ESPE Yearbook of Paediatric Endocrinology

Brief summary: Growth Hormone (GH)-Insulin-Growth-Factor-1 (IGF-1) axis plays the major role in promoting growth, but novel factors seem to modulate GH-IGF1 axis functioning. The majority of circulating IGF-1 and IGF-2 are bound to IGF-binding proteins (IGF-BPs) which prolong their half-life and regulate their tissue distribution (1,2). Pappalysins (PAPP-A, PAPP-A2) increase IGF-1 bioavailability through cleavage of IGFBPs and are inhibited by stanniocalcins (STC1, STC2) (3,4). This translational study provides normative data about pappalysins, stanniocalcins and IGF-BPs in relation to Tanner pubertal stages and gestational age of newborns.

This descriptive cross-sectional study aims to delineate the trend of values of PAPPAs and STCs in different periods of life, from birth to adulthood. The study population included 190 appropriate-for-gestational-age (AGA) newborns, divided into 150 full term newborns and 40 preterm newborns and 1071 healthy individuals aged 1-30 years with normal height, weight, and BMI, subdivided ac-cording to their pubertal Tanner stage. Newborn samples were compared to 317 healthy children samples with Tanner pubertal stage I.

Blood levels of IGFBP-2, IGFBP-4, IGFBP-5, PAPP-As, STCs, the free IGF1/total IGF1 ratio were higher at birth than in childhood. In postnatal life, PAPP-A2 concentrations decreased progressively in concomitance with the free/total IGF-I ratio (positive correlation, P<.001) supporting the hypothesis that PAPP-A2 is one of the main regulators of IGF-I bioavailability (5). PAPP-A2 negatively correlated with the intact/total IGFBP-3 ratio (P<.001) and PAPP-A concentrations negatively correlated with intact/total IGFBP-4 ratio (P<.001), with PAPP-A concentrations being lower in females. Overall, STCs and PAPPAs levels showed a progressive decrease from prenatal to postnatal life except from a peak of STC2 in Tanner V females that could contribute to the deceleration in growth observed in this stage, as STC2 appears to be a more potent brake for linear bone growth than STC1 (6). In conclusion, this study provides for the first time reference data for PAPP-A, PAPP-A2, STC1 and STC2 relating these factors with the GH-IGf1 axis parameters, including IGF bioavailability at the different stages of development.

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