triiodothyronine--reverse and 3-3--diiodothyronine
triiodothyronine--reverse has been researched along with 3-3--diiodothyronine* in 26 studies
Reviews
3 review(s) available for triiodothyronine--reverse and 3-3--diiodothyronine
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Characteristics of type III iodothyronine deiodinase.
Type III iodothyronine deiodinase (ID-III) catalyzes the inner ring deiodination of T4 to rT3 and of T3 to 3,3'-T2, representing an important pathway for the inactivation of thyroid hormone. High activities of this "oncofetal" enzyme are found in rat brain, skin and fetal intestine, rat and human placenta, chick embryo liver, monkey hepatocarcinoma cells, human colon carcinoma cells, and tadpole liver. ID-III shows substrate preference for T3 over T4; Km values are approximately 10-fold lower for T3 than for T4 but Vmax values are similar. In contrast to the marked ontogenic pattern of ID-III in different tissues, the enzyme shows little change under pathophysiological conditions, such as fasting and thyroid dysfunction. Brain ID-III activity is decreased in hypo- and increased in hyperthyroidism, but the changes are small. Reaction of brain and placenta microsomes with BrAc 125I-T3 results in extensive labeling of a 32 kDa protein (p32). However, the relationship of p32 with ID-III is not clear, since labeling of p32 is also observed in tissues without ID-III activity and is not inhibited with a large excess of substrate. Topics: Animals; Cell Line; Diiodothyronines; Humans; Iodide Peroxidase; Isoenzymes; Substrate Specificity; Thyroid Hormones; Thyroxine; Tissue Distribution; Triiodothyronine, Reverse | 1992 |
The deiodination of the iodothyronines and of their derivatives in man.
Topics: Chemical Phenomena; Chemistry; Diiodothyronines; Diiodotyrosine; Glucuronates; Humans; Hyperthyroidism; Iodine; Kinetics; Phenyl Ethers; Radioimmunoassay; Sulfates; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse | 1984 |
Radioimmunoassay of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3, rT3), and 3,3'-diiodothyronine (T2).
Topics: Adult; Aging; Animals; Chemical Phenomena; Chemistry; Chloramines; Cross Reactions; Diiodothyronines; Humans; Rabbits; Radioimmunoassay; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyronines; Thyrotropin; Thyroxine; Tosyl Compounds; Triiodothyronine; Triiodothyronine, Reverse | 1982 |
Other Studies
23 other study(ies) available for triiodothyronine--reverse and 3-3--diiodothyronine
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Topics: Animals; Cell Line, Tumor; Chlorocebus aethiops; COS Cells; Diiodothyronines; Disease Models, Animal; Gene Knockdown Techniques; Humans; Immunoblotting; Immunohistochemistry; In Vitro Techniques; Mental Retardation, X-Linked; Mice; Mice, Knockout; Models, Molecular; Monocarboxylic Acid Transporters; Muscle Hypotonia; Muscular Atrophy; Sequence Alignment; Symporters; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse | 2019 |
Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism.
Cellular entry of thyroid hormone is mediated by plasma membrane transporters. We have identified rat monocarboxylate transporter 8 (MCT8) as an active and specific thyroid hormone transporter. The MCT8 gene is located on the X-chromosome. The physiological relevance of MCT8 has been demonstrated by the identification of hemizygous mutations in this gene in males with severe psychomotor retardation and elevated serum T(3) levels. We have characterized human (h) MCT8 by analysis of iodothyronine uptake and metabolism in cell lines transiently transfected with hMCT8 cDNA alone or together with cDNA coding for iodothyronine deiodinase D1, D2, or D3. MCT8 mRNA was detected by RT-PCR in a number of human cell lines as well as in COS1 cells but was low to undetectable in other cell lines, including JEG3 cells. MCT8 protein was not detected in nontransfected cell lines tested by immunoblotting using a polyclonal C-terminal hMCT8 antibody but was detectable in transfected cells at the expected size (61 kDa). Transfection of COS1 and JEG3 cells with hMCT8 cDNA resulted in 2- to 3-fold increases in uptake of T(3) and T(4) but little or no increase in rT(3) or 3,3'-diiodothyronine (3,3'-T(2)) uptake. MCT8 expression produced large increases in T(4) metabolism by cotransfected D2 or D3, T(3) metabolism by D3, rT(3) metabolism by D1 or D2, and 3,3'-T(2) metabolism by D3. Affinity labeling of hMCT8 protein was observed after incubation of intact transfected cells with N-bromoacetyl-[(125)I]T(3). hMCT8 also facilitated affinity labeling of cotransfected D1 by bromoacetyl-T(3). Our findings indicate that hMCT8 mediates plasma membrane transport of iodothyronines, thus increasing their intracellular availability. Topics: Affinity Labels; Animals; Biological Transport; Cell Extracts; Cell Line; Chlorocebus aethiops; Cloning, Molecular; COS Cells; Diiodothyronines; DNA, Complementary; Gene Expression; Humans; Immunoblotting; Iodide Peroxidase; Monocarboxylic Acid Transporters; Monoiodotyrosine; Symporters; Thyroid Hormones; Thyroxine; Transfection; Triiodothyronine; Triiodothyronine, Reverse; Tumor Cells, Cultured | 2006 |
Identification of thyroid hormone transporters.
Thyroid hormone action and metabolism are intracellular events that require transport of the hormone across the plasma membrane. We tested the possible involvement of the Na+/taurocholate cotransporting polypeptide (Ntcp) and organic anion transporting polypeptide (oatp1) in the hepatic uptake of the prohormone T4, the active hormone T3, and the metabolites rT3 and 3,3'-T2. Xenopus laevis oocytes were injected with 2.3 ng Ntcp or oatp1 cRNA and, after 2-3 days, incubated for 1 h at 25 degrees C with usually 0.1 microM 125I-labeled ligand. Uninjected oocytes showed marked uptake of iodothyronines and this was further increased by Ntcp and oatp1 cRNA, i.e., 1.9- and 2.8-fold for T4, 1.7- and 1.7-fold for T3, 1.8- and 6.0-fold for rT3, and 1.3- and 1.4-fold for 3,3'-T2, respectively. Mostly due to much lower uptake by uninjected oocytes, Ntcp and oatp1 cRNA induced larger, 12- to 76-fold increases in uptake of iodothyronine sulfates. The Ntcp cRNA-induced iodothyronine uptake was completely inhibited in Na+-deplete medium, whereas the oatp1 cRNA-induced uptake was not affected. These results suggest that hepatic uptake of thyroid hormones and their metabolites is mediated at least in part by Ntcp and oatp1. Topics: Animals; Anion Transport Proteins; Biological Transport; Carrier Proteins; Diiodothyronines; Female; Kinetics; Liver; Membrane Transport Proteins; Oocytes; Organic Anion Transporters, Sodium-Dependent; Rats; Recombinant Proteins; RNA, Complementary; Symporters; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse; Xenopus laevis | 1999 |
Sulfation of thyroid hormone by estrogen sulfotransferase.
Sulfation is one of the pathways by which thyroid hormone is inactivated. Iodothyronine sulfate concentrations are very high in human fetal blood and amniotic fluid, suggesting important production of these conjugates in utero. Human estrogen sulfotransferase (SULT1E1) is expressed among other tissues in the uterus. Here we demonstrate for the first time that SULT1E1 catalyzes the facile sulfation of the prohormone T4, the active hormone T3 and the metabolites rT3 and 3,3'-diiodothyronine (3,3'-T2) with preference for rT3 approximately 3,3'-T2 > T3 approximately T4. Thus, a single enzyme is capable of sulfating two such different hormones as the female sex hormone and thyroid hormone. The potential role of SULT1E1 in fetal thyroid hormone metabolism needs to be considered. Topics: Diiodothyronines; Estradiol; Estrone; Humans; Isoenzymes; Kinetics; Recombinant Proteins; Substrate Specificity; Sulfates; Sulfotransferases; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse | 1999 |
Effect of 3,3'-di-iodothyronine and 3,5-di-iodothyronine on rat liver mitochondria.
In the present study we report that 3,3',5-tri-iodothyronine (T3) as well as two iodothyronines (3,5-di-iodothyronine (3,5-T2) and 3,3'-di-iodothyronine (3,3'-T2)) significantly influence rat liver mitochondrial activity. Liver oxidative capacity (measured as cytochrome oxidase activity/g wet tissue) in hypothyroid compared with normal rats was significantly reduced (21%, P > 0.01) and the administration of T3 and both iodothyronines restored normal values. At the mitochondrial level, treatment with T3 stimulated respiratory activity (state 4 and state 3) and did not influence cytochrome oxidase activity. On the other hand, both the mitochondrial respiratory rate and specific cytochrome oxidase activity significantly increased in hypothyroid animals after treatment with 3,3'-T2 or 3,5-T2 (about 50 and 40% respectively). The actions of both iodothyronines were rapid and evident by 1 h after the injection. The hepatic mitochondrial protein content which decreased in hypothyroid rats (9.6 mg/g liver compared with 14.1 in normal controls, P < 0.05) was restored by T3 injection, while neither T2 was able to restore it. Our results suggest that T3 and both iodothyronines have different mechanisms of action. T3 acts on both mitochondrial mass and activity; the action on mitochondrial activity was not exerted at the cytochrome oxidase complex level. The action of the iodothyronines, on the other hand, is exerted directly on the cytochrome oxidase complex without any noticeable action on the mitochondrial mass. Topics: Animals; Diiodothyronines; Electron Transport Complex IV; Hypothyroidism; Male; Mitochondria, Liver; Proteins; Rats; Rats, Wistar; Triiodothyronine, Reverse | 1993 |
Concentrations of thyroxine, 3,5,3'-triiodothyronine, 3,3',5'-triiodothyronine, 3,3'-diiodothyronine, and 3',5'-diiodothyronine in human red blood cells.
A simple and rapid method for the estimation of cellular concentration of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,3'-diiodothyronine (3,3'-T2), and 3',5'-diiodothyronine (3',5'-T2) as well as their distribution between cytosol and membranes in human red blood cells (RBC) is presented. Concentrations of iodothyronines in RBC (RBC-T) were calculated by multiplying the total serum concentrations by the ratio of radioactivity in equal volumes of packed RBCs and serum, pre-incubated with 125I-labelled iodothyronines of high specific activity. Plasma and RBC were separated by centrifugation in capillary glass tubes. The separation of membranes and cystosol was performed by hypotone lysis and centrifugation. The median RBC-T of T4, T3, rT3, 3,3'-T2, and 3',5'-T2 from 17 euthyroid subjects were 360 pmol/l, 156 pmol/l, 2.77 pmol/l, 6.81 pmol/l, and 2.17 pmol/l, respectively. The cytosol/cytosol + membrane ration were 66%, 40%, 84%, 77%, and 97%, respectively. The differences in RBC-T were not similar to the differences in free serum concentrations. The ratio of RBC-T to free serum concentration differed considerably between T4 (16.6), T3 (24.4), and 3,3'-T2 (15.5) as compared to rT3 (5.8) and 3',5'-T2 (2.6). Data on three patients with thyroid diseases suggested that RBC-T values were increased in hyperthyroidism and decreased in hypothyroidism, whereas the cytosol/cytosol + membrane-ratio was unaltered. Topics: Adult; Aged; Blood Proteins; Diiodothyronines; Erythrocytes; Female; Humans; Hypothyroidism; Male; Middle Aged; Receptors, Thyroid Hormone; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse; Ultrafiltration | 1989 |
Comparative aspects of the distribution, metabolism, and excretion of six iodothyronines in the rat.
We have studied the kinetics of 3 iodothyronines, 3,3'-diiodothyronine (T2), 3',5'-T2, and 3'-monoiodothyronine (T1), in groups of young adult male rats maintained under normal steady state physiological conditions. We have also performed a comparative analysis of these results, combined with corresponding kinetic indices of T4, T3, and rT3, to obtain a more comprehensive understanding of normal thyroid hormone production, distribution, and metabolism. Tracer doses of 125I-labeled 3,3'-T2, 3',5'-T2, and 3'-T1 were separately injected iv, and blood samples were collected 6-12 times for each iodothyronine in optimized sequential kinetic studies designed to maximize the precision of kinetic parameters. Labeled iodothyronines were separated quantitatively from their metabolites in each plasma sample by Sephadex G-25 column chromatography. Conventional kinetic analysis of the resulting data generated distribution volume, clearance, turnover, and mean residence time indices for each iodothyronine, and concomitant compartmental analysis of the same data provided additional results useful for integration and comparative analysis of the 6 iodothyronines. Kinetic parameters for all but T4 and T3 were similar, suggesting that similar mechanisms are responsible for the transport, metabolism, and distribution of nonhormonal iodothyronines. All but T4 and T3 (and, to a much lesser extent, 3'-T1) were almost completely and irreversibly metabolized, whereas 24-30% of the hormones (and 6% of 3'-T1) were excreted as such in feces only. Three-pool models fitted individual plasma kinetic data sets best in all cases (for all 6 iodothyronines), each with a plasma, a slowly exchanging (slow), and a rapidly exchanging (fast) pool, and kinetic parameters of interest were quantified for each iodothyronine (Ti). Quantitative analysis of an integrated 18-pool model for all 6 Tis revealed several other features of physiological interest. The fractional transport rate of T3 into the fast pool (liver, at least) is about an order of magnitude larger than that for all other Tis, supporting the hypothesis that transport of T3 into fast tissues (e.g. liver cells) is selectively amplified relative to that of the 5 other iodothyronines studied. Simultaneous and direct comparison of the 6 plasma kinetic data sets also supports this result. In addition, composite slow tissue pools, which probably exclude liver and kidney, contained the largest whole body fractions of all Tis (greater than 50%) Topics: Animals; Diiodothyronines; Iodine Radioisotopes; Kinetics; Male; Rats; Rats, Inbred Strains; Thyronines; Thyroxine; Tissue Distribution; Triiodothyronine; Triiodothyronine, Reverse | 1988 |
Handling of iodothyronines by the liver and kidney in patients with chronic liver disease.
Possible arterio-venous gradients of T4, T3, rT3 and 3,3'-diiodothyronine (3,3'-T2) across the liver and the kidneys were measured in 9 patients with varying degrees of liver failure undergoing diagnostic catheterization. Plasma iodothyronine levels were measured in peripheral, hepatic and renal veins before and at 10-min intervals until 60 min after iv injection of 400 micrograms of TRH. In 2 patients estimated hepatic plasma flow and effective renal plasma flow were determined as well. In these 2 patients, no significant differences between iodothyronine levels in arterial and peripheral venous plasma were found. T4 and T3 levels were not significantly different between peripheral, renal and hepatic veins. Hepatic vein rT3 and 3,3'-T2 concentrations were 10.7 +/- 8.3% (mean +/- SD, P less than 0.005) and 36 +/- 18% (P less than 0.001) lower than those in the peripheral vein (N = 9). Renal vein rT3 was just (6.2 +/- 7.5%, P less than 0.05) lower than rT3 in peripheral vein, whereas 3,3'-T2 was not different between the two veins. Estimates of hepatic and renal plasma flow were in agreement with values from the literature. On the basis of these data approximate hepatic clearance rates of 110 and 380 1/day for rT3 and 3,3'-T2 and a renal clearance rate of about 35 1/day for rT3 were calculated. Sixty min after TRH, plasma T3 was increased to 147 +/- 56% (P less than 0.05) and 3,3'-T2 in peripheral plasma was increased to 142 +/- 36% (P less than 0.025), whereas plasma T4 and rT3 did not change.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Adult; Aged; Chronic Disease; Diiodothyronines; Female; Humans; Kidney; Liver; Liver Diseases; Male; Middle Aged; Thyroid Hormones; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse | 1987 |
Hepatic iodothyronine 5-deiodinase activity in Rana catesbeiana tadpoles at different stages of the life cycle.
Conversion of T4 to T3 cannot be demonstrated in vivo in Rana catesbeiana tadpoles until just before metamorphic climax, suggesting that 5'-deiodinase (5'D) activity is not present until this time. In the present study the role of 5-deiodinase (5 D) systems in the metabolism of T4 and T3 in the developing tadpole was examined. 5 D activity capable of converting T3 to 3,3'-diiodothyronine, and T4 to rT3 was present in hepatic microsomes from pre- and prometamorphic tadpoles, but it declined to undetectable levels during metamorphic climax. The preferred substrate was T3. The Vmax for T3 in premetamorphic tadpoles was 30.4 +/- (SE) 6.37 fmol/min X mg microsomal protein, and the Michaelis-Menten constant (Km) was 3.6 +/- 0.72 nM, respectively. The characteristics of the system are similar to those of the type III iodothyronine deiodinase present in mammals. The system has its counterpart in vivo; administration of T3 or T4 to tadpoles resulted in the generation of detectable amounts of the corresponding 5-deiodinated product. rT3 was also shown to be a naturally occurring iodothyronine in this species. Although generation of T3 from T4 was readily demonstrable in vivo in tadpoles that had entered metamorphic climax, hepatic 5'D activity determined in vitro was found to be extremely low at all stages of development. On the basis of these findings, the following alternative explanation for the failure to observe T4 to T3 conversion before climax is offered. In pre- and prometamorphic tadpoles, any T3 produced from T4 is rapidly converted to 3,3'-diiodothyronine by the 5 D system and thus accumulation is prevented. Once climax has begun, 5 D activity declines and thus the T3 generated is able to accumulate. Whether the increased T3 accumulation is also facilitated by an increase in T3 production due to increased 5'D activity remains to be determined. Topics: Animals; Diiodothyronines; Iodide Peroxidase; Larva; Liver; Metamorphosis, Biological; Microsomes, Liver; Rana catesbeiana; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse | 1987 |
Metabolism of reverse triiodothyronine by isolated rat hepatocytes.
Reverse triiodothyronine (rT3) is metabolized predominantly by outer ring deiodination to 3,3'-diiodothyronine (3,3'-T2) in the liver. Metabolism of rT3 and 3,3'-T2 by isolated rat hepatocytes was analyzed by Sephadex LH-20 chromatography, high performance liquid chromatography, and radioimmunoassay, with closely agreeing results. Deiodinase activity was inhibited with propylthiouracil (PTU) and sulfotransferase activity by sulfate depletion or addition of salicylamide or dichloronitrophenol. Normally, little 3,3'-T2 production from rT3 was observed, and 125I- was the main product of both 3,[3'-125I]T2 and [3',5'-125I]rT3. PTU inhibited rT3 metabolism but did not affect 3,3'-T2 clearance as explained by accumulation of 3,3'-T2 sulfate. Inhibition of sulfation did not affect rT3 clearance but 3,3'-T2 metabolism was greatly diminished. The decrease in I- formation from rT3 was compensated by an increased recovery of 3,3'-T2 up to 70% of rT3 metabolized. In conclusion, significant production of 3,3'-T2 from rT3 by rat hepatocytes is only observed if further sulfation is inhibited. Topics: Animals; Cells, Cultured; Diiodothyronines; Iodide Peroxidase; Liver; Nitrophenols; Rats; Salicylamides; Sulfates; Triiodothyronine, Reverse | 1987 |
Renal handling of thyroxine, 3,5,3'- and 3,3',5'-triiodothyronine, 3,3'- and 3',5'-diiodothyronine in man.
The 24-h urinary excretion and renal clearance of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,3'-diiodothyronine (3,3'-T2), and 3',5'-diiodothyronine (3',5'-T2) were measured in 17 healthy subjects. The median urinary excretion was (pmol/24h) T4: 1242, T3: 828, rT3: 12.9, 3,3'-T2: 331, and 3',5'-T2: 5.8. The corresponding renal clearances were in median (ml/min) T4: 31, T3: 133, rT3: 15, 3,3'-T2: 683, and 3',5'-T2: 4.5. The clearances differed mutually (P less than 0.01) as well as from the creatinine clearance (P less than 0.01) which was in median 87 ml/min. Thus, all iodothyronines studied were subject to tubular transport mechanisms besides glomerular filtration. The 3 iodothyronines with 2 iodine atoms in the phenolic ring of the thyronine molecule, T4, rT3 and 3',5'-T2, were mainly tubularly reabsorbed, whereas those with only one iodine atom in the phenolic ring, T3 and 3,3'-T2, were mainly tubularly secreted. It might be hypothesized that the number of iodine atoms in the phenolic ring determines the direction of the tubular transport (presence of 2 iodine atoms is associated with tubular reabsorption, and of one iodine atom with secretion), whereas the rate of tubular transport decreases with decreasing number of iodine atoms in the tyrosylic ring. Topics: Adult; Aged; Creatinine; Diiodothyronines; Female; Humans; Kidney; Male; Middle Aged; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse | 1987 |
Multisite inhibition by ipodate of iodothyronine secretion from perfused dog thyroid lobes.
Cholecystographic radiocontrast agents interfere with thyroid hormones in several ways. In the present study 1 mM ipodate induced a rapid sustained and reversible inhibition of the secretion of T4, T3, rT3, 3,3'-diiodothyronine, and 3',5'-diiodothyronine from perfused dog thyroid lobes. This effect was not reproduced by infusion of 3 mM iodide and not affected by 2 mM methimazol or 2 mM perchlorate. One millimolar of ipodate inhibited secretion of T4 to 23.7 +/- 2.8% of control (+/- SE, n = 6), 0.3 mM ipodate to 59.6 +/- 3.01 (n = 4), and 0.1 mM ipodate to 80.4 +/- 5.7% of control (n = 4). In search of the site of action in the thyroid of this inhibitory compound it was found that 1 mM ipodate inhibited TSH-induced increase in thyroidal cAMP, cAMP-induced generation of intracellular colloid droplets, and liberation of T4 and T3 from thyroglobulin by acid proteases and peptidases. These processes are those thought to be inhibited during iodide inhibition of thyroid secretion, via gradual formation of an unknown iodine-containing organic intermediate. It is suggested that the inhibition of thyroid secretion observed in the present study is due to structural similarities between ipodate and this putative iodine-containing mediator of the iodide-induced inhibition of thyroid secretion. Topics: Animals; Cyclic AMP; Diiodothyronines; Dogs; Iodine; Ipodate; Perfusion; Thyroglobulin; Thyroid Gland; Thyronines; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse | 1985 |
Effects of small doses of bovine TSH on serum levels of free and total thyroid hormones, their degradation products, and diiodotyrosine.
Bovine TSH was administered iv to 10 normal volunteers in doses of 2.5, 7.5, 15 and 30 mU/kg. Brisk elevations of serum diiodotyrosine occurred already after the smallest dose (mean, +183%) while larger doses had only slight additional effects. T3 rose much higher than T4 (+71% compared to +23% after 15 mU bTSH/kg), and free thyroid hormones exhibited changes similar to total T3 and total T4. The mean absolute increase in serum fT3 ranged from 2.03 to 9.04 pmol/l and proved to be an easily measurable parameter for the TSH effect. Dose-response effects were seen for the increase of fT4, fT3 and T3. TBG and rT3 did not change but the degradation product 3,3'-T2 showed large increments of serum levels. There was no correlation between the response of T3 and T4, fT3 and fT4, or diiodotyrosine and any of the other parameters of thyroid function. The interindividual differences in the magnitude of thyroid hormone response to TSH were considerable, and there was no relationship between this response and thyroid volume by ultrasound. We conclude that direct stimulation of the thyroid gland with bTSH in small doses leads to consistent increases of thyroid hormones, especially T3 and fT3, that the response varies between individuals, and that the precursor diiodotyrosine is released together with thyroid hormones. Topics: Adult; Diiodothyronines; Diiodotyrosine; Dose-Response Relationship, Drug; Humans; Thyroglobulin; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse | 1985 |
Synthesis and some properties of sulfate esters and sulfamates of iodothyronines.
In the present study, convenient methods have been developed for the synthesis of sulfate derivatives of iodothyronines. Reaction with chlorosulfonic acid in dimethylformamide gave rise to formation of the sulfate ester with the phenolic hydroxyl group. Reaction with the sulfurtrioxide-trimethylamine complex in alkaline medium afforded the sulfamate with the alpha-amino group of the alanine side chain. The sulfated products were isolated by adsorption onto Sephadex LH-20 in acidic medium, followed by desorption with water. Iodide was not retarded on these columns, whereas elution of native iodothyronines required alkaline ethanol mixtures. The yield of both reactions varied between 70-90%. The sulfates and sulfamates of T4, T3, rT3, and 3,3'-diiodothyronine could be separated by reverse phase HPLC. The sulfamates exhibited high cross-reactivities with antibodies against free iodothyronines, in contrast to the low activities of the sulfates. Products were further characterized by proton nuclear magnetic resonance, TLC, and hydrolysis by acid or sulfatase activity. The availability of large quantities of pure iodothyronine sulfates and sulfamates should facilitate the study of the importance of sulfate conjugation in the metabolism of thyroid hormone. Topics: Chemical Phenomena; Chemistry; Chromatography; Chromatography, High Pressure Liquid; Diiodothyronines; Dimethylformamide; Esters; Hydrolysis; Magnetic Resonance Spectroscopy; Methylamines; Sulfates; Sulfonic Acids; Sulfur Oxides; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse | 1985 |
Proton nuclear magnetic resonance assignments of thyroid hormone and its analogues.
1H NMR data of a series of thyroid hormone analogues, e.g., thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,3'-diiodothyronine (3,3'-T2), 3,5-diiodothyronine (3,5-T2), 3',5'-diiodothyronine (3',5'-T2), 3-monoidothyronine (3-T1), 3'-monoiodothyronine (3'-T1), and thyronine (TO) in dimethylsulfoxide (DMSO) have been obtained on a 300 MHz spectrometer. The chemical shift and coupling constant are determined and tabulated for each aromatic proton. The inner tyrosyl ring protons in T4, T3, and 3,5-T2 have downfield chemical shifts with respect to those of the outer phenolic ring protons. Four-bond cross-ring coupling has been observed in all the monoiodinated rings. However, this long-range coupling does not exist in T4, diiodinated on both rings, and T0, containing no iodines on the rings. There is no evidence that at 30 degrees C these iodothyronines have any motional constraint in DMSO solution. In addition to identification of the hormones, the potential use of some characteristic peaks as probes in binding studies is discussed. Topics: Diiodothyronines; Magnetic Resonance Spectroscopy; Thyroid Hormones; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse | 1985 |
Serum free T4, T3, rT3, 3,3'-diiodothyronine and 3',5'-diiodothyronine measured by ultrafiltration.
A simple and accurate method for estimation of the free fractions (FFT) of T4, T3, rT3, 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) in serum is presented. The method is based on ultrafiltration of serum pre-incubated with tracers of high specific activity, followed by purification of the ultrafiltrate on small Sephadex columns. The addition of tracer only dilutes serum negligible (about 5%) and the ultrafiltration procedure only removes about 7% of the volume of serum, thus probably not disturbing the equilibrium between the free and protein bound fraction of iodothyronine. Progressive reduction of tracer to less than 10% of the amount usually used did not reduce the FFT of any of the iodothyronines. In contrast, addition of T4 to serum led to an increase of all FFTs except that of 3',5'-T2. These data suggest that FFT of T4, T3, rT3 and 3,3'-T2 primarily is determined by the amount of T4 present in serum and that significant amounts of these iodothyronines are bound to TBG, whereas 3',5'-T2 possibly primarily is bound to albumin. The median FFT of T4, T3, rT3, 3,3'-T2 and 3',5'-T2 in serum from euthyroid subjects (n = 38) was: 0.030, 0.29, 0.14, 1.10 and 1.07%, respectively. The corresponding median free concentrations in pmol/l were: 30, 4.79, 0.59, 0.44 and 0.77, respectively. Pregnant women in 3rd trimester had normal levels of free T4, free T3 and free rT3, whereas the median free 3,3'-T2 was reduced in contrast to elevated median free 3',5'-T2.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Adult; Aged; Diiodothyronines; Female; Humans; Hyperthyroidism; Kidney Failure, Chronic; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Pregnancy; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse; Ultrafiltration | 1984 |
Sulfation facilitates hepatic deiodination of iodothyronines.
The metabolism of 3,3',5'-triiodothyronine (rT3), 3,3'-5-triiodothyronine (T3) and 3,3'-diiodothyronine (3,3'-T2) by isolated rat hepatocytes in primary culture was studied by radioimmunoassay and by Sephadex LH-20 chromatography. The first step in the metabolism of rT3 is outer ring deiodination which is inhibited by thiouracil. In incubations with outer ring-labeled 3,3'-T2 or T3 the main products observed are iodide in the absence of thiouracil and the sulfate conjugates in the presence of the inhibitor. Rates of sulfation and iodide formation were both determined by the phenol sulfotransferase activity of the cells. Inner ring deiodination of T3 sulfate and subsequent outer ring deiodination of 3,3'-T2 sulfate by rat liver microsomes are much faster than the corresponding reactions for the non-conjugated iodothyronines. The results strongly suggest that sulfation precedes and in effect accelerates hepatic deiodination of T3 and 3,3'-T2. Topics: Animals; Arylsulfotransferase; Cells, Cultured; Diiodothyronines; Kinetics; Liver; Rats; Structure-Activity Relationship; Sulfurtransferases; Thiouracil; Thyronines; Triiodothyronine; Triiodothyronine, Reverse | 1984 |
Metabolism of 3,3'-diiodothyronine in rat hepatocytes: interaction of sulfation with deiodination.
Production of 3,3'-diiodothyronine (3,3'-T2) is an important step in the peripheral metabolism of thyroid hormone in man. The rapid clearance of 3,3'-T2 is accomplished to a large extent in the liver. We have studied in detail the mechanisms of this process using monolayers of freshly isolated rat hepatocytes. After incubation with 3,[3'-125I]T2, chromatographic analysis of the medium revealed two major metabolic routes: outer ring deiodination and sulfation. We recently demonstrated that sulfate conjugation precedes and in effect accelerates deiodination of 3,3'-T2. In media containing different serum concentrations the cellular clearance rate was determined by the nonprotein-bound fraction of 3,3'-T2. At substrate concentrations below 10(-8) M 125I- was the main product observed. At higher concentrations deiodination became saturated, and 3,3'-T2 sulfate (T2S) accumulated in the medium. Saturation of 3,3'-T2 clearance was found to occur only at very high (greater than 10(-6)M) substrate concentrations. The sulfating capacity of the cells exceeded that of deiodination by at least 20-fold. Deiodination was completely inhibited by 10(-4) M propylthiouracil or thiouracil, resulting in the accumulation of T2S while clearance of 3,3'-T2 was little affected. No effect was seen with methimazole. Hepatocytes from 72-h fasted rats showed a significant reduction of deiodination but unimpaired sulfation. Other iodothyronines interfered with 3,3'-T2 metabolism. Deiodination was strongly inhibited by 2 microM T4 and rT3 (80%) but little by T3 (15%), whereas the clearance of 3,3'-T2 was reduced by 27% (T4 and rT3) and 12% (T3). It is concluded that the rapid hepatic clearance of 3,3'-T2 is determined by the sulfate-transferring capacity of the liver cells. Subsequent outer ring deiodination of the intermediate T2S is inhibited by propylthiouracil and by fasting, essentially without an effect on overall 3,3'-T2 clearance. Topics: Animals; Cell Count; Culture Media; Diiodothyronines; Fasting; Iodine; Iodine Radioisotopes; Liver; Propylthiouracil; Rats; Sulfates; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse | 1984 |
Simultaneous turnover studies of thyroxine, 3,5,3' and 3,3',5'-triiodothyronine, 3,5-, 3,3'-, and 3',5'- diiodothyronine, and 3'-monoiodothyronine in chronic renal failure.
The present study evaluates the sequential extra-thyroidal monodeiodination of thyroid hormones through tri-, di-, and monoiodothyronines in chronic renal failure (CRF) in man. Simultaneous turnover studies of T4, T3, rT3, 3,5-diiodothyronine (3,5-T2), 3,3'-T2, 3',5'-T2, 3'5'-T2, and 3'-monoiodothyronine (3--T1) were conducted in six patients with CRF (creatinine clearance, 9-18 ml/min) using the single-injection, noncompartmental approach. Serum levels of T4, T3, and 3,5-T2 were reduced to two thirds of control levels (P less than 0.05), whereas serum rT3 and 3,3'-T2 levels were reduced to a minor degree. Serum 3'-5'-T1 was doubled (p less than 0.05). The MCRs of T4, rT3, and 3',5'-T2 were enhanced to 168%, 127%, and 187% of normal (P less than 0.05), respectively, whereas those of T3, 3,5-T2, 3,3'-T2, and 3'-T1 were unaffected. The mean production rates (PRs) of the iodothyronines in CRF were as follows (CRF vs. control values, expressed as nanomoles per day/70 kg): T4, 119 vs. 125; T3, 26 vs. 44 (P less than 0.01); rT3, 49 vs, 48; 3,5-T2, 3.5 vs. 7.2 (P less than 0.001); 3,3'-T2, 25 vs. 35 (P less than 0.01); 3',5'-T2, 25 vs. 14 (P less than 0.01); and 3'-T1, 39 vs. 30. Previous studies have demonstrated reduced phenolic ring (5'-) deiodination of T4 in CRF, which is supported by the present finding of unaltered PR of T4 and reduced PR of T3. In contrast the 5'-deiodination of T3 leading to the formation of 3,5-T2 was found unaffected by CRF, since the conversion rate (CR) of T3 to 3,5-T2 (PR 3,5-T2/PR T3) was unaltered (16% vs. 15% in controls). The tyrosylic ring (5-) deiodination of T4 to rT3 was unaffected in patients with CRF, the CR being 42% vs. 40% in controls, in contrast to an enhanced CR of rT3 to 3',5'-T2 (53% vs. 29%, P less than 0.01), which also is a 5-deiodination step. In conclusion, our data show that CRF profoundly changes the kinetics of all iodothyronines studied. Furthermore, our data are compatible with the existence of more than one 5'-deiodinase as well as more than one 5-deiodinase in man. Topics: Adult; Aged; Diiodothyronines; Female; Humans; Iodine Radioisotopes; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Serum Albumin; Thyroid Hormones; Thyronines; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse | 1983 |
Characteristics of rT3 5'-monodeiodination in rat brain: comparison with T4 and T3 5-monodeiodinations.
The present study revealed the existence and some characteristics of rT3 5'-deiodinase in rat brain by measuring the production of 3,3'-T2 from rT3 by radioimmunoassay. The conversion of rT3 to 3,3'-T2 was dependent on the duration of the incubation, tissue amount, temperature and pH (the optimal pH was 8.0), suggesting its enzymatic nature. Apparent Km was estimated to be 0.16 microM and the Vmax was 139.3 fmol/mg protein/min. The converting activity was dependent on the concentration of dithiothreitol (DTT). In contrast to T4 or T3 5-deiodinase, rT3 5'-deiodinase activity in the rat brain was the highest in cerebellum and the activity was low in the neonatal rat brain. Moreover, the 5'-deiodinase activity was inhibited by propylthiouracil (PTU). These differences between rT3 5'-deiodinase and T4 or T3 5-deiodinase suggest that different deiodinases are present in rat brain, and the local conversion of thyroid hormone is important for its action in the central nervous system. Topics: Age Factors; Animals; Brain; Cerebellum; DDT; Diiodothyronines; Iodide Peroxidase; Male; Peroxidases; Propylthiouracil; Radioimmunoassay; Rats; Rats, Inbred Strains; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse | 1982 |
Inner ring monodeiodination of thyroxine and 3,5,3'-L-triiodothyronine in rat brain.
To elucidate the metabolism of thyroid hormone in the central nervous system (CNS), 5-monodeiodinating activities were studied by incubating T4 or T3 with an aliquot of the P2 fraction of the rat brain in the presence of dithiothreitol and measuring the amounts of rT3 or 3,3'-L-diiodothyronine (3,3'-T2) produced by RIA. The production of rT3 or 3,3'-T2 was dependent upon duration of the incubation, amount of tissue used, temperature, and pH (the optimal pH was 8.0). These findings show that these reactions are enzymic in nature. For the conversion of T4 to rT3, the Km was estimated to be 1.33 microM, and the Vmax was 173 fmol/mg protein . min. For the conversion of T3 to 3,3'-T2, the Km was estimated to be 2.31 microM, and the Vmax was 94 fmol/mg protein . min. Both the conversion of T4 to rT3 and that of T3 to 3,3'-T2 were dependent on the concentration of dithiothreitol, but were not inhibited by propylthiouracil, the well known inhibitor of 5'-deiodinating activity. Both activities were mainly found in the synaptosomal fractions. The P2 fraction from fetal and neonatal rat brains had significantly higher activity than that from the adult brain. These findings demonstrate the presence of 5-monodeiodinating activities in the rat brain. Topics: Aging; Animals; Animals, Newborn; Brain; Diiodothyronines; Dithiothreitol; Fetus; Kinetics; Male; Propylthiouracil; Rats; Rats, Inbred Strains; Subcellular Fractions; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse | 1981 |
3,3',5'-TRIIODOTHYRONINE AND 3,3'-DIIODOTHYRONINE: PARTIALLY DEIODINATED INTERMEDIATES IN THE METABOLISM OF THE THYROID HORMONES.
Topics: Autoradiography; Biliary Fistula; Chromatography; Diiodothyronines; Dogs; Hepatectomy; Iodine Isotopes; Metabolism; Pharmacology; Rats; Research; Thyroid Hormones; Thyronines; Triiodothyronine; Triiodothyronine, Reverse; Urine | 1963 |
On the metabolism of 3,3'-diiodothyronine and 3,3',5'-triiodothyronine.
Topics: Diiodothyronines; Thyronines; Triiodothyronine; Triiodothyronine, Reverse | 1959 |