Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone
Steroid receptor co‐activator 1 (SRC‐1) is a transcription co‐factor that enhances the hormone‐dependent action, mediated by the thyroid hormone (TH) receptor (TR) and other nuclear receptors. In vitro studies have shown that SRC‐1 is necessary for the full expression of TH effect. SRC‐1 knockout mi...
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Published in | The EMBO journal Vol. 18; no. 7; pp. 1900 - 1904 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Chichester, UK
John Wiley & Sons, Ltd
01.04.1999
Blackwell Publishing Ltd |
Subjects | |
Online Access | Get full text |
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Summary: | Steroid receptor co‐activator 1 (SRC‐1) is a transcription co‐factor that enhances the hormone‐dependent action, mediated by the thyroid hormone (TH) receptor (TR) and other nuclear receptors. In vitro studies have shown that SRC‐1 is necessary for the full expression of TH effect. SRC‐1 knockout mice (SRC‐1−/−) provide a model to examine the role of this co‐activator on TH action in vivo. At baseline, SRC‐1−/− mice display resistance to TH (RTH) as evidenced by a 2.5‐fold elevation of serum TSH levels, despite a 50% increase in serum free TH levels as compared with wild‐type (SRC‐1+/+) mice. When mice were made hypothyroid, TSH levels increased, obliterating the difference between SRC‐1+/+ and SRC‐1−/− mice observed at baseline. In contrast, the decline of TSH by treatment with L‐triiodothyronine was severely blunted in SRC‐1−/− mice. These data indicate that SRC‐1 is not required for the upregulation of TSH in TH deficiency. However, SRC‐1 enhances the sensitivity of TSH downregulation by TH. This is the first demonstration of RTH caused by a deficient co‐factor other than TR. It supports the hypothesis that a putative defect in the SRC‐1 gene or another co‐factor could be the cause of RTH in humans without mutations in the TR genes. |
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Bibliography: | ArticleID:EMBJ7591617 istex:D3777B24B5D017B28C90D9B4D4B8F93A7164FBCB ark:/67375/WNG-FMDTZMBK-N ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0261-4189 1460-2075 1460-2075 |
DOI: | 10.1093/emboj/18.7.1900 |