| First Author | Ying H | Year | 2005 |
| Journal | Mol Cell Biol | Volume | 25 |
| Issue | 17 | Pages | 7687-95 |
| PubMed ID | 16107715 | Mgi Jnum | J:100538 |
| Mgi Id | MGI:3588815 | Doi | 10.1128/MCB.25.17.7687-7695.2005 |
| Citation | Ying H, et al. (2005) Dual functions of the steroid hormone receptor coactivator 3 in modulating resistance to thyroid hormone. Mol Cell Biol 25(17):7687-95 |
| abstractText | Mutations of the thyroid hormone receptor beta (TRbeta) gene cause resistance to thyroid hormone (RTH). RTH is characterized by increased serum thyroid hormone associated with nonsuppressible thyroid-stimulating hormone (TSH) and impaired growth. It is unclear how the actions of TRbeta mutants are modulated in vivo to affect the manifestation of RTH. Using a mouse model of RTH that harbors a knockin mutation of the TRbeta gene (TRbetaPV mouse), we investigated the effect of the steroid hormone receptor coactivator 3 (SRC-3) on RTH. In TRbetaPV mice deficient in SRC-3, dysfunction of the pituitary-thyroid axis and hypercholesterolemia was lessened, but growth impairment of RTH was worsened. The lessened dysfunction of the pituitary-thyroid axis was attributed to a significant decrease in growth of the thyroid and pituitary. Serum insulin-like growth factor 1 (IGF-1) was further reduced in TRbetaPV mice deficient in SRC-3. This effect led to reduced signaling of the IGF-1/phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway that is known to mediate cell growth and proliferation. Thus, SRC-3 modulates RTH by at least two mechanisms, one via its role as a receptor coregulator and the other via its growth regulatory role through the IGF-1/PI3K/AKT/mTOR signaling. |
