Serum levels of insulin‐like growth factor binding proteins in Ecuadorean children with growth hormone insensitivity

Abstract

RG. Serum levels of insulin-like growth factor binding proteins in Ecuadorean children with growth hormone insensitivity. Acta Prediatr 1999; Suppl428: 185-91. Stockholm. ISSN 0803-5326 Although insulin-like growth factor binding proteins (IGFBPs) are known to be important modulators of the action of insulin-like growth factors (IGFs), regulation of their production in vivo is not completely understood. Serum concentrations of IGFBP-3, -4 and -5 and acid-labile subunit (ALS) were therefore examined in 20 children with growth hormone (GH) insensitivity before and after 6 months of therapy with recombinant human IGF-I (80 or 120 y g k g twice daily). The IGFBP concentrations in these children were compared with those in 62 GH-deficient children receiving GH therapy for 3 months. Serum levels of IGFBP-3, -4 and -5 and ALS all increased significantly ( p < 0.0001) in GH-deficient children in response to GH therapy, whereas no significant increases occurred in the children with GH insensitivity. These findings indicate that GH is responsible for the regulation of serum levels of IGFBP-3, -4 and -5 and ALS, and that IGF-I does not directly regulate the concentrations of these circulating IGFBPs. 0 Growth hormone, growth hormone insensitivity, insulin-like growth factor I, insulin-like growth factor binding protein are simultaneously or sequentially required at the growth plate to stimulate the changes involved in growth (8).Recognition of the importance of IGFBPs in modulating I J Fig. 1. The three hypothetical mechanisms of GH action in inducing longitudinal growth.

Diagnostic interest of acid-labile subunit measurement in relationship to other components of the IGF system in pediatric patients with growth or eating disorders

“…Low ALS concentrations in GHD patients have been reported previously (1,5,6). The patients with short stature and normal GH secretion included in this study had normal serum ALS concentrations; it is also known that GH therapy in patients with GH insensitivity does not change serum ALS concentrations (15). These findings suggest that GH is the main regulator of ALS and that the action of IGF-I on this glycoprotein is exerted by supressing GH secretion (16).…”

Evidence for a Continuum of Genetic, Phenotypic, and Biochemical Abnormalities in Children with Growth Hormone Insensitivity

“…In GHR mutations, IGF-I, IGFBP-3, and ALS levels are usually severely decreased, although the degree of the deficiencies is variable, supporting the evidence for a continuum. Most homozygous GHR mutations cause extreme deficiency of all GH-dependent peptides, associated with increase in basal and stimulated GH secretion (8,116,120,121). However, a range of IGF-I and IGFBP-3 deficiencies was present, particularly in some of the less homogeneous populations such as the European GHI series where subtle differences, particularly in IGFBP-3, being less sensitive to GH, was noticeable (116).…”

Increased serum concentration of IGFBP-4 and IGFBP-5 in healthy adults during one month’s treatment with supraphysiological doses of growth hormone

“…Inter-and intra-assay variations were less than 8%. Both these assays have been used extensively for measurements of serum levels of IGFBPs in various physiological and pathological situations [21,22,[25][26][27][28][29][30].…”

“…Thirty healthy, physically active volunteers (15 men and 15 women), mean age 25.9, range 18-35 (men 27.4 years, range 18-35, and women 24.8 years, range [21][22][23][24][25][26][27][28][29][30], participated in the study. Baseline characteristics and demographic data are presented in Table 1.…”