Endocrine Abstracts

Thyroid hormone (TH) actions and metabolism are intracellular events that require the transport of TH across the plasma membrane in target cells. Consequently, impaired uptake of TH can lead to tissue- specific TH deprivation independent of the TH concentrations in the circulation. A prominent example for such a scenario represents the Allan-Herndon-Dudley syndrome (AHDS). This syndrome is caused by inactivating mutations in the X-linked Slc16a2 gene encoding the monocarboxyla...

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) 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 clinical picture (also known as Al...

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...

Disturbed brain development and function represents a hallmark of Mct8/Oatp1c1 double knockout (DKO) mice, a well-established mouse model for human MCT8 deficiency. This phenotype can be explained by an impaired TH transport across brain endothelial cells causing a profound brain TH deficiency. Yet, to which extent the brain capillary network formation is compromised in DKO mice has not been elucidated. Here, we examined brain capillary network formation in wildtype, single ko...

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...