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Aortic effects of thyroid hormone in male mice

Gachkar, Sogol; Nock, Sebastian; Geissler, Cathleen; Oelkrug, Rebecca; Johann, Kornelia; Resch, Julia; Rahman, Awahan; Arner, Anders LU ; Kirchner, Henriette and Mittag, Jens (2019) In Journal of Molecular Endocrinology 62(3). p.91-99
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-shaped curve with maximal constrictive... (More)

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-shaped 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 1 mg/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 TRβ knockout mice. To identify targets of genomic thyroid hormone action, we analysed 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 occurring in the hyperthyroid aorta.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
aorta, gene expression, hyperthyroidism, hypothyroidism, thyroid hormone receptor β, vasoconstriction
in
Journal of Molecular Endocrinology
volume
62
issue
3
pages
9 pages
publisher
Society for Endocrinology
external identifiers
  • scopus:85067615399
ISSN
1479-6813
DOI
10.1530/JME-18-0217
language
English
LU publication?
yes
id
9bc4e0c1-bcc2-4387-bce2-72ec586e69ab
date added to LUP
2019-07-05 15:58:17
date last changed
2019-07-30 05:06:14
@article{9bc4e0c1-bcc2-4387-bce2-72ec586e69ab,
  abstract     = {<p>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-shaped 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 1 mg/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 TRβ knockout mice. To identify targets of genomic thyroid hormone action, we analysed 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 occurring in the hyperthyroid aorta.</p>},
  author       = {Gachkar, Sogol and Nock, Sebastian and Geissler, Cathleen and Oelkrug, Rebecca and Johann, Kornelia and Resch, Julia and Rahman, Awahan and Arner, Anders and Kirchner, Henriette and Mittag, Jens},
  issn         = {1479-6813},
  keyword      = {aorta,gene expression,hyperthyroidism,hypothyroidism,thyroid hormone receptor β,vasoconstriction},
  language     = {eng},
  number       = {3},
  pages        = {91--99},
  publisher    = {Society for Endocrinology},
  series       = {Journal of Molecular Endocrinology},
  title        = {Aortic effects of thyroid hormone in male mice},
  url          = {http://dx.doi.org/10.1530/JME-18-0217},
  volume       = {62},
  year         = {2019},
}