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Endocrine Abstracts (2024) 101 PS2-10-04 | DOI: 10.1530/endoabs.101.PS1-10-04

Instituto de Investigaciones Biomédicas Sols-Morreale Csic-Uam, Department of Neurological Diseases and Aging, Madrid, Spain


It has long been known that thyroid hormones (TH) are essential to orchestrate the correct development of the brain. For many years it has also been recognised that TH need of transporter proteins to access target tissues and cells. Moreover, in the last 20 years the Monocarboxylate transporter 8 (MCT8) has emerged as a TH transporter of great physiopathological importance, as mutations in MCT8 lead to severe neurological alterations already from prenatal stages. Despite the importance of TH action during brain development and the pathophysiological relevance of MCT8, its role during brain development has not been fully addressed. Previous studies in mice lacking MCT8 have suggested its deficiency leads to a transient state of brain hyperthyroidism during development, although increased expression of alternative TH transporters in the brain has hindered the interpretation of these findings. The aim of this study is to elucidate the role of MCT8 during early mouse brain development. Firstly, we have delineated the anatomical expression of MCT8 in the mouse brain during early development. Furthermore, we have investigated the different types of neural cells expressing MCT8 during perinatal stages of brain development. Using a mouse model with a point mutation in MCT8, we have demonstrated that these mice also present a transient state of brain hyperthyroidism. Importantly, this hyperthyroidism occurs without an increase in alternative TH transporters, indicating that the perinatal brain hyperthyroidism is not due to enhanced TH transport through other transporter proteins. Moreover, we have further explored this state of perinatal state of brain hyperthyroidism running RNAseq analysis and RNAscope in mice brain samples and digital PCR in human brain samples of a 30th gestational week foetus with a mutation in MCT8.

Volume 101

46th Annual Meeting of the European Thyroid Association (ETA) 2024

European Thyroid Association 

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