Endocrine Abstracts

The application of proteomics in clinical thyroid logy is innovative and is a novel tool to decipher Pathophysiologie-inherent changes in protein function, which cannot be comprehensively studied by the more widely applied transcriptome methods.In this talk we will provide an overview on methods of thyroid proteomics and their possible pitfalls, present current studies on this topic and discuss our own experience with the application of proteomics techno...

BackgroundThyroid hormone transporting proteins Mct8 and Mct10 have been detected at the plasma membrane of thyroid epithelial cells, whereas Lat2 was found predominantly at vesicular membranes. In this study we look into the effects of inhibiting thyroid hormone transporters on their subcellular localisation to better understand their fate and trafficking pathways in thyrocytes. Thus, a pharmacological intervention study with specific inhibitors of thyr...

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 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...

Ischemic heart disease (IHD) is one of the leading causes of death worldwide. TH have impact on cardiac function and even appear to improve outcome after acute ischemia/reperfusion and in chronic heart failure. This project aims to investigate the influence of TH receptor alpha (TRα) on IHD using specific mouse models to assess the contribution of canonical vs. non-canonical TH signaling. Mice underwent permanent ligation of the left descending coronary artery and were tr...

Human tissue kallikreins (KLKs) are serine proteases expressed in various organs including thyroid hormone-generating and target tissues. Besides their involvement in important physiological processes, KLKs are mainly recognized for their association with pathological conditions like cancer. Previously, KLK2 and KLK3 transcripts were detected in normal thyroid and carcinoma tissue, while the levels and subcellular distribution of KLK proteins remained largely elusive. Since th...

Cysteine cathepsins are endo-lysosomal proteases that play crucial roles in thyroid physiology. However, in thyroid cancer, cathepsin B is overexpressed and secreted into the extracellular space, thus promoting migratory phenotypes of thyroid carcinoma cells through excessive extracellular matrix degradation. In addition, we have shown that N-terminally truncated forms of cathepsins B and V which lack the signal peptide and parts of the pro-peptide are localized to the nuclei ...

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...

Anaplastic thyroid carcinoma (ATC) is a rare and aggressive malignancy with only limited effective systemic treatment options. The identification of actionable genetic lesions and its exploitation has expanded therapeutic approaches and especially for the subset of BRAFV600E mutated ATC (11-25%) combined BRAF- and MEK-inhibition indicated meaningful activity. Still, further effective therapeutic options are required for patients without identifiable driver mutations. The role ...