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27.05.2010 | 1:53 PM

New insights into thyroid hormone replacement therapy.

It is widely accepted that thyroid hormone replacement for patients with hypothyroidism can be fully accomplished with levothyroxine monotherapy, as assessed by serum thyroid function tests. However, approximately 10% of hypothyroid patients are dissatisfied with the outcome of levothyroxine monotherapy, and physicians continue to report benefits from combined levothyroxine-triidothyronine therapy for some hypothyroid patients. Recently, […]

09.01.2010 | 1:44 PM

Expression of Uncoupling Protein 1 in Mouse Brown Adipose Tissue Is Thyroid Hormone Receptor- Isoform Specific and Required for Adaptive Thermogenesis.

Cold-induced adaptive (or nonshivering) thermogenesis in small mammals is produced primarily in brown adipose tissue (BAT). BAT has been identified in humans and becomes more active after cold exposure. Heat production from BAT requires sympathetic nervous system stimulation, T3, and uncoupling protein 1 (UCP1) expression. Our previous studies with a thyroid hormone receptor- (TR ) […]

09.11.2009 | 10:31 AM

Activation and inactivation of thyroid hormone by deiodinases: Local action with general consequences.

The thyroid hormone plays a fundamental role in the development, growth, and metabolic homeostasis in all vertebrates by affecting the ex- pression of different sets of genes. A group of thioredoxin fold-containing selenoproteins known as deiodinases control thyroid hormone action by acti- vating or inactivating the precursor molecule thyro- xine that is secreted by the […]

17.09.2009 | 9:39 AM

Thyroid Hormone-Related Regulation of Gene Expression in Human Fatty Liver.

Context: Fatty liver is an important complication of obesity; however, regulatory mechanisms mediating altered gene expression patterns have not been identified. Objective: The aim of the study was to identify novel transcriptional changes in human liver that could contribute to hepatic lipid accumulation and associated insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis. Design: We […]

26.08.2009 | 10:12 AM

A TRb-selective agonist confers resistance to diet-induced obesity.

Thyroid hormone receptor b (TRb also listed as THRB on the MGI Database)-selective agonists activate brown adipose tissue (BAT) thermogenesis, while only minimally affecting cardiac activity or lean body mass. Here, we tested the hypothesis that daily administration of the TRb agonist GC- 24 prevents the metabolic alterations associated with a hypercaloric diet. Rats were […]

03.08.2009 | 9:53 AM

The E3 Ubiquitin Ligase TEB4 Mediates Degradation of Type 2 Iodothyronine Deiodinase.

The endoplasmic reticulum resident thyroid hormone-activating type 2 deiodinase (D2) is inactivated by ubiquitination via the hedgehog-inducible WSB-1. Ubiquitinated D2 can then be subsequently taken up by the proteasomal system or be reactivated by USP-33/20-mediated deubiquitination. Given that heterologously expressed D2 accumulates in Saccharomyces cerevisiae lacking the E3 ligase Doa10, we tested whether the human […]

09.06.2009 | 2:11 PM

Covering the Base-Pairs in Iodothyronine Deiodinase-1 Biology: Holes Remain in the Lineup.

Deiodinases are well known to thyroid aficionados as enzymes that can activate product of the thyroid gland, by converting it to 3,5,30- triiodothyironine (T3), the molecule ultimately responsible for thyroid hormone–regulated gene transcription. For about 40 years now, it has been well documented that most circulating T3 (>80% in humans) originates from outside of the […]

06.06.2009 | 12:00 PM

Mice lacking Pctp/StarD2 exhibit increased adaptive thermogenesis and enlarged mitochondria in brown adipose tissue.

Pctp/mice that lack phosphatidylcholine transfer protein (Pctp) exhibit a marked shift toward utilization of fatty acids for oxidative phosphorylation, suggesting that Pctp may regulate the entry of fatty acyl-CoAs into mito- chondria. Here, we examined the influence of Pctp expres- sion on the function and structure of brown adipose tissue (BAT), a mitochondrial-rich, oxidative tissue […]

09.05.2009 | 2:00 PM

For Some, L-Thyroxine Replacement Might Not Be Enough: A Genetic Rationale.

Although the thyroid gland secretes a very small amount of active thyroid hormone (triiodothyronine or T ), the major circulating form is thyroxine (T4), and it is widely accepted that thyroid hormone replacement in patients with hypothyroid- ism can be fully accomplished with L-T4 monotherapy [see 1995 American Thyroid Association guidelines (Ref. 1)]. The mech- […]

10.04.2009 | 9:22 AM

Type 2 Deiodinase Expression Is Induced by Peroxisomal Proliferator-Activated Receptor – Agonists in Skeletal Myocytes.

The thyroid hormone activating type 2 deiodinase (D2) is known to play a role in brown adipose tissue-mediated adaptive thermogenesis in rodents, but the finding of D2 in skeletal muscle raises the possibility of a broader metabolic role. In the current study, we examined the regulation of the D2 pathway in primary skeletal muscle myoblasts […]