Article

Cloning of the mammalian Type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues

Department of Medicine, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
Journal of Clinical Investigation (Impact Factor: 13.22). 08/1996; 98(2):405-17. DOI: 10.1172/JCI118806
Source: PubMed

ABSTRACT

The deiodination of thyroid hormones in extrathyroidal tissues plays an important role in modulating thyroid hormone action. The type II deiodinase (DII) converts thyroxine to the active hormone 3,5,3'-triiodothyronine, and in the rat is expressed in the brain, pituitary gland, and brown adipose tissue (BAT). Complementary DNAs (cDNAs) for the types I and III deiodinases (DI and DIII, respectively) have been isolated and shown to code for selenoproteins. However, information concerning the structure of the mammalian DII remains limited, and the pattern of its expression in human tissues is undefined. We report herein the identification and characterization of rat and human DII cDNAs. Both code for selenoproteins and exhibit limited regions of homology with the DI and DIII. In the rat pituitary and BAT, DII mRNA levels are altered more than 10-fold by changes in the thyroid hormone status of the animal. Northern analysis of RNA derived from human tissues reveals expression of DII transcripts in heart, skeletal muscle, placenta, fetal brain, and several regions of the adult brain. These studies demonstrate that: (a) the rat and human DII are selenoproteins, (b) DII expression in the rat is regulated, at least in part, at the pretranslational level in some tissues, and (c) DII is likely to be of considerable physiologic importance in thyroid hormone economy in the human fetus and adult.

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    • "Dio2 was massively down regulated in hypothalamus, BAT and skeletal muscle and could have short-term effects on the DIO2 protein level due to its short half-life of 2 h (Baqui et al., 2003). The classical reason for dio2 down regulation is a high intracellular T3 concentration (Croteau et al., 1996). This would contradict the fact that T3 inhibits torpor and that transcription of T3 target genes ucp1 and ucp3 was inhibited in BAT of our hamsters. "

    Preview · Article · Nov 2015
    • "was massively down regulated in hypothalamus, BAT and skeletal muscle and could have short-term effects on the DIO2 protein level due to its short half-life of 2h (Baqui et al., 2003). The classical reason for dio2 down regulation is a high intracellular T3 concentration (Croteau et al., 1996). This would contradict the fact that T3 inhibits torpor and that transcription of T3 target genes ucp1 and ucp3 was inhibited in BAT of our hamsters. "
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    ABSTRACT: Thyroid hormones (TH) play a key role in regulation of seasonal as well as acute changes in metabolism. Djungarian hamsters (Phodopus sungorus) adapt to winter by multiple changes in behaviour and physiology including spontaneous daily torpor, a state of hypometabolism and hypothermia. We investigated effects of systemic TH administration and ablation on the torpor behaviour in Djungarian hamsters adapted to short photoperiod. Hyperthyroidism was induced by giving T4 or T3 and hypothyroidism by giving methimazole (MMI) and sodium perchlorate via drinking water. T3 treatment increased water, food intake and body mass, whereas MMI had the opposite effect. Continuous recording of body temperature revealed that low T3 serum concentrations increased torpor incidence, lowered Tb and duration, whereas high T3 serum concentrations inhibited torpor expression. Gene expression of deiodinases (dio) and uncoupling proteins (ucp) were analysed by qPCR in hypothalamus, brown adipose tissue (BAT) and skeletal muscle. Expression of dio2, the enzyme generating T3 by deiodination of T4, and ucps, involved in thermoregulation, indicated a tissue specific response to treatment. Torpor per se decreased dio2 expression irrespective of treatment or tissue, suggesting low intracellular T3 concentrations during torpor. Down regulation of ucp1 and ucp3 during torpor might be a factor for the inhibition of BAT thermogenesis. Hypothalamic gene expression of neuropeptide Y, propopiomelanocortin and somatostatin, involved in feeding behaviour and energy balance, were not affected by treatment. Taken together our data indicate a strong effect of thyroid hormones on torpor, suggesting that lowered intracellular T3 concentrations in peripheral tissues promote torpor.
    No preview · Article · Oct 2015 · Hormones and Behavior
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    • "Transcriptomic analysis also revealed that genes involved in thyroid hormone generation (GO category GO:0006590; Table 1; Table S6) were differentially expressed, suggesting a regulatory connection between regeneration of the lizard tail and musculoskeletal transformations during amphibian metamorphosis. The lizard dio2 gene is the ortholog of deiodinase, iodothyronine, type I, which in mammals converts thyroxine prohormone (T4) to bioactive 3,3',5-triiodothyronine (T3) [82]. In Xenopus laevis, T3 is the key signal for the process of metamorphosis from tadpole to adult frog [83]. "
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    ABSTRACT: Lizards, which are amniote vertebrates like humans, are able to lose and regenerate a functional tail. Understanding the molecular basis of this process would advance regenerative approaches in amniotes, including humans. We have carried out the first transcriptomic analysis of tail regeneration in a lizard, the green anole Anolis carolinensis, which revealed 326 differentially expressed genes activating multiple developmental and repair mechanisms. Specifically, genes involved in wound response, hormonal regulation, musculoskeletal development, and the Wnt and MAPK/FGF pathways were differentially expressed along the regenerating tail axis. Furthermore, we identified 2 microRNA precursor families, 22 unclassified non-coding RNAs, and 3 novel protein-coding genes significantly enriched in the regenerating tail. However, high levels of progenitor/stem cell markers were not observed in any region of the regenerating tail. Furthermore, we observed multiple tissue-type specific clusters of proliferating cells along the regenerating tail, not localized to the tail tip. These findings predict a different mechanism of regeneration in the lizard than the blastema model described in the salamander and the zebrafish, which are anamniote vertebrates. Thus, lizard tail regrowth involves the activation of conserved developmental and wound response pathways, which are potential targets for regenerative medical therapies.
    Full-text · Article · Aug 2014 · PLoS ONE
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