Cellular mechanisms of thyroid hormone homeostasis

Abstract

The title of this thesis covers the whole world of local thyroid hormone (TH) transport, metabolism and action. Normal TH homeostasis is dependent on the intracellular availability of TH, as the genomic actions of TH are mediated by nuclear TH receptors (TRs) bound to promoter elements of TH responsive genes. The intracellular availability of TH, is dependent on adequate function of transporter proteins and deiodinating enzymes that convert T4 to the active form T3, as well as degradation of T3. Although we know that all described key players are important for normal TH homeostasis, many issues are still unresolved. The work in this thesis presents studies in which key players of TH homeostasis, in health and disease, are investigated. First, we discussed the impact of genetic variation in the type 2 deiodinase (D2). Next, new insights in the TH transport characteristics of the L-type amino acid transporters (LAT) 1-5 and monocarboxylate transporters (MCT) 8 and 10 were described. After that we discussed the ability of T4 to stimulate transcription of TH responsive genes and we explored gender differences in the age-related suppression of TH signalling. Finally, the associations between TH and trace elements were discussed.