Abstract

1,25‐Dihydroxyvitamin D3 [1,25(OH)2D3] is known to prompt monocytic differentiation of a variety of leukemic lines. We previously extended these observations to non‐transformed bone marrow macrophage precursors by demonstrating that the steroid enhances plasma membrane expression of the macrophage‐specific mannose‐fucose receptor (Clohisy et al., J Biol Chem 262:15922–15929, 1987). Because this membrane protein is involved in non‐opsonin mediated endocytosis, these observations raised the possibility that 1,25(OH)2D3 globally upregulates endocytic receptors. The present study, aimed at addressing this issue, turns to the transferrin receptor as a paradigm for endocytic receptors and explores the impact of 1,25(OH)2D3 on its expression. We found that in contrast to the mannose‐fucose receptor, plasma membrane transferrin receptor expression by bone marrow‐derived macrophage precursors declines by at least 30% in a dose‐dependent fashion with exposure to 1,25(OH)2D3. The effect reflects diminished receptor capacity with no change in Kd, and is independent of cell cycle. Moreover, while Vmax of receptor‐ligand internalization mirrors plasma membrane occupancy, Kuptake remains unaltered in the presence of vitamin D3, indicating that the down‐regulating event does not reflect on enhanced rate of endocytosis. Further, pulse chase experiments show parallel cell surface, intracellular, and medium redistribution of radioligand with time steroid‐treated and control cells. In a similar vein, while total cell‐associated radioligand falls in the presence of vitamin D3, the percentage of intracellular and surface bound counts at equilibrium are constant in both groups. Finally, immunoprecipitation studies reveal that the down‐regulating effects of 1,25(OH)2D3 cannot be explained by inhibition of transferrin receptor synthesis. Thus, the decrease in total cellular transferrin binding sites is likely to represent either enhanced degradation or synthesis of [cryptic] receptors which fail to recognize 125 I‐transferrin.

Original languageEnglish
Pages (from-to)303-309
Number of pages7
JournalJournal of Cellular Physiology
Volume145
Issue number2
DOIs
StatePublished - Nov 1990

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