| Autor: |
Geist, Daniela, Hönes, Georg Sebastian, Grund, Susanne Camilla, Pape, Janina, Siemes, Devon, Spangenberg, Philippa, Tolstik, Elen, Dörr, Stefanie, Spielmann, Nadine, Fuchs, Helmut, Gailus-Durner, Valerie, Hrabe de Angelis, Martin, Mittag, Jens, Engel, Daniel Robert, Führer, Dagmar, Lorenz, Kristina, Moeller, Lars Christian |
| Předmět: |
|
| Zdroj: |
Thyroid; Jun2024, Vol. 34 Issue 6, p785-795, 11p |
| Abstrakt: |
Background: Stimulation of ventricular hypertrophy and heart rate are two major cardiac effects of thyroid hormone (TH). The aim of this study was to determine in vivo which TH receptor (TR)—α or β—and which mode of TR action—canonical gene expression or DNA-binding independent noncanonical action—mediate these effects. Methods: We compared global TRα and TRβ knockout mice (TRαKO; TRβKO) with wild-type (WT) mice to determine the TR isoform responsible for T3 effects. The relevance of TR DNA binding was studied in mice with a mutation in the DNA-binding domain that selectively abrogates DNA binding and canonical TR action (TRαGS; TRβGS). Hearts were studied with echocardiography at baseline and after 7 weeks of T3 treatment. Gene expression was measured with real-time polymerase chain reaction. Heart rate was recorded with radiotelemetry transmitters for 7 weeks in untreated, hypothyroid, and T3-treated mice. Results: T3 induced ventricular hypertrophy in WT and TRβKO mice, but not in TRαKO mice. Hypertrophy was also induced in TRαGS mice. Thus, hypertrophy is mostly mediated by noncanonical TRα action. Similarly, repression of Mhy7 occurred in WT and TRαGS mice. Basal heart rate was largely dependent on canonical TRα action. But responsiveness to hypothyroidism and T3 treatment as well as expression of pacemaker gene Hcn2 were still preserved in TRαKO mice, demonstrating that TRβ could compensate for absence of TRα. Conclusions: T3-induced cardiac hypertrophy could be attributed to noncanonical TRα action, whereas heart rate regulation was mediated by canonical TRα action. TRβ could substitute for canonical but not noncanonical TRα action. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
