Nuclear binding of triiodothyronine and thyroxine in lymphocytes from subjects with hyperthyroidism, hypothyroidism and resistance to thyroid hormones.
Binding of triiodothyronine (T3) and thyroxine (T4) to nuclei of intact human lymphocytes was studied. The binding characteristics were analysed by Scatchard's method. In lymphocytes from euthyroid healthy subjects there was a single set of saturable nuclear T3 and T4 binding sites with an apparent mean equilibrium association constant of 3.3 X 10(10) l/mol and 1.7 X 10(10) l/mol, respectively. The estimated mean maximal specific binding capacity for T3 was 50 fmol/mg DNA and for T4 was 55 fmol/mg DNA, indicating that these two hormones may have a common receptor. In hyperthyroid and hypothyroid patients nuclear affinity for T3 and T4 was very similar to that for euthyroid reference subjects. In hyperthyroidism, T3 and T4 binding capacity was unaltered, whereas in hypothyroidism it was nearly twice as high as in euthyroidism. Lymphocytes from three members of a family with hereditary peripheral resistance to thyroid hormone action were studied. One set of saturable T3 and T4 nuclear binding sites with affinity constants similar to those in the euthyroid group was found. However, in these subjects the estimated binding capacity for T3 and T4 was rather low, indicating that the biochemical defect in this family might be a mild deficiency of nuclear receptor protein. Incubation with diphenylhydantoin and salicylate added in vitro did not alter the binding of T3 and T4 to lymphocyte nuclei. Nuclear binding was also not affected in patients receiving therapeutic amounts of diphenylhydantoin.
D000328:Adult; D001667:Binding, Competitive / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D010672:Phenytoin / Q000494:pharmacology; D012459:Salicylates / Q000494:pharmacology; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
D012459:Salicylates; D014284:Triiodothyronine; D010672:Phenytoin; D013974:Thyroxine