Endocrine Abstracts

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...

Objectives: Acute liver failure (ALF) is a rare but life-threatening condition with severe liver dysfunction. In ALF liver regeneration capacity is exceeded due to loss of hepatocyte function. A well-known trigger of ALF is paracetamol (acetaminophen, APAP) intoxication. Unfortunately, based on the poor prognosis and rapidly increasing mortality rate liver transplantation offers the so far only effective therapeutic strategy. Even if the underlying mechanisms of ALF are not ye...

The systemic function of thyroid hormones (TH) is highly dependent on their local action in distinct cell populations. A major target of TH are immune cells, yet knowledge on the effect of TH on immune responses is still incomplete. Within this study we aimed to determine the impact of TH on T cells, key players of immune responses, in more detail. To this end, we analyzed the activation and function of T cells from mice lacking TRα (TRα0/0) or expressing ...

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...

As thyroid hormones (TH) are essential for the normal heart function, a low TH state in ischemic cardiovascular events is often correlated to a poor prognosis. While clinical and experimental data suggests that TH intervention in acute myocardial infarction might be beneficial, a detailed insight in the mechanisms on TH action in IR injury or post infarct recovery of the heart is still lacking. In this study, we examined the effect of thyroid hormone pre- and postconditioning ...

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...