Identification of 3,3′-Diiodothyroacetic Acid Sulfate: A Major Metabolite of 3,3′,5-Triiodothyronine in Propylthiouracil-Treated Rats*

Rutgers, Marja; Heusdens, Frank A.; Bonthuis, Fred; Rooda, Sebojan Eelkman; Visser, Theo J.

doi:10.1210/endo-127-4-1617

Cited by 4 publications

(4 citation statements)

References 24 publications

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“…They used HPLC of bile after the administration of '251-T4 and suggested T3-glucuronate to rT3-glucuronate ratio as a sensitive indicator of type I deiodinase inhibition. The same authors later found the accumulation of some T3 metabolites in plasma as early as 1 h after the administration of 1 mg/lOO g PTU (Rutgers et al, 1990). Our results appear to be in aggreement with those findings with the exception of T3.…”

Section: Resultssupporting

confidence: 90%

“…The administration of PTU results in a decrease of thyroxine (T4) to triiodothyronine (T3) conversion in peripheral tissues which further results in decreased serum T3 and increased serum reverse triiodothyronine (rT3). Recently, marked accumulation of 3,3'-diiodothyroacetic acid sulphate and triiodothyronine sulphate was found in the plasma of PTU administerd rats (Rutgers et al, 1990) which apparently resulted from the impaired activity of type I deiodinase. Leonard and Visser (1986) reported a covalent binding of PTU to a cystein residue at the enzyme's active site to form an inactive mixed disulphide (i.e.…”

Section: Introductionmentioning

confidence: 99%

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Immediate and Dose-Response Related Increase of Biliary Excretion of Reverse Triiodothyronine after Propylthiouracil Administration

Langer¹,

Gschwendtová²

2009

Exp Clin Endocrinol Diabetes

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In a group of rats infused with L-thyroxine (0.13 micrograms T4 in 0.6 ml alkaline saline per hour) for 6 h to which an infusion of propylthiouracil (PTU) was added beginning from the 3rd hour (2 mg PTU in 0.6 ml saline per hour) a significant increase of biliary excretion of reverse triiodothyronine (rT3) was found. In another experiment a dose-response related rT3 excretion by bile was observed in groups of rats infused with 0.05, 0.10, 0.20 or 0.40 mg PTU in 1.2 ml alkaline saline per 2 h, all animals receiving a pulse dose of 1 micrograms rT3 at the beginning of PTU infusion. It was concluded that the increase of rT3 excretion results from the inhibition of 5'-deiodinase type I activity in the liver caused by PTU. It thus appears that such phenomenon may be used as in vivo marker of that enzyme activity.

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Section: Resultssupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Immediate and Dose-Response Related Increase of Biliary Excretion of Reverse Triiodothyronine after Propylthiouracil Administration

Langer¹,

Gschwendtová²

2009

Exp Clin Endocrinol Diabetes

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“…Alternatively, the relatively stable level of TriacS could be due to a reduction in the removal of TriacS by outer-ring deiodination, mediated by type I deiodinase, to 3,3=-DiacS (19 -21). The role of glucuronidation of Triac is less well characterized in sheep (21,22); in addition, the enzyme activity is significantly less in ovine fetal liver (23). The observed rapid reduction of serum TriacS levels in newborns compared with fetuses ( Fig.…”

Section: Discussionmentioning

confidence: 99%

3′-Monoiodothyronine Sulfate and Triac Sulfate Are Thyroid Hormone Metabolites in Developing Sheep

Polk

Huang³

et al. 2008

Pediatr Res

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ABSTRACT:We used novel 3=-monoiodothyronine sulfate (3=-T 1 S) and 3,3=,5-triiodothyroacetic acid sulfate (TriacS) RIAs to characterize sulfation pathways in fetal thyroid hormone metabolism. 3=-T 1 S and TriacS levels were measured in serum samples obtained from fetal (n ϭ 21, 94 -145 d gestational age), newborn (NB, n ϭ 5), and adult sheep (AD, n ϭ 5) as well as from fetuses after total thyroidectomy (Tx), or sham-operated twin fetuses controls, conducted at gestational age 110 -113 d (n ϭ 5). Peak levels (expressed as ng/dL) of both 3=-T 1 S and TriacS occurred at 130 d gestation. These levels in fetuses were higher than those in NB and AD. In Tx fetuses, there was a significant decrease in the mean serum level of 3=-T 1 S, but not TriacS. The decrease in 3=-T 1 S in Tx is similar to that observed for thyroxine sulfate (T 4 S) and 3,3=,5=-triiodothyronine sulfate (rT 3 S), whereas TriacS levels were not altered in the hypothyroid state, similarly to 3,3=,5-triiodothyronine sulfate (T 3 S). These data demonstrate that 3=-T 1 S and TriacS are normal thyroid hormone metabolites in ovine serum and that TriacS is likely derived from T 3 S or from the same precursor(s) as T 3 S. W e have identified the sulfated iodothyronines, thyroxine sulfate (T 4 S), 3,3=,5-triiodothyronine (T 3 S), 3,3=,5=-triiodothyronine sulfate (reverse T 3 S) (rT 3 S), and 3,3=-diiodothyronine sulfate (3,3=-T 2 S), as important thyroid hormone metabolites in ovine and human fetal fluids (1-5). The relatively high concentrations of these sulfated iodothyronines in the developing fetus probably reflect the low type I deiodinase activities observed in fetal tissues (6,7). To further characterize metabolism of the sulfated iodothyronines in ovine fetuses, we developed sensitive and specific 3=-T 1 S and 3,3=-5-triiodothyroacetic acid sulfate (TriacS) RIAs to quantify 3=-T 1 S and TriacS levels in normal and hypothyroid fetal and maternal serum. In previous studies of hypothyroid fetuses, we found significant reductions of mean serum concentrations of T 4 S and rT 3 S, but not T 3 S, suggesting that T 3 , presumably the precursor of T 3 S, was derived from T 3 in tissue. Hypothyroidism may result in a compensatory increase in activity of type II 5=-deiodinase, which tends to maintain tissue T 3 in a relatively normal range (8,9). The present study is to determine whether serum levels of TriacS and/or 3=-T 1 S are reduced in fetal hypothyroidism. MATERIALS AND METHODS 3=-T 1 S and TriacS RIAs. 3=-T 1 S and 3=-[125 I]T 1 S as well as TriacS and [ 125 I]TriacS were prepared by the method of Eelkman-Rooda and co-workers (10,11). 3=-T 1 S and TriacS in 0.025 N NaOH (4 mg/mL) were further purified and quantitatively recovered by reverse-phase HPLC with a preparative column (Biochrom 1010 ODS; Regis, Morton Grove, IL). The products were eluted isocratically with a mixture of acetonitrile and 20 mM ammonium acetate, pH 4.0 (22:78 vol/vol), at a solvent flow of 10 mL/min. 3=-T 1 S and TriacS were recovered with purity Ͼ99%, as assessed by HPLC.The RIA fo...

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“…Additionally, T1AC has been detected in vivo at about 300 pg/g in mouse brain , (Figure , Table S1). Early studies also found sulfated 3,3′-diiodothyroacetic acid (3,3′-T2ACS) in human and rat serum after T3AC administration, suggesting that further metabolism of T3AC involves deiodination and sulfation. , Sulfation of T3AC and 3,3′-T2AC has been observed in rat liver microsomes . Sulfation of T3AC is believed to promote its deiodination .…”

Section: Thyroid Hormone Metabolism and Their Distributionmentioning

confidence: 98%

Thyroid Hormone Biomonitoring: A Review on Their Metabolism and Machine-Learning Based Analysis on Effects of Endocrine Disrupting Chemicals

Chen,

Yu,

Yao

et al. 2024

Environ. Health

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The thyroid is an essential endocrine organ in human body, and thyroid hormones (THs) are pivotal signaling molecules and mediators in various physiological processes. THs, particularly in their free form, play a critical role in regulating body temperature and in the metabolism of lipid and glucose, making the maintenance of TH levels crucial for human health. THs undergo a series of metabolic processes, producing TH metabolites (THMs). THMs are significant in endocrine regulation, such as 3,5-diiothyronine (3,5-T2) and 3-iodothyronamine (3-T1AM), which exhibit activities akin to THs. The production and distribution of THMs are intricately linked to the function of specific organs and tissues, highlighting the need for advanced research into the determination and mechanisms of THMs in body. Exposure to endocrine disrupting chemicals (EDCs) can significantly affect the levels of thyroid stimulating hormone (TSH) and THs. This review utilizes machine learning to analyze epidemiological data, identifying potential EDCs that pose risks of hyperthyroidism and hypothyroidism. Additionally, it delves into the toxicological mechanisms of these EDCs, examining their effects on TH production, binding processes, related proteins, and metabolic enzymes. This approach effectively bridges the gap between epidemiological studies and toxicological researches, laying the groundwork for future research trends. By integrating epidemiological studies with machine learning, this review offers insightful perspectives on the potential risks associated with chemical exposure and underscores the necessity for further research in understanding the impact of EDCs on TH metabolism and TH-related health effects.

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Identification of 3,3′-Diiodothyroacetic Acid Sulfate: A Major Metabolite of 3,3′,5-Triiodothyronine in Propylthiouracil-Treated Rats*

Cited by 4 publications

References 24 publications

Immediate and Dose-Response Related Increase of Biliary Excretion of Reverse Triiodothyronine after Propylthiouracil Administration

Immediate and Dose-Response Related Increase of Biliary Excretion of Reverse Triiodothyronine after Propylthiouracil Administration

3′-Monoiodothyronine Sulfate and Triac Sulfate Are Thyroid Hormone Metabolites in Developing Sheep

Thyroid Hormone Biomonitoring: A Review on Their Metabolism and Machine-Learning Based Analysis on Effects of Endocrine Disrupting Chemicals

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