Plasma Insulin-like Growth factor-I Research Articles

Effect of Prepartum Energetic Supplementation on Productive and Reproductive Characteristics, and Metabolic and Hormonal Profiles in Dairy Cows under Grazing Conditions

The effect of cracked corn grain supplementation (3.5 kg/day) during 3 weeks before the expected calving date on milk production and composition, body condition score (BCS), metabolic and hormonal profiles and length of postpartum anoestrus was evaluated in multiparous Holstein dairy cows under grazing conditions (Energy supplemented group, n = 10; Control group, n = 10). Body condition score was weekly recorded during the peripartum period, from days -21 to +35 (parturition = day 0). Non-esterified fatty acids, beta-hydroxybutyrate, cholesterol, urea, insulin, insulin-like growth factor I (IGF-I), leptin, thyroxine (T(4)) and 3,3''5-triiodothyroinine (T(3)) were weekly determined in plasma from days -21 to +35. The reinitiation of ovarian cyclicity was twice weekly determined by ovarian ultrasonography and confirmed by plasma progesterone concentrations. Cows fed energy concentrate prepartum had higher BCS during the prepartum and postpartum and produced more milk. Non-esterified fatty acids plasma concentrations were significantly higher in the energy group, while cholesterol was higher in the control group. Treated cows had higher levels of plasma insulin, IGF-I and leptin pre-calving. IGF-I, leptin and T(4) were diminished during the early postpartum period in both groups. Insulin levels were also diminished in the control group, but levels remained high in the energy-supplemented group. Treated cows ovulated sooner after parturition than controls. We conclude that Energetic supplementation prepartum in cows under grazing conditions increased milk production and reduced the reinitiation of ovarian activity, consistent with a better EB (BCS), higher prepartum levels of IGF-I, leptin and insulin, and higher insulin levels during early postpartum.

Endocrine effects of growth hormone overexpression in transgenic coho salmon

Non-transgenic (wild-type) coho salmon ( Oncorhynchus kisutch), growth hormone (GH) transgenic salmon (with highly elevated growth rates), and GH transgenic salmon pair fed a non-transgenic ration level (and thus growing at the non-transgenic rate) were examined for plasma hormone concentrations, and liver, muscle, hypothalamus, telencephalon, and pituitary mRNA levels. GH transgenic salmon exhibited increased plasma GH levels, and enhanced liver, muscle and hypothalamic GH mRNA levels. Insulin-like growth factor-I (IGF-I) in plasma, and growth hormone receptor (GHR) and IGF-I mRNA levels in liver and muscle, were higher in fully fed transgenic than non-transgenic fish. GHR mRNA levels in transgenic fish were unaffected by ration-restriction, whereas plasma GH was increased and plasma IGF-I and liver IGF-I mRNA were decreased to wild-type levels. These data reveal that strong nutritional modulation of IGF-I production remains even in the presence of constitutive ectopic GH expression in these transgenic fish. Liver GHR membrane protein levels were not different from controls, whereas, in muscle, GHR levels were elevated approximately 5-fold in transgenic fish. Paracrine stimulation of IGF-I by ectopic GH production in non-pituitary tissues is suggested by increased basal cartilage sulphation observed in the transgenic salmon. Levels of mRNA for growth hormone-releasing hormone (GHRH) and cholecystokinin (CCK) did not differ between groups. Despite its role in appetite stimulation, neuropeptide Y (NPY) mRNA was not found to be elevated in transgenic groups.

IGF1 is a modifier of disease risk in hereditary non‐polyposis colorectal cancer

Patients diagnosed with HNPCC harbouring a confirmed germline mutation in DNA mismatch repair (MMR) genes have an 80% lifetime risk of developing an epithelial malignancy. There is, however, considerable variation in the age of disease onset in these patients. Insulin-like growth factor-I (IGFI) has been implicated in colorectal cancer (CRC), and elevated plasma IGFI levels are associated with both sporadic and hereditary CRC risk. In this study, we further investigate the cytosine-adenine (CA) dinucleotide repeat polymorphism located near the promoter region of IGF1 and its relation to early onset CRC risk in 443 Australian and Polish MMR gene mutation carriers using DNA sequencing, Kaplan-Meier survival curves and Cox proportional hazard regression analysis. A significantly smaller number of IGF1 CA repeats was observed in the Polish patient population, which was associated with an earlier age of disease onset compared to the Australian patients. The threshold for the observed modifying effect was again shown to be in patients with 17 or less CA repeats compared to those with 18 or more. Furthermore, when MMR mutation group (i.e., MLH1 or MSH2), gender and family clustering were included in the final Cox model we observed a more robust trend for the role of the IGF1 CA repeat in predicting age of disease onset in HNPCC patients. In addition, this effect was shown to be equal in both MLH1 and MSH2 mutation carrier groups and not restricted to a particular MMR subgroup (p = 0.001). We conclude that the IGF1 CA repeat is an important modifier of disease onset in HNPCC and the first polymorphism to yield consistent results across different populations.

Changes of leptin and IGF-I in addescents with anorexia nervosa

Objective To study the changes of leptin and insulin-like growth factor-Ⅰ (IGF-Ⅰ) in adoles-cents with anorexia nervosa(AN) before and after three months of therapy. Methods The plasma levels of leptin and IGF-Ⅰ were measured in 11 adolescents with AN before and after three months of therapy and 11 normal ado-lescents of the same age,and their height,weight were examined and their body mass index(BMI) was calculated,and the results were compared before and after therapy, and were compared with those from age-matched normal adolescents respectively. Results (1)The plasma levels of leptin and IGF-Ⅰ , as well as the BMI in the AN patients after three months of therapy were significantly higher, than those before the therapy, and both were significantlylower than those in the controls. (2)Significant correlations between the plasma leptin levels and IGF-Ⅰ and BMI were detected in the AN patients both before and after the therapy, as well as in the controls. (3)Significant correla-tions between the plasma leptin levels and IGF-Ⅰ were detected in the AN patients both before and after the thera-py, as well as in the controls. Conclusion The plasma levels of leptin and IGF-Ⅰ resulted in significant changes, and these changes were consistent with body fat content in adolescents with AN. Key words: Leptin; Insulin-like growth factor-Ⅰ ; Anorexia nervosaiAdolescents

Plasma insulin-like growth factor-I concentrations and growth in juvenile halibut ( Hippoglossus hippoglossus): Effects of photoperiods and feeding regimes

The effects of photoperiod and feeding regimes on plasma IGF-I levels and their relationship with growth rate of juvenile halibut (initial mean weight 364 g) were investigated by rearing fish under five different photoperiod regimes and two feeding regimes for 14 months. The entire photoperiod experiment was divided into 3 phases where the fish in each phase were exposed to either natural photoperiod (N), stimulated photoperiod with long day and short night (S) or continuous light (L). Thus, the following five photoperiod combinations were tested: a) Control group (NNN) b) Group 2A (NLN) c) Group 2B (NNL) d) Long day-natural group (SNN) e) Production group (LNN). In addition, the Control group was split into two parts and fed according to two different feeding regimes: a) Continuous fed group: Fish fed every day. b) Starvation/re-fed group: Fish were starved for 5 weeks and then re-fed for 10 weeks, and the treatment repeated during the whole experimental period. The analyses of IGF-I were performed from individually tagged fish in all groups in September 2005 and March 2006. In order to test how rapidly starvation affects circulating IGF-I levels samples were taken from the Starvation/re-fed group after a 10 days starvation (September) and immediately after 10 weeks of feeding (March). A significant relationship between IGF-I levels and individual growth in the preceding period and photoperiod and starvation treatment was found on both occasions. In conclusion, the present study indicates that plasma IGF-I levels are correlated to growth in Atlantic halibut, and affected by photoperiod treatment or compensatory growth during re-feeding. Correlation between individual growth rate and IGF-I levels was low, but significant, highlighting the complexity of how environmental factors affect the endocrine and physiological regulation of growth in fish.

Variation in Plasma Concentrations of Insulin-Like Growth Factor-I in Pasture-Fed Holstein Cows

The objective of this 5-wk study was to determine dietary effects on plasma concentrations of insulin-like growth factor-I (IGF-I), as well as milk production and milk components in pasture-fed dairy cows. Thirty-two Holstein cows 4 to 5wk postpartum were randomly assigned to 4 dietary subgroups. Feed was provided twice daily ad libitum at 0900 and 1600h composed of fresh-cut pasture, meadow hay, and pelleted cereal grain to achieve differing levels of DMI and ME density (LL: 16.6kg of DMI and 174 MJ of ME; HL: 17.3kg of DMI and 181.1 MJ of ME; LH: 15.4kg of DMI and 183.1 MJ of ME; HH: 17.9kg of DMI and 213.3 MJ of ME, with the first letter indicating DMI and the second ME, and with H indicating high and L indicating low, respectively). The first day cows were placed on their diets was designated d 0. Concentrations of IGF-I were measured in frozen-thawed samples of plasma using a verified ELISA. Dietary treatment had affected plasma concentrations of IGF-I by d 7 with cows on high ME diets having greater IGF-I concentrations at d 14 (83.7 vs. 45.6ng/mL) than cows on the low ME diets. The level of DMI had less effect on plasma concentrations of IGF-I at d 14 (72.2 vs. 57.1ng/mL). Dietary treatment effects on these concentrations had stabilized by d 21. Day-to-day variation in mean plasma concentrations of IGF-I within each dietary treatment was low during an intensive period of daily sampling for 14 d (from d 22 to 35). Within-cow day-to-day variation was also low compared with that among cows within the same dietary group and was associated with a high repeatability in the day-to-day concentration of IGF-I in individual cows. Intraclass correlation coefficients for IGF-I ranged from 0.56 (± 0.14) to 0.88 (± 0.06) with a combined (pooled) value for the 4 subgroups of 0.77 (± 0.05). The ME and DMI effects (H vs. L) at d 35 were 79.3 vs. 41.4 and 62.0 vs. 55.7ng/mL, respectively. Although the ME and DMI differences also affected milk yield and compositional parameters, the effects were not as proportionately great as those measured for IGF-I. Altering the ME or DMI components of the pasture-based diets produced changes in plasma IGF-I concentrations that did not become stabilized for 3wk, but were then highly repeatable for individual cows within each dietary group. Both observations have relevance to interpreting data related to plasma concentrations of IGF-I in lactating Holstein cows.

Osmoregulation and expression of ion transport proteins and putative claudins in the gill of Southern Flounder ( Paralichthys lethostigma)

The southern flounder is a euryhaline teleost that inhabits ocean, estuarine, and riverine environments. We investigated the osmoregulatory strategy of juvenile flounder by examining the time-course of homeostatic responses, hormone levels, and gill Na +,K +-ATPase and Na +,K +,2Cl − cotransporter protein expression after salinity challenge. Transfer of freshwater (FW)-acclimated flounder to sea water (SW) induced an increase in plasma osmolality and cortisol and a decrease in muscle water content, plasma insulin-like growth factor I (IGF-I) and hepatic IGF-I mRNA, all returning to control levels after 4 days. Gill Na +,K +-ATPase and Na +,K +,2Cl − cotransporter protein levels were elevated in response to SW after 4 days. Transfer of SW-acclimated flounder to FW reduced gill Na +,K +-ATPase and Na +,K +,2Cl − cotransporter protein, increased plasma IGF-I, but did not alter hepatic IGF-I mRNA or plasma cortisol levels. Gill claudin-3 and claudin-4 immunoreactive proteins were elevated in FW versus SW acclimated flounder. The study demonstrates that successful acclimation of southern flounder to SW or FW occurs after an initial crisis period and that the salinity adaptation process is associated with changes in branchial expression of ion transport and putative tight junction claudin proteins known to regulate epithelial permeability in mammalian vertebrates.

Plasma Insulin-Like Growth Factor I Is Inversely Associated with Colorectal Adenoma Recurrence: A Novel Hypothesis

The insulin-like growth factor I (IGF-I) axis has been proposed to be a significant factor in the development of certain cancers, including colorectal. However, results from epidemiologic studies suggest modest effects on colorectal cancer risk. Using cross-sectional and prospective study designs within the same cohort of men who had at least one adenoma at baseline, we investigated whether plasma IGF-I, IGF-I binding protein 1, and IGF-I binding protein 3 were associated with colorectal adenoma characteristics at baseline and whether their levels were related to odds for adenoma recurrence. Plasma levels of each marker were measured at baseline in 299 male participants in the Wheat Bran Fiber Trial, who were followed prospectively for recurrence of their adenomatous lesions. In cross-sectional analyses, plasma IGF-I was significantly positively associated with the presence of adenomas with any villous features (P = 0.04). In contrast, IGF-I levels were inversely associated with odds of colorectal adenoma recurrence, with adjusted odds ratios (95% confidence interval) of 0.55 (0.29-1.01) and 0.49 (0.26-0.91) for the second and third tertiles of IGF-I, respectively, compared with the first tertile (P(trend) = 0.02). The inverse association was stronger for advanced adenoma recurrence (P(trend) = 0.02) than for nonadvanced recurrence (P(trend) = 0.10). These results suggest that, once an adenoma is removed, higher IGF-I levels reduce the odds of the formation of new lesions in the colorectum.

Metabolic profile and oxidative status in goats during the peripartum period

The aim of this study was to monitor the metabolic profile and oxidative status in goats during the peripartum period. A blood sample was taken from 10 Red Syrian goats on days −21, −3, +1, +14, and +28 from delivery. Samples were assayed for glutathione peroxidase and superoxide dismutase activities, and reactive oxygen metabolites, insulin, insulin-like growth factor-I, free triiodothyronine (fT3), free thyroxine (fT4), leptin, urea, non-esterified fatty acids, triglycerides, cholesterol, total protein, albumin, globulin, calcium and inorganic phosphorus concentrations. Blood glutathione peroxidase activity decreased during the postpartum period and its values were significantly (P < 0.05) lower on days 14 and 28 postpartum. Albumin levels were significantly (P < 0.05) lower on days −3, 1 and 28 from delivery compared with day −21. Plasma urea levels significantly (P < 0.001) decreased starting from day −3 from delivery. No effect of time from delivery was noted on reactive oxygen metabolites, non-esterified fatty acids, triglycerides, cholesterol, total protein, calcium and inorganic phosphorus, insulin and leptin concentrations and superoxide dismutase activity. Plasma concentrations of fT3 were significantly (P < 0.01) higher on days 14 and 28 compared with days −21, −3 and 1 from delivery. Plasma levels of fT4 were significantly (P < 0.01) lower on days −3 and 1 from delivery. Plasma insulin-like growth factor-I values slowly decreased during the postpartum period and its values were significantly (P < 0.05) lower on day 28. This study indicates that goats experienced moderate oxidative stress during the peripartum period.

Development of mammary glands of fat sheep submitted to restricted feeding during late pregnancy

Mammary gland development in sheep occurs mainly during puberty and pregnancy. We have investigated the effects of a late gestation feed restriction on mammary gland development in sheep. Five control ewes were slaughtered d −38 from parturition, whereas 10 ewes were fed ad libitum and another 10 ewes were fed restrictedly (50% of energy and protein requirements) the last 38 days of pregnancy. Half the ewes in each feeding treatment group were slaughtered d −6 from parturition. Both mammary glands were collected at slaughter. From the remaining five sheep in each feeding group, blood and mammary biopsies were collected on d −16, d −6, d 5 and d 30 from parturition. Fetus weights, weight of mammary parenchyma, amount of mammary epithelium and rate of mammary cell proliferation increased from d −38 to d −6 from parturition, but was not significantly affected by late gestation feed restriction. Colostrum yield was reduced ( P = 0.02) by feed restriction, but milk yield at d 5 and d 30 was not ( P = 0.12). Mammary gene expressions of alpha-lactalbumin ( P = 0.97), leptin ( P = 0.36), Bcl-2 ( P = 0.35), Bax ( P = 0.21), insulin-like growth factor I (IGF-I) ( P = 0.81) and cyclin D1 ( P = 0.43) were not affected by feed restriction, although plasma IGF-I ( P = 0.13) and leptin ( P = 0.04) concentrations were reduced by feed restriction. Our results suggest that extensive mobilization of body tissues occurred during late gestation feed restriction, which compensated for the reduced dietary nutrient supply, thereby maintaining fetal and mammary gland development, and this was likely explained by a high initial level of body fat in the experimental ewes. The colostrum yield was impaired by feed restriction, but our results show that in multiparous sheep, adequate post-partum nutrition can support lactational performance. In conclusion, mammary redevelopment in between successive lactations is not significantly affected by feed restriction during late pregnancy in fat sheep.

Effects of aluminum on insulin-like growth factor I levels and antioxidant status

The aim of this research was to investigate the toxic effects of aluminum (Al) on plasma insulin-like growth factor I (IGF-I) levels and on the liver, the main production site of IGF-I. In addition, we analyzed the influence of Al on liver malondialdehyde (MDA) and glutathione (GSH) levels, and how the antioxidant vitamin E (vit E) affects the altered levels of these parameters. Adult male rats (n = 28) were randomly divided into the following four groups: Al alone, Al + vit E, vit E alone, and untreated control group. The Al group received 1 mg/200 g body weight of aluminum sulfate (AlSO4) thrice weekly for two weeks. The Al + vit E group received the same dose of AlSO4 plus 100 mg/kg of vit E once daily. The Vit E group received a daily dose of vit E alone. Control animals received physiologic saline daily. Liver GSH levels were decreased in the Al group but recovered with vit E administration. Liver IGF-I levels significantly decreased in the Al group compared with the control. With the use of vit E, the liver IGF-I levels increased, but this increase was not statistically significant. The results of this study show that plasma and liver IGF-I levels decrease with Al use. Also liver GSH levels decreased with Al while this recovered with vit E use together with Al.

Response of the salmon somatotropic axis to growth hormone administration under two different salinities

We compared the response of plasma insulin-like growth factor-I (IGF-I) to growth hormone (GH) administration under two different salinities to test the hypothesis that environmental salinity alters the “activity” of the GH–IGF-I axis. In July, postsmolt coho salmon reared in fresh water (FW) were transferred to either FW or half seawater (1/2 SW) (15 ppt) tank. During the experiment, water temperature was maintained at 10 °C for both salinities; photoperiod was adjusted to that of Seattle (48°N), and fish were not fed. Two days after transfer, fish were injected once with porcine GH (pGH) at a dose of 2 or 8 μg/g body weight. Liver and blood samples were collected 1, 2 and 3 days after injection. Liver GH receptor (GHR) mRNA expression was analyzed by quantitative real-time RT-PCR, and plasma IGF-I, 41-kDa IGF-binding protein (main carrier of IGF-I) and pGH were quantified by radioimmunoassays. Transfer to 1/2 SW resulted in transient increases in basal levels of liver GHR mRNA and 41 kDa IGF-binding protein (IGFBP) but not IGF-I. The GH injection increased liver GHR mRNA, plasma IGF-I and 41-kDa IGFBP in fish in both FW and 1/2 SW. However, the time course and magnitude of the response differed between salinities. Fish in FW receiving 8 μg/g pGH had the highest IGF-I levels (63.7±6.8 ng/ml) one day after injection, whereas fish in 1/2 SW showed a peak (88.8±14.3 ng/ml) two days after injection of the same dose. It is speculated that the prolonged response to GH by fish in 1/2 SW may be due to slower disappearance of pGH from the circulation in fish in 1/2 SW. The transient increase in basal liver GHR mRNA may also contribute to a greater response for fish in 1/2 SW. These results suggest that salinity is capable of altering the “activity” of the GH–IGF-I axis in salmon.

Differential hormonal responses of Atlantic salmon parr and smolt to increased daylength: A possible developmental basis for smolting

In order to elucidate the developmental basis for smolting, Atlantic salmon, Salmo salar, parr (<11.5 cm) and smolts (>12.5 cm) were exposed to natural daylength (LDN) and increased daylength (LD16:8) starting in late February and gill Na+,K+–ATPase activity and circulating hormone levels monitored from January to May. Gill Na+,K+–ATPase activity remained low and constant in both groups of parr. In smolts, gill Na+,K+–ATPase began increasing in late February in both photoperiods, but was significantly higher in the LD16:8 group from March through April. Smolts exposed to LD16:8 had dramatically elevated plasma GH within one week of increased daylength that remained high through April, whereas plasma GH of LDN smolts increased steadily beginning in late February and peaking in late April. Plasma GH levels of parr remained low in spring and did not respond to increased daylength. Plasma insulin-like growth factor I (IGF-I) levels were substantially higher in smolts than parr in January. Plasma IGF-I levels of parr increased steadily from January to May, but there was no influence of increased daylength. In smolts, plasma IGF-I of LD16:8 fish initially decreased in early March then increased in late March and April, whereas plasma IGF-I of LDN smolts increased steadily to peak levels in early April. Plasma cortisol was low in parr throughout spring and did not differ between photoperiod treatments. Plasma cortisol of LD16:8 smolts increased in early March and remained elevated through April, whereas in LDN smolts plasma cortisol did not increase until early April and peaked in late April. Plasma thyroid hormones were generally higher in smolts than in parr, but there was no clear effect of increased daylength in parr or smolts. The greater capacity of the GH/IGF-I and cortisol axes to respond to increased daylength may be a critical factor underlying smolt development.

Regular Physical Activity Influences Plasma Ghrelin Concentration in Adolescent Girls

We examined the effect of regular physical activity on plasma ghrelin concentration after onset of puberty in girls. In addition, we also examined the association of fasting plasma ghrelin concentration with various plasma biochemical, body composition, and aerobic capacity variables in healthy adolescent girls. Fifty healthy schoolgirls ages 11 to 16 yr were divided either into a physically active (N = 25) or a physically inactive (N = 25) group. The physically active group consisted of swimmers who had trained on an average of 6.2 +/- 2.0 h.wk(-1) for the last 2 yr, whereas the inclusion criterion for the physically inactive group was the participation in physical education classes only. The subjects were matched for age (+/- 1 yr) and body mass index (BMI; +/- 2 kg.m(-2)). Maturation I group (14 matched pairs) included pubertal stages 2 and 3, and maturation II group (11 matched pairs) included pubertal stages 4 and 5. Physically active girls had significantly higher (P < 0.05) mean plasma ghrelin levels than the physically inactive girls (maturation I: 1152.1 +/- 312.9 vs 877.7 +/- 114.8 pg.mL(-1); maturation II: 1084.0 +/- 252.5 vs 793.4 +/- 164.9 pg.mL(-1)). Plasma ghrelin concentration was negatively related to percent body fat, fat mass, peak oxygen consumption per kilogram of body mass, leptin, estradiol, insulin, and insulin-like growth factor-I (IGF-I) (r > -0.298; P < 0.05). Multivariate linear regression analysis to determine the predictors of ghrelin concentration using the variables that were significantly associated with ghrelin concentration demonstrated that plasma IGF-I was the most important predictor of plasma ghrelin concentration (beta = -0.396; P = 0.008). Regular physical activity influences plasma ghrelin concentrations in girls with different pubertal maturation levels. Plasma IGF-I concentration seems to be the main determinant of circulating ghrelin in healthy, normal-weight adolescent girls.

Endocrine systems in juvenile anadromous and landlocked Atlantic salmon ( Salmo salar): Seasonal development and seawater acclimation

The present study compares developmental changes in plasma levels of growth hormone (GH), insulin-like growth factor I (IGF-I) and cortisol, and mRNA levels of their receptors and the prolactin receptor (PRLR) in the gill of anadromous and landlocked Atlantic salmon during the spring parr-smolt transformation (smoltification) period and following four days and one month seawater (SW) acclimation. Plasma GH and gill GH receptor (GHR) mRNA levels increased continuously during the spring smoltification period in the anadromous, but not in landlocked salmon. There were no differences in plasma IGF-I levels between strains, or any increase during smoltification. Gill IGF-I and IGF-I receptor (IGF-IR) mRNA levels increased in anadromous salmon during smoltification, with no changes observed in landlocked fish. Gill PRLR mRNA levels remained stable in both strains during spring. Plasma cortisol levels in anadromous salmon increased 5-fold in May and June, but not in landlocked salmon. Gill glucocorticoid receptor (GR) mRNA levels were elevated in both strains at the time of peak smoltification in anadromous salmon, while mineralocorticoid receptor (MR) mRNA levels remained stable. Only anadromous salmon showed an increase of gill 11β-hydroxysteroid dehydrogenase type-2 (11β-HSD2) mRNA levels in May. GH and gill GHR mRNA levels increased in both strains following four days of SW exposure in mid-May, whereas only the anadromous salmon displayed elevated plasma GH and GHR mRNA after one month in SW. Plasma IGF-I increased after four days in SW in both strains, decreasing in both strains after one month in SW. Gill IGF-I mRNA levels were only increased in landlocked salmon after 4 days in SW. Gill IGF-IR mRNA levels in SW did not differ from FW levels in either strain. Gill PRLR mRNA did not change after four days of SW exposure, and decreased in both strains after one month in SW. Plasma cortisol levels did not change following SW exposure in either strain. Gill GR, 11β-HSD2 and MR mRNA levels increased after four days in SW in both strains, whereas only the anadromous strain maintained elevated gill GR and 11β-HSD2 mRNA levels after one month in SW. The results indicate that hormones and receptors of the GH and cortisol axes are present at significantly lower levels during spring development and SW acclimation in landlocked relative to anadromous salmon. These findings suggest that attenuation of GH and cortisol axes may, at least partially, result in reduced preparatory upregulation of key gill ion-secretory proteins, possibly a result of reduced selection pressure for marine adaptations in landlocked salmon.

Development of Method for Estimating Diplotype Associations with Linear or Binomial Outcomes

We developed a simulation method to account for phase uncertainty in associations between outcomes and diplotypes imputed from genotypes. Participants were 582 black and 402 white premenopausal women (age 35–49 years) randomly selected from an urban health plan and enrolled in the NIEHS Uterine Fibroid Study. Thirty IGF-I (insulin-like growth factor-I) and 15 IGFBP-3 (IGF binding protein-3) single nucleotide polymorphisms (SNPs) were genotyped based on previous research, functional significance, or haplotype-tagging properties. Diplotypes were estimated using PHASE version 2.1, which reports posterior probabilities reflecting uncertainty of individual diplotype assignments. Our approach uses information on all possible diplotypes from women with data for at least 50% of the SNPs in each gene. Using SAS V9.1, we simulated the study population separately by race 100,000 times and 1) randomly assigned diplotypes to each woman according to her posterior probability of having each possible diplotype; 2) used linear regression to model associations between diplotypes and plasma IGF-I and IGFBP-3 levels; 3) used binary regression to estimate prevalence differences for uterine fibroids; and 4) drew a random variable from a normal distribution to simulate ordinary sampling error. Simulation results are summarized by the mean and the 2.5th and 97.5th percentiles of the simulated distributions. Preliminary results for IGFBP-3 confirm the feasibility of the method, which allowed us to retain about 10% of observations that ordinarily would be excluded because of low posterior probabilities. This approach uses complete diplotype information, reduces the number of excluded observations, and can be used to estimate associations with both binary and continuous outcomes. It can be applied to any exposure for which potential misclassification (probability of exposure) can be estimated for each individual.

Effect of capsaicin on plasma and tissue levels of insulin-like growth factor-I in spontaneously hypertensive rats

Objective Plasma levels of insulin-like growth factor-I (IGF-I), an important substance for maintaining cardiovascular homeostasis, are lower in spontaneously hypertensive rats (SHR) than in normotensive Wistar Kyoto rats (WKY). Calcitonin gene-related peptide (CGRP) increases IGF-I production in vitro and in vivo, suggesting that stimulation of sensory neurons might increase the production of IGF-I in SHR. Design Levels of CGRP and IGF-I in plasma, kidneys and heart in WKY and SHR and cellular cyclic AMP levels in dorsal root ganglion neurons (DRGs) isolated from WKY and SHR were measured by an ELISA-based method. Results Levels of CGRP and IGF-I in plasma, kidneys and heart of SHR were about half of those of WKY. Administration of capsaicin significantly increased levels of CGRP and IGF-I in plasma and tissues of SHR to the levels in WKY and these increases were completely reversed by pretreatment with capsazepine, an inhibitor of vanilloid receptor-1 activation. CGRP release and cellular levels of cAMP in DRGs isolated from SHR were significantly lower than those in DRGs isolated from WKY. Capsaicin increased both CGRP release and cellular cAMP levels in DRGs isolated from SHR to the levels in DRGs isolated from WKY. Conclusions Sensory neuron activation might be lower in SHR than in WKY probably due to decreased production of cAMP in sensory neurons, explaining why IGF-I levels in plasma and tissues are lower in SHR than in WKY.

Temperature and salinity effects on plasma insulin-like growth factor-I concentrations and growth in juvenile turbot ( Scophthalmus maximus)

The effects of temperature and salinity on plasma IGF-I levels and its interrelationship with growth, daily feed intake and feed conversion of juvenile turbot (initial mean weight 14 g) were investigated by rearing fish at 10, 14, 18 and 22 °C and 15, 25 and 33.5‰ for 3 months. The plasma IGF-I levels increased with increasing temperatures reaching a plateau around 18 °C. Further, both temperature and salinity had a significant effect on growth, daily feed intake and feed conversion efficiency in juvenile turbot. Growth, food consumption, and food conversion efficiency were highest at 18 °C and 15‰, and lowest at 10 °C and 33.5‰. Although there was a high variation between IGF-I values within all groups there was a positive relationship between IGF-I levels and specific growth rates and daily feed intake. The levels of IGF-I were almost three times higher for fish with higher growth rates than for those with lower growth. In addition, the results show evidence for an increased appetite in fish with high plasma IGF-I levels. Interestingly, there was no correlation between environmental salinity and IGF-I levels, although decreased salinity improves growth and feed conversion efficiency.

Association of CA repeat polymorphism at intron 1 of insulin-like growth factor (IGF-I) gene with circulating IGF-I concentration, growth, and fatness in swine

Evidence is accumulating that intronic polymorphic cytosine-adenosine (CA) repeats may play a role in gene expression. In this work, we investigated whether a polymorphic CA short tandem repeat (STR) located at the first intron of the pig insulin-like growth factor I (IGF-I) gene influences plasma IGF-I concentration in pigs as well as phenotypic variation in growth and fatness traits. We measured plasma IGF-I levels at one to four time points from 35 to 215 days of age in 340 performance-tested Landrace and Duroc pigs previously genotyped for the IGF-I STR. Data were analyzed within breed with a linear mixed model with the number of CA repeats as a covariate. At least five alleles were segregating in each breed, differing in one to seven repeats. The results showed that in each breed, circulating IGF-I at 160 days of age increased with the length of the shortest allele, accounting for an average trend of 4.38 +/- 1.28 ng/ml of IGF-I per additional repeat (P = 0.001). Longer repeats were associated with early growth in Landrace boars (1.92 +/- 0.92 kg per CA at 160 days; P = 0.038) and with back fat thickness (-0.57 +/- 0.20 mm per CA; P = 0.005) and lean content (7.52 +/- 3.00 g/kg per CA at 105 kg; P = 0.013) adjusted for carcass weight in Duroc barrows, as expected from the effect of circulating IGF-I on these traits. The consistency of the results across populations supports the hypothesis that the length of the CA repeats at intron 1 of the IGF-I gene is associated with circulating IGF-I levels, and that this effect is not neutral with respect to growth and fatness.

Effect of δ-aminolevulinic acid on growth performance, nutrient digestibility, blood parameters and the immune response of weanling pigs challenged with Escherichia coli lipopolysaccharide

This study investigated the effects of dietary δ-aminolevulinic acid (ALA) on growth performance, nutrient digestibility, blood parameters and whether ALA improved the immune response of weanling pigs challenged with Escherichia coli lipopolysaccharide (LPS). Eighty pigs (body weight = 7.21 ± 0.51 kg) were allotted to four dietary treatments, with four pens per treatment and five pigs per pen. Basal diets were supplemented with 0, 5, 10, and 15 mg/kg ALA (as-fed basis) and fed for 35 days. At the end of the feeding period, 10 pigs were selected from both the 0- and 10-mg/kg ALA treatment groups; five were injected i.p. with LPS (50 μg/kg BW) and the other five pigs with an equivalent amount of sterile saline, resulting a 2 × 2 factorial arrangement. Blood sample and rectal temperature data were collected at 0, 2, 4 and 12 h after challenge. Growth performance was not affected by dietary treatments over the total experimental period. However, dry matter (DM) and nitrogen (N) digestibility was improved in the 15-mg/kg ALA treatment group at day 35 ( P < 0.05). Serum hemoglobin (Hb) and iron levels were also increased, with the 10-mg/kg ALA treatment showing the highest concentration ( P < 0.05). On day 35, red (RBC) and white blood cell (WBC) counts were elevated, with the 5- and 10-mg/kg ALA treatments having the highest counts ( P < 0.05). During challenge, LPS injection elevated rectal temperature at 2 and 4 h postchallenge ( P < 0.05). Plasma cortisol concentration was also increased by LPS injection at 2 and 4 h postchallenge and an ALA-alleviating effect was evident at 2 h postchallenge ( P < 0.01). Concentration of plasma insulin-like growth factor-I (IGF-I) was increased in the ALA-supplemented treatments at 2 h postchallenge ( P < 0.05). LPS injection increased plasma tumor necrosis factor-α (TNF-α) concentrations at 2, 4 and 12 h ( P < 0.01), while an ALA-alleviating effect was observed at 2 and 4 h postchallenge ( P < 0.05 and P < 0.10, respectively). Challenge with LPS decreased WBC counts at 2 and 4 h postchallenge ( P < 0.01). At 12 h postchallenge, RBC, WBC and lymphocyte counts were affected by LPS challenge, while an ALA effect was only observed on WBC count ( P < 0.05). In conclusion, dietary supplementation of ALA in weanling pigs can improve DM and N digestibilities, and iron status and have a beneficial effect on the immune response during inflammatory challenge.