| First Author | Bassett JH | Year | 2007 |
| Journal | Mol Endocrinol | Volume | 21 |
| Issue | 8 | Pages | 1893-904 |
| PubMed ID | 17488972 | Mgi Jnum | J:123118 |
| Mgi Id | MGI:3717075 | Doi | 10.1210/me.2007-0157 |
| Citation | Bassett JH, et al. (2007) Thyroid Status during Skeletal Development Determines Adult Bone Structure and Mineralization. Mol Endocrinol 21(8):1893-1904 |
| abstractText | Childhood hypothyroidism delays ossification and bone mineralization, whereas adult thyrotoxicosis causes osteoporosis. To determine how effects of thyroid hormone (T(3)) during development manifest in adult bone, we characterized TRalpha1(+/m)beta(+/-) mice, which express a mutant T(3) receptor (TR) alpha1 with dominant-negative properties due to reduced ligand-binding affinity. Remarkably, adult TRalpha1(+/m)beta(+/-) mice had osteosclerosis with increased bone mineralization even though juveniles had delayed ossification. This phenotype was partially normalized by transient T(3) treatment of juveniles and fully reversed in compound TRalpha1(+/m)beta(-/-) mutant mice due to 10-fold elevated hormone levels that allow the mutant TRalpha1 to bind T(3). By contrast, deletion of TRbeta in TRalpha1(+/+)beta(-/ -) mice, which causes a 3-fold increase of hormone levels, led to osteoporosis in adults but advanced ossification in juveniles. T(3)-target gene analysis revealed skeletal hypothyroidism in TRalpha1(m/+)beta(+/-) mice, thyrotoxicosis in TRalpha1(+/+)beta(-/-) mice, and euthyroidism in TRalpha1(+/)beta(-/-) double mutants. Thus, TRalpha1 regulates both skeletal development and adult bone maintenance, with euthyroid status during development being essential to establish normal adult bone structure and mineralization. |
