Kathrin Engels1, Helena Rakov1, Denise Zwanziger1, Lars C Moeller1, Georg Homuth2, Josef Köhrle3, Klaudia Brix4, Dagmar Führer1. 1. Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany. 2. Department of Functional Genomics, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany. 3. Institute of Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany. 4. Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany.
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. 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 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. 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.
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 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. 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.
Authors: B Biondi; E A Palmieri; S Fazio; C Cosco; M Nocera; L Saccà; S Filetti; G Lombardi; F Perticone Journal: J Clin Endocrinol Metab Date: 2000-12 Impact factor: 5.958
Authors: T Abe; M Kakyo; H Sakagami; T Tokui; T Nishio; M Tanemoto; H Nomura; S C Hebert; S Matsuno; H Kondo; H Yawo Journal: J Biol Chem Date: 1998-08-28 Impact factor: 5.157
Authors: Alexandra M Dumitrescu; Xiao-Hui Liao; Roy E Weiss; Kathleen Millen; Samuel Refetoff Journal: Endocrinology Date: 2006-05-18 Impact factor: 4.736
Authors: E C Friesema; R Docter; E P Moerings; B Stieger; B Hagenbuch; P J Meier; E P Krenning; G Hennemann; T J Visser Journal: Biochem Biophys Res Commun Date: 1999-01-19 Impact factor: 3.575
Authors: Amanda H Mortensen; Qing Fang; Michelle T Fleming; Thomas J Jones; Alexandre Z Daly; Kenneth R Johnson; Sally A Camper Journal: Mamm Genome Date: 2019-02-18 Impact factor: 2.957
Authors: Helena Rakov; Kathrin Engels; Georg Sebastian Hönes; Karl-Heinz Strucksberg; Lars Christian Moeller; Josef Köhrle; Denise Zwanziger; Dagmar Führer Journal: Biol Sex Differ Date: 2016-08-24 Impact factor: 5.027
Authors: Helena Rakov; Kathrin Engels; Georg Sebastian Hönes; Klaudia Brix; Josef Köhrle; Lars Christian Moeller; Denise Zwanziger; Dagmar Führer Journal: Biol Sex Differ Date: 2017-12-22 Impact factor: 5.027
Authors: Christin Krause; Martina Grohs; Alexander T El Gammal; Stefan Wolter; Hendrik Lehnert; Oliver Mann; Jens Mittag; Henriette Kirchner Journal: Endocr Connect Date: 2018-12 Impact factor: 3.335
Authors: Hannah Kohler; Soeren Latteyer; Georg Sebastian Hönes; Sarah Theurer; Xiao-Hui Liao; Sandra Christoph; Denise Zwanziger; Johannes H Schulte; Jukka Kero; Hendrik Undeutsch; Samuel Refetoff; Kurt W Schmid; Dagmar Führer; Lars C Moeller Journal: Thyroid Date: 2019-10-08 Impact factor: 6.568