title: IGF-IR signal transduction protein content and its activation by IGF-I in human placentas: relationship with gestational age and birth weight.
abstract: BACKGROUND
  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).
  
  
  CONCLUSIONS
  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.
authors: Institute of Maternal and Child Research, University of Chile, Santiago, Chile.
authors: Germán
authors: G
authors: Iñiguez
authors: Institute of Maternal and Child Research, University of Chile, Santiago, Chile.
authors: Juan José
authors: JJ
authors: Castro
authors: Hospital Clínico San Borja-Arriarán, University of Chile, Santiago, Chile.
authors: Mirna
authors: M
authors: Garcia
authors: Hospital Clínico San Borja-Arriarán, University of Chile, Santiago, Chile.
authors: Elena
authors: E
authors: Kakarieka
authors: Institute of Maternal and Child Research, University of Chile, Santiago, Chile.
authors: M Cecilia
authors: MC
authors: Johnson
authors: Institute of Maternal and Child Research, University of Chile, Santiago, Chile.
authors: Fernando
authors: F
authors: Cassorla
authors: Institute of Maternal and Child Research, University of Chile, Santiago, Chile.
authors: Verónica
authors: V
authors: Mericq
mesh_terms: D001724:Birth Weight; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism; D005865:Gestational Age; D006801:Humans; D007230:Infant, Low Birth Weight / Q000378:metabolism; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008297:Male; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D007334:Insulin-Like Growth Factor I; C546842:MTOR protein, human; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases