title: Relationship between nocturnal growth hormone concentrations, serum IGF-I/IGFBP-3 levels, insulin sensitivity and GH receptor allelic variant in small for gestational age children.
abstract: Growth hormone may help to increase final height in patients with short stature, but its efficacy is variable. It has been recently reported that the isoform of the GH receptor (GHR) that lacks exon 3 (d3-GHR) is associated with a greater growth response to GH therapy. We hypothesized that nocturnal growth hormone concentrations, basal IGF-I and IGFBP-3 levels, and insulin sensitivity might show variations among individuals depending on their GHR allelic variant. To test this hypothesis, we studied 38 prepubertal LBW children with nocturnal GH concentrations, IGF-I and IGFBP-3 levels and insulin sensitivity during OGTT and Insulin test. The GHR allelic variant was analyzed through multiplex PCR analysis in DNA from peripheral leukocytes. Characteristics of the overnight GH secretion [(mean GH: 6.8 +/- 0.6 vs. 6.2 +/- 0.5 ng/ml), (AUC: 3,227 +/- 280 vs. 2,908 +/- 212 ng/ml.min), (peak number: 4.4 +/- 0.3 vs. 4.4 +/- 0.2), (amplitude: 12 +/- 1.1 vs. 10.8 +/- 1.1 ng/ml)] did not differ between groups (f1/f1 vs. f1/d3 plus d3/d3). In addition, we did not observe any significant differences in serum IGF-I SDS (-0.49 +/- 0.26 vs. -0.40 +/- 0.35) or IGFBP-3 SDS (-1.21 +/- 0.24 vs. -0.89 +/- 0.21) nor in insulin sensitivity (WIBSI: 12 +/- 1.2 vs. 10.8 +/- 1.1) in LBW children with full length GHR compared to children carrying at least one GHRd3 allele. The distribution of the f1/f1 allelic variant and fi/d3 or d3/d3 was similar in the LBW children with or without catch-up growth. These results suggest that the GHR allelic variant does not play a significant role in the regulation of GH-IGF-I/BP3 axis or in insulin sensitivity in prepubertal LBW children.
authors.affiliation: Faculty of Medicine, Institute of Maternal and Child Research, University of Chile, Santiago, Chile. vmericq@med.uchile.cl
authors.forename: Verónica
authors.initials: V
authors.lastname: Mericq
authors.forename: Rossana
authors.initials: R
authors.lastname: Román
authors.forename: Germán
authors.initials: G
authors.lastname: Iñiguez
authors.forename: Bárbara
authors.initials: B
authors.lastname: Angel
authors.forename: Teresa
authors.initials: T
authors.lastname: Salazar
authors.forename: Alejandra
authors.initials: A
authors.lastname: Avila
authors.forename: Francisco
authors.initials: F
authors.lastname: Perez-Bravo
authors.forename: Fernando
authors.initials: F
authors.lastname: Cassorla
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002940:Circadian Rhythm; D005260:Female; D014644:Genetic Variation; D005951:Glucose Tolerance Test; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male
chemical_list: D002352:Carrier Proteins; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C051815:somatotropin-binding protein