Immunohistochemical localization of adrenomedullin in fetal and neonatal lung

Adrenomedullin is a potent hypotensive peptide that has been demonstrated to increase pulmonary blood flow in fetal sheep. To examine whether adrenomedullin plays a role in the transitional changes of human pulmonary blood flow at birth, we have evaluated, by immunohistochemistry, its presence and distribution in fetal lung during gestation using a polyclonal antibody directed toward human adrenomedullin 1-52. We collected lung specimen from abortive fetuses (n = 6), preterm neonates (n = 4), and term infants (n = 3). Two adult lung specimen were used as controls. Immunoreactive adrenomedullin was detected in fetal lung collected as early as at 18 wk of gestation and in all tissues throughout gestation. Adrenomedullin was localized predominantly in the epithelial cells of bronchi, with an apical distribution. Endothelial cells also stained for adrenomedullin. The intensity of staining and the percentage of positive bronchial epithelial cells increased as gestation progressed; but staining for adrenomedullin was absent in tissues collected after breathing and in the adult controls. These findings indicate that adrenomedullin may play an important role in respiratory homeostasis at birth. Moreover, the immunohistochemical expression of AM in the late organogenetic period and its increasing staining during fetal lung development may suggest a possible role in the mechanisms of fetal lung differentiation and/or maturation.