Concentration of <sc>l</sc>-Thyroxine and <sc>l</sc>-Triiodothyronine Specifically Bound to Nuclear Receptors in Rat Liver and Kidney: <i>QUANTITATIVE EVIDENCE FAVORING A MAJOR ROLE OF T<sub>3</sub> IN THYROID HORMONE ACTION</i>

Martin I. Surks; Jack H. Oppenheimer

doi:10.1172/JCI108807

Concentration of l-Thyroxine and l-Triiodothyronine Specifically Bound to Nuclear Receptors in Rat Liver and Kidney: QUANTITATIVE EVIDENCE FAVORING A MAJOR ROLE OF T₃ IN THYROID HORMONE ACTION

Martin I. Surks and Jack H. Oppenheimer

Published September 1, 1977 - More info

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Abstract

To estimate the relative contribution of l-triiodothyronine (T₃) and l-thyroxine (T₄) to thyroidal effects, we have measured the concentration of iodothyronine bound to specific hepatic nuclear receptor sites by three different techniques: (a) specific radioimmunoassay after separation of T₃ and T₄ by preparative paper chromatography; (b) in vivo kinetic approaches as reported previously; and (c) isotopic equilibration. By these three methods, receptor concentration of T₃ and T₄ in liver was 0.51±0.19 (SD) and 0.08±0.06; 0.52±0.12 and 0.08±0.02; and 0.50±0.13 and 0.10±0.03 pmol/mg DNA, respectively. The percentage contribution of T₃ and T₄ to total receptor iodothyronine was thus 86.8±9.0 and 13.2±9.4; 86.3±3.5 and 13.7±3.5; and 83.7±5.6 and 16.3±5.6%, respectively. In kidney, specifically bound nuclear T₃ and T₄ were estimated both by isotopic equilibration and by in vivo kinetic techniques to be 0.28±0.11 and 0.03±0.01 pmol/mg DNA, respectively. Thus, T₃ constituted 89.4±3.2% of total receptor iodothyronine in this tissue. No other iodothyronines or analogs were bound to the nuclear sites in either tissue. Kidney and liver nuclear T₃ concentrations also were identical to values previously reported with in vivo kinetic techniques. Other studies from this laboratory have suggested that thyroid effect is related to the molar concentration of iodothyronine bound to specific nuclear sites, that the sites are similar in various tissues, and that iodothyronine in plasma is in equilibrium with nuclear T₃. If these relationships are assumed, T₃ contributes between 85 and 90% of thyroidal effects in the euthyroid rat. The remaining 10-15% of thyroidal effect appears to result from the intrinsic activity of T₄.