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Differences in Mouse Hepatic Thyroid Hormone Transporter Expression with Age and Hyperthyroidism

  • Background: Clinical features of thyroid dysfunction vary with age, and an oligosymptomatic presentation of hyperthyroidism is frequently observed in the elderly. This suggests age modulation of thyroid hormone (TH) action, which may occur, for example, by alterations in TH production, metabolism and/or TH action in target organs. Objectives: In this paper, we address possible changes in TH transporter expression in liver tissues as a mechanism of age-dependent variation in TH action. Methods: Chronic hyperthyroidism was induced in 4- and 20-month-old C57BL6/NTac male mice (n = 8-10) by intraperitoneal injections of 1 µg/g body weight <smlcap>L</smlcap>-thyroxine (T<sub>4</sub>) every 48 h over 7 weeks. Control animals were injected with PBS. Total RNA was isolated from liver samples for analysis of the TH transporter and TH-responsive gene expression. TH concentrations were determined in mice sera. Results: Baseline serum free T<sub>4</sub> (fT<sub>4</sub>) concentrations were significantly higher in euthyroid young compared to old mice. T<sub>4</sub> treatment increased total T<sub>4</sub>, fT<sub>4</sub> and free triiodothyronine to comparable concentrations in young and old mice. In the euthyroid state, TH transporter expression was significantly higher in old than in young mice, except for Mct8 and Oatp1a1 expression levels. Hyperthyroidism resulted in upregulation of Mct10, Lat1 and Lat2 in liver tissue, while Oatp1a1, Oatp1b2 and Oatp1a4 expression was downregulated. This effect was preserved in old animals. Conclusion: Here, we show age-dependent differences in TH transporter mRNA expression in the euthyroid and hyperthyroid state of mice focusing on the liver as a classical TH target organ.

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Metadaten
Author: Kathrin Engels, Helena Rakov, Denise Zwanziger, Lars C. Moeller, Georg Homuth, Josef Köhrle, Klaudia Brix, Dagmar Führer
URN:urn:nbn:de:gbv:9-opus-31284
URL:http://www.karger.com/etj
DOI:https://doi.org/10.1159/000381020
ISSN:2235-0640
ISSN:2235-0802
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=26601077
Parent Title (English):European Thyroid Journal
Publisher:S. Karger AG
Place of publication:Basel, Switzerland
Document Type:Article
Language:English
Date of first Publication:2015/05/27
Release Date:2020/09/29
Tag:Aging, Hyperthyroidism, Liver, Thyroid
GND Keyword:-
Volume:4
Issue:Suppl 1
First Page:81
Last Page:86
Faculties:Universitätsmedizin / Arbeitsgruppe "Funktionelle Genomforschung"
Licence (German):License LogoUrheberrechtlich geschützt