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 journalArticle

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 languageEnglish (US)
Pages (from-to)5-12
Number of pages8
JournalMetabolism
Volume35
Issue number1
DOIs
StatePublished - 1986
Externally publishedYes

Fingerprint

Thyroid Hormone Receptors
Hyperthyroidism
Binding Sites
Cytoplasmic and Nuclear Receptors
Hypothyroidism
Thyroid Hormones
DNA
Propylthiouracil
Cell Nucleus
Myocardium
Molecular Weight

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Modulation of myocardial L-triiodothyronine receptors in normal, hypothyroid, and hyperthyroid rats. / Ladenson, Paul W; Kieffer, J. David; Farwell, Alan P.; Ridgway, E. Chester.

In: Metabolism, Vol. 35, No. 1, 1986, p. 5-12.

Research output: Contribution to journalArticle

Ladenson, Paul W ; Kieffer, J. David ; Farwell, Alan P. ; Ridgway, E. Chester. / Modulation of myocardial L-triiodothyronine receptors in normal, hypothyroid, and hyperthyroid rats. In: Metabolism. 1986 ; Vol. 35, No. 1. pp. 5-12.
@article{524b27646c414f038b79a9bfa7d8c560,
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}",
year = "1986",
doi = "10.1016/0026-0495(86)90088-0",
language = "English (US)",
volume = "35",
pages = "5--12",
journal = "Metabolism: Clinical and Experimental",
issn = "0026-0495",
publisher = "W.B. Saunders Ltd",
number = "1",

}

TY - JOUR

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

PY - 1986

Y1 - 1986

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.

UR - http://www.scopus.com/inward/record.url?scp=0022578321&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022578321&partnerID=8YFLogxK

U2 - 10.1016/0026-0495(86)90088-0

DO - 10.1016/0026-0495(86)90088-0

M3 - Article

C2 - 3001476

AN - SCOPUS:0022578321

VL - 35

SP - 5

EP - 12

JO - Metabolism: Clinical and Experimental

JF - Metabolism: Clinical and Experimental

SN - 0026-0495

IS - 1

ER -