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, J. H. Oppenheimer

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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.

Original languageEnglish (US)
Pages (from-to)555-562
Number of pages8
JournalJournal of Clinical Investigation
Volume60
Issue number3
StatePublished - 1977

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Triiodothyronine
Cytoplasmic and Nuclear Receptors
Thyroxine
Thyroid Hormone Receptors
Kidney
Liver
Paper Chromatography
DNA
Radioimmunoassay
Thyroid Gland

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{8c07bc3f175d421b825e761a0ed33eb1,
title = "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",
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.",
author = "Surks, {Martin I.} and Oppenheimer, {J. H.}",
year = "1977",
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pages = "555--562",
journal = "Journal of Clinical Investigation",
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T1 - 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

AU - Surks, Martin I.

AU - Oppenheimer, J. H.

PY - 1977

Y1 - 1977

N2 - 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.

AB - 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.

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