Effects of triiodothyronine on turnover rate and metabolizing enzymes for thyroxine in thyroidectomized rats

Nagao, Hidenori; Sasaki, Makoto; Imazu, Tetsuya; Takahashi, Kenjo; Aoki, Hironori; Minato, Kouichi

doi:10.1016/j.lfs.2014.09.016

Cited by 4 publications

(5 citation statements)

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“…Intracellular T 4 and T 3 levels decrease after Tx [24]. Moreover, we previously reported that activity and mRNA expression of D2 in brain, BAT, and muscle were increased after Tx in rats [25]. Thus, our findings suggest that the BAs (CA, CDCA, and TCDCA) act as a signaling molecule to increase intracellular T 3 levels in local tissues by accelerating the above mechanisms (the BA-TGR5-cAMP-D2-T 3 pathway).…”

Section: Discussionsupporting

confidence: 57%

“…Intracellular T 3 concentrations in BAT and brain are supplied at a ratio of 50:50 and 20:80 from these two pathways, respectively [30,31]. Moreover, we have previously reported that activity and mRNA expression of D2 in local tissues of Tx rats were maintained at high levels after T 3 replacement [25]. These results indicate that serum BA levels were maintained at a high level because intracellular TH concentrations in Tx rats were not normalized to physiological levels by T 3 replacement.…”

Section: Discussionmentioning

confidence: 99%

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Serum Metabolomics Reveals Cholic Acid, Chenodeoxycholic Acid, and Taurochenodeoxycholic Acid as Potential Biomarkers for Hypothyroid Rats

Nagao¹

2015

AJLS

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Hypothyroidism decreases energy metabolism including carbohydrate and lipid metabolism and protein synthesis, due to reduced serum levels of the thyroid hormones thyroxine (T 4) and triiodothyronine (T 3). Although many endogenous serum metabolites are influenced by hypothyroidism, serum metabolomic profiling has rarely been applied to the study of hypothyroidism. In the present study, we investigated potential biomarkers for hypothyroidism using serum metabolomics, and then measured serum levels of these endogenous metabolites using an analytical method: ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. There was a significant difference in the metabolic profiles of thyroidectomized (Tx) and normal rats. We found that many bile acid (BA) levels were significantly changed in serum of Tx rats. Simultaneous measurement of 12 different BAs in serum revealed that cholic acid (CA), chenodeoxycholic acid (CDCA), and taurochenodeoxycholic acid (TCDCA) levels significantly increased in Tx rats by approximately 25-fold, 11-fold, and 3-fold, respectively, compared with those of control rats. In Tx rats with active hormone T 3 replacement, serum T 3 levels were returned to physiological levels. However, these changes in BA levels were maintained at a high level. These results indicate that T 3 replacement does not normalize the thyroid hormonal milieu. Thus, increased CA, CDCA, and TCDCA levels in serum after Tx may be a homeostatic response to not only T 3 but also pro-thyroid hormone T 4 deficiency. This study is the first to report that CA, CDCA, and TCDCA may be potential biomarkers for hypothyroidism and the efficacy of thyroid hormone replacement therapy in hypothyroidism.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Serum Metabolomics Reveals Cholic Acid, Chenodeoxycholic Acid, and Taurochenodeoxycholic Acid as Potential Biomarkers for Hypothyroid Rats

Nagao¹

2015

AJLS

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“…According to our data, D2 mRNA level in mesenteric arteries is several times lower than that in saphenous artery. The D2 mRNA level was shown to correlate with the D2 enzyme activity in brain, skeletal muscle and brown adipose tissue of rats (Nagao et al 2014). Assuming such correlation in vascular tissue, we would expect lower D2 activity as a reason for particular susceptibility of the mesenteric arteries to the thyroid hormones deficiency.…”

Section: Ptu Effects In Dams and Their Male Offspringmentioning

confidence: 90%

Antenatal/early postnatal hypothyroidism alters arterial tone regulation in 2-week-old rats

Софронова

Gaynullina

Shvetsova

et al. 2017

Journal of Endocrinology

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The mechanisms of vascular alterations resulting from early thyroid hormones deficiency are poorly understood. We tested the hypothesis that antenatal/early postnatal hypothyroidism would alter the activity of endothelial NO pathway and Rho-kinase pathway, which are specific for developing vasculature. Dams were treated with propylthiouracil (PTU, 7 ppm) in drinking water during gestation and 2 weeks after delivery, and their progeny had normal body weight but markedly reduced blood levels of thyroid hormones (ELISA). Small arteries from 2-week-old male pups were studied using wire myography, qPCR and Western blotting. Mesenteric arteries of PTU pups, compared to controls, demonstrated smaller maximum response to α-adrenergic agonist methoxamine and reduced mRNA contents of smooth muscle differentiation markers α-actin and SERCA2A. Inhibition of basal NO synthesis by l-NNA led to tonic contraction of mesenteric arteries and augmented their contractile responses to methoxamine; both l-NNA effects were impaired in PTU pups. PTU pups demonstrated lower blood level of NO metabolites compared to control group (Griess reaction). Rho-kinase inhibitor Y27632 strongly reduced mesenteric arteries responses to methoxamine in PTU pups, that was accompanied by elevated Rho-kinase content in their arteries in comparison to control ones. Unlike mesenteric, saphenous arteries of PTU pups, compared to controls, had no changes in α-actin and SERCA2A contents and in responses to l-NNA and Y27632. In conclusion, thyroid hormones deficiency suppresses the anticontractile effect of NO and potentiates the procontractile Rho-kinase effects in mesenteric arteries of 2-week-old pups. Such alterations disturb perinatal cardiovascular homeostasis and might lead to cardiovascular pathologies in adulthood.

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“…On the contrary, the results of animal and human studies on the L-T3/L-T4 combination therapy are very different. The results from studies conducted in animals mostly suggested combined therapy (7,25). However, outcomes of the human studies did not suggest the same (10,11).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Triiodothyronine Level in Patients Treated with Levothyroxine for Different Causes of Hypothyroidism

Hemmatabadi¹,

Azizimanesh²,

Esfahanian³

et al. 2020

Turk J Endocrinol Metab

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Objective: Several lines of evidence suggest that the symptoms of hypothyroidism, including psychological symptoms and metabolic effects, persist in a significant percentage of patients treated with levothyroxine (L-T4). A hypothesis to explain this phenomenon is that the triiodothyronine (L-T3) serum levels may not be completely normalized. This study aimed to compare the level of serum free T3 (FT3) in patients who are biochemically euthyroid after L-T4 monotherapy with different underlying causes of hypothyroidism. Material and Methods: This cross-sectional study was conducted on patients with hypothyroidism who received L-T4 monotherapy and were biochemically euthyroid. The serum levels of thyroid-stimulating hormone (TSH), free T4 (FT4), FT3, and FT3/FT4 ratio were measured in these patients. Patients were divided into three groups based on the cause of hypothyroidism (radioiodine therapy, thyroidectomy and Hashimoto), and the results of biochemical tests of the thyroid were compared in three groups. Results: Of the 78 patients studied, 12 (15.4%) cases were male, and 66 (84.6%) cases were female. Among the variables studied, only the mean value of FT3 was significantly different in the three groups (p=0.006), where the highest mean value was seen in the Hashimoto group, and the lowest mean value was seen in the radioiodine therapy group. Conclusion: The results of this study showed that although hypothyroidism patients can be optimally treated with L-T4 alone, in many of these patients, the level of FT3 will not be in therapeutic range, and the mean serum FT3 levels in these patients could be related to their hypothyroidism causes.

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Effects of triiodothyronine on turnover rate and metabolizing enzymes for thyroxine in thyroidectomized rats

Cited by 4 publications

References 45 publications

Serum Metabolomics Reveals Cholic Acid, Chenodeoxycholic Acid, and Taurochenodeoxycholic Acid as Potential Biomarkers for Hypothyroid Rats

Serum Metabolomics Reveals Cholic Acid, Chenodeoxycholic Acid, and Taurochenodeoxycholic Acid as Potential Biomarkers for Hypothyroid Rats

Antenatal/early postnatal hypothyroidism alters arterial tone regulation in 2-week-old rats

Comparison of Triiodothyronine Level in Patients Treated with Levothyroxine for Different Causes of Hypothyroidism

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