| First Author | Costa-e-Sousa RH | Year | 2012 |
| Journal | Endocrinology | Volume | 153 |
| Issue | 10 | Pages | 5049-57 |
| PubMed ID | 22878400 | Mgi Jnum | J:191436 |
| Mgi Id | MGI:5461760 | Doi | 10.1210/en.2012-1504 |
| Citation | Costa-e-Sousa RH, et al. (2012) The thyroid axis is regulated by NCoR1 via its actions in the pituitary. Endocrinology 153(10):5049-57 |
| abstractText | TSH is the most important biomarker in the interpretation of thyroid function in man. Its levels are determined by circulating thyroid hormone (TH) levels that feed back centrally to regulate the expression of the subunits that comprise TSH from the pituitary. The nuclear corepressor 1 (NCoR1), is a critical coregulator of the TH receptor (TR) isoforms. It has been established to play a major role in the control of TSH secretion, because mice that express a mutant NCoR1 allele (NCoRDeltaID) that cannot interact with the TR have normal TSH levels despite low circulating TH levels. To determine how NCoR1 controls TSH secretion, we first developed a mouse model that allowed for induction of NCoRDeltaID expression postnatally to rule out a developmental effect of NCoR1. Expression of NCoRDeltaID postnatally led to a drop in TH levels without a compensatory rise in TSH production, indicating that NCoR1 acutely controls both TH production and feedback regulation of TSH. To demonstrate that this was a cell autonomous function of NCoR1, we expressed NCoRDeltaID in the pituitary using a Cre driven by the glycoprotein alpha-subunit promoter (P-DeltaID mice). Importantly, P-DeltaID mice have low TH levels with decreased TSH production. Additionally, the rise in TSH during hypothyroidism is blunted in P-DeltaID mice. Thus, NCoR1 plays a critical role in TH-mediated regulation of TSH in the pituitary by regulating the repressive function of the TR. Furthermore, these studies suggest that endogenous NCoR1 levels in the pituitary could establish the set point of TSH secretion. |
