Growth Hormone-Binding Protein In Children Research Articles

Insulin-Like Growth Factor I, Its Binding Proteins 1 and 3, and Growth Hormone-Binding Protein in Children and Adolescents with Insulin-Dependent Diabetes Mellitus: Clinical Implications1

Values of IGF-I after extraction, its binding proteins, and the high affinity GH-binding protein (BP) are not well established in pediatric patients with insulin-dependent diabetes mellitus (IDDM). We report data for IGF-I, IGFBP-1, and -3, and GHBP in 92 Spanish children with IDDM, separated according to pubertal stage: prepubertal (n = 49); pubertal onset (n = 17); mid-puberty (n = 17), and complete puberty (n = 9), as well as to metabolic control (HbA1 < 9% or > or = 9%). IGF-I levels in IDDM patients increased throughout development (p < 0.001), but were diminished at every developmental stage when compared with marched control subjects. IGF-I concentrations showed a negative correlation with the degree of metabolic control, in particular during the prepubertal stage of development. A negative correlation (r = -0.22; p < 0.005) between IGF-I concentrations and HbA1 was found. Serum IGFBP-I levels diminish during maturation in diabetic patients (p < 0.001). However, IDDM patients have significantly higher levels of IGFBP-1 than control subjects at every stage of development, and IDDM patients with inadequate metabolic control exhibit even greater differences when compared with matched control subjects. A positive correlation (r = 0.22; p < 0.005) between IGFBP-1 concentrations and HbA1 was found. IGFBP-3 serum levels were similar to those observed in normal subjects, and no correlation was observed in relation to the metabolic control. In IDDM patients, GHBP levels change significantly during maturation, as they do in normal control subjects; however, significantly lower GHBP levels were found in prepubertal and pubertal IDDM patients. GHBP levels were independent of metabolic control, although a tendency toward lower levels of GHBP was seen when HbA1 levels increased. We suggest that a partial GH resistance syndrome exists in IDDM patients, and this may be related to the metabolic control. Hence, the biochemical markers measured here may be of value in evaluating the smaller pubertal growth spurt in diabetic patients.

Reduced concentration of serum growth hormone-binding protein in children with idiopathic short stature. National Cooperative Growth Study

Reduced concentration of serum growth hormone-binding protein in children with idiopathic short stature. National Cooperative Growth Study

Reduced concentration of serum growth hormone-binding protein in children with idiopathic short stature. National Cooperative Growth Study.

One possible explanation for the growth failure in children with idiopathic short stature (ISS) is reduced peripheral responsiveness to GH. In Laron syndrome, growth retardation is caused by GH resistance due to GH receptor (GH-R) defects, which are associated in most cases with absent or low serum concentrations of the GH-R-related GH-binding protein (GHBP). We tested the hypothesis that some children with ISS have reduced serum concentrations of GHBP and that this may reflect decreased sensitivity to GH. A ligand-mediated immunofunctional assay was used to measure biochemically active GHBP in serum from 1549 children, including 773 controls, 573 with ISS, 107 with GH deficiency (GHD), and 96 with Turner syndrome (TS). Ages ranged from 1-17 yr. Serum GHBP concentrations in children with GHD, ISS, and TS were converted to SD scores and compared to controls by analysis of variance. In male and female ISS subjects, approximately 90% had GHBP concentrations below the age- and sex-adjusted mean for controls, and 20% had GHBP concentrations below the normal range. The mean serum GHBP SD score was lower in both males and females with GHD (-0.6) or ISS (-1.2) than in controls (both P < 0.005). The mean for ISS males was significantly lower than that for GHD males (P < 0.0001). The mean GHBP SD score for girls with TS (-0.3) did not differ significantly from that of the control females. The decreased levels of serum GHBP in some children with idiopathic short stature suggest that these children could have a defect at the level of the GH-R.

Growth hormone insensitivity associated with elevated circulating growth hormone-binding protein in children with Alagille syndrome and short stature.

The purpose of this study was to assess GH sensitivity in children with Alagille syndrome (syndromic intrahepatic bile duct paucity) by examining their response to short term administration of recombinant human GH (rhGH). Serum levels of insulin-like growth factor-I (IGF-I) were low despite elevated overnight integrated serum GH concentrations. Administration of rhGH (0.05 mg/kg.day for 3 days) to four growth-retarded children with Alagille syndrome did not significantly alter the serum concentrations of IGF-I and insulin, blood urea nitrogen, or urinary calcium excretion. In contrast, circulating IGF-I increased 2-fold in two children with Alagille syndrome and normal stature. In the control group, consisting of seven prepubertal children with GH deficiency, the predicted changes in response to rhGH in serum concentrations of IGF-I and insulin, urea nitrogen, and urinary calcium excretion were observed. Serum GH-binding protein levels, measured by a ligand-mediated immunofunctional assay, were significantly higher in children with Alagille syndrome than in children with cirrhosis or GH deficiency. We conclude that growth-retarded children with Alagille syndrome are insensitive to GH. The growth disturbances and metabolic defects may be due in part to failure to increase IGF-I concentrations in response to GH, implying that growth-retarded children with Alagille syndrome may benefit from IGF-I treatment.

Growth hormone insensitivity associated with elevated circulating growth hormone-binding protein in children with Alagille syndrome and short stature

Growth hormone insensitivity associated with elevated circulating growth hormone-binding protein in children with Alagille syndrome and short stature

Diminished growth hormone-binding protein in children with insulin- dependent diabetes mellitus

Diminished growth hormone-binding protein in children with insulin- dependent diabetes mellitus

Diminished growth hormone-binding protein in children with insulin-dependent diabetes mellitus

Two distinct GH-binding proteins (GHBP) are present in circulation in the human. The major GHBP (high affinity GHBP) is homologous to the extracellular portion of the GH receptor and the concentration of this protein in circulation may reflect the status of the GH receptor in the tissues. To gain information about the concentration of GHBPs in children with insulin-dependent diabetes mellitus (IDDM), we measured GHBP in the serum of 46 children with IDDM and compared it to that in 53 healthy control subjects matched for age and sexual maturity. The total GHBP concentration in the group of pubertal and postpubertal IDDM patients was lower than that measured in the control group (mean +/- SEM: 7.8 +/- 0.4 vs. 9.0 +/- 0.5%, P = 0.05). The diabetic children in stages II to IV of puberty had a lower GHBP level compared to their healthy controls (7.6 +/- 0.4 vs. 9.1 +/- 0.5%, P = 0.02), whereas the difference between the diabetic and control group of postpubertal children was not statistically different (8.3 +/- 0.7 vs. 9.7 +/- 0.7%, P = 0.1). In a randomly selected subset of eight patients and eight controls, the concentration of the individual GHBPs (i.e. high affinity and low affinity (GHBP) was estimated by gel chromatography. There was no difference in the low affinity GHBP between the two groups (9.9 +/- 0.6% vs. 9.9 +/- 0.4%), but the high affinity GHBP was less in the diabetic group than in the control group (10.5 +/- 0.9 vs. 15.6 +/- 1.0%, P less than 0.01). In the diabetic group, there was no correlation between the GHBP levels and age, duration of diabetes, hemoglobin A1, or insulin dose. We conclude that in IDDM there is less of the high affinity GHBP, suggesting a decrease in the number of GH receptors in these patients. This decrease may contribute to GH resistance manifesting as decreased insulin-like growth factor-I levels despite high GH levels in patients with IDDM.