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PubMed1989

Direct and indirect techniques for free thyroxin compared in patients with nonthyroidal illness. II. Effect of prealbumin, albumin, and thyroxin-binding globulin.

We studied the correlation of thyroxin (T4)-binding proteins with the apparent free T4 (FT4) in 101 patients with nonthyroidal illness (NTI). Most patients (95%) were seriously ill at the time of blood collection. Concentrations of T4-binding prealbumin (transthyretin), albumin, and T4-binding globulin (TBG) often were low in the sera of these patients. Albumin was the most frequently subnormal, TBG the least. FT4 in serum was determined by five methods represented in 16 different assays. With few exceptions, analog (one-step) FT4 RIAs--both the binding-rate-based RIA and the related FT4 indices (calculated from triiodothyronine-macroaggregated albumin uptake and total T4)--and T4/TBG ratios correlated positively and usually highly significantly (P less than 0.01) with concentrations of prealbumin, albumin, and TBG. Equilibrium dialysis values for FT4 did not correlate with prealbumin concentrations but showed a weakly (P less than 0.03) positive association with albumin and a highly significant (P less than 0.002) positive correlation with TBG. Of the three two-step FT4 RIAs tested, the only statistically significant but weakly (P less than 0.02) positive correlation with T4-binding proteins was between Spiria FT4 and TBG. Thus, in these NTI patients, FT4 estimates vary with methodology and, to a lesser extent, with the particular assay used. The results from two-step FT4 RIAs are least associated with binding protein concentrations.

Humans↗
PubMed1980

Hereditary abnormalities of thyroxine-binding globulin concentration. A study of 19 kindreds with inherited increase or decrease of thyroxine-binding globulin.

Nineteen families with hereditary abnormalities of thyroxine-binding globulin (TBG) have been studied, comprising a total of 15 males with absent TBG, and 15 females heterozygotic for this condition, and 14 males with excess of TBG and 44 heterozygotic females. Hereditary TBG excess was associated with thyrotoxicosis in four instances, and with myxoedema in three. The typical biochemical features of TBG abnormality are described, with the clinical histories of patients in whom diagnostic and management problems occurred.

Adult↗
PubMed1979

Thyroxine uptake and metabolism by fetal sheep after intra-amniotic thyroxine injection.

Thyroxine (T4) uptake from amniotic fluid was investigated in fetal sheep. Samples of fetal and maternal blood and of amniotic fluid were obtained from indwelling catheters at specific intervals after intra-amniotic injection of T4. T4 and reverse T3 (rT3) were measured by radioimmunoassay. Basal levels of T4 were 7.3 +/- 0.92, less than 2, and 6.28 +/- 0.49 microgram/dl in the fetus, amniotic fluid, and ewe, respectively. Basal levels of rT3 were 3,858 +/- 214, 189 +/- 62, and 385 +/- 20 pg/ml in the fetus, amniotic fluid, and ewe, respectively. T4 and rT3 rose progressively in the fetus with maximum concentrations of 25 to 30 microgram/dl T4 by 10 hours and 11,000 to 14,000 pg/ml rT3 by 20 hours after intra-amniotic injection of 500 microgram of T4. These concentrations returned toward baseline by 50 and 70 hours for T4 and rT3, respectively. The increase of fetal T4 was proportional to the amount of T4 injected in a range of 250 and 2,500 microgram. Esophageal ligation abolished the changes in fetal T4 but not rT3. Amniotic fluid rT3 increased with time after intra-amniotic injection of T4 and returned to baseline long after amniotic fluid T4 had reached basal levels. This pattern persisted despite esophageal ligation. T4 was converted to rT3 during incubation in amniotic fluid in vitro. It is concluded that (1) substantial amounts of T4 are taken up by fetal fetal sheep from the amniotic fluid by deglutition, (2) increases in fetal concentrations of T4 and rT3 are related to the amount of T4 added to the amniotic fluid, (3) amniotic fluid and fetal rT3 concentrations increase following intra-amniotic injection of T4 in the absence of significant uptake of T4 by the fetus, and (4) significant amounts of T4 may be converted to rT3 in vitro during incubation of T4 in amniotic fluid.

Amnion↗
PubMed1992

Male rat hepatic UDP-glucuronosyltransferase activity toward thyroxine. Activation and induction properties--relation with thyroxine plasma disappearance rate.

Detergent-activation of UDP-glucuronosyltransferase (UGT) isoenzyme(s) involved in thyroxine (T4) glucuronidation in control, phenobarbital (PB)- and 3-methylcholanthrene (3-MC)-treated rats showed that between the four tested detergents, i.e. Triton X-100, Brij 58, Lubrol Px and 3-(3-cholamidopropyl)dimethylammonio-1-propanesulfonic acid (CHAPS), optimal activation of T4 UGT was displayed by the zwitterion CHAPS. "Native" versus optimal detergent-activated T4 UGT activity determination revealed that the latency of T4 UGT in microsomes from 3-MC-treated rats was decreased while the latency of T4 UGT in microsomes from PB-treated rats was increased compared to control, and suggest that the UGT isoenzyme(s) involved in the hepatic glucuronidation of T4 is (are) different in PB-treated rats than in 3-MC-treated rats. After a 7-day treatment with 20 mg/kg 3-MC, the activity of T4 UGT was increased 5-fold when determined in "native" and 4-fold when determined in optimal detergent-activated microsomes compared to controls. After a 7-day treatment with 75 mg/kg PB, T4 UGT was equivalent to the control when determined in "native", and increased 1.3-fold when determined in optimal detergent-activated microsomes. The results thus extend evidence that both 3-MC and PB induce the synthesis of UGT protein(s) involved in the glucuronidation of T4, 3-MC being a strong and PB a weak inducer. Hyperthyroid and hypothyroid status, achieved respectively by a 7-day treatment with 100 microns/kg T4 or a 7-day treatment with 10 mg/kg of one of the antithyroid drugs propylthiouracile or methymazole, did not modify T4 UGT activity, suggesting that the isoenzyme(s) conjugating T4 in microsomes from control rats is (are) unlikely to be either 4-nitrophenol or bilirubin UGT isoenzymes. After 14 days of treatment with 75 mg/kg PB, the hepatic glucuronidation rate of T4 was not different from the control when enzyme activity was expressed per mg microsomal protein but was significantly increased 1.4-fold when expressed per whole liver. A significant (1.5-fold) increase in the 125I-T4 plasma elimination rate was also observed in PB-treated rats compared to controls. A strong (3.6-fold) increase in the T4 glucuronidation rate was observed in rats treated with 5 mg/kg 3-MC for 14 days while the 125I-T4 plasma elimination rate was equivalent to the controls. These results demonstrate that there is no direct relation between T4 UGT activity (and subsequent biliary secretion of T4-glucuronides) and T4 plasma clearance and suggest an important contribution of the intestinal exchangeable thyroid hormone pool to the maintenance of blood thyroid hormone levels.

Animals↗
PubMed1985

Thyroxine deiodination, cytoplasmic distribution and nuclear binding of thyroxine and triiodothyronine in liver and brain of young and aged rats.

This study examines (a) the effects of aging on plasma thyroid hormone concentration and (b) in vivo binding and cytoplasmic distribution of thyroid hormones as well as the conversion of thyroxine (T4) to triiodothyronine (T3) in liver and cerebral hemispheric tissue. The results show that (a) in male Long-Evans rats aging decreases plasma T4 concentration but does not affect plasma T3 concentration and (b) the in vivo nuclear T3 binding does not change significantly. However, nuclear T3 binding derived from T4 is decreased as a consequence of reduced T4 to T3 conversion in both tissues. The nuclear T4 binding is also depressed, perhaps due to the decrease in the T4 of the protein free cytoplasmic compartment. Aging was also found to change protein free and protein bound cytoplasmic distribution of T4. That is, an increase was observed in protein bound cytoplasmic T4 and a decrease in the protein free cytoplasmic T4 of both tissues. These results indicate an overall alteration in thyroid hormone production and peripheral tissue binding and processing of thyroid hormones with a consequent suboptimal thyroid state with aging.

Aging↗
PubMed1982

Effect of L-thyroxine on metabolism in Japanese quails (Cotournix cotournix japonica)--II. Activity of GOT and GPT in liver, LDH and ICDH in heart and kidney after multiple injections of L-thyroxine.

1. Quails hatched from eggs incubated at physiological temperature (37.5 degrees C--normal quails) and elevated (39.3 degrees C--warm quails) were injected with L-thyroxine (T4) at the dose of 600 micrograms/kg of body weight, every 48 hr for 17 days. 2. Twenty-four hours after the last injection activity of aspartate aminotransferase (GOT), alanine aminotransferase (GPT) was determined in liver homogenates and lactate dehydrogenase and isocitrate dehydrogenase in homogenates of heart and kidney. 3. Significant increase of the activity of GPT in liver homogenates was observed in normal and warm quails up to 252.9 and 186.8% of control, respectively). 4. The activity of aspartate aminotransferase increased significantly in liver homogenates of T4-treated normal quails, while such changes in the warm quails were not observed. 5. Activities of lactate dehydrogenase (LDH) and isocitrate dehydrogenase (ICDH) in heart and kidney homogenates in both T4-treated groups of birds did not change.

Alanine Transaminase↗
PubMed1995

Characterization of thyroxine-albumin binding using high-performance affinity chromatography. II. Comparison of the binding of thyroxine, triiodothyronines and related compounds at the warfarin and indole sites of human serum albumin.

High-performance affinity chromatography was used to examine the binding of thyroid hormones and related compounds at the warfarin and indole sites of human serum albumin (HSA). This was studied by continuously applying L-triiodothyronine (L-T3), L-reverse triiodothyronine (L-rT3) or structural analogs of these compounds to an immobilized HSA column while making injections of site-specific probe molecules (i.e. R-warfarin and L-tryptophan). The results were compared with those obtained previously for L-thyroxine (L-T4). Equilibrium association constants and thermodynamic parameters measured by this approach showed good agreement with previous models reported for L-T4 and L-T3 at their high-affinity sites on HSA. This data confirmed that the phenol groups of L-T4 and L-T3 played a significant role in the binding of these compounds at the indole site. Work performed at the warfarin site and with other solutes (e.g. L-rT3) indicated that additional factors, such as interactions through the thyronine backbone or terminal amine and carboxyl groups of these compounds, could also be involved in the binding of thyroid hormones to HSA.

Binding Sites↗
PubMed1983

Thyroxine action on the rat liver nuclear thyroid-hormone receptors. Binding of thyroxine to the nuclear non-histone protein and induction of mitochondrial alpha-glycerophosphate dehydrogenase activity.

The possibility that thyroxine (T4) itself exerts the hormonal effect in vivo on the rat liver nuclear receptor was studied with the aid of iopanoic acid (IOP), an inhibitor of the conversion of T4 into tri-iodothyronine (T3). After administration of 2.4 micrograms of T4/100 g body weight to hypothyroid rats for 7 days, T4 and T3 concentrations in serum and in the liver nuclear non-histone protein (NHP) were all increased to the hyperthyroid range. Hepatic mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) activity and DNA content increased significantly. The equilibrium association constant (Ka) of the nuclear T3 receptor was unchanged and the maximal binding capacity (Cmax.) increased 1.4-fold. Simultaneous administration of IOP (5 mg/100 g body weight) to the rats given 2.4 micrograms of T4/100 g body weight completely blocked the conversion into T3. The serum T4 was even more increased, whereas the serum T3 decreased to the hypothyroid range. Although the NHP-bound T4 was at a concentration comparable with the rats given T4 alone, no NHP-bound T3 was detected. Yet the alpha-GPD activity was elevated 2.8-fold and the DNA content increased to the same extent as observed in the rats given T4 alone. The Ka and Cmax. of the nuclear receptor were significantly decreased. After administration of 48 or 480 micrograms of T4/100 g body weight for 3 days, serum T4 and T3 were markedly increased. The NHP-bound T3 was also increased, but no NHP-bound T4 was detected. The alpha-GPD activity was markedly elevated, but the DNA content was unchanged. The Cmax. per g of liver was increased, whereas the Ka remained unchanged. Simultaneous administration of IOP to these animals could not completely block the T4 conversion. The observed hormonal effects in the absence of nuclear T3 indicate that T4 possesses the intrinsic hormonal activities on the rat liver. T4 is less potent in induction of alpha-GPD activity but as potent in increment of hepatic DNA as T3. Although the binding site for T4 is not fully characterized, it appears to be acidic NHP. T4 is an active hormone, yet is also a prohormone of T3, offering the closest analogy with testosterone.

Animals↗
PubMed1990

The influence of circulating thyroxine serum concentration on hepatic thyroxine deiodinating activity in rats.

The influence of varying thyroid metabolic states, induced by thyroxine (T4) application, upon type I T4 deiodinating activity has been assessed in the rat liver. A series of 18 rats was thyroidectomized and treated with T4 at various doses, ranging from 0 to 50 micrograms/kg b.w. Microsomal T4 to triiodothyronine (T3) deiodinating activity (5'DA) and T4 to reverse T3 (rT3) deiodinating activity (5DA) as well as cytosolic non protein bound thiol content (NP-SH) were determined in the liver; concentrations of T4, T3, and rT3 were measured in the serum. In the experimental rats, T4 serum concentrations ranged from 1.3 micrograms/dl to 15.6 micrograms/dl (controls, 5 +/- 0.2 micrograms/dl, mean +/- SEM), T3 varied between 33 ng/dl and 150 ng/dl (91 +/- 3 ng/dl), and rT3 between 2 ng/dl and 25 ng/dl (7 +/- 2 ng/dl). Relating T4 to T3 serum levels, a curvilinear relationship (power function, r = 0.94, p less than 0.001), as described previously in man, was confirmed in the rats, as was the linear relationship between T4 and rT3 serum levels (r = 0.75, p less than 0.001). Individual 5'DA increased by more than fourfold, from 531 pg/mg.min to 2,234 pg/mg.min (controls, 1,419 +/- 67 pg/mg.min), when passing from low to high T4 serum values. The increase in 5'DA was steeper in the low T4 range, while it was progressively flattened under T4 levels above the controls' range. The particular changes in 5'DA can be illustrated by calculating the ratio of 5'DA and T4 serum levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Thyroxine an triiodothyronine kinetics and extrathyroidal peripheral conversion rate of thyroxine to triiodothyronine in healthy elderly humans.

The influence of age on the kinetics of thyroxine (T4) and triiodothyronine (T3), and on peripheral conversion of T4 to T3, has been studied, comparing a group of euthyroid, healthy, elderly individuals to a group of young individuals. A monocompartment model was adopted for the kinetics of T4, while a bicompartment model was used for T3. No significant difference (p greater than 0.05) could be found in any of the kinetic parameters of T4 between the elderly and young groups. However, the following significant (p less than 0.05) changes were noted for T3: an increased disposition constant in the phase of slow distribution (beta), shortening of the half-life of this phase (T 1/2 beta ), elevation of the central distribution volume Vc and the elimination constant K23, reduction of the K12: K23 ratio, and increased plasma metabolic clearance and hormonal daily turnover. No significant differences (p greater than 0.05) were observed for the percent turnover of T4 converted to T3.

Adult↗
PubMed1996

Study of binding of thyroxin-conjugates to the thyroxin-binding proteins.

In this work we studied the effects of the molecular weight (M.W.) of thyroxin (T4)-conjugates and the sample dilution factor on the binding potential (C) of serum T4-binding proteins for these T4-conjugates. We prepared six T4-conjugates with great difference in molecular weight with proteins such as IgG, apoferritin, ferritin, transferrin, and thyroglobulin using p-benzoquinone as bifunctional reagent. The conjugates prepared were characterized in terms of their M.W., the molar ratio of T4 to the carrier protein, and their affinity to bind with the anti-Tr antibody. The binding potential values of serum T4-binding proteins for the T4-conjugates were determined, following appropriate mathematical interpretation of the results, obtained through an assay system containing 125I-labeled conjugated tracers, anti-T4 antibody in great excess compared with the concentration of the tracers, and increasing concentration of T4-binding proteins. We conclude that the M.W. of the conjugates is a parameter which significantly influences the binding of a conjugate to the T4-binding proteins. Additionally, for conjugates of very high M.W. (> 650,000), zero C values were obtained using 20-fold sample dilution in the final incubation mixture.

Animals↗
PubMed1998

Complete deficiency of thyroxine-binding globulin (TBG-CD Buffalo) caused by a new nonsense mutation in the thyroxine-binding globulin gene.

Complete deficiency of thyroxine-binding globulin (TBG-CD) is defined as undetectable TBG in the serum of affected hemizygous subjects. Four distinct mutations have been identified in the TBG gene that cause this phenotype: TBG-CDJ (Japan), TBG-CD6, TBG-CD5, and TBG-CD Yonago. We report a new mutation producing TBG-CD phenotype. Five family members were studied, including two affected males with undetectable TBG in serum and two obligatory heterozygote females with borderline low values. Sequencing of the exons encoding the mature protein, adjacent introns and the promoter region, revealed differences in two nucleotides compared to the common type TBG, both located in exon 3: TGG (Trp) TAG (Stop) at codon 280 and TTG (Leu) TTT (Phe) at codon 283. The former mutation was not previously described and the latter is a polymorphic variant. Genotyping revealed that the two affected males had the mutant and polymorphic allele and their obligatory heterozygous mothers have each a common type and a mutant allele associated with the polymorphic variant. The mutant TBG Trp280Stop causes premature termination of translation that results in the production of a truncated protein that lacks 116 carboxyl terminal amino acids. The latter is believed to be responsible for the TBG-CD either because the aberrant protein is not secreted or because of reduced abundance of its mRNA.

Adult↗
PubMed1998

Simultaneous measurement of free thyroxine and free 3,5,3'-triiodothyronine in undiluted serum by direct equilibrium dialysis/radioimmunoassay: evidence that free triiodothyronine and free thyroxine are normal in many patients with the low triiodothyronine syndrome.

UNLABELLED: We have devised a practical, sensitive and specific method for simultaneous measurement of free thyroxine (FT4) and free triiodothyronine (FT3) in undiluted serum by direct equilibrium dialysis radioimmunoassay (RIA). Two hundred microliters serum sample was dialyzed against buffer (pH 7.4) for 20 hours at 37 degrees C and approximately 800 microL of the dialysate was used for measuring FT4 and FT3 simultaneously. The assay was set up in polystyrene tubes coated with anti-T4 antibody and available commercially for FT4 measurement (Quest-Nichols Institute, San Juan Capistrano, CA). The mean +/- SE (range) FT4 concentration (ng/dL) was 1.2 +/- 0.04 (0.7.0 to 2.30) in 54 normal subjects. It was significantly increased (3.6 +/- 0.4 [1.8 to 9.6], n = 20) in hyperthyroidism and clearly decreased (0.40 +/- 0.04 [1.10 to 0.70], n = 26] in hypothyroidism. All nonthyroid illness (NTI) patients had normal FT4 except 3, 2 of whom were on amiodarone and 1 had received heparin. Serum FT4 concentration was minimally elevated in 18 newborn cord blood serum (1.40 +/- 0.08 [0.90 to 2.2], cf. normal p < .05). The mean serum FT3 concentration (pg/dL) was 285 +/- 10 (134 to 454) in 54 normal sera. It was clearly increased in hyperthyroidism (1033 +/- 98 [593 to 2134], n = 20, p < .001). However, serum FT3 varied widely in hypothyroidism (27 to 597, mean 235 +/- 24, NS) as did serum total T3 (19 to 175). Interestingly, however, the mean serum FT3 concentration was normal (273 +/- 28 [62 to 575, NS]) in 25 NTI patients. All of these patients had low serum total T3 (46 +/- 5.0 [10 to 84], ng/dL; normal 84 to 160, p < 0.001), while FT3 was clearly normal in 21 of 25 patients and low in the remaining 4 patients. Similarly, among 18 newborn cord blood sera serum FT3 concentration was normal in 15 and subnormal only in the remaining 3 while all had clearly subnormal total T3 (28 to 74 ng/dL). CONCLUSIONS: (1) A practical, sensitive, and specific assay for simultaneous measurement of FT4 and FT3 is described; (2) FT3 is consistently elevated in hyperthyroidism while FT4 is elevated in most (approximately 85%) cases; (3) FT4 is consistently decreased in hypothyroidism but FT3 varies widely; (4). Serum FT3 concentration is normal in approximately 83% of patients with the low T3 syndrome in NTI and newborn cord blood serum. These data suggest that normal FT3 may explain clinical euthyroidism in many patients with the low T3 syndrome.

Dialysis↗
PubMed2000

Accuracy of free thyroxine measurements across natural ranges of thyroxine binding to serum proteins.

Systemic inaccuracies, proportional to the concentrations of serum proteins and the thyroxine (T4) they carry, have been reported in direct free T4 immunoassays. However, analytical recoveries of free T4 have not been carefully examined in most current methods, and they have not previously been examined across the pathophysiological range of serum T4 binding. In the present study we investigated ranges of serum T4 binding using free and total T4 measurements from 1359 individuals. Carefully characterized, gravimetrically calibrated, serum-based free T4 test solutions were then prepared with a constant normal free T4 concentration (12 ng/L) and varied serum T4 binding (approximately 300:1 to 24,000:1, ng protein bound T4: ng free T4). These standardized test solutions were analyzed using five T4 analog based free T4 methods. Analytical recoveries were calculated as ratios of actual free T4 measurements to the target value, and expressed as a percent of the target. Analytical recoveries were directly proportional to the extent of serum T4 binding and ranged 2% to 155%, 25% to 131%, 53% to 106%, 37% to 93%, and 37% to 73%, lowest to highest, in different methods. These systemic inaccuracies will confound interpretations of free T4 test results in clinical conditions with altered T4 binding. Future investigations into free T4 status must examine the analytical recovery of the free T4 method(s) used, as they relate to the extent of serum T4 binding in the clinical condition(s) studied.

Adolescent↗
PubMed1993

Thyroxine and triiodothyronine distribution and metabolism in thyroxine-replaced athyreotic dogs and normal humans.

Reported parenteral L-thyroxine (T4) replacement doses (10-20 micrograms.kg-1 x day-1) are larger than T4 production rates (2.5 micrograms.kg-1 x day-1) in athyreotic dogs but not humans. Furthermore, initial volumes of 3,5,3'-triiodothyronine (T3) tracer distribution exceed those for T4 in both species. To evaluate these discrepancies, serum T4 and T3 tracer kinetic studies from T4-replaced athyreotic dogs (5 micrograms.kg-1 x day-1 sc) and euthyroid humans were analyzed in a three-pool model (rapidly and slowly equilibrating pools with serum). Dogs had lower total T4 (41%) and T3 (31%) and higher free fractions of T4 (432%) and T3 (456%) than humans. Initial T3 distribution volumes were 454% those for T4 in dogs and 149% in humans, 498% of predicted plasma volumes in dogs and 121-138% in humans. Thus plasma volumes were used as time 0 estimates for T3 data analysis. Dogs had higher fractional T4 and T3 transfer rates from serum to the rapid pools (440-451%), total T4 clearance (353%) and production rates (147%), similar total T3 clearance, but lower free T3 clearance (32%) and production rates (45%) than humans. These findings suggest: 1) higher fractional transfer rates of T4 and T3 from serum to tissues and total serum T4 clearance rates in dogs than humans relate to lower canine serum T4 and T3 binding, and 2) parenteral L-T4 replacement doses required to achieve upper-normal serum total T4 concentrations in athyreotic dogs (5 micrograms.kg-1 x day-1) correspond to T4 production rates (6.8 micrograms.kg-1 x day-1).

Adult↗
PubMed1986

Effect of chronic treatment with estrogen and thyroxine, alone and combined, on the rate of deiodination of L-thyroxine to 3,5,3'-triiodothyronine in vitro.

The effect of administration of thyroxine (T4) and estradiol benzoate (EB), alone and combined (EB + T4), to female rats for 35 days on their serum concentrations of T4 and triiodothyronine (T3), and on the rate of conversion of T4 to T3 by homogenates of their liver and kidneys was studied. Administration of T4 (50 micrograms/kg b.w./day) resulted in an increase, while administration of EB (57 micrograms/kg b.w./day) resulted in a decrease in serum levels of T4. In EB + T4-treated rats, the serum concentration of T4 was less than that of either the T4-treated or control groups, while the serum T3 concentration was greater than that of the EB-treated group. Administration of T4 resulted in a rate of hepatic generation of T3 which was 180% of control, while the rate of renal T3 generation was 152% of control. Activity of T4 5'-monodeiodinase in hepatic homogenates was not affected significantly by administration of EB, while that in renal homogenates was inhibited by 44%. Administration of T4 in combination with EB resulted in a rate of conversion of T4 to T3 by hepatic homogenates which was 334% of control and significantly higher than that achieved by T4 alone. The rate of renal T3 generation by this group was 129% of control, but less than that achieved by administration of T4 alone. Administration of EB + T4 potentiated the effect of T4 on hepatic T4 to T3 converting activity and is likely responsible for the reduction in serum T4 concentration of these animals.

Animals↗
PubMed1985

Nuclear thyroxine receptors and cellular metabolism of thyroxine in obese subjects before and after fasting.

Nuclear binding of thyroxine (T4), cellular deiodination of T4 and nuclear accumulation of endogenous triiodothyronine (T3) were investigated in mononuclear blood cells in 5 obese persons before and after 7 days of total fast. Serum-free T4, serum-free T3 and serum thyrotropin (TSH) did not differ between lean persons and obese fed subjects, but fasting induced a significant decrease of serum-free T4 and serum-free T3 (T4 from 16.6 to 14.4 pmol/l, T3 from 5.7 to 3.2 pmol/l). The maximal specific binding capacity (MBC) for T4 was decreased in fed obese subjects (MBC = 0.6 fmol T4/100 micrograms DNA, p less than 0.05) compared to normal weight persons (MBC = 1.3 fmol T4/100 micrograms DNA), whereas the equilibrium association constant (ka) did not differ. During complete fast, the MBC increased (MBC = 1.5 fmol T4/100 micrograms DNA, p less than 0.05). Neither total deiodination of T4 nor endogenous nuclear T3 accumulation differed between the groups suggesting that cellular T4 to T3 conversion is independent of the nutritional state. We suggest that the observed increase in nuclear T4 receptor capacity may compensate the decrease in serum thyroid hormone levels.

Cell Nucleus↗
PubMed1972

Studies on human thyroxine-binding globulin. VI. The nature of slow thyroxine-binding globulin.

A model system utilizing a highly purified partially desialylated thyroxine-(T(4)) binding protein (STBG) was studied. STBG was prepared by the same affinity chromatographic method we have reported for preparation of highly purified T(4)-binding globulin (TBG). The necessary prerequisite for preparation of STBG was the use of T(4)-substituted Sepharose which had been repeatedly exposed to large volumes of serum for purification of TBG. STBG moved more slowly on cellulose acetate electrophoresis than TBG but had the same molecular weight and antigenic determinants as TBG. It bound T(4) with a 1: 1 molar ratio but its affinity for T(4) was about 10 times less than that of TB. STBG had about onefourth the sialic acid content of TBG and the electrophoretic mobility of this protein was similar to that of a T(4)-binding protein with a mobility slower than that of TBG which has been seen in the electrophoretic patterns of some normal human serums and in serums of patients with hepatic cirrhosis and which does not appear to be an artifact caused by storage and freezing of serum. This fourth slowly migrating T(4)-binding region in electrophoretograms of cirrhotic serums is completely abolished by prior incubation with rabbit antiserum to TBG. The in vitro production of partially desialylated TBG from T(4)-Sepharose which had been previously exposed to large volumes of serum may be due to adsorption of neuraminidases to the Sepharose either directly from serum or as the result of bacterial contamination. Partial desialylation of TBG in vivo may be an early step in the catabolism of this protein.

Animals↗