Endocrine Abstracts

Altered metabolism in tumor cells is required for rapid proliferation but also can influence other phenotypes that affect clinical outcomes such as metastasis and sensitivity to chemotherapy. Integration of metabolome and transcriptome data for the NCI-60 panel of cancer cells lines allowed us to identify ecto-5′-nucleotidase (NT5E or CD73) and miRNA-22 as a major determinants of metabolic phenotypes in cancer cells. NT5E expression and associated metabolome variations w...

In the last decade, cell-secreted extracellular vesicles (EVs) have been isolated from most of the fluids of the body. There are many different types of EVs that include different subpopulations of exosomes, microvesicles and apoptotic bodies, all of them varying in size, composition and intracellular origin. Many laboratories around the world have shown that its composition of lipids, proteins, messenger and micro RNAs is cell-type specific, and subject to changes in patholog...

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Resistance to thyroid hormone due to THRA mutations (RTHα) is a recently discovered genetic disease with high variability in its clinical presentation. This variability may result from the fact that patients bear different types of mutations, which may impact in different ways the functionality of thyroid hormone receptor α1 (TRα1). Our aim was to understand the relationship between specific THRA mutations and symptoms, using mouse models. CRISPR/Cas9 genome edi...

In my short methodological talk, I will present why we need a detailed structural description of membrane proteins such as the TSH receptors (TSHR) of the endocrine system and how can we succeed to get three-dimensional structures. The talk includes a methodical toolbox of protein-production or -stabilization and advanced structural biology techniques like protein X-ray crystallography and cryo-electron microscopy for selected examples....

Thyroid-stimulating hormone (TSH, thyrotropin) is an activator of the TSH receptor (TSHR) in the hypothalamic-pituitary-thyroid axis leading to biosynthesis and secretion of thyroid hormones. We have developed an orally available small molecule, allosteric TSHR agonist, E2, for follow up diagnosis of patients with thyroid cancer. This ligand could replace recombinant human TSH (rhTSH, Thyrogen) which is currently used in the clinic. In a mouse model, oral administration of E2 ...

The biological regulatory system through which the organism responds to environmental pressures is mediated by epigenetic modifications of the genome without altering the DNA sequence. Among the epigenetic processes, DNA methylation is perhaps the best understood epigenetic adaption and most common DNA modification. This mechanism plays an important role in regulating the gene expression of many biological processes and has wide-ranging effects on health. Aberrant epigenetic r...