Expression of adrenomedullin by human placental cytotrophoblasts and choriocarcinoma JAr cells

Adrenomedullin is a multifunctional peptide expressed in a variety of tissu es. This study was conducted to investigate the expression of adrenomedulli n and its mRNA by human trophoblasts and the possible existence of adrenome dullin receptor in those cells. Human placentas in all three trimesters wer e obtained from patients undergoing therapeutic abortions and deliveries. T otal RNA was extracted from placental trophoblastic tissues and JAr chorioc arcinoma cells, and the expression of adrenomedullin mRNA was determined by RT-PCR. Immunohistochemical analysis was performed by the avidin/biotin im munoperoxidase method using a specific antibody to adrenomedullin. The secr etion of adrenomedullin by JAr cells cultured in medium containing [S-35]cy steine-[S-35]methionine was determined by immunoprecipitation followed by P AGE. The presence of adrenomedullin receptor in JAr cells was examined usin g a binding assay with [I-125]rat adrenomedullin. Adrenomedullin mRNA was e xpressed by human placental trophoblastic tissues in all three trimesters a nd by JAr cells. Immunohistochemical analysis revealed that adrenomedullin is expressed by cytotrophoblasts in placentas in all three trimesters, but not by syncytiotrophoblasts. The expression of adrenomedullin in the cytotr ophoblast was most abundant in first trimester placenta and became less abu ndant during the course of pregnancy. JAr cells synthesized and secreted im munoreactive adrenomedullin. Binding assay with [I-125]rat adrenomedullin d emonstrated specific binding of adrenomedullin to JAr cells, indicating the existence of a specific receptor for adrenomedullin in trophoblastic cells . Adrenomedullin is transcribed and secreted by cytotrophoblastic cells that possess adrenomedullin receptor. Adrenomedullin may play a potential role a s an autocrine/paracrine factor in the growth of cytotrophoblasts, especial ly in early gestation.