Exp Clin Endocrinol Diabetes 2015; 123 - P12_05
DOI: 10.1055/s-0035-1547739

Induced hyper- and hypothyroidism results in altered maturation states of thyroglobulin processing proteases in the mouse thyroid gland

M Rehders 1, J Weber 2, K Engels 3, H Rakov 3, S Hönes 3, EK Wirth 4, U Schweizer 5, L Moeller 3, H Heuer 6, K Brix 2
  • 1Jacobs University Bremen; Department of Life Sciences and Chemistry; Department of Life Sciences and Chemistry
  • 2Jacobs University Bremen; Department of Life Sciences and Chemistry
  • 3University Duisburg-Essen; Department of Endocrinology and Metabolism
  • 4Charité-Universitätsmedizin Berlin; Institut für Experimentelle Endokrinologie
  • 5Rheinische Friedrich-Wilhelms-Universität Bonn; Institut für Biochemie und Molekularbiologie
  • 6Leibniz-Institut für Umweltmedizinische Forschung; Leibniz Institute for Age Research/Fritz Lipmann Institute (Fli)

Appropriate availability of thyroid hormones (TH) in target tissues depends critically on the combined action of the cysteine proteases cathepsins B, K, L, and S, and the aspartyl protease cathepsin D which cleave thyroglobulin (Tg) for extra- and intracellular liberation of T3 and T4. Thyroidal release of TH is enabled by subsequent transport across cellular membranes mediated by TH transporters like Lat2 and Mct8. Mice deficient in one or more Tg-processing cathepsins show signs resembling classical goiter phenotypes associated with hypo- and hyperthyroidism.

In this study, thyroidal cathepsin expression levels were investigated in mice with induced hypo- and hyperthyroidism. In thyroid glands of hypothyroid mice, cathepsins B and L were down-regulated with regard to both, their pro- and mature forms whereas expression levels and maturation states of cathepsin D were not changed. Hyperthyroidism resulted in reduced levels of pro- and mature cathepsin D, lowered levels of mature cathepsins B and L (heavy chain), as well as the complete loss of the single chain form of cathepsin L. In contrast, expression levels of procathepsin B were elevated in hyperthyroid animals. Altered expression levels of TH transporters were already observed in cathepsin-deficient mouse thyroid tissue, while localization and expression of Tg-processing cathepsins were altered in TH transporter-deficiency.

We conclude that these results indicate a regulatory interaction between Tg-processing proteases and TH transporter expression. Furthermore, altered levels of TH showed an effect on the regulation of cathepsin maturation and protein amounts in the thyroid gland of mice. Since cathepsins are involved in a variety of cellular activities in physiological and pathological conditions besides their Tg-processing abilities, these results highlight the importance of a healthy thyroid function with balanced thyroid hormone levels.

Supported by DFG, SPP 1629, BR1308/11 – 1.