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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 […]

06.11.2013 | 10:14 PM

T4 restores myelination and clinical recovery after brain hemorrhage. PMID: 24174657

Intraventricular hemorrhage (IVH) remains a major cause of white matter injury in preterm infants with no viable therapeutic strategy to restore myelination. Maturation of oligodendrocytes and myelination is influenced by thyroid hormone (TH) signaling, which is mediated by TH receptor α (TRα) and TRβ. In the brain, cellular levels of TH are regulated by deiodinases, […]

28.10.2013 | 11:19 PM

D2 is retrotranslocated to the cytoplasm and proteasomes via p97/Atx3 complex. PMID: 24196352

The type II iodothyronine deiodinase (D2) is a type I endoplasmic-reticulum (ER)-resident thioredoxin fold-containing selenoprotein that activates thyroid hormone. D2 is inactivated by ERassociated ubiquitination and can be reactivated by two USP-class D2-interacting deubiquitinases (DUBs). Here, we used D2-expressing cell models to define that D2 ubiquitination (UbD2) occurs via K48-linked ubiquitin chains and that exposure […]

16.07.2013 | 10:00 AM

Cardiac expression of D2 decreases mortality caused by cardiotoxic drug. PMID: 23861374

Altered glucose metabolism in heart is an important characteristic of cardiovascular and metabolic disease. Since thyroid hormones have major effects on peripheral metabolism, we examined the metabolic effects of heart-selective increase in 3,5,3`-triiodothyronine (T3) using transgenic mice expressing human type 2 iodothyronine deiodinase (D2) under the control of the α-myosin heavy chain (MHC) promoter (MHC-D2). […]

01.04.2013 | 10:00 AM

Hypothalamus-pituitary axis is wired to defend serum T3. PMID: 23524969

Type II deiodinase (D2) activates thyroid hormone by converting thyroxine (T4) to 3,5,3′-triiodothyronine (T3). This allows plasma T4 to signal a negative feedback loop that inhibits production of thyrotropin-releasing hormone (TRH) in the mediobasal hypothalamus (MBH) and thyroid-stimulating hormone (TSH) in the pituitary. To determine the relative contributions of these D2 pathways in the feedback […]