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J Mol Endocrinol. 2019 Jan 1. pii: JME-18-0217.R1. doi: 10.1530/JME-18-0217. [Epub ahead of print]

Aortic Effects of Thyroid Hormone in Male Mice.

Author information

1
S Gachkar, Internal Medicine I, University of Luebeck, Luebeck, Germany.
2
S Nock, Internal Medicine I, University of Luebeck, Luebeck, Germany.
3
C Geissler, Internal Medicine I, University of Luebeck, Luebeck, Germany.
4
R Ölkrug, CBBM, Molecular Endocrinology, UKSH Lübeck, Lübeck, Germany.
5
K Johann, CBBM, Molecular Endocrinology, UKSH Lübeck, Lübeck, Germany.
6
J Resch, Internal Medicine I, University of Luebeck, Luebeck, Germany.
7
A Rahman, Comparative Medicine, Karolinska Institutet, Stockholm, Sweden.
8
A Arner, Med, Lund University, Lund, Sweden.
9
H Kirchner, Internal Medicine I, University of Luebeck, Luebeck, Germany.
10
J Mittag, CBBM, Universitat zu Lubeck Sektion Medizin, Lubeck, Germany.

Abstract

It is well established that thyroid hormones are required for cardiovascular functions; however, the molecular mechanisms remain incompletely understood, especially the individual contributions of genomic and non-genomic signalling pathways. In this study, we dissected how thyroid hormones modulate aortic contractility. To test the immediate effects of thyroid hormones on vasocontractility, we used a wire-myograph to record the contractile response of dissected mouse aortas to the adrenergic agonist phenylephrine in the presence of different doses of T3 (3,3',5-triiodothyronine). Interestingly, we observed reduced vasoconstriction under low and high T3 concentrations, indicating an inversed U-shape curve with maximal constrictive capacity at euthyroid conditions. We then tested for possible genomic actions of thyroid hormones on vasocontractility by treating mice for 4 days with 1mg/L thyroxine in drinking water. The study revealed that in contrast to the non-genomic actions the aortas of these animals were hyperresponsive to the contractile stimulus, an effect not observed in endogenously hyperthyroid TR knockout mice. To identify targets of genomic thyroid hormone action, we analyzed aortic gene expression by microarray, revealing several altered genes including the well-known thyroid hormone target gene hairless. Taken together, the findings demonstrate that thyroid hormones regulate aortic tone through genomic and non-genomic actions, although genomic actions seem to prevail in vivo. Moreover, we identified several novel thyroid hormone target genes that could provide a better understanding of the molecular changes occuring in the hyperthyroid aorta.

PMID:
30608905
DOI:
10.1530/JME-18-0217

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