The Thyroid Hormone-Plasma Protein Complex in Man. I. Differences in Different States of Thyroid Function12

Hamolsky, Milton W.; Ellison, Haskell E.; Freedberg, A. Stone

doi:10.1172/jci103545

Cited by 18 publications

(4 citation statements)

References 25 publications

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“…Also, Hamolsky, Ellison and Freedberg have shown that labeled thyroxine is more avidly incorporated by guinea pig diaphragm in vitro from sera of patients with Graves' disease than from sera of subjects with toxic nodular goiter or sera from normals enriched in vitro to hyperthyroid levels of PBI (13). By contrast, they found that labeled thyroxine mixed with sera from subjects with Graves' disease disappeared more rapidly from the circulation of recipient dogs than when mixed with sera from normals or subjects with toxic nodular goiter.…”

Section: Discussionmentioning

confidence: 99%

Studies of the Rate of Disappearance of Labeled Thyroxine From the Intravascular Compartment*

Lennon¹,

Engbring²,

Engstrom³

1961

J. Clin. Invest.

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The reversible combination of thyroxine with certain of the plasma proteins clearly provides an efficient transport mechanism enabling microgram quantities of the hormone to be carried to tissue sites with minimal losses via glomerular filtration and other nonselective excretory pathways. The demonstration of thyroxine-binding proteins in other extracellular fluids (1) and within cells (2) suggests a means by which thyroxine may be selectively distributed to tissues according to their individual needs.The role, if any, of the plasma thyroxine-binding proteins in various thyroid disorders is not clear. In vitro studies of the protein-thyroxine complex involve alterations of pH, Pco2, temperature and other aspects of the biochemical environment and may not give an accurate index of in vivo relationships. Furthermore, such studies neglect interactions of plasma thyroxine-binding proteins and extravascular thyroxine-binding proteins.It seemed reasonable to suppose that the rate of disappearance of I131-labeled L-thyroxine (T4*) from the intravascular compartment during an acute experiment might yield information about the rate at which equilibrium between intra-and extravascular compartments was approached. The rate of disappearance should reflect the ability of the serum proteins to bind thyroxine and retain it within the vascular compartment in the face of all ambient forces favoring its removal. Conventional studies of labeled thyroxine survival (measured in days) are presumed to measure primarily the rate of thyroxine disposal after equilibration between labeled and stable thyroxine has been attained throughout the body. In preliminary studies, attempts were made to measure the rate

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Section: Discussionmentioning

confidence: 99%

Studies of the Rate of Disappearance of Labeled Thyroxine From the Intravascular Compartment*

Lennon¹,

Engbring²,

Engstrom³

1961

J. Clin. Invest.

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“…At least three serum proteins and perhaps four have been described which bind thyroxine (7). Less direct methods of studying this binding of the thyroid hormones consist of measurement of the "uptake" of triiodothyronine by erythrocytes (8) and the rate of dialysis of T4 through a cellophane membrane (9). By these techniques several compounds have been found that appear to alter the binding of T4 to serum proteins when studied by these techniques but if whole serum is used, the effect cannot be localized to specific proteins.…”

mentioning

confidence: 99%

Thyroxine Displacement From Serum Proteins and Depression of Serum Protein-Bound Iodine by Certain Drugs

Wolff¹,

Standaert²,

Rall³

1961

J. Clin. Invest.

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A number of compounds such as 2,4-dinitrophenol,' salicylate, tetrachlorothyronine, and diphenylhydantoin have been shown to lower the protein-bound iodine level of the blood (1-5). In the case of DNP and salicylate, it was concluded that they acted in part via an inhibition of the pitutary TSH mechanism and partly by an accelerated loss of T4 from the circulation (2, 6). A likely site of action was, therefore, expected to involve binding of T4 to serum proteins.The ability of various analogs of thyroxine to bind to proteins of serum has been extensively studied with electrophoretic techniques. At least three serum proteins and perhaps four have been described which bind thyroxine (7). Less direct methods of studying this binding of the thyroid hormones consist of measurement of the "uptake" of triiodothyronine by erythrocytes (8) and the rate of dialysis of T4 through a cellophane membrane (9). By these techniques several compounds have been found that appear to alter the binding of T4 to serum proteins when studied by these techniques but if whole serum is used, the effect cannot be localized to specific proteins. Thus it has been suggested from dialysis studies that salicylates and DNP act by inhibiting T4 binding to serum proteins. Electrophoretic studies in barbital buffer of sera containing salicylate failed to show any influence on the distribution of T4 between TBG and albumin, nor was there any change in the T4 binding capacity measured under these conditions (2). Since then it has been shown that barbital buffer inhibits T4 binding to prealbumin (10) and Ingbar has stated that 1 The following abbreviations have been used: DNP = 2,4-dinitrophenol; PBI = protein-bound iodine, T4 = thyroxine; TBG = thyroxine-binding globulin of the interalpha zone in paper electrophoresis; TBPA = thyroxinebinding prealbumin; TCT=DL-tetrachlorothyronine; TSH =thyroid-stimulating hormone.salicylate could interfere with T4 binding in electrophoretic systems in buffers other than barbital (11). It was therefore desired to examine T4 binding in the presence of these four agents in a system where prealbumin binding of T4 could be observed. Furthermore, the possible correlation between the effect of inhibition of thyroxine binding to TBPA and to TBG by various drugs with the in vivo effect of these drugs on the PBI was studied. METHODSA single batch of pooled normal human serum obtained from the Baxter Laboratories was used in all the studies. Butanol solutions of thyroxine were evaporated to dryness in vacuo prior to the addition of serum. The mixtures were incubated at 4°C for at least 24 hours before use and were kept in the cold until used.Electrophoresis in 0.12 M ammonium carbonate buffer, pH 8.4, was performed at room temperature on 3.75 X 49 cm strips of Whatman no. 3 MM filter paper. The edges of the strips were coated with a thin border of paraffin. The strips were saturated with buffer and suspended horizontally between two plastic clamps in a closed system. The strips were equilibrated for at least 1 hour before the ...

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“…Thus, uptake of T 4 by tissue slices of different species and organs was found to be dependent on temperature but not on metabolic activity (i.e., anoxia [4]). The authors suggested, as others did as well for erythrocytes (5,6), that the distribution of hormone between medium and tissues in equilibrium situation is governed by the relative thyroid hormone-binding protein capacities outside and inside the cells, while the free hormone moieties pass the cell membranes passively. This vision prevailed over many years.…”

Section: Cellular Uptake Of Thyroid Hormonesmentioning

confidence: 82%

Notes on the History of Cellular Uptake and Deiodination of Thyroid Hormone

Hennemann¹

2005

Thyroid

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In this mini review on the history of the research devoted to thyroid hormone metabolism two pathways are discussed, i.e. uptake and subsequent deiodination in cells and tissues. In the 1950's the investigations of these processes were greatly stimulated when 131I became available for research purposes. The true nature of both mechanisms surfaced in the 1970's when it became apparent that transport of thyroid hormones into cells was a regulated carrier mediated process, while deiodination appeared to be catalyzed by different types of enzymes. Kinetic data indicated that these processes were of great importance in the ultimate regulation of thyroid hormone bio-availability.

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The Thyroid Hormone-Plasma Protein Complex in Man. I. Differences in Different States of Thyroid Function12

Cited by 18 publications

References 25 publications

Studies of the Rate of Disappearance of Labeled Thyroxine From the Intravascular Compartment*

Studies of the Rate of Disappearance of Labeled Thyroxine From the Intravascular Compartment*

Thyroxine Displacement From Serum Proteins and Depression of Serum Protein-Bound Iodine by Certain Drugs

Notes on the History of Cellular Uptake and Deiodination of Thyroid Hormone

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