Mechanism of L-triiodothyronine (T3) uptake by glial C6 cells: regulation by butyrate.

The mode of entry of triiodothyronine (T3) and its regulation by butyrate was studied in cultured glial C6 cells. Uptake of [125I]T3 increases for at least 60 min in C6 cells. The amount of cell-associated radioactivity is 2- to 4-fold higher during the entire time-course in cells previously exposed to 2 mM butyrate for 48 h. Uptake was non-saturable since uptake velocity was linearly related to the extracellular hormone concentration between 0.2 and 800 nM T3 in control and butyrate-treated cells. Uptake velocity increased by more than 3-fold in the cells incubated with the fatty acid. T3 uptake was temperature dependent and the effect of butyrate was observed at the different temperatures examined. Preincubation with metabolic inhibitors did not block [125I]T3 uptake in either group, and monodansylcadaverine was also ineffective. Present results suggest that in C6 cells T3 uptake proceeds by a passive, energy-independent, non-saturable process, that is markedly affected by short-chain fatty acids. Additionally, this is the first study documenting that a natural compound directly influences the entry of thyroid hormones into cells.