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Claus Oxvig

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Masanobu Fujimoto, University of Cincinnati College of Medicine, Tottori University
  • ,
  • Jane C. Khoury, University of Cincinnati College of Medicine
  • ,
  • Philip R. Khoury, University of Cincinnati College of Medicine
  • ,
  • Bhanu Kalra, Ansh Laboratories LLC
  • ,
  • Ajay Kumar, Ansh Laboratories LLC
  • ,
  • Patrick Sluss, Ansh Laboratories LLC
  • ,
  • Claus Oxvig
  • Vivian Hwa, University of Cincinnati College of Medicine
  • ,
  • Andrew Dauber, University of Cincinnati College of Medicine, Children’s National Hospital, George Washington University

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.

Original languageEnglish
JournalEuropean Journal of Endocrinology
Volume182
Issue3
Pages (from-to)363-374
Number of pages12
ISSN0804-4643
DOIs
Publication statusPublished - 2020

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