| First Author | Amma LL | Year | 2001 |
| Journal | Mol Endocrinol | Volume | 15 |
| Issue | 3 | Pages | 467-75 |
| PubMed ID | 11222747 | Mgi Jnum | J:67946 |
| Mgi Id | MGI:1931724 | Doi | 10.1210/mend.15.3.0605 |
| Citation | Amma LL, et al. (2001) Distinct Tissue-Specific Roles for Thyroid Hormone Receptors beta and alpha1 in Regulation of Type 1 Deiodinase Expression. Mol Endocrinol 15(3):467-75 |
| abstractText | Type 1 deiodinase (D1) metabolizes different forms of thyroid hormones to control levels of T(3), the active ligand for thyroid hormone receptors (TR). The D1 gene is itself T(3)-inducible and here, the regulation of D1 expression by TRalpha1 and TRbeta, which act as T(3)-dependent transcription factors, was investigated in receptor-deficient mice. Liver and kidney D1 mRNA and activity levels were reduced in TRbeta(-/-) but not TRalpha1(-/-) mice. Liver D1 remained weakly T(3) inducible in TRbeta(-/-) mice whereas induction was abolished in double mutant TRalpha1(-/-)TRbeta(-/-) mice. This indicates that TRbeta is primarily responsible for regulating D1 expression whereas TRalpha1 has only a minor role. In kidney, despite the expression of both TRalpha1 and TRbeta, regulation relied solely on TRbeta, thus revealing a marked tissue restriction in TR isotype utilization. Although TRbeta and TRalpha1 mediate similar functions in vitro, these results demonstrate differential roles in regulating D1 expression in vivo and suggest that tissue-specific factors and structural distinctions between TR isotypes contribute to functional specificity. Remarkably, there was an obligatory requirement for a TR, whether TRbeta or TRalpha1, for any detectable D1 expression in liver. This suggests a novel paradigm of gene regulation in which the TR sets both basal expression and the spectrum of induced states. Physiologically, these findings suggest a critical role for TRbeta in regulating the thyroid hormone status through D1-mediated metabolism. |
