Disease relevance of REVERSE TRIIODOTHYRONINE

• Metabolic effect of 3,3',5'-triiodothyronine in cultured growth hormone-producing rat pituitary tumor cells. Evidence for a unique mechanism of thyroid hormone action [1].
• Letter: Reverse T3 in screening for neonatal hypothyroidism [2].
• Propranolol influences serum T3 and reverse T3 in hyperthyroidism [3].
• Reverse triiodothyronine (rT3) levels were low in persons with AIDS-related complex (0.21 +/- 0.02 nmol/L, P less than 0.001) and in AIDS outpatients (0.17 +/- 0.02 nmol/L, P less than 0.001) [4].
• Peripheral conversion of T4 to T3 was apparently inhibited by diabetic ketoacidosis and there was a concomitant increase in rT3 levels, suggesting that conversion of T4 to rT3 was increased during acute ketoacidosis [5].

Psychiatry related information on REVERSE TRIIODOTHYRONINE

• Increased cerebrospinal fluid levels of 3,3',5'-triiodothyronine in patients with Alzheimer's disease [6].
• The TSH response to TRH (delta max TSH) and the serum concentrations of free thyroxine (FT4), 3,5,3'-, and 3,3',5'-triiodothyronine (FT3 and FrT3) were studied in two groups of patients with endogenous depression before and after clinical recovery following electroconvulsive treatment (ECT) [7].
• The significance of the present finding is unknown, but measurement of reverse T3 levels as a potential tool in differential diagnosis of affective disorders and in psychobiological research should be explored further [8].
• Low free T4, TSH and reverse T3 level associated with glue sniffing in our patient were compatible with central hypothyroidism [9].

High impact information on REVERSE TRIIODOTHYRONINE

• We have cloned and expressed a 2.1-kb human placental D3 cDNA which encodes a 32-kD protein with a Km of 1.2 nM for 5 deiodination of T3 and 340 nM for 5' deiodination of reverse T3 [10].
• However, the in vivo administration to rats of IOP or 3,3',5'-triiodothyronine (rT3) resulted in a noncompetitive pattern of inhibition of 5'DI in the liver, kidney, and thyroid gland, whereby marked decreases in maximal enzyme velocity (V max) were noted, with no change in the value of the Michaelis-Menten constant [11].
• Physiologic levels of 3,3',5'-triiodothyronine (rT3) are generally believed to have minimal metabolic effects in the pituitary gland and other tissues [1].
• The changes in serum thyroid-stimulating hormone (TSH), serum total T4, 3,5,3'-triiodothyronine (T3), free T3, and 3,5',3'-triiodothyronine (reverse T3, rT3) were measured, and the pituitary reserve in TSH was evaluated by a thyrotropin-releasing hormone (TRH) test [12].
• While 3, 3', 5'-triiodothyronine (reverse T3, rT3) has been detected both in human serum and in thyroglobulin, no quantitative assessment of its metabolic clearance rate (MCR), production rate (PR), or secretion by the thyroid is yet available [13].

Chemical compound and disease context of REVERSE TRIIODOTHYRONINE

• A combination of prothrombin time, aminopyrine breath test results, and rT3 and T3 determinations gave significant predictive information about survival in patients with cirrhosis [14].
• These data suggest: (a) T4, T3, and reverse T3 are all capable of bidirectional transfer across the blood brain barrier, (b) T3 may be a better agent than T4 in treating patients with myxedema coma because T3 crosses more rapidly and more completely from serum to CSF [15].
• Serum levels of free thyroxine (fT4), thyroid-stimulating hormone (TSH), reverse T3 (rT3), cortisol, insulin, and lactate were monitored in 16 patients before and after brain death and in 14 additional patients who were similarly compromised but did not become brain dead [16].
• Serum thyroxine (T4), triiodothyronine (T3), and reverse triiodothyronine (rT3) were followed for 24 h in dogs resuscitated following 9 min of controlled cardiac arrest (CA) [17].
• Amiodarone, a drug that has electrophysiologic actions resembling those of hypothyroidism, increases serum levels of T4 and reverse T3 (rT3) and decreases T3 [18].

Biological context of REVERSE TRIIODOTHYRONINE

• Peak levels of interleukin 6 correlated negatively with T3 (P =.005) and positively with rT3 (P<.05), suggesting that down-regulation before AMI may be cardioprotective [19].
• Reverse T3 (rT3) rose from 11 to 22 wk gestation without any effect of iodine status [20].
• 3,3',5'-Triiodothyronine inhibits collagen-induced human platelet aggregation [21].
• In those who survived, the most important changes within 48 h were seen in a normalization of cortisol and ACTH levels, but without a circadian rhythm; a decrease of rT3 and an increase in the T3/rT3 ratio; and a decrease in the levels of the nonesterified free fatty acids and an unaltered high urinary nitrogen excretion [22].
• The binding protein for reverse T3 (NrT3BP) in the rat liver nuclear extract was neither immunoprecipitated nor influenced in its rT3-binding activity by 4BII-IgG [23].

Anatomical context of REVERSE TRIIODOTHYRONINE

• Maternal thyroid function is the major determinant of amniotic fluid 3,3',5'-triiodothyronine in the rat [24].
• This activity: (a) manifested a Km for 3,3',5'-triiodothyronine of 0.24 microM, (b) was sensitive to inhibition by 6-n-propyl-2-thiouracil, and (c) was associated with the membrane fraction of oocyte homogenates [25].
• In addition, these studies demonstrate that 3,3'T2 is normally present in the peripheral circulation and suggest that reverse T3 is the major source of 3,3'T2 in both amniotic fluid and cord blood [26].
• Thyroidal secretion of reverse T3 was assessed by measurements in samples obtained from the internal carotid artery and jugular vein of sheep following the administration of thyrotropin releasing hormone (TRH) or bovine thyrotropin (TSH) [27].
• In thyroidectomized fetuses the levels of thyroxine (T4), tri-iodothyronine (T3) and reverse T3 (rT3) were very low except in one fetus which showed biochemical evidence of thyroid regeneration towards the end of gestation [28].

Associations of REVERSE TRIIODOTHYRONINE with other chemical compounds

• Pharmacokinetic significance of serum reverse T3 levels during amiodarone treatment: a potential method for monitoring chronic drug therapy [29].
• Affinity labeling of p27 by 0.4 nM BrAc[125I]L-T4 was blocked by 0.1 microM of the alkylating ligands BrAcT4, BrAcT3, or 100 microM iodoacetate, by 10 microM concentrations of the non-alkylating, reversible ligands N-acetyl-L-thyroxine, 3,3',5'-triiodothyronine, 3,5-diiodosalicylate, and EMD 21388, a T4-antagonistic flavonoid [30].
• Patients with supranormal serum free T4 concentrations (21 percent) ahd higher serum T4, lower serum T3, and higher serum reverse T3 (rT3) concentrations than other patients, but the measured changes in serum T4, TBG and TBPA levels could only partly account for the magnitude of the free T4 elevation [31].
• Significant increases in TSH, T4, fT4, T3, fT3, rT3, and cortisol and decreases in prolactin levels occurred during the night of SD, compared to the pattern during the night of sleep [32].
• Both pregnancy and estrogen administration were associated with increases in serum reverse T3 concentrations presumably because of their ability to augment thyroxine binding globulin synthesis [27].

Gene context of REVERSE TRIIODOTHYRONINE

• Apparent K(m) values for 3,3',5-triiodothyronine (T(3)), 3, 3'-diiodothyronine (3,3'-T(2)), 3',5',3-triiodothyronine (rT(3)), and 3,3',5,5'-tetraiodothyronine (T(4)) with SULT1C1 were 28.7, 10.3, 10.2, and 59.3 microM, respectively [33].
• METHODS: Fifty-two HIV-infected children receiving HAART were assessed for signs of thyroid dysfunction and serum concentrations of thyrotropin (TSH), free thyroxin (FT4), free triiodothyronine (FT3), thyroglobulin (TG), reverse triiodothyronine (rT3), anti-TG and antimicrosomal (anti-TSM) antibodies [34].
• The pro-hormone T4 (3,3',5,5'-triiodothyronine) is converted in the brain to its active form, T3, or its inactive metabolite, reverse T3, mainly by the action of deiodinase type 2 (DIO2) [35].
• Studies on the nature of thyroidal suppression during acute falciparum malaria: integrity of pituitary response to TRH and alterations in serum T3 and reverse T3 [36].
• Two groups of rats were infused with leptin for 6 days, one of them being additionally treated with reverse triiodothyronine (rT3), an inhibitor of D2 [37].

Analytical, diagnostic and therapeutic context of REVERSE TRIIODOTHYRONINE

• Radioimmunoassay for 3,3',5'-triiodo-L-thyronine in unextracted serum: method and clinical results [38].
• Effect of caloric restriction and dietary composition of serum T3 and reverse T3 in man [39].
• There was a significant negative relationship between body mass and body mass index and free T4, total T4, and 3,3',5'-triiodothyronine (rT3) [40].
• Neither thyroidectomy nor "reverse" T3 (rT3) (500 micrograms/kg) produced an effect on either receptor type [41].
• Esophageal ligation abolished the changes in fetal T4 but not rT3 [42].

References