Study Title:

Thyroid-specific mitochondrial dysfunction results in abnormal thyrotropin responses.

Study Abstract

Background: Optimal production of cellular energy and metabolites in mitochondria is one of the most important factors in endocrine organs that accomplish the momentary adaptation to ligand stimulation, such as insulin secretion and aldosterone biosynthesis. Although it has been suggested that thyroid gland function is also largely dependent on mitochondrial function, functional behavior of thyroid gland on compromised mitochondrial function remained to be identified. In this study, we have developed the new animal model of thyroid-specific mitochondrial dysfunction using standard gene targeting technology to understand the role of mitochondria OxPhos dysfunction in thyroid gland.

Methods: We have analyzed the histological and functional phenotypes of the mice which has thyroid specific mitochondrial dysfunction by targeting Crif1 gene which is involved in intramitochondrial production of OxPhos complex subunits.

Results: We analyzed the phenotypes of the mice with mitochondrial OxPhos deficiency. Homozygote thyroid-specific mitochondrial dysfunction (ThyCKO) mice retarded growth and died prematurely in PN21 to 35 days with severe thyroid dysfunction. Histology of homozygote ThyCKO mice showed distortion of thyroid follicles and oncocytic change of cells. Serum TSH and thyroid hormone levels showed no difference between 10 week old wild type and heterozygote ThyCKO mice. Unexpectedly, TSH injections (6 μg/day) to 10 week old heterozygote ThyCKO mice exacerbated ER swelling combined with destruction of mitochondrial cristae structure, resulting in lower secretion of thyroid hormone.

Conclusion: This study suggested that mitochondrial OxPhos defect may cause structural and functional changes of thyrocyte which may lead the progressive chronic nonautoimmune failure of thyroid gland.

Study Information

Endocrine Abstracts (2018) 56 GP251 | DOI: 10.1530/endoabs.56.GP251

Full Study

https://www.endocrine-abstracts.org/ea/0056/ea0056gp251