Exp Clin Endocrinol Diabetes 2014; 122 - P150
DOI: 10.1055/s-0034-1372167

Investigation of potential effects on thyroglobulin processing enzymes and thyroid hormone transporters in thyroid glands of mice with induced hypo- or hyperthyroidism

M Rehders 1, J Weber 1, K Engels 2, H Rakov 2, S Hönes 2, D Führer 2, H Biebermann 3, E Wirth 4, U Schweizer 5, H Heuer 6, L Möller 2, K Brix 1
  • 1Jacobs University Bremen, Bremen, Germany
  • 2Universität Duisburg-Essen, Klinik für Endokrinologie und Stoffwechselerkrankungen, Essen, Germany
  • 3Charité Universitätsmedizin Berlin, Institut für Experimentelle Pädiatrische Endokrinologie, Berlin, Germany
  • 4Charité Universitätsmedizin Berlin, Institut für Experimentelle Endokrinologie, Berlin, Germany
  • 5Rheinische Friedrich-Wilhelms-Universität Bonn, Institut für Biochemie und Molekularbiologie, Bonn, Germany
  • 6IUF – Leibniz-Institut für umweltmedizinische Forschung gGmbH, Düsseldorf, Germany

Thyroid dysfunctions such as hypo- and hyperthyroidism belong to the most common endocrine disorders and are characterized by de-regulated levels of TSH as well as the thyroid hormones (TH) T4 and T3, highlighting the importance of adequate TH levels for homeostasis of almost every organ, including the thyroid gland itself. Moreover, appropriate availability of TH in target tissues depends critically on the combined action of the cathepsin B, K, L, and S, which process the prohormone thyroglobulin (Tg) in thyroid follicles for TH liberation, and their subsequent release into the blood mediated by TH transporters.

In mice, deficiencies of Tg-processing cathepsins result in thyroid gland enlargement, resembling a goiter phenotype. However, especially in case of cathepsin K deficiency, TH and TSH levels remained unaltered despite a significant enlargement of the thyroid that was further characterized by flat epithelia and enlarged lysosomes. The symptoms of cathepsin K-deficient mice point to a mis-regulation of Tg processing while the classical feedback mechanisms of the HPT-axis were seemingly unaffected. Moreover, altered expression of TH transporters was observed in cathepsin-deficient mouse thyroid tissue, while localization and expression of Tg-processing cathepsins was altered in TH transporter-deficiency, pointing to regulatory interactions between the activities of Tg-processing proteases and TH transporter expression levels.

In order to gain insights about the effects of hypo- and hyperthyroid conditions on Tg-processing enzymes, we have now employed mouse models in which a standard protocol is established for the inspection of thyroid phenotypes, including TH transporter expression, and protease activity assays in correlation with biochemical and morphological features of thyroid epithelial cells, under experimentally induced hypo- and hyperthyroid conditions.

Supported by Deutsche Forschungsgemeinschaft, SPP 1629, BR1308/11 – 1.