Regulation of transferrin receptor expression and distribution in in vitro cultured human cytotrophoblasts

Abstract

During gestation the transplacental iron transport is very important to the fetus. Iron uptake by the placenta can be studied in cultured cytotrophoblasts. The influence of culture time and human differic transferrin on the number and distribution of transferrin receptors (TfRs) was investigated in human cytotrophoblasts. Cytotrophoblasts cultured for 2.5 h had few TfRs (0.28 pmol/mg protein). With time, total TfR amounts increase (4.14 pmol/mg protein at 70 h). They increase to a higher level in cells cultured in iron-poor medium, indicating that iron has an effect on the TfR synthesis/breakdown ratio. TfRs were distributed between two 'active' (located at the cell surface and intracellularly) and one 'inactive' (located intracellularly) receptor pools. TfR distribution among these pools was modulated by culture time and iron. Trophoblasts regulated iron uptake by variation of number of surface TfRs via changes in total TfRs and redistribution of TfRs among the receptor pools.

Regulation of transferrin receptor synthesis by human cytotrophoblast cells in culture

“…The data are expressed relative to total protein synthesis. Compared to both the control and the FAC series, TfR synthesis was significantly lower in the It was previously shown that cytotrophoblast cells in culture express TfRs and that the total number of TfRs as well as the number of surface TfRs increased with culture time [2,5,7].…”

“…Expression of TfRs is part of the biochemical differentiation of the trophoblast cells towards syncytiotrophoblast or syncytiotrophoblast-like structures [7,12]. The total number of TfRs (as well as the surface TfR population) could, to some degree, be up-or downregulated, depending on the culture conditions with respect to iron depletion or iron supplementation [5,13,14]. This suggests that the differentiating trophoblast cell is able to adjust the rate of TfR synthesis to the momentary needs.…”

“…An increased maternal iron supply will probably induce a reduction of TfR number or density. These adjustments can in principle be achieved by TfR redistribution between cell interior and cell surface [5], and/or by adjustments in the rate of TfR synthesis. Using the primary culture of trophoblast cells from term human placentas [6,7], we investigated the influences of iron supplementation and withdrawal on denovo TfR synthesis.…”

Iron Uptake in Blood‐Brain Barrier Endothelial Cells Cultured in Iron‐Depleted and Iron‐Enriched Media

“…The large BBB microvascular surface area and the presence of TfRs on the luminal side of the BBB-ECs suggest that the BBB-ECs are of major importance to iron transport. If so, it is conceivable that iron transport is regulated through a modulation of TfR quantity, TfR distribution, and/or TfR kinetics in these BBB-ECs (Starreveld et al, 1993).…”

“…Depending on the type of experiment, we used either 1251 and/or 59Fe-labeled Tf. Labeling procedures were adapted from a method described by Starreveld et al (1993). Porcine If was dialyzed for 24 h against an acetate buffer (pH 5.0) containing 0.04 mol/L EDTA, to remove all Tf-bound iron.…”