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Pappalysins and Stanniocalcins and Their Relationship With the Peripheral IGF Axis in Newborns and During Development
Álvaro Martín-Rivada1, Santiago Guerra-Cantera1,2, Ana Campillo-Calatayud1
1Hospital Infantil Universitario Niño Jesús, Departments of Pediatrics & Pediatric Endocrinology, Research Institute "La Princesa," Department of Pediatrics, Universidad Autónoma de Madrid, E-28009, Madrid, Spain.
Insights
Pappalysins and stanniocalcins, crucial for growth, show declining serum levels from birth through childhood. This study establishes normative data for these factors, aiding in understanding growth regulation.
Area of Science:
- Endocrinology
- Growth Factor Biology
- Biochemistry
Background:
- Pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC1, STC2) are key regulators of insulin-like growth factor I (IGF-I) bioavailability.
- These proteins influence body growth by cleaving IGF-binding proteins (IGFBPs) and are subject to inhibition by stanniocalcins.
- Established normative data for pappalysins, stanniocalcins, free IGF-I, and specific IGFBP fractions are limited.
Purpose of the Study:
- To determine serum concentrations of PAPP-A, PAPP-A2, STC1, and STC2 in relation to other growth hormone (GH)-IGF axis parameters during human development.
- To establish normative reference values for these novel growth-related factors.
Main Methods:
- Serum samples were collected from 150 full-term newborns, 40 preterm newborns, and 1071 healthy individuals aged 1-30 years.
- Participants were categorized by Tanner stages (I-V) for both males and females.
- Concentrations of PAPP-A, PAPP-A2, STC1, STC2, IGFBP-2, total IGFBP-4, and total IGFBP-5 were measured.
Main Results:
- Serum concentrations of PAPP-A, PAPP-A2, STC1, STC2, IGFBP-2, total IGFBP-4, and total IGFBP-5 were highest at birth and decreased throughout childhood.
- PAPP-A2 levels correlated positively with the free/total IGF-I ratio and negatively with the intact/total IGFBP-3 ratio.
- PAPP-A concentrations, lower in females, inversely correlated with the intact/total IGFBP-4 ratio, indicating age-specific roles in GH-IGF axis regulation.
Conclusions:
- This study provides essential reference values for pappalysins and stanniocalcins.
- These findings highlight the role of pappalysins and stanniocalcins in modulating IGF-I activity through altered IGFBP cleavage.
- The data contribute to a better understanding of growth regulation and the GH-IGF axis across different developmental stages.
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 ± 1.10 weeks), 40 preterm newborns (30.87 ± 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 < .001) and negatively with the intact/total IGFBP-3 ratio (r = -0.23; P < .001). PAPP-A concentrations inversely correlated with intact/total IGFBP-4 ratio (r = -0.21; P < .001), with PAPP-A concentrations being lower in females at all ages. Association studies indicate the importance of stanniocalcins and pappalysins in the control of this axis in an age-specific manner.
Conclusion:
This study provides reference values of pappalysins and stanniocalcins, which modulate IGF-I activity by changing the concentrations of cleaved and uncleaved IGFBPs.
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