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This Article Full Text Full Text (PDF) All Versions of this Article: 285/5/E1135    most recent 00506.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (16) Citing Articles via Google Scholar Google Scholar Articles by Freitas, F. R. S. Articles by Gouveia, C. H. A. Search for Related Content PubMed PubMed Citation Articles by Freitas, F. R. S. Articles by Gouveia, C. H. A.

Spared bone mass in rats treated with thyroid hormone receptor TR-selective compound GC-1

Departments of ¹Anatomy and ²Histology, Institute of Biomedical Sciences, and ³School of Medicine, University of Sao Paulo, 05508-900 Sao Paulo, Brazil; ⁴Departments of Pharmaceutical Chemistry and Cellular and Molecular Pharmacology, University of California, San Francisco 94143; ⁵Molecular Endocrinology Laboratory, Veterans Affairs Greater Los Angeles Healthcare System and Departments of Medicine and Physiology, UCLA School of Medicine, Los Angeles, California 91301; and ⁶Thyroid Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

Submitted 18 November 2002 ; accepted in final form 29 July 2003

Thyrotoxicosis is frequently associated with increased bone turnover and decreased bone mass. To investigate the role of thyroid hormone receptor- (TR) in mediating the osteopenic effects of triiodothyronine (T₃), female adult rats were treated daily (64 days) with GC-1 (1.5 µg/100 g body wt), a TR-selective thyromimetic compound. Bone mass was studied by dual-energy X-ray absorptiometry of several skeletal sites and histomorphometry of distal femur, and the results were compared with T₃-treated (3 µg/100 g body wt) or control animals. As expected, treatment with T₃ significantly reduced bone mineral density (BMD) in the lumbar vertebrae (L₂-L₅), femur, and tibia by 10–15%. In contrast, GC-1 treatment did not affect the BMD in any of the skeletal sites studied. The efficacy of GC-1 treatment was verified by a reduction in serum TSH (–52% vs. control, P < 0.05) and cholesterol (–21% vs. control, P < 0.05). The histomorphometric analysis of the distal femur indicated that T₃ but not GC-1 treatment reduced the trabecular volume, thickness, and number. We conclude that chronic, selective activation of the TR isoform does not result in bone loss typical of T₃-induced thyrotoxicosis, suggesting that the TR isoform is not critical in this process. In addition, our findings suggest that the development of TR-selective T₃ analogs that spare bone mass represents a significant improvement toward long-term TSH-suppressive therapy.

thyrotoxicosis; osteopenia; osteoporosis; bone mineral density; bone histomorphometry

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				C. M Villicev, F. R S Freitas, M. S Aoki, C. Taffarel, T. S Scanlan, A. S Moriscot, M. O Ribeiro, A. C Bianco, and C. H A Gouveia Thyroid hormone receptor {beta}-specific agonist GC-1 increases energy expenditure and prevents fat-mass accumulation in rats J. Endocrinol., April 1, 2007; 193(1): 21 - 29. [Abstract] [Full Text] [PDF]