thyronines and 3-3--diiodothyronine

Topics: Adult; Diiodothyronines; Female; Humans; Middle Aged; Pregnancy; Reference Values; Thyronines

Topics: Chemical Phenomena; Chemistry; Diiodothyronines; Diiodotyrosine; Glucuronates; Humans; Hyperthyroidism; Iodine; Kinetics; Phenyl Ethers; Radioimmunoassay; Sulfates; Thyronines; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

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

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

Hypothyroidism and low iodine intake may be important aetiological factors in oestrogen dependent tumours of the breast, uterus and ovary. They are preventable risk factors. Iodine supplementation will hopefully lead to a decreased incidence of these cancers in future generations. The present author proposes that the tyrosyl residue in the hydrophobic oestrogen binding site of the oestrogen receptor is post translationally modified to monoiodotyrosine and hence 3,3' di-iodothyronine monoamine (T2) by peroxidase activity. He has previously proposed that various monoamine receptors are also T2 based. The densities of these receptors are increased in hypothyroidism and they exert control over release of prolactin and other hormones, including melatonin at multiple sites in the hypothalamic--pituitary axis. Melatonin is a metabolite of serotonin and hence melatonin receptors may be T2 or rT3 based as well. These factors could be significant in the aetiology of breast cancer as high prolactin and melatonin levels may be protective. Oestrogen receptor density may be increased in hypothyroidism as is certain monoamine receptor density. This would amplify the effect of high circulation oestrogen levels in hypothyroidism and may help explain why hypothyroidism and low iodine intake are risk factors for breast, uterine and ovarian cancer.

Topics: Breast Neoplasms; Diiodothyronines; Dopamine; Female; Humans; Hypothyroidism; Iodine; Melatonin; Models, Biological; Prolactin; Receptors, Estrogen; Thyronines

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

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

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

To further characterize the effect of TSH administration on thyroid iodothyronine monodeiodinating activity, we have evaluated the in vitro conversion of T4 to T3 (outer ring deiodination) and T3 to 3,3'-diiodothyronine (T2; inner ring deiodination) by mouse thyroid, liver, and kidney homogenates, comparing tissues from TSH-treated mice (0.1-200 mU bovine TSH, ip, for 1-3 days) with tissues from saline-treated controls. The in vitro conversion activity was studied in the presence of 1-20 mM dithiothreitol; most of the studies were carried out at 4 mM. Studies were carried out at optimal pH 6.5 for outer ring and 7.8 for inner ring deiodination. The iodothyronine monodeiodinase in mouse thyroid is similar to the ones in liver and kidney. It is heat labile (inactivated at 56 C for 5 min), inhibited by propylthiouracil (0.2 mM) and ipodate (0.2 mM), and unaffected by methimazole (up to 20 mM), ascorbate (up to 0.1 M) or KI (up to 20 mM). The mean +/- SE baseline rates of T4 to T3 and T3 to T2 conversion were 100 +/- 6.3 and 56.5 +/- 2.9 pmol/mg thyroid protein X 30 min at 37 C, respectively. A significant increase in each conversion activity was found after TSH treatment (0.2 U, ip, daily for 3 days); T4 to T3 conversion rose to 282 +/- 15.4, and T3 to T2 increased to 153 +/- 7.4 pmol/mg thyroid protein (P less than 0.001). A 12.8% increase in thyroid weight was found in the TSH-treated group (P less than 0.03 compared with saline control group). Similar but less marked increased in monodeiodinating activities were seen in the liver. A minimal but significant increase in inner ring monodeiodination with no significant increase in T4 to T3 converting activity was found in kidney, which, in the mouse, has markedly less outer ring deiodinase than liver or thyroid. The iodothyronine monodeiodinating activities did not increase until 12 h in thyroid and 48 h in liver after the first dose of TSH. Significant increases in T4 to T3 and T3 to T2 conversion were seen with doses of TSH as low as 0.1 mU (ip, daily for 3 days), and there was a linear dose-response thereafter. The decay of the increased iodothyronine monodeiodinating activities after a single dose of TSH (0.2 U) appeared to be linear, with a decay t 1/2 of 1.3 days for T4 to T3 conversion and about 1.0 day for T3 to T2 conversion.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Diiodothyronines; Female; Kidney; Liver; Mice; Mice, Inbred Strains; Organ Size; Proteins; Thyroid Gland; Thyronines; Thyrotropin; Thyroxine; Triiodothyronine

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

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

T4-analogs modified at the aliphatic side chain R are substrates for rat liver microsomal iodothyronine-5'(3')-deiodinase (ITH-D). The variation of the substrate constitution allows a mapping of the ITH-D substrate ligand-binding site. Highest affinity for the ITH-5'(3')-D was presented by Tetrac among a homologous series of carboxylic acid side chain analogs. A net negative charge of the side chain and/or the blockage of the amino function increase the affinity of the enzyme-ligand interaction. However, not only charge (electrostatic interactions), but also steric (constitution) and configurational (D-, L-alanine) contributions affect the ligand-binding site interaction. These studies present further evidence that the route of deiodination is dependent on properties of the ligand-binding site and/or catalytically-active site of the enzyme, and not on the pKa-value of the 4'-OH-group of the ITH-analogue ligands. Alterations of incubation-pH change the dissociation state of the thiolate-imidazolium ion-pair of the enzyme ligand-binding site. This can provoke changes in the enzymic route of the T4-monodeiodination cascade from 5'(3')- to the 5(3)-deiodination pathway and vice versa. The same shift can be obtained by the choice of the configuration of the alanine side chain. ITH-D exhibits substrate (ligand) binding characteristics similar to both TBPA and the nuclear T3-receptor with respect to the ITH-analogue side chain constitution: All three prefer acetic acid derivatives as ligands. In contrast to the nuclear T3-receptor both ITH-D and TBPA prefer ITH-(analogues) with a 3',5'-disubstitution which yields a dissociated 4'-phenoxi group of the molecule. These similarities may suggest that ITH-binding proteins, ITH-receptors and ITH-metabolizing enzymes may represent a closely related family of proteins. They may possibly be derived from a common ancestral ITH-binding protein. The limited substrate specificity of rat liver ITH-D, which fulfills a major contribution in ITH-metabolism in vivo, may be of physiological relevance for the poorly characterized metabolism of naturally occurring (Tetrac) and pharmacologically important (D-T4) ITH-analogs.

Topics: Animals; Diiodothyronines; Iodide Peroxidase; Kinetics; Microsomes, Liver; Peroxidases; Radioimmunoassay; Rats; Structure-Activity Relationship; Substrate Specificity; Thyronines; Triiodothyronine

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

The splanchnic extraction of 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) was studied in 7 hyperthyroid patients and 20 normal subjects employing the hepatic venous catheterization technique. A significant net uptake by splanchnic tissues was found for both diiodothyronines . The fractional splanchnic extraction calculated as the arterio-hepatic venous plasma concentration difference divided by the arterial concentration was unaffected by hyperthyroidism as compared to normal values. There was a close positive correlation between the arterio-hepatic venous concentration difference and arterial concentration, 3,3'-T2: r = 0.988, and 3',5'-T2: r = 0.932 (P less than 0.001). The splanchnic extraction was nonsaturable at endogenous plasma concentrations of 3,3'-T2 up to at least 17.0 ng/dl and of 3',5'-T2 up to at least 15.2 ng/dl. The data suggest that the splanchnic extraction of 3,3'-T2 and 3',5'-T2 obeys first order kinetics, the fractional extraction being unaffected by hyperthyroidism. Furthermore, changes in the net splanchnic extraction of 3,3'-T2 and 3',5'-T2 do not seem to contribute to changes in circulating levels of these iodothyronines. It is suggested that tissues other than the liver contribute significantly to the deiodination process both in normal and in hyperthyroid man.

Topics: Adolescent; Adult; Diiodothyronines; Female; Humans; Hyperthyroidism; Kinetics; Liver; Male; Mesentery; Middle Aged; Thyronines

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

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

To investigate the thyroid hormone metabolism in altered states of thyroid function, serum concentrations of 3, 3'-diiodothyronine (3, 3'-T2), 3', 5'-T2 and 3, 5-T2 as well as T4, T3 and rT3 were determined by specific radioimmunoassays in 17 hyperthyroid and 10 hypothyroid patients, before and during the treatment. Serum T4, T3, rT3, 3, 3'-T2 and 3', 5'-T2 concentrations were all higher in the hyperthyroid patients than in age-matched controls and decreased to the normal ranges within 3 to 4 months following treatment with antithyroid drugs. In the hypothyroid patients, these iodothyronine concentrations were lower than in age-matched controls and returned to the normal ranges after 2 to 3 months treatment with T4. In contrast, serum 3, 5-T2 concentrations in hyperthyroid patients (mean +/- SE : 4.0 +/- 0.5 ng/dl) were not significantly different from those in controls (3.9 +/ 0.4 ng/dl), although they tended to decrease in 3 of 6 patients after the antithyroid drug therapy. Serum 3, 5-T2 levels in the hypothyroid patients (3.8 +/- 0.6 ng/dl) were also within the normal range and showed no significant change following the T4 replacement therapy. However, serum 3, 5-T2 as well as 3, 3'T2 concentrations rose significantly with a marked rise in serum T3 following T3 administration, 75 micrograms/day for 7 days, in Graves' patients in euthyroid state.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Diiodothyronines; Humans; Hyperthyroidism; Hypothyroidism; Middle Aged; Thyronines; Thyroxine; Triiodothyronine

A RIA for 3-monoiodothyronine (3T1) using tritiated ligand, has been validated for measurement of extracted serum. The mean euthyroid level of serum 3T1 was 2.9 +/- 1.7 ng/dl. In thyrotoxic patients, the mean serum 3T1 was significantly higher: 6.2 +/- 3.9 ng/dl (P less than 0.001) and in hypothyroid patients, the mean level was 2.1 +/- 1.5 ng/dl, lower but not significantly lower than the mean euthyroid level (P greater than 0.05). The mean serum level in severely ill patients was 2.5 +/- 1.5 ng/dl (P greater than 0.05) and in cord blood was significantly higher at 9.1 +/- 2.6 ng/dl (P less than 0.001). The appearance of 3T1 within 5 min in two normal volunteers after iv injection of 3,3'-diiodothyronine was followed over 2 1/2 h. Thus 3T1 is a normal constituent of human plasma and is derived from 3,3'-diiodothyronine. Its concentrations appear to be severalfold higher than those reported for 3'T1.

Topics: Adult; Contraceptives, Oral; Diiodothyronines; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Radioimmunoassay; Thyronines

Topics: Adult; Aged; Diiodothyronines; Female; Humans; Hyperthyroidism; Hypothyroidism; Kinetics; Male; Metabolic Clearance Rate; Middle Aged; Thyronines

The effect of complete fasting on the serum concentrations of the iodothyronines 3,5-diiodothyronine (3,5-T2), 3,3'T2, 3', 5'-T2 and 3'-monoiodothyronine (3'-T1) was evaluated. Fourteen obese women underwent a complete fasting for 4 days. Caloric restriction resulted in the following serum hormone levels (before vs 3. day): T4: 103 vs 109 nmol/l (NS), T3: 1.83 vs 1.24 nmol/l (p less than 0.01), rT3: 0.276 vs 0.407 nmol/l (P less than 0.01), 3.5-T2: 70 pmol/l (NS), 3.3'-T2: 42 vs 39 pmol/l (p less than 0.01), 3',5'-T2: 63 vs 93 pmol/l (P less than 0.01), and 3'-T1 60 vs 116 pmol/l (P less than 0.01). All subjects were refed with 200 g (800 kcal, 3350 kJ) d-glucose per day in divided doses for 2 days. Refeeding tended to normalize the changed iodothyronine concentrations and there was no difference whether the glucose was administered by the oral (n = 7) or the intravenous route. In can be concluded that starvation in man is accompanied by profound changes in peripheral metabolism of the T2's and 3'T1. There seems to be no qualitative difference of the effect on the thyroid hormone metabolism of d-glucose administered by the oral or the intravenous route.

Topics: Administration, Oral; Adolescent; Adult; Diiodothyronines; Eating; Fasting; Female; Glucose; Humans; Injections, Intravenous; Obesity; Thyronines

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

RIAs for the estimation of 3',5'-diiodothyronine (3',5'-T2) and 3,3'-diiodothyronine (3,3'-T2) in human urine have been established. The urinary excretion of both glucuronide and sulfate conjugates of T2 and of T4, T3, and rT3 were estimated by means of enzymatic deconjugation. In healthy controls, the mean excretion (picomoles per 24 h) of free T4 was 1820, that of free T3 was 813, that of free rT3 was 77, that of free 3',5'-T2 was 13, and that of free 3,3'-T2 was 674. The total excretion of free and conjugated T4 was 2941, that of T3 was 1283, that of rT3 was 791, that of 3',5'-T2 was 709, and that of 3,3'-T2 was 2688. Significant amounts of sulfated T4 and T3 could not be demonstrated, amounts of sulfated T4 and T3 could not be demonstrated, whereas the excretion of sulfated rT3 was higher than that of glucuronidated rT3 (P less than 0.001). In contrast, glucuronidated and sulfated 3',5'-T2 as well as glucuronidated and sulfated 3,3'-T2 were found in the urine in equal amounts. In hyperthyroidism, the excretions of free and glucuronidated iodothyronines were increased, whereas the increase of the excretions of sulfated iodothyronines were less pronounced, only reaching statistical significance for 3,3'-T2 (P less than 0.02). In hypothyroidism, the excretions of both free, glucuronidated and sulfated iodothyronines were reduced. Significant amounts of sulfated T4 and T3 could not be demonstrated in urine from hyperthyroid or hypothyroid patients. Our data demonstrate that the amounts of free iodothyronines excreted in the urine vary considerably, suggesting active renal handling. The amounts of urinary glucuronidated and sulfated conjugates of the different iodothyronines studied vary considerably and are affected by thyroid function.

Topics: Cross Reactions; Diiodothyronines; Glucuronates; Humans; Hyperthyroidism; Hypothyroidism; Radioimmunoassay; Sulfuric Acids; Thyroid Gland; Thyronines

An heterologous radioimmunoassay for measurement of 3'-monoiodothyronine (3'T1) has been developed using pure 3'T1 as standard, (125I)DL3'T1 and an anti 3,3'L-diiodothyronine antiserum. The assay utilizes Sephadex G25F minicolumns to separate 3'T1 from other endogenous iodothyronines. 8-anilino-1-naphthalene sulphonic acid was used to inhibit binding of 3'T1 to serum binding proteins. Sensitivity was approximately 3.2 pmol/l. The mean serum 3'T1 concentration was 7.4 pmol/l in normal subjects, 30.8 pmol/l in thyrotoxic patients, 4.1 pmol/l in hypothyroid patients, 23.2 pmol/l in patients with severe non-thyroidal illness and 109.8 pmol/l in cord blood. Increased levels of 3'T1 were found in two normal volunteers who were injected with 3,3'T2, demonstrating that 3'T1 is derived from 3,3'T2 in extrathyroidal tissues. These studies suggest that 3'T1 is a minor iodothyronine metabolite in the human. It is unlikely to have significant biological relevance.

Topics: Adult; Diiodothyronines; Female; Fetal Blood; Humans; Hyperthyroidism; Hypothyroidism; Infant, Newborn; Male; Middle Aged; Radioimmunoassay; Reference Values; Thyronines

Previous studies employing perfused dog thyroid lobes have shown that thyroidal secretion is modulated by intrathyroidal deiodination of T4 to T3 and rT3. To characterize further the intrathyroidal iodothyronine-deiodinating processes 3,3'-diiodothyronine (3,3'-T2) and T4 were measured in hydrolysate and effluent from isolated dog thyroid lobes during single passage perfusion with a synthetic hormone-free-medium. In five experiments the concentrations in effluent from unstimulated thyroid lobes were: 3,3'-T2, 208 +/- 62 pmol/liter; and T4, 12.8 +/- 2.8 nmol/liter (mean +/- SE). During the infusion of 100 microU/ml TSH, there was a parallel increase in the secreton of 3,3'-T2 and T4. After approximately 90 min of TSH infusion, effluent concentrations were: 3,3'-T2, 2490 +/- 420 pmol/liter; and T4, 204 +/- 24 nmol/liter. In a pronase hydrolysate of the thyroid lobes, the amounts were: 3,3'-T2, 2.44 +/- 0.56 pmol/mg; and T4, 1070 +/- 125 pmol/mg. Expressed as a percent of T4, the amount of 3,3'-T2 in thyroid effluent was approximately 10 times higher than that in thyroid hydrolysate. This relative hypersecrection of 3,3'-T2 was abolished by the infusion of 10(-3) or 10(-5) M propylthiouracil, an inhibitor of peripheral and intrathyroidal iodothyronine deiodination. Thus, thyroid secretion contains small amounts of 3,3'-T2, most of which seems to originate from intrathyroidal deiodination of T3 and/or rT3.

Topics: Animals; Diiodothyronines; Dogs; In Vitro Techniques; Perfusion; Propylthiouracil; Thyroid Gland; Thyronines; Thyrotropin; Thyroxine

Topics: Autoradiography; Biliary Fistula; Chromatography; Diiodothyronines; Dogs; Hepatectomy; Iodine Isotopes; Metabolism; Pharmacology; Rats; Research; Thyroid Hormones; Thyronines; Triiodothyronine; Triiodothyronine, Reverse; Urine

Topics: Diiodothyronines; Thyronines; Triiodothyronine; Triiodothyronine, Reverse

Topics: Animals; Diiodothyronines; Health Services; Swine; Thyroglobulin; Thyroid Gland; Thyronines; Triiodothyronine; Viscera