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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 […]

14.02.2013 | 10:00 AM
Dexamethasone reduces energy expenditure. PMID: 23408649

Objective: To investigate how long-term treatment with dexamethasone affects energy expenditure and adiposity in mice and whether this is influenced by feeding on a high fat diet (HFD). Design and Methods: Mice were placed on a HFD for 2 weeks and started on dexamethasone at 5mg/kg every other day during the next 7 weeks. Results: […]

21.09.2012 | 10:00 AM
Major role played by β1-adrenergic receptor in BAT. PMID: 22728333

Brown adipose tissue (BAT) is predominantly regulated by the sympathetic nervous system (SNS) and the adrenergic receptor signaling pathway. Knowing that a mouse with triple b-receptor knockout (KO) is cold intolerant and obese, we evaluated the independent role played by the b1 isoform in energy homeostasis. First, the 30 min i.v. infusion of norepinephrine (NE) […]

20.06.2012 | 10:00 AM
Neuronal hypoxia induces nuclear import of D3. PMID: 22723689

D3 redirection and accumulation in the cell nucleus is part of the hypoxia-induced reduction in thyroid hormone signaling. Inactivation of thyroid hormone in the nucleus, physically closer to where thyroid hormone receptors (TRs) are located, constitutes an advantageous mechanism to dampen thyroid hormone signaling and reduce metabolism. Studies of directed D3 glycosylation indicated that D3 […]