Pappalysins and Stanniocalcins and Their Relationship With the Peripheral IGF Axis in Newborns and During Development

J Clin Endocrinol Metab. 2022 Sep 28;107(10):2912-2924. doi: 10.1210/clinem/dgac453.

Abstract

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.

Keywords: IGF-I; IGFBP; growth; normative data; pappalysin; stanniocalcin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Female
  • Glycoproteins
  • Growth Hormone / metabolism
  • Humans
  • Infant
  • Infant, Newborn
  • Insulin-Like Growth Factor Binding Protein 2
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Protein 4* / metabolism
  • Insulin-Like Growth Factor Binding Protein 5
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I* / metabolism
  • Male
  • Pregnancy-Associated Plasma Protein-A / metabolism

Substances

  • Glycoproteins
  • Insulin-Like Growth Factor Binding Protein 2
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Protein 4
  • Insulin-Like Growth Factor Binding Protein 5
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I
  • teleocalcin
  • Growth Hormone
  • Pregnancy-Associated Plasma Protein-A