Type I 5′-iodothyronine deiodinase activity and mRNA are remarkably reduced in renal clear cell carcinoma

Pachucki, Janusz; Ambroziak, Michał; Tański, Zbigniew; Luczak, J.; Nauman, J; Nauman, A

doi:10.1007/bf03343855

Cited by 40 publications

(31 citation statements)

References 48 publications

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“…Downregulation of D1 expression was also reported in other human neoplasias. Lower levels of D1 mRNA were described in samples of renal clear cell carcinoma, the most frequent renal cancer (Pachucki et al 2001). Interestingly, several variants of DIO1 transcripts were found in this type of neoplasias, all of them underexpressed in tumor tissue as compared with normal renal tissue.…”

Section: Human Neoplasiasmentioning

confidence: 91%

Type 1 iodothyronine deiodinase in human physiology and disease

Maia

Goemann²,

Meyer³

et al. 2011

Journal of Endocrinology

196

123

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Thyroid hormone is essential for the normal function of virtually all tissues. The iodothyronine deiodinases catalyze the removal of an iodine residue from the pro-hormone thyroxine (T 4 ) molecule, thus producing either the active form triiodothyronine (T 3 ; activation) or inactive metabolites (reverse T 3 ; inactivation). Type I deiodinase (D1) catalyzes both reactions. Over the last years, several studies have attempted to understand the mechanisms of D1 function, underlying its effects on normal thyroid hormone metabolism and pathological processes. Although peripheral D1-generated T 3 production contributes to a portion of plasma T 3 in euthyroid state, pathologically increased thyroidal D1 activity seems to be the main cause of the elevated T 3 concentrations observed in hyperthyroid patients. On the other hand, D1-deficient mouse models show that, in the absence of D1, inactive and lesser iodothyronines are excreted in feces with the loss of associated iodine, demonstrating the scavenging function for D1 that might be particularly important in an iodine deficiency setting. Polymorphisms in the DIO1 gene have been associated with changes in serum thyroid hormone levels, whereas decreased D1 activity has been reported in the nonthyroid illness syndrome and in several human neoplasias. The current review aims at presenting an updated picture of the recent advances made in the biochemical and molecular properties of D1 as well as its role in human physiology.

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Section: Human Neoplasiasmentioning

confidence: 91%

Type 1 iodothyronine deiodinase in human physiology and disease

Maia

Goemann²,

Meyer³

et al. 2011

Journal of Endocrinology

196

123

View full text Add to dashboard Cite

show abstract

“…Expression of selenoprotein P is decreased, for example, in prostate cancer (25). Finally, it is well established that expression and activity of the selenoprotein type I 5Ј-deiodinase (5ЈD1), involved in thyroid hormone metabolism, is lost, namely in thyroid carcinomas or cell lines derived therefrom as well as in carcinomas of the prostate and the kidney (26)(27)(28). The exact role of 5ЈD1 activity in the thyroid gland is not yet clarified.…”

Section: Introductionmentioning

confidence: 99%

Selenoprotein Expression in Hürthle Cell Carcinomas and in the Human Hürthle Cell Carcinoma Line XTC.UC1

Menth¹,

Schmutzler

Mentrup

et al. 2005

Thyroid

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Hürthle cell carcinomas (HTC) are characterized by mitochondrial amplification and enhanced oxygen metabolism. To clarify if defects in enzymes scavenging reactive oxygen species are involved in the pathogenesis of HTC, we analyzed selenium (Se)-dependent expression of various detoxifying selenoproteins in the HTC cell line XTC.UC1. Glutathione peroxidase and thioredoxin reductase activity was found both in cell lysates and conditioned media of XTC.UC1 cells and was increased by Na(2)SeO(3). Western blot analysis demonstrated the presence of thioredoxin reductase both in cell lysates and conditioned media and of glutathione peroxidase 3 in conditioned media. Type I 5'-deiodinase, another selenoprotein that catalyzes thyroid hormone metabolism, was detectable only in cell lysates by enzyme assay and Western blot, and responded to stimulation by both Na(2)SeO(3) and retinoic acid. A selenoprotein P signal was detected in conditioned media by Western blot, but was not enhanced by Na(2)SeO(3) treatment. In situ hybridization revealed glutathione peroxidase mRNAs in HTC specimen; glutathione peroxidase 3 mRNA levels were reduced. These data suggest adequate expression and Se-dependent regulation of a couple of selenoproteins involved in antioxidant defense and thyroid hormone metabolism in XTC.UC1 cells, so far giving no evidence of a role of these proteins in the pathogenesis of HTCs.

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“…The change in enzyme activity was observed in all subjects, while five out of eight demonstrated a rise in mRNA expression. This highlights a lack of correlation between mRNA expression and enzyme activity which has been reported in other biological enzyme systems (20,21). While given the small number of subjects studied, and the possibility that a type 2 error exists, important factors other than gene expression affect functional enzyme activity, including protein translation, posttranslational modification, protein-protein interactions and substrate availability.…”

Section: Discussionmentioning

confidence: 80%

Skeletal muscle 11β hydroxysteroid dehydrogenase type 1 activity is upregulated following elective abdominal surgery

Jang

Obeyesekere²,

Alford³

et al. 2009

European Journal of Endocrinology

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Objective: Cortisol has been traditionally implicated in the causation of peri-operative skeletal muscle (SkM) insulin resistance, but cortisol levels return to normal within 72 h of surgery. Tissue cortisol bioactivity may be prolonged by local upregulation of the enzyme 11bHSD1. We aimed to investigate the changes of SkM 11bHSD1 enzyme activity and mRNA expression, relative to plasma cortisol, insulin and glucose levels following elective abdominal surgery. Patients and design: Eight non-diabetic subjects (two male, six female) underwent serial plasma hormone sampling and muscle biopsy of vastus lateralis at baseline and on day 5 following elective laparoscopic cholecystectomy. Methods: SkM 11bHSD1 and H6PDH mRNA levels were measured by quantitative RT-PCR and enzyme activity by % conversion of 3 H cortisone to cortisol. Plasma glucose, insulin, free fatty acids (FFA), tumour necrosis factor-a and cortisol by standardised assays.

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Type I 5′-iodothyronine deiodinase activity and mRNA are remarkably reduced in renal clear cell carcinoma

Cited by 40 publications

References 48 publications

Type 1 iodothyronine deiodinase in human physiology and disease

Type 1 iodothyronine deiodinase in human physiology and disease

Selenoprotein Expression in Hürthle Cell Carcinomas and in the Human Hürthle Cell Carcinoma Line XTC.UC1

Skeletal muscle 11β hydroxysteroid dehydrogenase type 1 activity is upregulated following elective abdominal surgery

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