1. Increased IGFBP Proteolysis, IGF-I Bioavailability, and Pappalysin Levels in Children With Prader-Willi Syndrome.
- Author
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Barrios V, Martín-Rivada Á, Martos-Moreno GÁ, Canelles S, Moreno-Macián F, De Mingo-Alemany C, Delvecchio M, Pajno R, Fintini D, Chowen JA, and Argente J
- Subjects
- Humans, Child, Male, Female, Adolescent, Child, Preschool, Biological Availability, Insulin-Like Growth Factor Binding Proteins blood, Insulin-Like Growth Factor Binding Proteins metabolism, Insulin-Like Growth Factor Binding Protein 3 blood, Insulin-Like Growth Factor Binding Protein 3 metabolism, Intercellular Signaling Peptides and Proteins blood, Case-Control Studies, Insulin-Like Growth Factor I metabolism, Insulin-Like Growth Factor I analysis, Prader-Willi Syndrome metabolism, Prader-Willi Syndrome blood, Prader-Willi Syndrome drug therapy, Pregnancy-Associated Plasma Protein-A metabolism, Pregnancy-Associated Plasma Protein-A analysis, Glycoproteins blood, Glycoproteins metabolism, Human Growth Hormone blood, Proteolysis
- Abstract
Context: Prader-Willi syndrome (PWS) is associated with impaired growth hormone (GH) secretion and decreased insulin-like growth factor (IGF)-I levels. Pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC-1, STC-2) regulate IGF binding-protein (IGFBP) cleavage and IGF bioavailability, but their implication in PWS is unknown., Objective: We determined serum levels of PAPP-As and STCs in association with IGF axis components in prepubertal and pubertal patients with PWS, also analyzing the effect of GH treatment., Methods: Forty children and adolescents with PWS and 120 sex- and age-matched controls were included. The effect of GH was evaluated at 6 months of treatment in 11 children., Results: Children with PWS had lower levels of total IGF-I, total and intact IGFBP-3, acid-labile subunit, intact IGFBP-4, and STC-1, and they had higher concentrations of free IGF-I, IGFBP-5, and PAPP-A. Patients with PWS after pubertal onset had decreased total IGF-I, total and intact IGFBP-3, and intact IGFBP-4 levels, and had increased total IGFBP-4, and STCs concentrations. GH treatment increased total IGF-I, total and intact IGFBP-3, and intact IGFBP-4, with no changes in PAPP-As, STCs, and free IGF-I levels. Standardized height correlated directly with intact IGFBP-3 and inversely with PAPP-As and the free/total IGF-I ratio., Conclusion: The increase in PAPP-A could be involved in increased IGFBP proteolysis, promoting IGF-I bioavailability in children with PWS. Further studies are needed to establish the relationship between growth, GH resistance, and changes in the IGF axis during development and after GH treatment in these patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2024
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