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

Research output: Contribution to journalArticle

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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
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume285
Issue number5 48-5
StatePublished - Nov 1 2003

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Thyroid Hormone Receptors
Rats
Bone
Bone and Bones
Femur
Thyrotoxicosis
Bone Density
Protein Isoforms
Minerals
Lumbar Vertebrae
Bone Remodeling
Photon Absorptiometry
Triiodothyronine
Tibia
Cholesterol
GC 1 compound
Animals
Chemical activation
Serum
X rays

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Freitas, F. R. S., Moriscot, A. S., Jorgetti, V., Soares, A. G., Passarelli, M., Scanlan, T. S., ... 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).

Spared bone mass in rats treated with thyroid hormone receptor TRβ-selective compound GC-1. / Freitas, Fatima R S; Moriscot, Anselmo S.; Jorgetti, Vanda; Soares, Antonio G.; Passarelli, Marisa; Scanlan, Thomas S.; Brent, Gregory A.; Bianco, Antonio C.; Gouveia, Cecilia H A.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 285, No. 5 48-5, 01.11.2003.

Research output: Contribution to journalArticle

Freitas, FRS, Moriscot, AS, Jorgetti, V, Soares, AG, Passarelli, M, Scanlan, TS, Brent, GA, Bianco, AC & Gouveia, CHA 2003, 'Spared bone mass in rats treated with thyroid hormone receptor TRβ-selective compound GC-1', American Journal of Physiology - Endocrinology and Metabolism, vol. 285, no. 5 48-5.
Freitas FRS, Moriscot AS, Jorgetti V, Soares AG, Passarelli M, Scanlan TS et al. Spared bone mass in rats treated with thyroid hormone receptor TRβ-selective compound GC-1. American Journal of Physiology - Endocrinology and Metabolism. 2003 Nov 1;285(5 48-5).
Freitas, Fatima R S ; Moriscot, Anselmo S. ; Jorgetti, Vanda ; Soares, Antonio G. ; Passarelli, Marisa ; Scanlan, Thomas S. ; Brent, Gregory A. ; Bianco, Antonio C. ; Gouveia, Cecilia H A. / Spared bone mass in rats treated with thyroid hormone receptor TRβ-selective compound GC-1. In: American Journal of Physiology - Endocrinology and Metabolism. 2003 ; Vol. 285, No. 5 48-5.
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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.",
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AU - Soares, Antonio G.

AU - Passarelli, Marisa

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