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Role of the Thyroid Gland in Expression of the Thyroid Phenotype of Sbp2-Deficient Mice.

Authors
  • Fujisawa, Haruki1, 2
  • Korwutthikulrangsri, Manassawee1, 3
  • Fu, Jiao1, 4
  • Liao, Xiao-Hui1
  • Dumitrescu, Alexandra M1, 5
  • 1 Department of Medicine, University of Chicago, Chicago, Illinois.
  • 2 Department of Endocrinology and Metabolism, Fujita Health University, Toyoake, Aichi, Japan. , (Japan)
  • 3 Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. , (Thailand)
  • 4 Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, Xi'an, P.R. China. , (China)
  • 5 Committee on Molecular Metabolism and Nutrition, University of Chicago, Chicago, Illinois.
Type
Published Article
Journal
Endocrinology
Publisher
The Endocrine Society
Publication Date
May 01, 2020
Volume
161
Issue
5
Identifiers
DOI: 10.1210/endocr/bqz032
PMID: 31826256
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Selenocysteine insertion sequence-binding protein 2, SBP2 (SECISBP2), is required for selenoprotein synthesis. Partial SBP2 deficiency syndrome manifests characteristic thyroid function tests. The Sbp2 deficiency mouse model, Sbp2 inducible conditional knockout (iCKO), replicates this thyroid phenotype and was used for pathophysiologic investigations. As selenoproteins have an antioxidative role in thyroid gland function, their deficiencies have potential to affect thyroid hormone (TH) synthesis. Sbp2 iCKO mice had larger thyroids relative to body weight and increased thyroidal thyroxine (T4) and triiodothyronine (T3) content while 5' deiodinases enzymatic activities were decreased. Possible mechanisms for the discrepancy between the increased thyroidal T3 and normal circulating T3 were investigated in dynamic experiments. Treatment with bovine thyroid-stimulating hormone (TSH) resulted in increased delta T4 in Sbp2 iCKO mice, indicating increased availability of preformed thyroidal TH. Next, the recovery of TH levels was evaluated after withdrawal of chemical suppression. At one day, Sbp2 iCKO mice had higher serum and thyroidal T3 concomitant with lower TSH, confirming increased capacity of TH synthesis in Sbp2 deficiency. Decreased TH secretion was ruled out as serum and thyroidal TH were high in Sbp2 iCKO mice. Treatment with a low-iodine diet also ruled out thyroidal secretion defect as both serum levels and thyroidal TH content similarly declined over time in Sbp2-deficient mice compared to wild-type (Wt) mice. This study provides evidence for unsuspected changes in the thyroid gland that contribute to the thyroid phenotype of Sbp2 deficiency, with increased thyroidal T4 and T3 content in the setting of increased TH synthesis capacity contributing to the circulating TH levels while thyroidal secretion is preserved. © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: [email protected]

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