Decreased serum insulin-like growth factor-I associated with growth failure in newborn lambs with experimental cyanotic heart disease.

Bernstein, Daniel; Jasper, Jeffrey R.; Rosenfeld, Ron G.; Hintz, Raymond L.

doi:10.1172/jci115693

Cited by 31 publications

(14 citation statements)

References 34 publications

(42 reference statements)

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“…This is in agreement with our previous findings in intrauterine growth retardation fe tuses, which also showed a marked increase in serum IGFBP-1 and IGFBP-2 levels [12]. Chronic hypoxia in newborn lambs has also been reported to increase the 28-kD band, although the identity of this band was not deter mined [27], Northern blot analysis indicates that only the increase in IGFBP-1 is due to increased production in the hypoxic dams. The lack of changes in IGFBP-2 expres sion between the groups suggests that only IGFBP-1 is transcriptionally regulated by hypoxia.…”

Section: Discussionsupporting

confidence: 92%

Hypoxia-lnduced Changes in Insulin-Like Growth Factors and Their Binding Proteins in Pregnant Rats

et al. 1997

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Pregnancy is associated with important changes in the insulin-like growth factor (IGF)-insulin-like growth factor binding protein (IGFBP) axis, but the importance of these growth factors for fetal growth is not well understood. We have recently established a maternal hypoxia model that results in significant intrauterine growth retardation in the fetus, and characterized the IGF-IGFBP axis in growth-retarded fetuses. To determine if maternal IGFs and their binding proteins are similarly regulated by hypoxia, we examined their expression in 6 hypoxic dams (13% oxygen, days 14-21 of gestation) and 6 control dams (21 % oxygen). There was no significant difference in the food intake between the groups. The mean body weight of hypoxic dams, however, was 20% less than that of controls. Of all the organs, the lungs were most affected by hypoxia, weighing 17% more in the hypoxic dams than in the control dams; placental weight was reduced by 10% in the hypoxic dams. Liver and brain weights were not changed significantly by hypoxia. The mean concentration of immunoreactive IGF-I was 123 ± 11 ng/ml in the hypoxic dams and 130 ± 18 ng/ml in the control dams (nonsignificant). Similarly, there was no significant difference in hepatic IGF-I mRNA levels determined by solution hybridization nuclease-protection assay. An increase in IGFBP-1, IGFBP-2 and IGFBP-4 concentrations, however, could be observed by Western ligand blotting of the sera of hypoxic dams, compared to control dams. As assessed by Northern blot analysis, there was a 2.8-fold increase in IGFBP-1 mRNA expression in the livers of hypoxic dams compared to controls. Hepatic IGFBP-4 expression was also slightly increased (1.25-fold) in the hypoxic dams. No difference in hepatic IGFBP-2 or IGFBP-3 mRNA was found. Our results show parallel patterns in fetal and maternal IGF and IGFBP responses to hypoxia. This suggests that hypoxia may inhibit fetal growth by both directly affecting the fetus and via inhibition of placental growth.

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Section: Discussionsupporting

confidence: 92%

Hypoxia-lnduced Changes in Insulin-Like Growth Factors and Their Binding Proteins in Pregnant Rats

et al. 1997

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“…Hypoxia can serve as a potential trigger of reduced dietary intake (8,15,30) and decreased circulating IGF-I and IGFBP-3 (5,16,21,22). Total body energy balance (V O 2 /daily food intake), hemoglobin and lactate levels, and arterial oxygenation were similar to those of the control group, within normal physiological range (12,27).…”

Section: The Experimental Modelmentioning

confidence: 76%

Chronic upper airway resistive loading induces growth retardation via the GH/IGF-I axis in prepubescent rats

Tarasiuk¹,

Segev²

2007

Journal of Applied Physiology

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Tarasiuk A, Segev Y. Chronic upper airway resistive loading induces growth retardation via the GH/IGF-I axis in prepubescent rats. J Appl Physiol 102: [913][914][915][916][917][918] 2007. First published November 30, 2006; doi:10.1152/japplphysiol.00838.2006.-The effect of upper airway loading on longitudinal bone growth and various components of the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis has not been fully elucidated. In the present study, the effect of chronic resistive airway loading (CAL) in a prepubescent rat model on linear bone growth and weight gain was investigated. We hypothesize that CAL induced in prepubescent rats will lead to impaired longitudinal growth due to impairment in circulating and liver GH/IGF-I parameters. The tracheae of 22-day-old rats were obstructed by tracheal banding to increase inspiratory esophageal pressure. The GH/IGF-I markers were analyzed using ELISA, RT-PCR, and Western immunoblot analysis 14 days after surgery. Animals exhibited impaired longitudinal growth as demonstrated by reduction of tibia and tail length gains by 40% (P Ͻ 0.0001) and body weight gain by 24% (P Ͻ 0.0001). No differences were seen in total body energy balance, i.e., oxygen consumption, daily food intake, or arterial blood gases. Circulating GH, IGF-I, and IGF binding protein-3 (IGFBP-3) levels were reduced by 40% (P ϭ 0.037), 30% (P Ͻ 0.006), and 27% (P ϭ 0.02), respectively, in the CAL group. Liver IGF-I mRNA level decreased by 20% (P Ͻ 0.0002), whereas GH receptor mRNA and protein expression were unchanged. We conclude that impaired longitudinal growth in prepubescent CAL rats is related to a decrease in GH, IGF-I, and IGFBP-3 levels. chronic resistive loading; growth hormone; insulin-like growth factor I; insulin-like growth factor binding protein-3; prepuberty ONE OF THE CONSEQUENCES OF chronic resistive airway loading (CAL) in adult rats is malfunction in body weight gain (12, 27) without effect on longitudinal bone growth (35). The failure to gain weight was not related to decreased caloric intake (12) and was recently attributed to a decline in serum insulin-like growth factor I (IGF-I) levels (35). The endocrine effect of pituitary-secreted growth hormone (GH) is induction of IGF-I and IGF binding protein-3 (IGFBP-3) synthesis in various organs, including the liver; both are highly correlated with the 24-h mean GH levels (3, 7). This effect is mediated via activation of GH receptor (GHR), which is extensively distributed throughout many tissues (9). Impairment of the GH/IGF-I axis in prepubescent rats, before bone growth is completed, leads to skeletal growth retardation (31). The effect of CAL on the GH/IGF-I axis and longitudinal growth in prepuberty rats is not known.In the present study, the effect of CAL on longitudinal growth and weight gain was studied using the prepubescent rat model. We hypothesize that CAL will impair the GH/IGF-I axis, consequently leading to longitudinal growth retardation. We explored the effect of CAL on linear growth, serum GH, IGF-I, and ...

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“…In recent animal models of cyanotic heart disease, decreased levels of IGF-1 were associated with chronic hypoxemia, and growth failure (18) . D ü ndar et al (3) evaluated serum IGF-1 levels, oxygen saturation, and nutritional status in C children with CHD compared with controls.…”

Section: Discussionmentioning

confidence: 99%

The effect of corrective surgery on serum IGF-1, IGFBP-3 levels and growth in children with congenital heart disease

Surmeli-Onay

Cındık

Kinik

et al. 2011

Journal of Pediatric Endocrinology and Metabolism

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The aim of this study is to evaluate growth and insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) levels in infants with congenital heart disease (CHD) pre-and postoperatively over a period of a year. Anthropometric values and serum levels of IGF-1 and IGFBP-3 of 40 infants with CHD (20 cyanotic and 20 acyanotic) were compared with 32 healthy controls. Acyanotic infants and infants with pulmonary hypertension (PH) presented signifi cantly more growth failure. Preoperatively, serum IGF-1 and IGFBP-3 levels were lower in the acyanotic group than the cyanotic and the control groups (p = 0.22; p < 0.01). The upward trend in IGF-1 and IGFBP-3 levels in this year-long study demonstrated that the values in the third month and the fi rst year were higher than the preoperative values (p < 0.05). The parallel increase of weight gain and IGF-1, IGFBP-3 levels were the best evidence that these parameters are good nutritional indicators. Timing the corrective surgery before chronic malnutrition or PH develops is an important issue to maintain a normal growth for children with CHD.

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Decreased serum insulin-like growth factor-I associated with growth failure in newborn lambs with experimental cyanotic heart disease.

Cited by 31 publications

References 34 publications

Hypoxia-lnduced Changes in Insulin-Like Growth Factors and Their Binding Proteins in Pregnant Rats

Hypoxia-lnduced Changes in Insulin-Like Growth Factors and Their Binding Proteins in Pregnant Rats

Chronic upper airway resistive loading induces growth retardation via the GH/IGF-I axis in prepubescent rats

The effect of corrective surgery on serum IGF-1, IGFBP-3 levels and growth in children with congenital heart disease

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