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12.08.2016 | 11:04 AM

Type 2 deiodinase disruption in astrocytes results in anxiety-depressive-like behavior in male mice. PMID: 27501182

Millions of levothyroxine-treated hypothyroid patients complain of impaired cognition despite normal TSH serum levels. This could reflect abnormalities in the type-2 deiodinase (D2)-mediated T4-to-T3 conversion, given their much greater dependence on the D2 pathway for T3 production. T3 normally reaches the brain directly from the circulation or is produced locally by D2 in astrocytes. Here […]

23.06.2016 | 12:21 PM

Thyroid hormone activation by type 2 deiodinase mediates exercise-induced PGC-1a. PMID: 27302464

Thyroid hormone (TH) promotes expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a), which mediates mitochondrial biogenesis and oxidative capacity in skeletal muscle (SKM). Skeletal myocytes express the type 2 deiodinase (D2), which generates T3, the active TH. To test whether D2-generated T3 plays a role in exercise-induced PGC-1a expression, male rats and mice with […]

06.11.2015 | 10:54 AM

Perinatal hepatic D2 expression defines epigenetic susceptibility to liver steatosis and obesity. PMID: 26508642

Thyroid hormone binds to nuclear receptors and regulates gene transcription. Here we report that in mice, at around the first day of life, there is a transient surge in hepatocyte type 2 deiodinase (D2) that activates the prohormone thyroxine to the active hormone triiodothyronine, modifying the expression of ∼165 genes involved in broad aspects of […]

30.10.2015 | 5:09 PM

Nutrient availability and thyroid hormone activation. PMID: 26499800

The activity of the thyroid gland is stimulated by food availability via leptin-induced TRH/TSH expression. Here we show that food availability also stimulates thyroid hormone activation by accelerating conversion of T4-to- T3 via type 2 deiodinase (D2) in mouse skeletal muscle and in a cell model transitioning from 0.1 to 10% FBS. The underlying mechanism […]

09.10.2015 | 11:14 AM

D2 disruption in cultured human glial cells by polybrominated biphenyl ethers. PMID: 26004626

Polybrominated diphenyl ether (PBDE) flame retardants are endocrine disruptors and suspected neurodevelopmental toxicants. While the direct mechanisms of neurodevelopmental toxicity have not been fully elucidated, it is conceivable that alterations in thyroid hormone levels in the developing brain may contribute to these effects. Cells within the brain locally convert thyroxine (T4) to the biologically active […]

14.08.2015 | 5:01 PM

Skeletal muscle has D2, but only half is in the myocytes. PMID: 26214036

The type 2 deiodinase (D2) activates the prohormone T4 to T3. D2 is expressed in skeletal muscle (SKM) and its global inactivation (GLOB-D2KO mice) reportedly leads to skeletal muscle hypothyroidism and impaired differentiation. Here, floxed Dio2 mice were crossed with mice expressing Cre-recombinase under the myosin light chain 1f (cre-MLC) to disrupt D2 expression in […]

09.01.2015 | 12:24 PM

Polymorphism in Dio2 gene leaves a genetic fingerprint in the human brain. PMID: 25569702

Context: A common polymorphism in the gene encoding the activating deiodinase (Thr92Ala-D2) is known to be associated with quality of life in millions of patients with hypothyroidism and with several organ-specific conditions. This polymorphism results in a single amino acid change within the D2 molecule where its susceptibility to ubiquitination and proteasomal degradation is regulated. […]

04.12.2014 | 10:33 AM

Differences in hypothalamic D2 ubiquitination explain localized sensitivity to T4. PMID: 25555216

The current treatment for patients with hypothyroidism is levothyroxine (L-T4) along with normalization of serum thyroid- stimulating hormone (TSH). However, normalization of serum TSH with L-T4 monotherapy results in relatively low serum 3,5,3′-triiodothyronine (T3) and high serum thyroxine/T3 (T4/T3) ratio. In the hypothalamus-pituitary dyad as well as the rest of the brain, the majority of […]

05.06.2014 | 11:13 AM

Maternal inheritance of Dio3 gene Allele affects mouse b-cells. PMID: 24885572

Dio3 is the most distal gene of the imprinted Dlk1-Dio3 gene locus and is expressed according to parental origin. Dio3 encodes the type 3 deiodinase (D3), a thioredoxin-fold like containing selenoenzyme that inactivates thyroid hormone and dampens thyroid hormone signaling. Here we used heterozygous animals with disruption of the Dio3 gene to study the allelic […]

09.02.2014 | 9:54 PM

Tissue-specific inactivation of D2 reveals multi-level control of fatty acid oxidation by TH. PMID: 24487027

The type 2 deiodinase (D2) converts the pro-hormone T4 to the metabolically active molecule T3, but its global inactivation (GLOB-D2KO) unexpectedly lowers the respiratory exchange rate (RQ) and increases food intake. Here we used FloxD2 mice to generate systemically euthyroid FAT-specific (Fabp4-Cre), ASTROCYTE-specific (GFAP-Cre) or SKELETAL MUSCLE-specific (MLC-Cre) D2KO mice that were monitored continuously. The […]