Endocrine Abstracts

Objectives: Deiodinase type 1 (DIO1), a selenocysteine-containing enzyme belonging to the deiodinase (DIO) family, plays an essential role in the systemic and local modulation of thyroid hormone (TH) availability. However, DIO1 plays a dual role by not only converting the prohormone thyroxine (T4) to the active triiodothyronine (T3) but also degrading T3 to the inactive 3,3’-diiodothyronine (3,3’-T2). DIO1, by acting on sulfated TH metabolites, further contributes to...

In humans, inactivating mutations in the thyroid hormone transporter MCT8 result in a severe psychomotor retardation characterized by neurological impairments and frequent epileptic seizures of unknown etiology that are thought to derive from a reduced transport of TH across brain barriers and into neural cells. Here, we aimed to investigate the mechanisms underlying the seizure susceptibility in MCT8 deficiency by using Mct8/Oatp1c1 double knockout (dKO) mice, a well-establis...

Background: Disrupted thyroid hormone (TH) homeostasis has devastating effects on human neurodevelopment. THs are critical signaling molecules in neurodevelopment, acting on differentiation of neural cells, migration, synaptogenesis and myelination, with deiodinases governing intracellular TH concentrations in a spatiotemporal manner. It is remarkable that fetal neural cells, while being key target cells of TH, exhibit strong activity of the TH inactivating enzyme DIO3. Curren...

Background: The monocarboxylate transporter 8 (MCT8) is a transmembrane thyroid hormone-specific transporter expressed at the brain barriers, as the blood-brain barrier (BBB) and in neural cells, with a key role in maintaining cerebral thyroid hormone homeostasis. Inactivating mutations in the MCT8 gene (SLC16A2) lead to the developmental rare X-linked disease known as MCT8 Deficiency or Allan-Herndon-Dudley Syndrome (AHDS). This disease is characterized by peripheral...

The abnormal expression of miRNAs has been linked to the development of multiple tumors, including thyroid tumors 1,2. Dicer1 is an essential enzyme for the biogenesis of microRNAs that has been found to be dysregulated in various cancers, notably, its expression is decreased in papillary thyroid carcinoma (PTC) 3,4. Multiple studies suggest Dicer1 as haploinsufficient tumor suppressor gene: while the loss of one allele promotes tumorigenesis, the complet...

Differentiated thyroid cancer (DTC) has a high survival rate and is usually treated with surgery followed by treatment with radioactive iodine (RAI). However, some patients are refractory to RAI (RAI-R DTC) and show decreased survival. This leads to progression of the disease, and the only approved treatment for those patients are multikinase inhibitors, lenvatinib being the most widely used. However, patients end up developing resistance to MKIs. Here we aim to study the mech...