Supplementary material for the paper ‘Pappalysins and stanniocalcins and their relationship with the peripheral IGF axis in newborns and during development’

Pappalysins (PAPP-A, PAPP-A2) modulate body growth by increasing IGF-I bioavailability through cleavage of IGFBPs and are inhibited by stanniocalcins (STC1, STC2). Normative data of these novel factors, as well as of free IGF-I and uncleaved fractions of IGFBPs are not well established. Objective: To determine serum concentrations of PAPP-A, PAPP-A2, STC1 and STC2, in relationship with other GH-IGF axis parameters during development.

Patients and methods: Full-term newborns (150; gestational age: 39.30 ± 1.10 weeks), 40 preterm newborns (30.87 ± 3.35 weeks) and 1071 healthy individuals (1-30 years old) 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 total and free IGF-I, IGF-II, total IGFBP-3 and ALS rose gradually during development peaking in Tanner stages III-IV.

Concentrations of IGFBP-4 and IGFBP-5 were lower in prepubertal children. 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<0.001) and negatively with the intact/total IGFBP-3 ratio (r=-0.23, p<0.001). PAPP-A concentrations inversely correlated with intact/total IGFBP-4 ratio (r=-0.21, p<0.001), with PAPP-A concentrations being lower in females at all ages. Conclusion: This study provides reference values of pappalysins and stanniocalcins, which modulate IGF-I activity by changing the concentrations of uncleaved IGFBPs.