| First Author | Weiss RE | Year | 1999 |
| Journal | EMBO J | Volume | 18 |
| Issue | 7 | Pages | 1900-4 |
| PubMed ID | 10202153 | Mgi Jnum | J:54182 |
| Mgi Id | MGI:1334774 | Doi | 10.1093/emboj/18.7.1900 |
| Citation | Weiss RE, et al. (1999) Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone. EMBO J 18(7):1900-4 |
| abstractText | 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. |
