Endocrine Abstracts

Introduction: Mct8 is a thyroid hormone specific transporter located at the basolateral plasma membrane of thyrocytes. To investigate the significance of Mct8 to the thyroid gland while excluding peripheral effects observed in global knockout models, we used a Cre-LoxP thyroid-specific Mct8-deficient mouse model. Phenotypes of the angiofollicular unit encompassing the follicle and surrounding endothelial cells were investigated with respect to functional and morphological stat...

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...

The function of the thyroid gland is to maintain thyroid hormone (TH) levels in the blood circulation. Thyroid epithelial cells liberate TH from the precursor molecule thyroglobulin (Tg) by the combined proteolytic action of the cathepsin B, K, L, and S. Cathepsin L-deficiency in mice results in impaired processing of Tg and remnants of dead cells in the follicle lumen. Recently, we have shown that Trace amine-associated receptor 1 (Taar1) is localized on the primary cilia of ...

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 ...

Thyroid hormones thyroxine and triiodothyronine are essential for development, growth and metabolism. The prohormone thyroglobulin (Tg) is stored in high concentrations and in covalently cross-linked form within the lumen of thyroid follicles. Thyroid hormones are liberated from Tg in a regulated manner in that TSH triggers the secretion of lysosomal enzymes into the extracellular follicle lumen where they solubilize covalently cross-linked Tg and liberate thyroxine by partial...

Background: KEAP1 gene (Kelch-like ECH-associated protein 1) that encodes the main inhibitor of nuclear factor erythroid 2-related transcription factor 2 (Nrf2), a central mediator of antioxidant responses, has been found to be one of the mutated genes that lead to familial multinodular goiter (MNG). The proposed association of KEAP1 with familial MNG is based on only two loss-of-function mutations in respective Japanese families. To date, there is no experim...

The thyroid gland functions in supplying thyroid hormones (TH) to the body periphery, which is enabled by cathepsin-mediated thyroglobulin proteolysis and TH translocation across membranes by the Mct8, Mct10, and Lat2 transporters. Previously, we showed that cathepsin K-deficient mice feature normal thyroid phenotypes which is, in part, due to the functional compensation through cathepsin L upregulation that is independent of the classical hypothalamus–pituitary–thyr...