Regulation by hypoxia of adrenomedullin output and expression in human trophoblast cells

Objectives: Plasma adrenomedullin concentrations are increased in the fetal circulation in acute and chronic hypoxic conditions. The effect of hypoxia in regulating adrenomedullin synthesis and secretion was investigated in human placental trophoblast cells. Study design: Human trophoblast cells obtained from term placentas (n = 7) were cultured in hypoxic condition (3% oxygen). Cytotrophoblast cells were cultured for up to 48 h and syncytiotrophoblasts for 2, 8 and 24 h. Changes in adrenomedullin output compared to normoxic conditions were measured by radioimmunoassay. Protein expression was evaluated with Western blot and immunocytochemistry. Results: Hypoxia induced a time-dependent increase in adrenomedullin output and protein expression by placental trophoblast cells. Conclusions: Hypoxia regulates adrenomedullin secretion and expression by human placenta, thereby promoting increased adrenomedullin concentration in the fetal circulation in clinical circumstances characterized by reduced oxygen levels. (c) 2010 Elsevier Ireland Ltd. All rights reserved.