title: Differences in Mouse Hepatic Thyroid Hormone Transporter Expression with Age and Hyperthyroidism.
abstract: 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.
  
  
  OBJECTIVE
  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 L-thyroxine (T4) 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 T4 (fT4) concentrations were significantly higher in euthyroid young compared to old mice. T4 treatment increased total T4, fT4 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Engels
authors.affiliation: Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany.
authors.forename: Helena
authors.initials: H
authors.lastname: Rakov
authors.affiliation: Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Zwanziger
authors.affiliation: Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany.
authors.forename: Lars C
authors.initials: LC
authors.lastname: Moeller
authors.affiliation: Department of Functional Genomics, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Homuth
authors.affiliation: Institute of Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
authors.affiliation: Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Brix
authors.affiliation: Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Führer
keywords: Aging; Hyperthyroidism; Liver; Thyroid