| First Author | Kindblom JM | Year | 2001 |
| Journal | J Endocrinol | Volume | 171 |
| Issue | 1 | Pages | 15-22 |
| PubMed ID | 11572786 | Mgi Jnum | J:72045 |
| Mgi Id | MGI:2151665 | Doi | 10.1677/joe.0.1710015 |
| Citation | Kindblom JM, et al. (2001) GH substitution reverses the growth phenotype but not the defective ossification in thyroid hormone receptor alpha1-/-beta-/- mice. J Endocrinol 171(1):15-22 |
| abstractText | Thyroid hormone receptor alpha1, beta1 and beta2-deficient mice (TRalpha1-/-beta-/- mice) demonstrate growth retardation and defective ossification in the epiphyses associated with an inhibition of the GH/IGF-I axis. There are differences between TRalpha1-/-beta-/- mice (receptor deficient) and the hypothyroid animal model (ligand deficient). Such differences include possible repressive actions exerted by unliganded receptors in the ligand-deficient (hypothyroid) model but not in the receptor-deficient model. In the present study we have investigated whether or not GH substitution rescues the skeletal phenotype of TRalpha1-/-beta-/- mice. TRalpha1-/-beta-/- and wild-type (WT) mice were treated with GH from day 18 until 10 weeks of age. GH substitution of mutant mice resulted in a significant and sustained stimulatory effect on the body weight that was not seen in WT mice. GH-treated mutant mice but not GH-treated WT mice demonstrated increased length and periosteal circumference of the femur. However, GH substitution did not reverse the defective ossification seen in TRalpha1-/-beta-/- mice. TRalpha1-/-beta-/- mice displayed increased width of the proximal tibial growth plate, which was caused by increased width of the proliferative but not the hypertrophic layer. GH substitution did not restore the disturbed morphology of the growth plate in TRalpha1-/-beta-/- mice. In summary, GH substitution reverses the growth phenotype but not the defective ossification in TRalpha1-/-beta-/- mice. Our data suggest that TRs are of importance both for the regulation of the GH/IGF-I axis and for direct effects on cartilage. |
