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

Fatima R.S. Freitas, Anselmo S. Moriscot, Vanda Jorgetti, Antonio G. Soares, Marisa Passarelli, Thomas S. Scanlan, Gregory A. Brent, Antonio C. Bianco, Cecilia H.A. Gouveia

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55 Scopus citations

Abstract

Thyrotoxicosis is frequently associated with increased bone turnover and decreased bone mass. To investigate the role of thyroid hormone receptor-β (TRβ) in mediating the osteopenic effects of triiodothyronine (T 3), female adult rats were treated daily (64 days) with GC-1 (1.5 μg/100 g body wt), a TRβ-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 T 3-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 TRβ isoform does not result in bone loss typical of T 3-induced thyrotoxicosis, suggesting that the TRβ 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.

Original languageEnglish (US)
Pages (from-to)E1135-E1141
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume285
Issue number5 48-5
StatePublished - Nov 1 2003

Keywords

  • Bone histomorphometry
  • Bone mineral density
  • Osteopenia
  • Osteoporosis
  • Thyrotoxicosis

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

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    Freitas, F. R. S., Moriscot, A. S., Jorgetti, V., Soares, A. G., Passarelli, M., Scanlan, T. S., Brent, G. A., Bianco, A. C., & Gouveia, C. H. A. (2003). Spared bone mass in rats treated with thyroid hormone receptor TRβ-selective compound GC-1. American Journal of Physiology - Endocrinology and Metabolism, 285(5 48-5), E1135-E1141.