IGF-IR Signal Transduction Protein Content and Its Activation by IGF-I in Human Placentas: Relationship with Gestational Age and Birth Weight |
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Authors: | Germán I?iguez Juan José Castro Mirna Garcia Elena Kakarieka M Cecilia Johnson Fernando Cassorla Verónica Mericq |
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Institution: | 1. Institute of Maternal and Child Research, University of Chile, Santiago, Chile.; 2. Hospital Clínico San Borja-Arriarán, University of Chile, Santiago, Chile.; Medical Faculty, Otto-von-Guericke University Magdeburg, Medical Faculty, Germany, |
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Abstract: | IntroductionThe 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.ResultsThe 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).ConclusionThe 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. |
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