TY - JOUR
T1 - Spared bone mass in rats treated with thyroid hormone receptor TRβ-selective compound GC-1
AU - Freitas, Fatima R.S.
AU - Moriscot, Anselmo S.
AU - Jorgetti, Vanda
AU - Soares, Antonio G.
AU - Passarelli, Marisa
AU - Scanlan, Thomas S.
AU - Brent, Gregory A.
AU - Bianco, Antonio C.
AU - Gouveia, Cecilia H.A.
PY - 2003/11
Y1 - 2003/11
N2 - 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.
AB - 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.
KW - Bone histomorphometry
KW - Bone mineral density
KW - Osteopenia
KW - Osteoporosis
KW - Thyrotoxicosis
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M3 - Article
C2 - 12965872
AN - SCOPUS:0142052836
SN - 0193-1849
VL - 285
SP - E1135-E1141
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 5 48-5
ER -