Endocrine Abstracts

Mice with combined deficiency in the thyroid hormone transporters Mct8 and Oatp1c1 (Mct8/Oatp1c1 dko mice) display a strongly diminished TH brain content and, consequently, a disturbed neuronal maturation and myelination as well as locomotor abnormalities while serum T3 levels are highly elevated. This phenotype can be explained by an impaired transport of T4 and T3 into the CNS in the absence of both transporters. Yet, the exact cell-specific function of Mct8 and Oatp1c1 in b...

Patients with inactivating mutations in MCT8, known as Allan-Herndon-Dudley syndrome (AHDS), present a severe form of psychomotor retardation and, frequently, epileptic seizures of unknown etiology. These neurological symptoms are thought to arise due to an impaired transport of thyroid hormones (TH) across the blood brain barrier and/or into the neural cells. As a consequence of species-specific differences in the expression of the T4-specific organic anion transporter polype...

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...

Thyroid cancer (TC) is the most common endocrine malignancy, with an increasing number of diagnosis in the last decades. Of all TC histotypes, the poorly differentiated and anaplastic TCs (PDTC and ATC) have a very poor prognosis because of their invasiveness and metastatic behavior, as well as their insensitivity to radioactive-iodine treatment. In the last years, the stem-cell model has been proposed to further explain TC carcinogenesis. According to this model, only a subse...

The human thyroid gland acquires a differentiation program as early as weeks 3–4 of embryonic development. The onset of functional differentiation, which manifests by the appearance of colloid in thyroid follicles, takes place during gestation weeks10–11. By 12–13 weeks functional differentiation is accomplished and the thyroid is capable of producing thyroid hormones although at a low level. During maturation, thyroid hormones yield increases and physiological ...

Background: Conservation of genes involved in TH transport, metabolism and action can reveal clues about the origins of TH signaling. A deiodinase homologue (DdDio) was previously identified in the social amoeba Dictyostelium discoideum (Singh, 2014). Dictyostelium cells live as single cell amoebae in soil where they feed on bacteria. However, upon starvation a developmental program is initiated that results in the formation of a multicellular fruiti...

Thyroid hormones (TH) play a critical role during nervous system development and patients carrying coding variants of THRA or SLC16A2/MCT8 genes present a spectrum of neurological phenotypes presumably resulting from perturbed local TH action during early brain development. Monocarboxylate transporter MCT8 is a well-characterized TH membrane transporter and MCT8 mutations have been associated with the Allan-Herndon-Dudley Syndrome. Recent advances in stem cel...

Background and Objective: Disrupted thyroid hormone (TH) signaling has devastating effects on human neurodevelopment. The molecular mechanisms underlying TH regulation and action are largely based on animal models. However, animal models are limited in revealing some of the most fundamental aspects of neurodevelopment that are unique to humans. We employed human induced pluripotent stem cell (iPSC) technology to study the effects of T3 on neurodevelopmental processes in a huma...