The Transport of Thyroid Hormones

1983 ◽  
Vol 65 (4) ◽  
pp. 337-342 ◽  
Author(s):  
R. Hoffenberg ◽  
D. B. Ramsden
Keyword(s):  
Thyroid Hormones ◽  
Binding Proteins ◽  
Serum Proteins ◽  
High Capacity ◽  
Free Fraction ◽  
Total Serum ◽  
Free T4 ◽  
Specific Serum ◽  
Target Organs ◽  
Serum T4

1. Hormones have to be transported from their sites of synthesis to their target organs. For lipophilic hormones, such as steroids and thyroid hormones, transport is accomplished by binding to specific serum proteins, in the case of thyroxine (T4) and tri-iodothyronine (T3) to thyroxine-binding globulin (TBG) and prealbumin (PA). Normally about 70% of circulating T4 and 75–80% of T3 is bound to TBG, about 20% of T4 and 10% of T3 to PA and 10–15% of each to albumin, which has a low affinity but high capacity for both hormones [1, 2]. Apart from facilitating transport, binding to serum protein prevents excessive loss of hormone into the urine by glomerular filtration or flooding into cells, and may provide a readily available reservoir in times of need. The union between binding proteins and their ligands is reversible, so that a small proportion of hormone is non-protein-bound or ‘free’, in equilibrium with that which is protein-bound. For T4 this free fraction is normally 0.02-0.04% of the total serum T4 concentration, for T3 about 0.3% [3, 4]. 2. The major binding proteins of T4 and T3 will briefly be described and the nature of free T4 and T3 considered.

Effect of Sodium Ethylmercurithiosalicylate (Thimerosal) on Serum Binding of Thyroid Hormones

1973 ◽  
Vol 51 (2) ◽  
pp. 156-159 ◽  
Author(s):  
Diego Bellabarba ◽  
Raymonde Tremblay
Keyword(s):  
Thyroid Hormones ◽  
Binding Proteins ◽  
Serum Proteins ◽  
Free Fraction ◽  
Inhibitory Effect ◽  
Free T4 ◽  
Thyroxine Binding Globulin ◽  
Free T3 ◽  
Serum Binding Protein ◽  
Barbital Buffer

Sodium ethylmercurithiosalicylate (Thimerosal, Merthiolate) has been found to interfere with the binding of thyroid hormones to serum proteins. Dialysis studies showed that this compound, added to serum in concentrations varying from 90 to 360 mg/100 ml, caused an increase of the dialyzable or free fraction of thyroxine (T4) and triiodothyronine (T3). The increase was higher for the free T4 (3.8- to 18-fold) than for the free T3 fraction (2.3- to 5-fold). Electrophoretic studies on the distribution of tracer amounts of labeled T4 among the serum binding proteins revealed that the inhibitory effect of sodium ethylmercurithiosalicylate was exerted mainly on thyroxine binding globulin (TBG). In presence of this compound (180 mg/100 ml of serum) the percentage of tracer T4 bound to TBG was reduced from 53% to 9%. These findings were also confirmed by examining the binding of tracer amounts of labeled T4 and T3 in a serum diluted in barbital buffer, which inhibits the hormonal binding to thyroxine binding prealbumin and albumin. In presence of sodium ethylmercurithiosalicylate a significant displacement of both T4 and T3 from the serum binding protein (TBG) was observed.

scholarly journals A Direct Free Thyroxine (T4) Immunoassay with the Characteristics of a Total T4 Immunoassay

2007 ◽  
Vol 53 (5) ◽  
pp. 911-915 ◽  
Author(s):  
Kristofer S Fritz ◽  
R Bruce Wilcox ◽  
Jerald C Nelson
Keyword(s):  
Serum Protein ◽  
Binding Proteins ◽  
Serum Proteins ◽  
Equilibrium Dialysis ◽  
Free Thyroxine ◽  
Free T4 ◽  
Serum T4 ◽  
Presence And Absence

Abstract Background: Direct free thyroxine (T4) measurements have been linked to both T4-binding serum protein concentrations and protein-bound T4 concentrations. Whether this is evidence of a relationship to total T4 concentrations has not been reported. Methods: We compared an analog-based direct free T4 immunoassay and a total T4 immunoassay. Each assay was applied to the fractions of serum T4 obtained by ultrafiltration and equilibrium dialysis. Both were applied to serum-based solutions in which free T4, T4-binding proteins, protein-bound T4, and total T4 were systematically varied, held constant, or excluded. Results: Neither the free T4 assay nor the total T4 assay detected dialyzable or ultrafilterable serum T4. Both assays detected and reported the T4 retained with serum proteins. Both free and total T4 results were related to the same total T4 concentrations in the presence and absence of T4-binding proteins. Both results were similarly related to total T4 concentrations when free T4 was held constant while total T4 was varied. Both were similarly related to a total T4 concentration that was held constant while free T4 progressively replaced protein-bound T4. These free T4 results, like total T4 results, were unresponsive to a 500-fold variation in dialyzable T4 concentrations. Conclusion: New experiments extend the characterization of a longstanding and incompletely characterized analog-based free T4 immunoassay. These free T4 measurements relate to total T4 concentrations in the same way that total T4 measurements do.

Decreased free fraction of thyroid hormones after prolonged Antarctic residence

1990 ◽  
Vol 69 (4) ◽  
pp. 1467-1472 ◽  
Author(s):  
H. L. Reed ◽  
D. Brice ◽  
K. M. Shakir ◽  
K. D. Burman ◽  
M. M. D'Alesandro ◽  
...  
Keyword(s):  
Thyroid Hormones ◽  
Free Fraction ◽  
Cardiovascular Responses ◽  
Free T4 ◽  
Before And After ◽  
Total Triiodothyronine ◽  
Serum T3 ◽  
Total Thyroxine ◽  
Normal Men ◽  
First Time

We investigated the effects of Antarctic residence (AR) on serum thyroid hormone and cardiovascular responses to a 60-min standard cold air (0 degree C) test (SCAT). Serum total thyroxine (TT4) and serum total triiodothyronine (TT3), free T4 (FT4) and T3 (FT3), thyrotropin (TSH), and percent free fraction of T4 (%FT4) and T3 (%FT3) were measured in normal men (n = 15) before and after each of three SCATs. The SCAT was first carried out in California and then repeated after 24 and 44 wk AR. Mean arterial pressure (MAP) and sublingual oral temperature (Tor) were measured before and during each SCAT. The SCAT did not alter thyroid hormones before or after AR. The %FT4 decreased from 0.0334 +/- 0.0017 to 0.0295 +/- 0.0007% (P less than 0.002) with 44 wk AR but without a significant change in TT4 or FT4 for the same period. The %FT3 also decreased from 0.2812 +/- 0.0128 to 0.2458 +/- 0.0067% (P less than 0.005) after 44 wk AR. FT3 decreased (P less than 0.003) but TT3 and TSH were unchanged with 44 wk AR. The decrease in %FT4 and %FT3 may be theoretically accounted for by a 10% increase in either the capacity or the affinity of the serum binding proteins. The SCAT in California increased MAP and did not change Tor. After 44 wk AR, the SCAT no longer increased MAP but did lower Tor. The shift in the Tor and MAP response to the SCAT is consistent with the associated occurrence of cold adaptation during AR. We describe for the first time a decrease in the free fraction of both serum T3 and T4 present with extended polar residence and independent of a SCAT, further characterizing the recently reported “polar T3 syndrome.”

Dependence of the thyroxin/thyroxin-binding globulin (TBG) ratio and the free thyroxin index on TBG concentrations.

1989 ◽  
Vol 35 (4) ◽  
pp. 541-544 ◽  
Author(s):  
J C Nelson ◽  
R T Tomei
Keyword(s):  
Binding Proteins ◽  
Free Fraction ◽  
The Other ◽  
Free T4 ◽  
Clinical Interest

Abstract We studied the dependence of the free thyroxin (T4) index and the ratio of T4 to thyroxin-binding globulin (TBG) on TBG concentrations, using sera from cases of congenital TBG deficiency and congenital TBG excess. Two such sera with similar concentrations of albumin, transthyretin, and free T4 were mixed to provide test samples with TBG concentrations covering the range of clinical interest without changes in the other T4-binding proteins. Total T4, free T4, TBG, triiodothyronine (T3) uptake, and the free fraction of T3 in serum were measured, and we calculated the free T4 indices, T4/TBG ratios, and the free fraction of T4. A 100-fold variation in TBG concentration was associated with a 10-fold variation in total T4, a fourfold variation in T3 uptake, and a 10-fold variation in the T4/TBG ratio. As TBG concentrations increased, the T4/TBG ratio decreased and the free T4 index increased. The free T4 index did not parallel the T4/TBG ratio, and neither the T4/TBG ratio nor the free T4 index reflected the concentrations of free T4 in serum.

scholarly journals Quantifying Spurious Free T4 Results Attributable to Thyroxine-Binding Proteins in Serum Dialysates and Ultrafiltrates

2007 ◽  
Vol 53 (5) ◽  
pp. 985-988 ◽  
Author(s):  
Kristofer S Fritz ◽  
R Bruce Wilcox ◽  
Jerald C Nelson
Keyword(s):  
Serum Protein ◽  
Total Protein ◽  
Binding Proteins ◽  
Serum Proteins ◽  
Equilibrium Dialysis ◽  
Free T4 ◽  
Serum Total Protein ◽  
Semipermeable Membranes ◽  
Serum Free ◽  
Thyroxine Binding Globulin

Abstract Background: Direct equilibrium dialysis and direct ultrafiltration free thyroxine (T4) assays rely on semipermeable membranes to exclude T4-binding serum proteins from dialysates and ultrafiltrates. The presence of these proteins in dialysates or ultrafiltrates will yield spuriously high free T4 values when free T4 is quantified by RIA. Methods: We used a nonanalog free T4 RIA that detects and quantifies dialyzable and ultrafilterable serum free T4 to detect T4-binding serum proteins. Two equilibrium dialysis devices and 3 ultrafiltration devices were used to illustrate this application. Displacements of [125I]T4 from anti-T4 by various concentrations of T4-depleted thyroxine-binding globulin, albumin, and serum total protein were compared to displacements by various concentrations of free T4. Results: Both dialysis devices excluded detectable T4-binding serum proteins from dialysates. Two of 3 ultrafiltration devices excluded detectable T4-binding serum proteins from ultrafiltrates. One did not, and its ultrafiltrate yielded spurious free T4 values that correlated directly with serum protein concentrations. Conclusion: The presence or absence of T4-binding proteins in dialysates and ultrafiltrates and the spurious free T4 values that these proteins cause can be documented using a nonanalog free T4 RIA.

Decrease of free thyroxin in serum of lactating women.

1987 ◽  
Vol 33 (7) ◽  
pp. 1217-1219 ◽  
Author(s):  
Y Iwatani ◽  
N Amino ◽  
O Tanizawa ◽  
H Mori ◽  
M Kawashima ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Binding Proteins ◽  
Albumin Concentration ◽  
Free T4 ◽  
Reverse T3 ◽  
Lactating Women ◽  
Significant Difference ◽  
Triiodothyronine Concentration

Abstract We measured thyroid hormones and thyroxin-binding proteins in serum from 62 normal lactating and 52 nonlactating women at three months postpartum, and compared these values with those for 42 nonpregnant control women of similar age. Mean thyroxin concentrations in the lactating and nonlactating women were significantly (P less than 0.001) lower than that of the nonpregnant controls, but there was no significant difference (P greater than 0.2) in triiodothyronine concentration among these three groups. Free T4 concentration was significantly (P less than 0.01) lower in lactating women than in controls. The reverse-T3 concentrations in both lactating and nonlactating women were significantly (P less than 0.001) lower than in controls, and were significantly (P less than 0.001) lower in lactating than in nonlactating women. The concentration of thyroxin-binding globulin was significantly higher in lactating women than in controls, and the albumin concentration was significantly lower in women postpartum than in controls. Evidently, regulation of thyroid hormone in women postpartum, especially during lactation, differs from that in nonpregnant women.

The influence of free fatty acids on the free fraction of thyroid hormones in serum as estimated by ultrafiltration

1987 ◽  
Vol 116 (1) ◽  
pp. 102-107 ◽  
Author(s):  
C. Bregengåard ◽  
C. Kirkegaard ◽  
J. Faber ◽  
S. Poulsen ◽  
K. Siersbæk-Nielsen ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Thyroid Hormones ◽  
Healthy Subjects ◽  
Binding Proteins ◽  
Free Fraction ◽  
Nonthyroidal Illness ◽  
Serum Free ◽  
Free Thyroid Hormones ◽  
Serum Pool ◽  
Somatic Illness

Abstract. Thyroid hormones are displaced from their binding proteins in serum during nonthyroidal somatic illness, and FFA have been claimed to contribute. It seems mandatory to evaluate this effect using techniques for the measurements of serum free thyroid hormones in which serum remains undiluted. We measured the effect of 7 common human FFA on the free fraction of T4, T3 and rT3 in serum from healthy subjects using an ultrafiltration technique by which serum is diluted only minimally. In addition we measured the effect of oleic acid on the free fractions of the iodothyronines in pooled serum from healthy subjects and in pooled serum from patients with nonthyroidal illness. All FFA tested were able to displace both T4, T3 and rT3, but to a varying degree, arachidonic and linoleic acid being the most potent ones. A 20% increase in the free fractions of T4, T3 and rT3, respectively, was obtained by adding between 1.7–3.3 mmol/l, 1.3–4.6 mmol/l and 1.0–2.4 mmol/l of the different FFA. A serum pool obtained from patients with nonthyroidal somatic illness was more sensitive to oleic acid than a serum pool obtained from healthy subjects, since 2–3 times less oleic acid was necessary to induce a 20% increase in the free fractions of thyroid hormones. It is concluded that FFA are able to displace both T4, T3 and rT3 from their serum binding proteins in healthy subjects as well as in patients with nonthyroidal illness. However, serum from patients with nonthyroidal illness was more sensitive to the displacing activity of oleic acid than serum from healthy subjects. This was possibly due to reduced affinity of the serum binding proteins to thyroid hormones, and it could be argued that a factor different from FFA seemed responsible.

MEASUREMENT OF STEROID BINDING PROTEINS

1970 ◽  
Vol 65 (1_Suppl) ◽  
pp. S104-S121 ◽  
Author(s):  
E. E. Baulieu ◽  
J. P. Raynaud ◽  
E. Milgrom
Keyword(s):  
Kinetic Parameters ◽  
Binding Proteins ◽  
Binding Specificity ◽  
Binding Parameters ◽  
Target Organs ◽  
Biological Mixtures ◽  
Steroid Binding Proteins ◽  
Steroid Binding ◽  
Steroid Binding Protein

ABSTRACT A brief review of the characteristics of steroid binding proteins found in the plasma and in some target organs is presented, followed by some general remarks on binding »specificity« and binding parameters. Useful techniques for measuring binding parameters at equilibrium are reported, both those which keep the equilibrium intact and those which implicate its disruption. A concept is developed according to which the determination of a specific steroid binding protein is based on the »differential dissociation« of the several steroid binding complexes present in most biological mixtures. Methods which allow determination of the kinetic parameters of the binding systems are also presented. Various representations of the binding and therefore different modes of graphic representation and calculation are discussed, including the recent »proportion graph« method.

scholarly journals The Effect of Dietary Intake and Nutritional Status on Anthropometric Development and Systemic Inflammation: An Observational Study

2021 ◽  
Vol 18 (11) ◽  
pp. 5635
Author(s):  
Roxana Maria Martin-Hadmaș ◽  
Ștefan Adrian Martin ◽  
Adela Romonți ◽  
Cristina Oana Mărginean
Keyword(s):  
Serum Proteins ◽  
Caloric Intake ◽  
Saturated Fat ◽  
The Body ◽  
Total Serum ◽  
Fat Intake ◽  
Trans Fats ◽  
Study Objective ◽  
Inflammatory Status ◽  
Total Fat

(1) Background: Daily caloric intake should aim to reduce the risk of obesity or poor anthropometric development. Our study objective was to analyze the association between food consumption, inflammatory status and anthropometric development; (2) Methods: We performed a prospective observational analytical research during September 2020 and April 2021 on a group of 160 healthy subjects, aged between 6 and 12 years old, by analyzing food ingestion, the basal metabolic rate, anthropometric development and the inflammatory status; (3) Results: IL-6 was significantly correlated to the sum of skinfolds, along with both serum proteins and triglycerides. The skin folds were significantly correlated with the caloric intake and with total fat intake, next to saturated and trans fats. Unlike the skin folds, the body weight was significantly correlated with the caloric intake along with some vitamins, such as Vitamin A and Vitamin B12. Inactive mass increased with excessive folic acid, Vitamin E, Vitamin K and saturated fat intake; (4) Conclusions: The inflammatory status was influenced by the ingestion of micronutrients, total serum lipids and proteins. The anthropometric development was associated with the ingestion of carbohydrates, energy balance and energy intake. We can conclude that daily menu and nutrition imbalances can influence both the risk of obesity and the inflammatory status.

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