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Anthropometric and biochemical correlates of PAPP-A2, free IGF-I, and IGFBP-3 in childhood.

Eur J Endocrinol. 2020 Mar;182(3):363-374
Masanobu Fujimoto 1 , Jane C Khoury 2 , Philip R Khoury 3 , Bhanu Kalra 4 , Ajay Kumar 4 , Patrick Sluss 4 , Claus Oxvig 5 , Vivian Hwa 6 , Andrew Dauber 7
Masanobu Fujimoto 1 , Jane C Khoury 2 , Philip R Khoury 3 , Bhanu Kalra 4 , Ajay Kumar 4 , Patrick Sluss 4 , Claus Oxvig 5 , Vivian Hwa 6 , Andrew Dauber 7
+ et al

[No authors listed]

Author information
  • 1 Division of Pediatrics and Perinatology, Tottori University Faculty of Medicine, Yonago, Japan.
  • 2 Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
  • 3 Heart Institute Research Core, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
  • 4 Ansh Labs, Webster, Texas, USA.
  • 5 Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.
  • 6 Cincinnati Center for Growth Disorders, Division of Endocrinology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
  • 7 Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.

摘要

OBJECTIVE:Pregnancy-associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that cleaves IGFBP-3 and IGFBP-5. Human mutations in PAPPA2 result in short stature with a low percentage of free IGF-I. Little is known about PAPP-A2 levels and the regulation of free IGF-I throughout childhood. We examined PAPP-A2 and intact IGFBP-3 levels in childhood and explored associations between PAPP-A2, free and total IGF-I, and total and intact IGFBP-3 and their relationship to the percentage of free to total IGF-I and anthropometric factors. DESIGN:Cross-sectional study at a single center. METHODS:PAPP-A2, free IGF-I, and intact IGFBP-3 levels were measured in childhood (3-18 years old) and an evaluation of the relationship between these proteins and anthropometric factors. RESULTS:In 838 children, PAPP-A2 consistently decreased throughout childhood. In contrast, free IGF-I increased. A pubertal peak in free IGF-I was present in females but was less evident in males. Intact and total IGFBP-3 increased throughout childhood; however, intact IGFBP-3 had a more marked rise than total IGFBP-3. Percent free IGF-I decreased with no distinct pubertal peak. PAPP-A2 levels positively correlated with the percent free IGF-I (Male, Female; r = 0.18, 0.38; P < 0.001) and negatively with intact IGFBP-3 (Male, Female; r = -0.58, -0.65; P < 0.0001). CONCLUSIONS:This is the first study to describe serum PAPP-A2 and intact IGFBP-3 in children between 3 and 18 years of age. Our correlative findings suggest that PAPP-A2 is an important regulator of the percent free IGF-I which can be a marker of perturbations in the GH/IGF-I axis.

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