Endocrine Abstracts

Deiodinases (Dio1-3) are selenium-dependent enzymes that catalyze the reductive removal of iodine from iodothyronines. Depending on the substrate and the position of the iodine removed, deiodination can generate T3 from T4 or inactivate T3 and T4. Local expression of Dio can help to adjust the intracellular levels of T3 to the physiological needs of the organ without changing circulating T3 concentrations. It has been suggested that hepatic Dio1 generates circulating T3. Howev...

Thyroid hormone transport into cells critically depends on plasma membrane transport proteins. One of these, monocarboxylate transporter 8 (MCT8), is mutated in patients suffering from a form of X-linked mental retardation, the Allan-Herndon-Dudley syndrome. These patients are characterized by abnormal thyroid hormone and TSH plasma levels indicating a role for MCT8 in the regulation of the thyroid hormone axis. Mice lacking the Mct8 gene replicate the thyroid hormone a...

Thyroid hormones are essential for the proper development of a variety of tissues, especially the nervous system. Their transport into target cells is mediated by specific thyroid hormone transporters like the monocarboxylate transporter 8 (MCT8). Mutations in this X-chromosomal gene in humans lead to a severe phenotype characterized by psychomotor retardation, hypotonia, and a striking derangement of serum thyroid hormone levels: high T3 in the presence of low T4, and no sign...

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...

Background and Aim: Hepatic thyroid hormone (TH) signalling plays an important role in onset and progression of liver diseases. Patients with altered thyroid hormone regulation in the liver, leading to a local hypothyroid, are at higher risk of developing non-alcoholic fatty liver disease (NAFLD). Treatment with thyroid hormones proved to be a promising therapy for these patients, slowing the progression of NAFLD to non-alcoholic steatohepatitis (NASH), a more advanced stage o...

Background and Aim: Altered hepatic thyroid hormone (TH) signalling is associated with the onset and progression of liver diseases. Local hepatic hypothyroidism is related to a higher incidence of developing non-alcoholic fatty liver disease (NASH) in humans and animal models. Thyroid hormone treatment proved to be a promising therapy, slowing the progression of NAFLD to non-alcoholic steatohepatitis (NASH), a more advanced stage of the disease characterized by inflammation an...