Helena Rakov1, Meri De Angelis2, Kostja Renko3, Georg Sebastian Hönes1, Denise Zwanziger1,4, Lars Christian Moeller1, Karl-Werner Schramm2,5, Dagmar Führer1. 1. Department of Endocrinology, Diabetes and Metabolism; Department of Endocrinology, Diabetes and Metabolism; University Hospital Essen, University Duisburg-Essen, Essen, Germany. 2. Molecular EXposomics, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Neuherberg, Germany. 3. Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 4. Clinical Chemistry-Division of Laboratory Research, Department of Endocrinology, Diabetes and Metabolism; University Hospital Essen, University Duisburg-Essen, Essen, Germany. 5. Department für Biowissenschaften, Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt, Technische Universität München, Freising, Germany.
Abstract
Background: Serum thyroid state in older adults correlates with extended longevity. We hypothesized that age impacts not only systemic but also organ-specific thyroid state and response to thyroxine (T4). Methods: Young (3 months) and old (23 months) male mice were analyzed at baseline and after acute T4 challenge. Age effects on circulating thyrotropin (TSH) and thyroid hormone (TH) concentrations, transcript expression in the pituitary and thyroid were compared with organ-specific responses characterized by hepatic and cardiac content of TH and TH metabolites and expression of TH-target genes, as well as hepatic deiodinase 1 activity. Results: Circulating TH concentrations and hepatic and cardiac TH content were lower in old versus young mice. After injection with T4, conversion of T4 to triiodothyronine was decreased in old mice while TH transport in liver and heart was not affected. Organ-specific TH response was augmented in old mice in liver but not heart, indicating age- and tissue-specific sensitivity to TH. A compensatory increase of thyroid stimulating hormone subunit beta expression in the pituitary and increased serum TSH concentrations, but reduced expression of thyroid differentiation markers were found in old mice. Conclusions: We suggest that a reduced activity of the aged thyroid is responsible for the systemic low TH state in old mice. Further, divergent TH metabolism and tissue response in liver and heart occur after T4 treatment in an aged organism. These rodent data are in agreement with a much narrower window for T4 substitution in the older adults to avoid overtreatment.
Background: Serum thyroid state in older adults correlates with extended longevity. We hypothesized that age impacts not only systemic but also organ-specific thyroid state and response to thyroxine (T4). Methods: Young (3 months) and old (23 months) male mice were analyzed at baseline and after acute T4 challenge. Age effects on circulating thyrotropin (TSH) and thyroid hormone (TH) concentrations, transcript expression in the pituitary and thyroid were compared with organ-specific responses characterized by hepatic and cardiac content of TH and TH metabolites and expression of TH-target genes, as well as hepatic deiodinase 1 activity. Results: Circulating TH concentrations and hepatic and cardiac TH content were lower in old versus young mice. After injection with T4, conversion of T4 to triiodothyronine was decreased in old mice while TH transport in liver and heart was not affected. Organ-specific TH response was augmented in old mice in liver but not heart, indicating age- and tissue-specific sensitivity to TH. A compensatory increase of thyroid stimulating hormone subunit beta expression in the pituitary and increased serum TSH concentrations, but reduced expression of thyroid differentiation markers were found in old mice. Conclusions: We suggest that a reduced activity of the aged thyroid is responsible for the systemic low TH state in old mice. Further, divergent TH metabolism and tissue response in liver and heart occur after T4 treatment in an aged organism. These rodent data are in agreement with a much narrower window for T4 substitution in the older adults to avoid overtreatment.
Authors: Małgorzata Karbownik-Lewińska; Jan Stępniak; Anna Żurawska; Andrzej Lewiński Journal: Int J Environ Res Public Health Date: 2020-03-23 Impact factor: 3.390