| First Author | Sadow PM | Year | 2003 |
| Journal | Mol Endocrinol | Volume | 17 |
| Issue | 5 | Pages | 882-94 |
| PubMed ID | 12576486 | Mgi Jnum | J:126521 |
| Mgi Id | MGI:3761456 | Doi | 10.1210/me.2002-0174 |
| Citation | Sadow PM, et al. (2003) Thyroid hormone receptor-specific interactions with steroid receptor coactivator-1 in the pituitary. Mol Endocrinol 17(5):882-94 |
| abstractText | Steroid receptor coactivator-1 (SRC-1) is a transcription cofactor that enhances the hormone-dependent action mediated by the thyroid hormone (TH) receptor (TR) as well as other nuclear receptors. However, it is not known whether the SRC-1-mediated activation of TH-regulated gene transcription is TR isoform specific in the pituitary. We generated mice that were deficient in TRalpha and SRC-1 (TRalpha(0/0)SRC-1(-/-)), as well in TRbeta and SRC-1 (TRbeta(-/-)SRC-1(-/-)), and thyroid function tests and effects of TH deprivation and TH treatment were compared with wild-type mice or mice with deletion of either TRs or SRC-1 alone. We have shown that 1) TRbeta(-/-)SRC-1(-/-) mice demonstrate more severe TH resistance than either the SRC-1(-/-) or TRbeta(-/-) mice; the additive effect indicates that SRC-1 has an independent role in TH action over that of TRbeta; 2) SRC-1 facilitates TRbeta and TRalpha-mediated down-regulation of TSH, as TRalpha(0/0)SRC-1(-/-) mice demonstrate TH resistance rather than hypersensitivity as seen in TRalpha(0/0)mice; and 3) a compensatory increase in SRC-1 expression is associated with the TH hypersensitivity seen in TRalpha-deficient animals. We conclude that SRC-1 action in the pituitary mediates TH action via specific TR subtypes. |
