Endocrine Abstracts

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....

Thyroid hormone (TH) signaling is essential for nervous system development. The clinical relevance of this simple statement is underscored by the severe neurological phenotypes resulting from global TH deficiency or perturbed local TH signaling during fetal development. A major aim of our research is to better understand the local action of TH during early human cortex development using cerebral organoids derived from human induced pluripotent stem cells (hiPSC) as a model sys...

Inactivating mutations in the thyroid hormones (TH) transporter monocarboxylate transporter 8 (MCT8) lead to the X-linked rare disease named MCT8 deficiency or Allan-Herndon-Dudley Syndrome (AHDS). AHDS pathophysiology is characterized by peripheral hyperthyroidism and cerebral hypothyroidism, which results in severe neurological impairments. Although AHDS leads to a spectrum of severe endocrine and neurological alterations, treatment options for MCT8-deficient patients are li...

Patients with resistance to thyroid hormone β (RTHβ) often display a neurocognitive phenotype, but the underlying biological defects have not been characterized. The predominant receptor isoform expressed in brain tissue is TRα1 leading to the assumption that this receptor accounts for most of the T3 effects. Nevertheless, TRα and TRβ are both expressed in brain therefore our study aims to understand the impact of a mutant THRβ on TH action in the...

Adequate thyroid hormone levels are crucial for cell homeostasis in the adult human brain. To supply neuronal and glial cells, thyroid hormone (TH) transporters such as the monocarboxylate transporter 8 (MCT8) are required. While implications in TH levels in the human brain seem to play a role in neurodegenerative diseases such as Alzheimer’s disease (AD), altered expression of TH transporters has not been described yet. Our study therefore aimed to evaluate MCT8 expressi...