ICEECE2012 Poster Presentations Thyroid (non-cancer) (188 abstracts)
Linking thyroid and central nervous system functions of cathepsin K: Implications for non-classical thyroid regulation
S. Dauth 1 , M. Rehders 1 , R. Sîrbulescu 1 , E. Wirth 2 , D. Braun 2 , B. Batbajar 1 , U. Schweizer 2 , M. Bröcker-Preuss 3 , D. Führer 3 , P. Saftig 4 , S. Jordans 1 & K. Brix 1
1Jacobs University, Bremen, Germany; 2Charité Universitätsmedizin, Berlin, Germany; 3Universitätsklinikum Essen, Essen, Germany; 4CAU Kiel, Kiel, Germany.
Cathepsin K is a cysteine protease known for its importance in bone remodelling. Inhibitors of cathepsin K are in clinical trials for osteoporosis treatment, but side effects included altered levels of related cathepsins in peripheral organs and in the central nervous system (CNS). Importantly, cathepsin K has been identified not only in osteoclasts but also in most epithelia and, recently, in brain parenchyma. Lately, we have also shown that cathepsin K deficiency in mice induces structural and functional alterations in the CNS which are associated with learning and memory deficits. In addition, we demonstrated that cathepsin K contributes to thyroid hormone (TH) liberation from the thyroid gland, because cathepsin K- and L-double deficient mice are considered hypothyroid due to reduced serum T4 levels and enlarged thyroids. These findings led us to hypothesize that brain and thyroid functions of cathepsin K are linked. Ctsk-/- mice exhibit enlarged thyroids but no alterations in serum or brain T4, T3 or TSH levels nor in brain deiodinase 2 activity were observed. Cerebellum development is TH dependent and altered upon hypothyroidism. However, we show here that neither the overall structure nor single cells, like Purkinje cells or Bergmann glia in the cerebellum, are altered in Ctsk-/- mice. Thus, Ctsk-/- mice do not suffer from classical hypothyroidism. Interestingly, trace amine associated receptors (TAAR) as well as TH transporters appeared deregulated in the CNS of Ctsk-/- animals compared to WT mice. Since all markers of classical TH action were comparable in WT and Ctsk-/- mice, but markers of non-classical TH action like the TH transporters and TAARs differed significantly, we believe to have identified an animal model suited to study non-classical TH actions on the CNS as a target organ.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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