학술논문
Pappalysins and Stanniocalcins and Their Relationship With the Peripheral IGF Axis in Newborns and During Development
Clinical Research Article
Clinical Research Article
Document Type
Academic Journal
Author
Martin-Rivada, Alvaro; Guerra-Cantera, Santiago; Campillo-Calatayud, Ana; Andres-Esteban, Eva Maria; Holgado, Maria Sanchez; A. Martos-Moreno, Gabriel; Pozo, Jesus; Guemes, Maria; Soriano-Guillen, Leandro; Pellicer, Adelina; Oxvig, Claus; Frystyk, Jan; Chowen, Julie A.; Barrios, Vicente; Argente, Jesus
Source
Journal of Clinical Endocrinology & Metabolism. October 2022, Vol. 107 Issue 10, p2912, 13 p.
Subject
Language
English
ISSN
0021-972X
Abstract
From fetal life to adolescence, growth velocity is one of the best indicators of health and nutritional status (1), with the growth hormone (GH)/insulin-like growth factor (IGF) axis being essential [...]
Context: Pappalysins (PAPP-A, PAPP-A2) modulate body growth by increasing insulin-like growth factor I (IGF-I) bioavailability through cleavage of insulin-like growth factor binding proteins (IGFBPs) and are inhibited by stanniocalcins (STC1, STC2). Normative data on these novel factors, as well as on free IGF-I and uncleaved fractions of IGFBPs, are not well established. Objective: This work aimed to determine serum concentrations of PAPP-A, PAPP-A2, STC1, and STC2 in relationship with other growth hormone (GH)-IGF axis parameters during development. Methods: Full-term newborns (150; gestational age: 39.30 [+or-] 1.10 weeks), 40 preterm newborns (30.87 [+or-] 3.35 weeks), and 1071 healthy individuals (aged 1-30 years) were included in the study and divided according to their Tanner stages (males and females): I:163 males, 154 females; II:100 males, 75 females; III:83 males, 96 females; IV: 77 males, 86 females; and V:109 males, 128 females. Results: Serum concentrations of PAPP-A, PAPP-A2, STC1, STC2, IGFBP-2, total IGFBP-4, and total IGFBP-5 were elevated at birth and declined throughout childhood. In postnatal life, PAPP-A2 concentrations decreased progressively in concomitance with the free/total IGF-I ratio; however, stanniocalcin concentrations remained stable. PAPP-A2 concentrations positively correlated with the free/total IGF-I ratio (r = +0.28; P Conclusion: This study provides reference values of pappalysins and stanniocalcins, which modulate IGF-I activity by changing the concentrations of cleaved and uncleaved IGFBPs. Key Words: growth, normative data, IGF-I, IGFBP, pappalysin, stanniocalcin Abbreviations: ALS, acid-labile subunit; BMI, body mass index; ELISA, enzyme-linked immunosorbent assay; fIGF, free insulin-like growth factor; GH, growth hormone; IGF, insulin-like growth factor; IGFBP-2, insulin-like growth factor binding protein-2; IGFBP-3, insulin-like growth factor binding protein-3; IGFBP-4, insulin-like growth factor binding protein-4; IGFBP-5, insulin-like growth factor binding protein-5; PAPP-A, pregnancy-associated plasma protein A; PAPP-A2, pregnancy-associated plasma protein A2; STC-1, stanniocalcin 1; STC-2, stanniocalcin 2.
Context: Pappalysins (PAPP-A, PAPP-A2) modulate body growth by increasing insulin-like growth factor I (IGF-I) bioavailability through cleavage of insulin-like growth factor binding proteins (IGFBPs) and are inhibited by stanniocalcins (STC1, STC2). Normative data on these novel factors, as well as on free IGF-I and uncleaved fractions of IGFBPs, are not well established. Objective: This work aimed to determine serum concentrations of PAPP-A, PAPP-A2, STC1, and STC2 in relationship with other growth hormone (GH)-IGF axis parameters during development. Methods: Full-term newborns (150; gestational age: 39.30 [+or-] 1.10 weeks), 40 preterm newborns (30.87 [+or-] 3.35 weeks), and 1071 healthy individuals (aged 1-30 years) were included in the study and divided according to their Tanner stages (males and females): I:163 males, 154 females; II:100 males, 75 females; III:83 males, 96 females; IV: 77 males, 86 females; and V:109 males, 128 females. Results: Serum concentrations of PAPP-A, PAPP-A2, STC1, STC2, IGFBP-2, total IGFBP-4, and total IGFBP-5 were elevated at birth and declined throughout childhood. In postnatal life, PAPP-A2 concentrations decreased progressively in concomitance with the free/total IGF-I ratio; however, stanniocalcin concentrations remained stable. PAPP-A2 concentrations positively correlated with the free/total IGF-I ratio (r = +0.28; P Conclusion: This study provides reference values of pappalysins and stanniocalcins, which modulate IGF-I activity by changing the concentrations of cleaved and uncleaved IGFBPs. Key Words: growth, normative data, IGF-I, IGFBP, pappalysin, stanniocalcin Abbreviations: ALS, acid-labile subunit; BMI, body mass index; ELISA, enzyme-linked immunosorbent assay; fIGF, free insulin-like growth factor; GH, growth hormone; IGF, insulin-like growth factor; IGFBP-2, insulin-like growth factor binding protein-2; IGFBP-3, insulin-like growth factor binding protein-3; IGFBP-4, insulin-like growth factor binding protein-4; IGFBP-5, insulin-like growth factor binding protein-5; PAPP-A, pregnancy-associated plasma protein A; PAPP-A2, pregnancy-associated plasma protein A2; STC-1, stanniocalcin 1; STC-2, stanniocalcin 2.