurs independently from malnutrition and inflammation processes. GHBP plasma levels, which reflect the number of GH receptors at the level of the liver, do not decline in our malnutrition-free elderly population, and thus are not involved in the decline of IGF I plasma levels with age. In the elderly, affinity and number of type 1 IGF receptor were close to those of younger subjects; the decline in IGF I plasma levels may account for the small rise in the number of type 1 IGF receptors binding sites per cell.     

Serum levels of beta-carotene, vitamin A, and zinc in male lung cancer cases and controls

The mean serum levels of beta-carotene and vitamin A in a multivariate analysis of data from 64 histologically confirmed male lung cancer cases were statistically significantly lower than those from 63 randomly selected male hospital controls, who were admitted for small surgical operations (p values for both beta-carotene and vitamin A less than 0.001). The mean serum levels of zinc were not statistically significantly different between cases and controls (p = 0.10). The levels of beta-carotene, vitamin A, or zinc were not statistically significantly influenced by either the extent of the cancer (p = 0.45) or the cancer cell type (p = 0.06). The possible biological significance of these findings is discussed briefly.     

Effects of chronic cysteamine treatment on growth enhancement and insulin-like growth factor I and II mRNA levels in common carp tissues

Insulin-like growth factors (IGF) belong to a family of growth factors with structural homology to proinsulin. In our previous studies, we found that both IGF-I and IGF-II gene expression showed growth hormone (GH) dependence in the brain and liver of juvenile common carp when treated in vivo with GH for a short time. This present work aimed to study the effects of both the short-term and long-term GH induction of IGF gene expression using cysteamine (CSH) and fasting/re-feeding. CSH is an agent that can deplete somatostatin to increase circulating GH level. IGF mRNA levels in the flesh (muscle) and liver of common carp were determined using real-time PCR.The chronic treatment of common carp with CSH was carried out for 63 d, with growth enhancement of the treated fish noted. Hepatic IGF-I and IGF-II mRNA levels increased in a dose-dependent manner with short-term CSH treatment, whereas IGF-I decreased and IGF-II increased in the liver after chronic CSH treatment. IGF-I and IGF-II mRNA levels in muscle were found to be elevated with the high-dose, long-term CSH treatment. Under the experimentally induced catabolic states of fasting, both hepatic IGF-I and IGF-II gene expression were significantly reduced, whereas they showed no change in muscle. After re-feeding, the hepatic expression of IGF-I in liver and muscle rebounded significantly. The hepatic IGF-II expression level showed no rebound after re-feeding, but the IGF-II level in muscle rebounded to the level of the fed group after re-feeding.     

Animal protein intake, serum insulin-like growth factor I, and growth in healthy 2.5-y-old Danish children

BACKGROUND: Studies from developing countries indicate that intake of animal protein, especially of milk, is associated with greater velocity of linear growth in childhood. Whether the same association exists in industrialized countries, where protein intake is high, is not clear. OBJECTIVE: Our objective was to examine associations between protein intake, serum insulin-like growth factor I (sIGF-I) concentrations, and height in healthy children. DESIGN: We analyzed the associations between protein intake, sIGF-I concentrations, and height in 2.5-y-old children. Diet (7-d record) and sIGF-I (radioimmunoassay) data were available from 90 children (54 boys). RESULTS: The 10th, 50th, and 90th percentiles of protein intake were 2.4, 2.9, and 4.0 g. kg(-1). d(-1), respectively; 63% was animal protein. In multiple linear regressions with adjustment for sex and weight, height (cm) was positively associated with intakes of animal protein (g/d) [0.10 +/- 0.038 (b +/- SE); P = 0.01] and milk (0.0047 +/- 0.002; P = 0.007), but not with those of vegetable protein or meat. The sIGF-I concentration was significantly associated with intakes of animal protein (1.4 +/- 0.53; P = 0.01) and milk (0.049 +/- 0.024; P = 0.045), but not with those of vegetable protein or meat. sIGF-I concentrations were positively associated with height (0.019 +/- 0.008; P = 0.02). CONCLUSION: Milk intake was positively associated with sIGF-I concentrations and height. An increase in milk intake from 200 to 600 mL/d corresponded to a 30% increase in circulating IGF-I. This suggests that milk compounds have a stimulating effect on sIGF-I concentrations and, thereby, on growth.     

食管癌血清转化生长因子-β1、胰岛素样生长因子-1变化与疾病恶性程度及与预后的关系

目的 探讨食管癌患者血清中转化生长因子-β1(transforming growth factor-β1,TGF-β1)、胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)的变化及其意义。 方法 选取濮阳市油田总医院确诊的90例食管癌患者为食管癌组、选取45例体检健康对象作为对照组,检测分析两组的血清IGF-1、TGF-β1水平,并分析不同TNM分期、肿瘤分化程度、肿瘤浸润程度、淋巴结转移情况的食管癌患者血清IGF-1、TGF-β1水平差异;采用Cox比例风险回归模型分析血清IGF-1、TGF-β1水平与患者预后的相关性。 结果 食管癌组患者的血清IGF-1、TGF-β1分别为(254.9±88.4)μg/L、(49.6±14.1)μg/L,高于对照组的(40.1±13.0)μg/L、(28.5±8.0)μg/L,差异均有统计学意义(均P<0.05);在不同TNM分期、是否发生淋巴结转移、不同分化程度的食管癌组患者的血清IGF-1水平组间比较,差异均有统计学意义(P<0.05);在不同TNM分期、是否发生淋巴结转移的食管癌组患者的血清TGF-β1水平组间比较,差异均有统计学意义(P<0.05);Cox比例风险模型进行分析显示:食管癌患者的TNM分期增高、分化程度降低、发生淋巴结转移、血清IGF-1及TGF-β1水平升高是患者不良预后的独立性危险因素(P<0.05)。 结论 食管癌组患者的血清IGF-1、TGF-β1水平较健康人群升高,并且与患者肿瘤恶性程度增加及预后不良有关。     

血清IGF-1、IGFBP-3水平和大肠癌关系的Meta分析

目的综合评价血清胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)水平和大肠癌的关系。方法利用Meta分析法对6篇关于血清IGF-1、IGFBP-3水平与大肠癌关系的研究文献进行定量综合分析。结果对于IGF-1，合并OR=1．56(95％CI：1．14～2．13)；按实验方法不同分层，间接酶联免疫吸附试验(ELISA)合并OR=1．92(95％CI：1．26～2．93)，IRMA法合并OR=1．23(95％CI：0．78～1．94)；对于IGFBP-3，合并OR=0．78(95％CJ：0．43～1．44)；按实验方法不同分层，ELISA法合并OR=0．46(95％CI：0．29～0．74)，免疫放射测定法(IRMA)合并OR=1．44(95％CI：0．93～2．23)。结论血清IGF-1高水平为大肠癌的独立危险因子，IGFBP-3与大肠癌的关联不具有统计学意义；IGFBP-3与大肠癌关系的各研究之间异质性是由实验方法不同而引起，但该结论尚需大样本并同时进行两种方法的测量证实。     

The potential role of insulin-like growth factor 1, insulin-like growth factor binding protein 3 and bone mineral density in patients with chronic hepatitis C virus in Cairo, Egypt

Insulin-like growth factor 1 (IGF-1) levels have been found to correlate with measurements of bone mineral density (BMD) in liver diseases. This study investigated the relationship between IGF-1, insulin-like growth factor binding protein 3 (IGFBP-3) and BMD in patients with chronic hepatitis C virus. This study was conducted for 30 patients with chronic hepatitis C virus infection (16 patients without and 14 patients with cirrhosis) and 11 healthy controls. Serum levels of IGF-1 and IGFBP-3 and BMD of the proximal femur and lumbar spine were measured in all subjects. Osteoporosis of the proximal femur and lumbar spine was found in 42.9% and 21.4%, respectively, of the patients with cirrhosis. Patients with liver cirrhosis and osteoporosis of the proximal femur and lumbar spine had lower IGF-1 (P < 0.001, P = 0.04, P = 0.04 respectively). BMD of the proximal femur was lower in cirrhotic patients compared with controls (P < 0.01). Patients with liver cirrhosis had lower IGFBP-3 than patients without cirrhosis and controls (P < 0.001). Patients with osteoporosis of the proximal femur had lower IGFBP-3 than those without osteoporosis (P < 0.01). IGF-1 and IGFBP-3 levels were lower in patients with liver cirrhosis. IGF-1 and IGFBP-3 may play a role in hepatic osteoporosis.     

中孕期血清可溶性血管内皮生长因子受体1、胎盘生长因子水平及其比值筛查妊娠期高血压疾病的效率

目的探讨中孕期血清可溶性血管内皮生长因子受体1(sFlt-1)、胎盘生长因子(PlGF)水平以及sFlt-1/PlGF比值在妊娠期高血压(GH)和子痫前期(PE)的筛查效率。方法选取2014年7月-2016年8月在杭州市2家医院接受产前筛查的孕妇,根据分娩结局轻重程度,将研究对象分为GH组、PE组、重度子痫前期(SPE)组、对照组,检测4组孕妇血清sFlt-1和PlGF水平,并比较其浓度分布及sFlt-1/PlGF比值情况。用受试者工作特征(ROC)曲线确定最佳临界值(cut-off)、曲线下面积(AUC),对sFlt-1、PlGF水平及sFlt-1/PlGF比值的筛查效能进行评价。结果 GH组sFlt-1水平低于对照组,PE组、SPE组sFlt-1水平高于对照组,4组差异有统计学意义(P <0. 001);GH组PlGF水平高于对照组,PE组、SPE组PlGF水平低于对照组,4组差异有统计学意义(P <0. 001);GH组sFlt-1/PlGF比值低于对照组,PE组、SPE组sFlt-1/PlGF比值高于对照组,4组孕妇sFlt-1/PlGF比值差异有统计学意义(P=0. 001)。GH组血清sFlt-1、PlGF和sFlt-1/PlGF比值的AUC分别为0. 692、0. 725和0. 795;PE组的AUC分别为0. 838、0. 852和0. 864,SPE组的AUC分别为0. 714、0. 791和0. 771。结论 sFlt-1/PlGF比值筛查GH和PE的效率优于单独sFlt-1、PlGF的筛查效率,但对SPE的效率没有优于sFlt-1、PlGF的筛查效率。     

IGFBP-1、CRP联合宫颈指数在早产预测中的价值

目的:探讨宫颈分泌物中高磷酸化IGFBP-1、血清中CRP、宫颈指数在早产预测中的价值。方法:对西丽人民医院诊治的91例先兆早产孕妇检测其宫颈分泌物中IGFBP-1、血清中C-反应蛋白,同时经会阴超声检测宫颈指数。随访至分娩,分析多指标联合应用在早产预测中的价值。结果:IGFBP-1、宫颈指数的阳性组中早产发生率明显高于阴性组(P<0.01),该两指标联合应用对早产的阳性预测值明显提高(P<0.01)。血清CRP在早产组与足月产组间无统计学差异(P>0.05)。结论:宫颈分泌物IGFBP-1联合宫颈指数可提高对早产预测的准确性。     

Relation of cord serum levels of growth hormone,insulin-like growth factors,insulin-like growth factor binding proteins,leptin, and interleukin-6 with birth weight,birth length,and head circumference in term and preterm neonates

OBJECTIVES: Fetal growth process is governed by multiple factors. We investigated the relation of insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), leptin, and interleukin-6 (IL-6) with intrauterine growth in preterm and term neonates. METHODS: Thirty-eight preterm and 43 term neonates were recruited. Anthropometric measures were recorded and umbilical cord blood samples were collected at birth. RESULTS: Birth weight (BW), birth length (BL), ponderal index, head circumference (HC), and cord serum levels of albumin, prealbumin, retinol-binding protein (RBP), total and free IGF-I, IGF-II, IGFBP-3, acid-labile subunit (ALS), and leptin were significantly lower, whereas levels of IGFBP-1, IGFBP-2, and IL-6 were significantly higher in preterm than in term neonates (P < 0.05). Total and free IGF-I, ALS, and leptin had significantly positive correlations, whereas IGFBP-2 had a significantly negative correlation, with BW and BL in preterm plus term neonates. Forward stepwise multivariate regression analysis showed that gestational age (GA), IGFBP-2, leptin, and free IGF-I are significant predictors of BW; GA, IGFBP-2, ALS, transferrin, and leptin are significant predictors of BL; and GA and free IGF-I are significant predictors of HC in preterm and term neonates. CONCLUSIONS: Our results suggest that IGF-I, IGF-II, IGFBP-2, ALS, and leptin play important roles in intrauterine growth.     

Nutrient balance and stage of lactation affect responses of insulin, insulin-like growth factors I and II, and insulin-like growth factor-binding protein 2 to somatotropin administration in dairy cows.

Six Holstein cows were used in a complete block design to examine effects of period of lactation and somatotropin (bST) administration on concentrations of insulin, insulin-like growth factors (IGF-I, IGF-II), and IGF-binding protein 2 (IGFBP-2). During late lactation, the dry period and the subsequent early lactation, cows received injections of NaHCO3 buffer for 5 d and bST for 7 d. Cows were in positive energy and protein balances during late lactation and the dry period and in slight negative balances during early lactation. Basal insulin concentrations were highest in late lactation (170 pmol/L), whereas bST concentrations were higher in early lactation (0.6 micrograms/L). Insulin was increased by bST in the dry period (255 pmol/L) and late lactation (149 pmol/L) but not in early lactation (14 pmol/L), probably because of greater availability of glucose during positive nutrient balance. Basal IGF-I was lowest in early lactation (63.6 micrograms/L) but was increased by bST during all periods. The IGF-I response to bST administration was lower during early lactation (74.1 micrograms/L) compared with late lactation (123.6 micrograms/L) and dry period (146.0 micrograms/L). The IGF-II concentrations were not affected by period of lactation of bST administration but IGF-II tended to be higher during bST administration when cows were dry. Concentration of IGFBP-2 was higher during early lactation when cows were in negative nutrient balance (479.5 micrograms/L) than during the dry period (289.2 micrograms/L) and was decreased with bST. These data support a role of insulin and IGF in regulation of milk production. Availability of nutrients may be involved in regulating these hormones, particularly during bST treatment.