Abnormalities of Triiodothyronine Binding to Lymphocyte and Fibroblast Nuclei from a Patient with Peripheral Tissue Resistance to Thyroid Hormone Action*

Abstract

T₃ binding to lymphocyte nuclei has been studied in normal individuals and in a patient (MaG) with peripheral resistance to thyroid hormone action. This syndrome is defined by the presence of hypothyroidism or euthyroidism with high plasma levels of thyroid hormone. T₃ bound to a single set of binding sites in normal adult lymphocyte nuclei with a mean Ka of 8.9 ± 7.1 × 10⁹m⁻¹, and a capacity of 4.4 ± 2.9 fmol/100 μg DNA. A single binding site was also disclosed in MaG's lymphocytes with a Ka of 0.43 × 10⁹m⁻¹ and a capacity of 10.5 fmol/100 μg DNA. This low affinity was not due to the presence of high plasma T₃ level in the patient, since administration of 100 μg T₃ to normal adult volunteers induced the presence of two different binding sites. The mechanism responsible for this phenomenon is unknown. T₃ binding was also studied using cultured fibroblasts which were incubated in serum-less medium before the binding experiments. One single binding site (Ka, 1.9 × 10¹⁰m⁻¹ capacity, 12.9 fmol/100 μg DNA) was detected in normal fibroblast nuclei. In contrast, a curvilinear Scatchard plot was obtained when MaG's fibroblasts were used. This result could be compatible with the presence of either two different binding sites or negative cooperativity. In support of the latter possibility, Hill plots gave a number lower than unity. The results suggest that the syndrome of peripheral tissue resistance to thyroid hormone action is due to a defect at the level of the nuclear receptors. The possible existence of similar syndromes due to an alteration at the level of a post-T₃-binding mechanism is not eliminated.