Hypothyroidism and Thyroxine-Induced Hyperthyroidism Differentially Affect Cathepsins, Mct8, and Thyroid Tissue Architecture in Male Mice
6 affiliations
- 1School of Science, Constructor University, Campus Ring 1, 28759 Bremen, Germany
- 2Department of Endocrinology, Diabetes and Metabolism, Center Endocrine Medicine (CEM), University Medicine Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany
- 3TissueGnostics GmbH, Taborstraße 10/2/8, 1020 Vienna, Austria
- 4School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane 4059, QLD, Australia
- 5Translational Research Institute, 37 Kent Street, Woolloongabba, Brisbane 4102, QLD, Australia
- 6Faculty of Health Sciences & Medicine, Visiting Academic at Bond University, Gold Coast 4229, QLD, Australia
Abstract
Adequate thyroid hormone concentrations are essential for tissue homeostasis, including in the thyroid gland. Thyrocyte function is regulated by the hypothalamic–pituitary–thyroid axis and by the coordinated action of thyroglobulin-processing cathepsins and thyroid hormone transporters such as monocarboxylate transporter 8 (Mct8). Here, we investigated the effects of hypothyroidism and thyroxine-induced exogenous hyperthyroidism on thyroid proteases and Mct8 expression in male mice. Thyroid follicular architecture was largely preserved in hyperthyroidism, whereas hypothyroidism resulted in increased thyrocyte extensions, collapsed follicular lumina, and enhanced thyroglobulin turnover. Cathepsin B was reduced in both conditions, pro-cathepsin D declined only in hyperthyroidism, and cathepsin L was upregulated in hypothyroidism. Consistently, thyroglobulin fragments were approximately two-fold more abundant in hypothyroid tissue. Mct8 expression remained unchanged in hyperthyroidism but was nearly absent in hypothyroidism. Hypothyroid tissue also exhibited markedly increased thyrocyte proliferation, while cell death rates were not altered across thyroid dysfunction. In addition, alterations in laminin indicated disbalanced extracellular matrix remodeling in hypothyroidism. Together, these findings demonstrate profound changes in thyroid architecture, proteolytic activity, and thyroid hormone transport under chronic thyroid dysfunction, particularly hypothyroidism. Further studies are needed to define the specific role of individual proteases in these processes.
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BibTeX
@article{rehders2026hypothyroidism,
title = {{Hypothyroidism and Thyroxine-Induced Hyperthyroidism Differentially Affect Cathepsins, Mct8, and Thyroid Tissue Architecture in Male Mice}},
author = {Maren Rehders and Helena Kerp and Robert Nica and Rupert Ecker and Dagmar Führer and Klaudia Brix},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209345},
url = {https://www.mdpi.com/1422-0067/27/20/9345},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hypothyroidism and Thyroxine-Induced Hyperthyroidism Differentially Affect Cathepsins, Mct8, and Thyroid Tissue Architecture in Male Mice
AU - Maren Rehders
AU - Helena Kerp
AU - Robert Nica
AU - Rupert Ecker
AU - Dagmar Führer
AU - Klaudia Brix
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209345
UR - https://www.mdpi.com/1422-0067/27/20/9345
AB - Adequate thyroid hormone concentrations are essential for tissue homeostasis, including in the thyroid gland. Thyrocyte function is regulated by the hypothalamic–pituitary–thyroid axis and by the coordinated action of thyroglobulin-processing cathepsins and thyroid hormone transporters such as monocarboxylate transporter 8 (Mct8). Here, we investigated the effects of hypothyroidism and thyroxine-induced exogenous hyperthyroidism on thyroid proteases and Mct8 expression in male mice. Thyroid follicular architecture was largely preserved in hyperthyroidism, whereas hypothyroidism resulted in increased thyrocyte extensions, collapsed follicular lumina, and enhanced thyroglobulin turnover. Cathepsin B was reduced in both conditions, pro-cathepsin D declined only in hyperthyroidism, and cathepsin L was upregulated in hypothyroidism. Consistently, thyroglobulin fragments were approximately two-fold more abundant in hypothyroid tissue. Mct8 expression remained unchanged in hyperthyroidism but was nearly absent in hypothyroidism. Hypothyroid tissue also exhibited markedly increased thyrocyte proliferation, while cell death rates were not altered across thyroid dysfunction. In addition, alterations in laminin indicated disbalanced extracellular matrix remodeling in hypothyroidism. Together, these findings demonstrate profound changes in thyroid architecture, proteolytic activity, and thyroid hormone transport under chronic thyroid dysfunction, particularly hypothyroidism. Further studies are needed to define the specific role of individual proteases in these processes.
SN - 1422-0067
ER -