Priority Programme: THYROID TRANS ACT
Translation of Thyroid Hormone Actions beyond Classical Concepts

Prof. Dr. Dr. Dagmar Führer, Prof. Dr. Ulrich Schweizer

Oral thyroxine resistance revisited – how thyroxine transpasses the gut-blood barrier

Oral levothyroxine (LT4) is one of the most frequently administered hormone treatments word-wide. In most cases LT4 replacement is uncomplicated, however, some patients require abnormally high LT4 doses to achieve euthyroidism or TSH suppression in case of thyroid cancer. “Levothyroxine malabsorption” comprises a very heterogeneous spectrum of disorders ranging from non-compliance to very rare cases of apparent oral levothyroxine resistance (OTR) of unknown cause. Since thyroid hormone (TH) transporters have been identified as gate-keepers that regulate the in- and efflux of TH across cellular membranes, we propose that genetic alterations in TH transporters could account for OTR and might also explain inter-individual variability in LT4 replacement dosage.  This project asks how TH transport across the intestinal epithelium is organized and which molecular mechanisms are implicated in disturbed intestinal T4 uptake. To this aim, we will 1) clinically characterize patients with OTR and establish a European database of patients with abnormal thyroid hormone uptake, 2) search for genetic alterations in intestinal TH transporters, 3) employ specific TH transporter-deficient models to elucidate the role of individual TH transport proteins in intestinal-endothelial T4 transpassage and 4) apply a genome wide approach to identify novel TH transporters that are crucial for intestinal TH passage.

 

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Project Coordinator(s):

Prof. Dr. Dr. Dagmar Führer
Universitätsklinikum Essen, Klinik für Endokrinologie und Stoffwechselerkrankungen
Zentrallabor - Bereich Forschung und Lehre
Hufelandstr. 55
45147 Essen
Phone: +49 201 723 6400
Fax: +49 201 723 5972
dagmar.fuehrer@uk-essen.de

Prof. Dr. Ulrich Schweizer
Rheinische Friedrich-Wilhelms-Universität Bonn
Institut für Biochemie und Molekularbiologie
Nussallee 11
53115 Bonn
Phone: +49 228 73 4444
uschweiz@uni-bonn.de