Disease relevance of 3,3'-T2

• 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) [1].
• Serum concentrations of 3,3'-T2 were measured in 4 groups of patients with nonthyroidal illnesses (NTI), i.e. brain injuries (n = 15), sepsis (n = 24), liver disease (n = 22), and brain tumors (n = 23) [2].
• Serum T4, T3, and 3,3'-T2 levels were reduced in patients with liver cirrhosis, whereas serum rT3 and 3',5'-T2 levels were increased, Serum 3'-T1 levels were unaltered [3].
• In conclusion, our results show that, contrary to expectation, a low T3 syndrome in NTI is not always associated with low serum concentrations of 3,3'-T2 [2].
• The inner ring monodeiodination [T4 to rT3, T3 to 3,3'-diiodothyronine(3,3'-T2)] as well as the outer ring monodeiodination (T4 to T3, rT3 to 3,3'-T2) was demonstrated with thyroid tissues obtained from patients with Graves' disease by measuring the products by RIAs [4].

High impact information on 3,3'-T2

• 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 [5].
• Plasma 3,3'-T2 as well as 3'5'-T2 levels were higher in the renal vein as compared to arterial values, 1.49 +/- 0.42 vs. 1.39 +/- 0.45 ng/dl (P < 0.05) and 2.35 +/- 0.83 vs. 2.09 +/- 0.81 ng/dl (P < 0.05), respectively [6].
• To determine the metabolism of 3,3'-T2 and 3',5'-T2 in human liver and kidneys plasma samples were obtained from (a) a brachial artery and a hepatic vein in 20 normal subjects, and from (b) a femoral artery and a renal vein in 11 normal subjects [6].
• Thyroid hormonelike actions of 3,3',5'-L-triiodothyronine nad 3,3'-diiodothyronine [7].
• In this orientation the 5-cyano group occupies the same site as the 3'-iodine in the TTR complex with 3,3'-diiodothyronine (Wojtczak, A., Luft, J., and Cody, V. (1992) J. Biol. Chem. 267, 353-357), which is 3.5 A deeper in the channel than thyroxine (Blake, C. C. F., and Oately, S. J., (1977) Nature 268, 115-120) [8].

Chemical compound and disease context of 3,3'-T2

• Serum levels of T4, T3, reverse T3, 3,3'-diiodothyronine and 3',5'-diiodothyronine in obesity, before and after jejuno-ileal bypass [9].
• Dynamics of serum rT3 and 3,3'-T2 during rT3 infusion in patients treated for thyrotoxicosis with propylthiouracil or methimazole [10].
• The cultured rat hepatoma cell (R117--21B) homogenates metabolized 3,[3',5'-125I]triiodothyronine by phenolic ring deiodination and produced radioactive iodide and 3,3'-diiodothyronine [11].

Biological context of 3,3'-T2

• A statistical disorder model for the ligand was applied with a 50% occupancy to account for the discrepancy between the crystallographic 2-fold symmetry of the binding sites and the lack of such symmetry for 3,3'-T2 [12].
• 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 [13].
• The latter submodel was patterned initially after 3,3'-diiodothyronine kinetics [14].
• The rabbit antiserum to rT3S was highly specific; T4, T3, rT3, and 3,3'-T2 showed less than 0.002% cross-reaction with the antiserum [15].
• 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 [16].

Anatomical context of 3,3'-T2

• In conclusion, significant production of 3,3'-T2 from rT3 by rat hepatocytes is only observed if further sulfation is inhibited [5].
• The inhibition profiles of the 3,3'-T2 sulfotransferase activities of liver and kidney cytosol obtained by addition of 10 micromol/L of the various analogs were better correlated with the inhibition profile of SULT1A1 than with that of SULT1A3 [17].
• After 20-h incubation, the percentage of added radioactivity present as conjugates in the media and oocytes amounted to 0.9 +/- 0.2 and 1.0 +/- 0.1 for T4, less than 0.1 and less than 0.1 for T3, 32.5 +/- 0.4 and 29.3 +/- 0.2 for rT3, and 3.8 +/- 0.3 and 2.3 +/- 0.2 for 3,3'-T2, respectively (mean +/- SEM; n = 3) [18].
• For the nonhormonal iodothyronines, about 6% of injected monoiodothyronine, 3% of injected 3',5'-T2, 2% of injected 3,3'-T2, and less than 1% of injected rT3 were excreted in feces as such, indicating that these substances are nearly completely deiodinated in vivo [19].
• As confirmed by incubations with isolated rat liver microsomes, direct inner ring deiodination of T3 is largely mediated by a low Km, PTU-insensitive, type III-like iodothyronine deiodinase, and production of 3,3'-T2 is only observed if its rapid sulfation is prevented [20].

Associations of 3,3'-T2 with other chemical compounds

• The three-dimensional structure of the thyroid hormone metabolite, 3,3'-diiodo-L-thyronine (3,3'-T2), complex with human serum transthyretin (TTR) has been refined to R = 18.5% for 8-2 A resolution data [12].
• Measurements of serum 3',5'-diiodothyronine and 3,3'-diiodothyronine concentrations in normal subjects and in patients with thyroid and nonthyroid disease: studies of 3',5'-diiodothyronine metabolism [21].
• A 3,3'-diiodothyronine sulfate cross-reactive compound in serum from pregnant women [22].
• Human placental homogenate deiodinates the tyrosyl ring of T4 and T3, converting these active thyroid hormones to the inactive iodothyronines, rT3 from T4, and 3,3'-diiodothyronine and 3'-monoiodothyronine from T3 [23].
• The extrathyroidal effect of D,L-propranolol on 3,3',5'-triiodothyronine, 3',5'-diiodothyronine, 3,3'-diiodothyronine, and 3'-monoiodothyronine kinetics [24].

Gene context of 3,3'-T2

• The apparent Km of PAPS (at 0.1 micromol/L 3,3'-T2) was 6.0 micromol/L for liver cytosol, 9.0 micromol/L for kidney cytosol, 0.65 micromol/L for SULT1A1, and 2.7 micromol/L for SULT1A3 [17].
• 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 [25].
• Type III iodothyronine deiodinase (D3) catalyzes the inner ring deiodination (IRD) of T4 and T3 to the inactive metabolites rT3 and 3,3'-diiodothyronine (3,3'-T2), respectively [26].
• Serum T4S and the activities of hepatic D1 and 3,3'-diiodothyronine (T2)-SULT and estrogen-SULT were determined [27].
• 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 [28].

Analytical, diagnostic and therapeutic context of 3,3'-T2

• In five experiments, the percent composition of 125I-labeled iodothyronines in the perfusion buffer and placenta effluent was 95.3 +/- 1.0 (mean +/- SE) and 70.2 +/- 2.1 for T3 (P less than 0.01), 2.5 +/- 0.7 and 20.1 +/- 1.8 for 3,3'-T2 (P less than 0.01), and 0 and 8.2 +/- 0.9 for 3'-T1 [29].
• The sulfates and sulfamates of T4, T3, rT3, and 3,3'-diiodothyronine could be separated by reverse phase HPLC [30].
• This low value was attributable to two factors: 1) the use of a diet low enough in iodine content to produce extreme iodine deficiency, and 2) the use of a paper chromatography system that successfully separates T4 from the minor iodothyronines, 3,3'-diiodothyronine (T2) and 3',5',3-triiodothyronine (reverse T3; T3') [31].
• The development of a highly sensitive and specific radioimmunoassay for 3,3'-di-iodothyronine (3,3'-T2) is described [32].
• The results indicate that the high serum rT3 observed during treatment with PTU is not due to an increase in rT3 production, but to a decrease in the metabolic clearance rate of rT3. rT3 infusion was followed by an increase in serum 3,3'-T2 which was similar whether PTU or MMI was given [10].

References