Endocrine Abstracts

Thyroid hormones (TH) are important regulators of human metabolism and development, which modulate expression of target genes via nuclear thyroid hormone receptors (TRs). Different isoforms of these classical TRs including TRβ isoforms TRβ1 and TRβ2 as well as TRα1 were shown to be functional TH-responsive transcription factors and have been extensively studied. In contrast, the cellular function of TRα2, an alternative splice variant of TRα1, is ...

Objectives: The canonical function of thyroid hormone receptors (TRs) as mediators of thyroid hormone action on target gene expression is well known. However, the physiological function of the thyroid hormone receptor α splice variant TRα2, that does not bind thyroid hormones, remains elusive. Initial studies addressing the function of TRα2 indicated that it might act as a TRα1 antagonist, but the mechanisms underlying the dominant-negative activity of TR&#...

Background: Ischemic heart disease (IHD) is one of the leading causes of death worldwide. Thus, there is the necessity to find new therapeutic approaches. Thyroid hormones (TH) have a major impact on cardiac function and even appear to improve the outcome after acute ischemia/reperfusion and in chronic heart failure. Still, TH signaling within the heart is not yet completely understood.Aim: This project aims to investigate the influence of TH receptor al...

The immune system is a major target of thyroid hormones (TH), as they have been shown to act on innate as well as adaptive immune cells affecting their proliferation, activation and survival. However, the local TH action within the immune system is still poorly understood. To improve our understanding of this interaction, we performed an immunophenotyping of mice at baseline using flow cytometry and ELISA. For this, we focused on mice with TRα or TRβ mutations leadin...

Objectives: The thyroid hormone receptor α (TRα) is crucial for organ development, regulation of growth, heart rate and energy homeostasis. In humans, THRA encodes for the two major TRα isoforms, TRα1 and TRα2. TRα2 is generated by alternative splicing and is unable to bind T3 and thus antagonizes TRα1 signaling. Therefore, the physiological effects of TRα require strictly controlled spatiotemporal expression of TRα isoform...

Anaplastic thyroid cancer (ATC) is the most aggressive thyroid cancer with a median survival of about 6 months. So far, no therapies offering a survival benefit are established. Thus, new therapeutic approaches are urgently needed. In general, genetic alterations leading to ATC increase PI3K and MAPK/ERK signaling and include mutations in receptor tyrosine kinases and tumor suppressor genes. They often occur together with the loss of P53, the most prevalent mutation in human A...

Thyroid hormones (TH) reduce liver steatosis. As steatosis is the initial step of alcoholic liver disease (ALD), we hypothesized that TH treatment could ameliorate ALD. Wildtype (WT) mice were treated with either ethanol (EtOH) or liquid control diet for 10 days followed by a single EtOH or maltose binge on day 11. In both groups, diet was supplemented with either T3 or solvent. Serum triglycerides (TG) were increased by EtOH and, surprisingly, further elevated by T3. Liver we...