Inhibitory effect of certain drugs on thyroid hormone binding by human liver cytosol.

Effects of dinitrophenol (DNP), salicylate, diphenylhydantoin (DPH) and heparin on thyroid-hormone binding by human liver cytosol were studied using Pevikon thin-layer electrophoresis. Thyroxine (T4) binding by the major cytosol T4-binding protein, hT4-2, was significantly depressed with these drugs, and the displaced T4 was bound by another cytosol binding protein, hT4-1. Triiodothyronine (T3) binding by the major cytosol T3-binding protein, hT3-2, was significantly decreased with DPH and heparin, but not with DNP and salicylate. Comparative studies using human serum indicated that T4 binding by serum T4-binding prealbumin (TBPA) was inhibited with DNP and salicylate, and that binding of T4 and T3 by serum T4-binding globulin (TBG) was decreased only with DPH. The results obtained indicate that these drugs inhibit thyroid-hormone binding by the liver cytosol binding proteins for T4 and T3, and that the displaced hormones may be responsible for changes in free hormone levels in serum, and within the cells, and for the accelerated turnover of hormones.