title: Molecules important for thyroid hormone synthesis and action - known facts and future perspectives.
abstract: Thyroid hormones are of crucial importance for the functioning of nearly every organ. Remarkably, disturbances of thyroid hormone synthesis and function are among the most common endocrine disorders affecting approximately one third of the working German population. Over the last ten years our understanding of biosynthesis and functioning of these hormones has increased tremendously. This includes the identification of proteins involved in thyroid hormone biosynthesis like Thox2 and Dehal where mutations in these genes are responsible for certain degrees of hypothyroidism. One of the most important findings was the identification of a specific transporter for triiodothyronine (T3), the monocarboxylate transporter 8 (MCT8) responsible for directed transport of T3 into target cells and for export of thyroid hormones out of thyroid epithelial cells. Genetic disturbances of MCT8 in patients result in a biochemical constellation of high T3 levels in combination with low or normal TSH and thyroxine levels leading to a new syndrome of severe X-linked mental retardation. Importantly mice lacking MCT8 presented only with a mild phenotype, indicating that compensatory mechanisms exist in mice. Moreover, it has become clear that not only genomic actions of T3 exist. T3 is also capable to activate adhesion receptors and it signals via activation of PI3K and MAPK pathways. Most recently, thyroid hormone derivatives were identified, the thyronamines which are decarboxylated thyroid hormones initiating physiological actions like lowering body temperature and heart rate, thereby acting in opposite direction to the classical thyroid hormones. So far it is believed that thyronamines function via the activation of a G-protein coupled receptor, TAAR1. The objective of this review is to summarise the recent findings in thyroid hormone synthesis and action and to discuss their implications for diagnosis of thyroid disease and for treatment of patients.
authors.affiliation: School of Engineering and Science, Jacobs University Bremen, Research II, Campus Ring 6, 28759 Bremen, Germany.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Brix
authors.affiliation: Universitätsklinikum Leipzig Medizinische Klinik III, 04103 Leipzig, Germany; as of June 2011: Klinik für Endokrinologie, Zentrum für Innere Medizin, Bereich Forschung und Lehre im Zentrallabor, 45147 Essen, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Führer
authors.affiliation: Institute of Experimental Pediatric Endocrinology, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Biebermann