Endocrine Abstracts

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...

Thyroid hormone (TH) actions and metabolism are intracellular events that require the transport of TH across the plasma membrane. This process is facilitated by TH transporters of which the monocarboxylate transporter 8 (MCT8), encoded by the Slc16a2 gene, has been most intensively analyzed. In humans, inactivating mutations in the X-linked MCT8 gene are associated with a severe form of psychomotor retardation in combination with abnormal serum TH parameters. The clin...

Inactivating mutations in highly specific thyroid hormone (TH) transporter MCT8 result in a severe form of psychomotor retardation characterized by neurological impairments and frequent epileptic seizures of unknown etiology. These symptoms are thought to be a consequence of impaired central TH uptake across brain barriers and/or into neural cells. Mct8/Organic anion transporting polypeptide 1c1 double knockout (M/O-dKO) mice replicate characteristics of human MCT8 deficiency....

Inactivating mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) result in a severe form of psychomotor retardation (known as Allan-Herndon-Dudley syndrome, AHDS) due to compromised TH access to the CNS. Consequently, TH-dependent processes both during brain development and in the adult CNS such as adult hippocampal neurogenesis are impaired. Using mice deficient in Mct8, we recently demonstrated a diminished neurogenesis in the adult hippoca...

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...

Impaired TH transport across brain barriers results in severe TH deficiency in Mct8/Oatp1c1 DKO mice, leading to disturbed neuronal development, myelination as well as locomotor abnormalities. Although brain-barrier associated cells (i.e. endothelial cells, astrocytes, choroid plexus epithelial cells) have been shown to express both transporters, the cell-specific function of Mct8 and Oatp1c1 has still not been defined. Here, we generated and analysed mouse mutants that lack M...

Inactivation of the thyroid hormone transporters Mct8/Oatp1c1 in mice causes a profound TH deficiency in the CNS due to an impaired TH transport across brain barrier cells. As oligodendrocyte maturation and myelin formation requires proper thyroid hormone (TH) signaling, Mct8/Oatp1c1 double knock-out (DKO) mice exhibit a persistent state of hypomyelination similar to the situation in MCT8 deficient patients. Yet, to which extent proper myelination is dependent on the presence ...

Innate immune cells, including macrophages, are functionally affected by thyroid hormone (TH). Macrophages can undergo phenotypical alterations, shifting between pro-inflammatory (M1) and anti-inflammatory (M2) profiles. Previous studies have established that increased TH concentrations shift macrophages into a more pro-inflammatory phenotype. Cellular TH concentrations are, in part, determined by TH transporters, cellular gateways facilitating bidirectional TH transport. An i...