Effect of Thyroxine on Cellular Oxygen-Consumption and Glucose Uptake: Evidence of an Effect of Total T₄ and not “Free T₄”

Summary

Recent studies of cellular T₄ and T₃ uptake have indicated active transport of the hormones into the cell rather than passive diffusion of the non-protein bound fraction. In order to study the significance of the extracellular environment, oxygen consumption and glucose uptake were examined in human mononuclear blood cells. Cells were incubated in protein free medium and in human serum totally depleted of thyroid hormones by resin treatment and fixed amounts of T₄ (total T₄ = 0-50-100-5000 nmol/l; free T₄ = 0-5-11-5600 pmol/l) were added. Thyroxine stimulated glucose uptake and oxygen-consumption in a dose dependent manner but the T₄ stimulation was dependent on the total concentration of T₄ and did not differ between serum incubation or non-protein containing medium. Addition of ANS (100 mg/l) which inhibits binding of T₄ to TBG, did not increase T₄ effect in serum. Inhibition of the NaK-ATPase by addition of ouabain (9-72 mg/l) did not inhibit T₄ stimulation, thus indicating that the ouabain sensitive NaK-ATPase is not a major component of the processes which initiate the intracellular effects of T₄. Therefore the stimulation of uptake of oxygen and glucose in human mononuclear blood cells seems to be dependent on the total concentration of T₄ and not on the non-protein bound (free) fraction suggesting active membrane uptake of T₄, as the limiting factor for intra-cellular hormone effect.

Key words

Glucose Uptake - Oxygen Consumption - Protein Bound T₄ - T₄ Uptake