EFFECTS OF IRON SUPPLEMENTATION ON IRON UPTAKE BY DIFFERENTIATING CYTOTROPHOBLASTS

Cultured in Medium-199, cytotrophoblasts isolated from human placentae differentiate morphologically (e.g. syncytium formation) as well as b iochemically (e.g. expression of transferrin receptors, TfRs) into syn cytiotrophoblast-like structures. The highest TfR numbers are observed in cells cultured in iron-poor culture medium. Investigated were the implications of the variation in surface TfR numbers on the uptake of iron by cytotrophoblasts cultured in iron-poor Medium-199. Despite dif ferences in TfR densities induced by culture time and iron availabilit y, the initial rate of iron uptake did not change (80-100 pmol/mg prot ein/h). Homeostasis of iron uptake could be explained by adaptive chan ges in the rate constant for TfR endocytosis (k(end)), exocytosis (k(e xo)) and TW cycle times. In undifferentiated cells (cultured for 18 h) k(end) was 0.299 min(-1). In differentiated cells (culture time 65 h, higher surface TfR densities), k(end) changed to 0.138 min(-1) Cultur e for 65 h in diferric transferrin-enriched medium resulted in interme diate TW densities together with an intermediate k(end) (0.210 min(-1) ). Adaptive changes in the corresponding rate constant of exocytosis w ere less pronounced (0.192, 0.192 and 0.260 min(-1) respectively). It is concluded that differentiating cytotrophoblasts regulate iron uptak e by variation of both TfR numbers and the rate of receptor-mediated e ndocytosis and exocytosis.