Modulation of myocardial L-triiodothyronine receptors in normal, hypothyroid, and hyperthyroid rats

Paul W. Ladenson; J. David Kieffer; Alan P. Farwell; E. Chester Ridgway

doi:10.1016/0026-0495(86)90088-0

Modulation of myocardial L-triiodothyronine receptors in normal, hypothyroid, and hyperthyroid rats

Paul W. Ladenson, J. David Kieffer, Alan P. Farwell, E. Chester Ridgway

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

Abstract

To characterize the nuclear receptor believed to mediate the thyroid hormones' actions on the heart, binding of L-[¹²⁵I]T3 to extracts of myocardial cell nuclei from normal, propylthiouracil, and T4-treated rats has been investigated. Analysis of in vitro iodothyronine binding to this solubilized nuclear preparation revealed multiple saturable, specific binding sites for T3. High affinity binding for T3 (Kd = 4.2 ± 1.0 × 10^-10 mol/L), and lower affinity (Kd ∼ 10^-8 mol/L) binding activity appeared to be independent (Hill plot slope = 1). The mean maximal binding capacity of the high affinity binding site for T3 in euthyroid rats (84 ± 8 fmol/mg DNA) was increased by approximately 50% in hypothyroidism (120 ± 6 fmol/mg DNA) and unchanged in hyperthyroidism (88 ± 25 fmol/mg DNA). The molecular weight of this T3 binding site is estimated to be 50,000-55,000 daltons. The properties of this solubilized binding activity from rat myocardial nuclei are consistent with its putative role as the biologic thyroid hormone receptor. The increase in binding capacity with hypothyroidism suggest regulation by thyroid hormone of its nuclear receptor in myocardium.

Original language	English (US)
Pages (from-to)	5-12
Number of pages	8
Journal	Metabolism
Volume	35
Issue number	1
DOIs	https://doi.org/10.1016/0026-0495(86)90088-0
State	Published - Jan 1986
Externally published	Yes

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Endocrinology

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10.1016/0026-0495(86)90088-0

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title = "Modulation of myocardial L-triiodothyronine receptors in normal, hypothyroid, and hyperthyroid rats",

abstract = "To characterize the nuclear receptor believed to mediate the thyroid hormones' actions on the heart, binding of L-[125I]T3 to extracts of myocardial cell nuclei from normal, propylthiouracil, and T4-treated rats has been investigated. Analysis of in vitro iodothyronine binding to this solubilized nuclear preparation revealed multiple saturable, specific binding sites for T3. High affinity binding for T3 (Kd = 4.2 ± 1.0 × 10-10 mol/L), and lower affinity (Kd ∼ 10-8 mol/L) binding activity appeared to be independent (Hill plot slope = 1). The mean maximal binding capacity of the high affinity binding site for T3 in euthyroid rats (84 ± 8 fmol/mg DNA) was increased by approximately 50% in hypothyroidism (120 ± 6 fmol/mg DNA) and unchanged in hyperthyroidism (88 ± 25 fmol/mg DNA). The molecular weight of this T3 binding site is estimated to be 50,000-55,000 daltons. The properties of this solubilized binding activity from rat myocardial nuclei are consistent with its putative role as the biologic thyroid hormone receptor. The increase in binding capacity with hypothyroidism suggest regulation by thyroid hormone of its nuclear receptor in myocardium.",

author = "Ladenson, {Paul W.} and Kieffer, {J. David} and Farwell, {Alan P.} and Ridgway, {E. Chester}",

note = "Funding Information: From the Thyroid Unit and Medical Service, Massachusetts General Hospital, and Harvard Medical School, Boston. Supported in part by a grant from the National Institutes of Health (AM-16791) and an American College of Physicians Teaching and Research Scholarship (Dr Ladenson). Address reprint requests to Dr Ladenson. Division of Endocrinology and Metabolism. Sinai Hospital of Baltimore, Baltimore, MD 21215. 0 1986 by Grune & Stratton, Inc. 0026-0495/86/3501-0002$03.00/0",

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T1 - Modulation of myocardial L-triiodothyronine receptors in normal, hypothyroid, and hyperthyroid rats

AU - Ladenson, Paul W.

AU - Kieffer, J. David

AU - Farwell, Alan P.

AU - Ridgway, E. Chester

N1 - Funding Information: From the Thyroid Unit and Medical Service, Massachusetts General Hospital, and Harvard Medical School, Boston. Supported in part by a grant from the National Institutes of Health (AM-16791) and an American College of Physicians Teaching and Research Scholarship (Dr Ladenson). Address reprint requests to Dr Ladenson. Division of Endocrinology and Metabolism. Sinai Hospital of Baltimore, Baltimore, MD 21215. 0 1986 by Grune & Stratton, Inc. 0026-0495/86/3501-0002$03.00/0

PY - 1986/1

Y1 - 1986/1

N2 - To characterize the nuclear receptor believed to mediate the thyroid hormones' actions on the heart, binding of L-[125I]T3 to extracts of myocardial cell nuclei from normal, propylthiouracil, and T4-treated rats has been investigated. Analysis of in vitro iodothyronine binding to this solubilized nuclear preparation revealed multiple saturable, specific binding sites for T3. High affinity binding for T3 (Kd = 4.2 ± 1.0 × 10-10 mol/L), and lower affinity (Kd ∼ 10-8 mol/L) binding activity appeared to be independent (Hill plot slope = 1). The mean maximal binding capacity of the high affinity binding site for T3 in euthyroid rats (84 ± 8 fmol/mg DNA) was increased by approximately 50% in hypothyroidism (120 ± 6 fmol/mg DNA) and unchanged in hyperthyroidism (88 ± 25 fmol/mg DNA). The molecular weight of this T3 binding site is estimated to be 50,000-55,000 daltons. The properties of this solubilized binding activity from rat myocardial nuclei are consistent with its putative role as the biologic thyroid hormone receptor. The increase in binding capacity with hypothyroidism suggest regulation by thyroid hormone of its nuclear receptor in myocardium.

AB - To characterize the nuclear receptor believed to mediate the thyroid hormones' actions on the heart, binding of L-[125I]T3 to extracts of myocardial cell nuclei from normal, propylthiouracil, and T4-treated rats has been investigated. Analysis of in vitro iodothyronine binding to this solubilized nuclear preparation revealed multiple saturable, specific binding sites for T3. High affinity binding for T3 (Kd = 4.2 ± 1.0 × 10-10 mol/L), and lower affinity (Kd ∼ 10-8 mol/L) binding activity appeared to be independent (Hill plot slope = 1). The mean maximal binding capacity of the high affinity binding site for T3 in euthyroid rats (84 ± 8 fmol/mg DNA) was increased by approximately 50% in hypothyroidism (120 ± 6 fmol/mg DNA) and unchanged in hyperthyroidism (88 ± 25 fmol/mg DNA). The molecular weight of this T3 binding site is estimated to be 50,000-55,000 daltons. The properties of this solubilized binding activity from rat myocardial nuclei are consistent with its putative role as the biologic thyroid hormone receptor. The increase in binding capacity with hypothyroidism suggest regulation by thyroid hormone of its nuclear receptor in myocardium.

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Modulation of myocardial L-triiodothyronine receptors in normal, hypothyroid, and hyperthyroid rats

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