Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan 20;14(1):1770.
doi: 10.1038/s41598-024-52074-8.

Pregnancy associated plasma protein-A2 (PAPP-A2) and stanniocalcin-2 (STC2) but not PAPP-A are associated with circulating total IGF-1 in a human adult population

Katharina Nimptsch  1 , Elif Ece Aydin  2 , Rafael Francisco Rios Chavarria  3 , Jürgen Janke  3   4   5 , Matthew N Poy  6 , Claus Oxvig  7 , Astrid Steinbrecher  3 , Tobias Pischon  3   2   4   5
Affiliations

Pregnancy associated plasma protein-A2 (PAPP-A2) and stanniocalcin-2 (STC2) but not PAPP-A are associated with circulating total IGF-1 in a human adult population

Katharina Nimptsch et al. Sci Rep. .

Abstract

The pappalysins pregnancy associated plasma protein-A (PAPP-A) and -A2 (PAPP-A2) act as proteinases of insulin-like growth factor-1 (IGF-1) binding proteins, while stanniocalcin-2 (STC2) was identified as a pappalysin inhibitor. While there is some evidence from studies in children and adolescents, it is unclear whether these molecules are related to concentrations of IGF-1 and its binding proteins in adults. We investigated cross-sectionally the association of circulating PAPP-A, PAPP-A2 and STC2 with IGF-1 and its binding proteins (IGFBPs) in 394 adult pretest participants (20-69 years) of the German National Cohort Berlin North study center. Plasma PAPP-A, PAPP-A2, total and free IGF-1, IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-5 and STC2 were measured by ELISAs. The associations of PAPP-A, PAPP-A2 and STC2 with IGF-1 or IGFBPs were investigated using multivariable linear regression analyses adjusting for age, sex, body mass index and pretest phase. We observed significant inverse associations of PAPP-A2 (difference in concentrations per 0.5 ng/mL higher PAPP-A2 levels) with total IGF-1 (- 4.3 ng/mL; 95% CI - 7.0; - 1.6), the IGF-1:IGFBP-3 molar ratio (- 0.34%; 95%-CI - 0.59; - 0.09), but not free IGF-1 and a positive association with IGFBP-2 (11.9 ng/mL; 95% CI 5.0; 18.8). PAPP-A was not related to total or free IGF-1, but positively associated with IGFBP-5. STC2 was inversely related to total IGF-1, IGFBP-2 and IGFBP-3 and positively to IGFBP-1. This first investigation of these associations in a general adult population supports the hypothesis that PAPP-A2 as well as STC2 play a role for IGF-1 and its binding proteins, especially for total IGF-1. The role of PAPP-A2 and STC2 for health and disease in adults warrants further investigation.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Schematic overview of the stanniocalcin-pappalysin-IGF-1 axis.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Miller BS, Rogol AD, Rosenfeld RG. The history of the insulin-like growth factor system. Horm. Res. Paediatr. 2022;95:619–630. doi: 10.1159/000527123. - DOI - PubMed
    1. Oxvig C, Conover CA. The stanniocalcin-PAPP-A-IGFBP-IGF axis. J. Clin. Endocrinol. Metab. 2023 doi: 10.1210/clinem/dgad053. - DOI - PubMed
    1. Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr. Rev. 2000;21:215–244. doi: 10.1210/edrv.21.3.0399. - DOI - PubMed
    1. Bailes J, Soloviev M. Insulin-like growth factor-1 (IGF-1) and its monitoring in medical diagnostic and in sports. Biomolecules. 2021;11:217. doi: 10.3390/biom11020217. - DOI - PMC - PubMed
    1. Agrogiannis GD, Sifakis S, Patsouris ES, Konstantinidou AE. Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review) Mol. Med. Rep. 2014;10:579–584. doi: 10.3892/mmr.2014.2258. - DOI - PMC - PubMed

MeSH terms

Substances

  NODES
Association 11
twitter 2