Endocrine Abstracts

Background and Aim: Thyroid hormone beta receptor (TRβ) agonists have shown promising results to improve non-alcoholic steatohepatitis in preclinical studies and clinical trials. However, a recent cross-sectional study on human liver biopsies found that TRβ expression decreases during non-alcoholic steatohepatitis (NASH), which may indicate developing thyroid hormone resistance and pose a challenge for TRβ agonists. We aim to study how the changes in TRβ ex...

It is well established that thyroid hormones (TH) possess the ability to regulate body temperature. Thermogenesis can be induced peripherally in fat and muscle, but the active hormone T3 can also act centrally in the brain to raise the body temperature via the sympathetic nervous system. In recent studies, T3 treatment in mice has been shown to elevate the body temperature even far below thermoneutrality. This indicates that the induced hyperthyroidism causes a state of pyrexi...

Thyroid hormones play a key role in cellular growth, development, and metabolism, and are known regulators of gene expression through genomic and non-genomic processes including DNA methylation. Using eight cohorts from the ThyroidOmics-Consortium and a standardized meta-analysis quality control pipeline, we conducted an epigenome-wide association study between blood-based leucocyte DNA methylation sites and thyroid hormones (TSH, free T3 and free T4) in up to 7,073 participan...

A normal thyroid status is crucial for correct tissue and organ function, including temperature homeostasis. The tissue-specific actions of thyroid hormone on body temperature regulation in humans and rodents are largely modulated via the nuclear thyroid hormone receptor TRα1. Consequently, mice expressing a mutant TRα1R384C display a reduced core body temperature at 22°C caused by excessive heat loss via the tail. Surprisingly, the hypothermic phenotype of TR&#...

Objectives: All known (>230) different mutations in thyroid hormone receptor β (TRβ) causing Resistance to Thyroid Hormone β (RTHβ), localise to three clusters within its hormone binding domain. Here, we report phenotypes and molecular studies in an unique family with RTHβ due to a mutation in the DNA binding domain (DBD) of TRβ.Methods: We ascertained clinical and biochemical features in four children and their parents ...

Objectives: Thyroid hormones (TH) affect cardiovascular functions via direct actions on the heart and via indirect actions on central nervous system. Mutations in TH receptor α1 (TRα1) cause Resistance to Thyroid Hormone α (RTHα), a disorder characterized by hypothyroidism in TRα1-expressing tissues including the heart.Methods: The current experiments aimed at investigating the role of peripheral and central TR&...

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...

Background: Resistance to thyroid hormone (TH) alpha (RTHα), caused by heterozygous mutations in THRA, is characterized by abnormal thyroid function tests and features due to tissue-specific hypothyroidism, including disproportional short stature, variable motor and cognitive defects, macrocephaly and macroglossia, constipation and anemia. Mutant receptors display defective T3 binding resulting in impaired transcriptional activity. Dominant negative inhibition of the WT r...