IGF-IR signal transduction protein content and its activation by IGF-I in human placentas: relationship with gestational age and birth weight

PLoS One. 2014 Jul 22;9(7):e102252. doi: 10.1371/journal.pone.0102252. eCollection 2014.

Abstract

Introduction: The human placenta expresses the IGF-I and IGF-IR proteins and their intracellular signal components (IRS-1, AKT and mTOR). The aim of this study was to assess the IGF-IR content and activation of downstream signaling molecules in placentas from newborns who were classified by gestational age and birth weight. We studied placentas from 25 term appropriate (T-AGA), 26 term small (T-SGA), 22 preterm AGA (PT-AGA), and 20 preterm SGA (PT-SGA) newborns. The total and phosphorylated IGF-IR, IRS-1, AKT, and mTOR contents were determined by Western Blot and normalized by actin or with their respective total content. The effect of IGF-I was determined by stimulating placental explants with recombinant IGF-I 10-8 mol/L for 15, 30, and 60 minutes.

Results: The IGF-IR content was higher in T-SGA compared to T-AGA placentas, and the IRS-1 content was higher in PT-placentas compared with their respective T-placentas. The effect of IGF-I on the phosphorylated forms of IGF-IR was increased in T-SGA (150%) and PT-SGA (300%) compared with their respective AGA placentas. In addition, AKT serine phosphorylation was higher in PT-SGA compared to PT-AGA and T-SGA placentas (90% and 390% respectively).

Conclusion: The higher protein content and response to IGF-I of IGF-IR, IRS-1, and AKT observed in SGA placentas may represent a compensatory mechanism in response to fetal growth restriction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Birth Weight*
  • Female
  • Fetal Growth Retardation / metabolism
  • Gestational Age*
  • Humans
  • Infant, Low Birth Weight / metabolism
  • Infant, Newborn
  • Insulin-Like Growth Factor I / physiology*
  • Male
  • Placenta / metabolism*
  • Pregnancy
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptor, IGF Type 1 / metabolism*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Tissue Culture Techniques

Substances

  • Insulin-Like Growth Factor I
  • MTOR protein, human
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases

Grants and funding

This work was supported by FONDECYT Grant 111 0240. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.