Spared bone mass in rats treated with thyroid hormone receptor TR beta-selective compound GC-1.
Thyrotoxicosis is frequently associated with increased bone turnover and decreased bone mass. To investigate the role of thyroid hormone receptor-beta (TR beta) in mediating the osteopenic effects of triiodothyronine (T3), female adult rats were treated daily (64 days) with GC-1 (1.5 microg/100 g body wt), a TR beta-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 microg/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 beta isoform does not result in bone loss typical of T3-induced thyrotoxicosis, suggesting that the TR beta 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.
Freitas
Fatima R S
FR
Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, 05508-900, Brazil.
Moriscot
Anselmo S
AS
Jorgetti
Vanda
V
Soares
Antonio G
AG
Passarelli
Marisa
M
Scanlan
Thomas S
TS
Brent
Gregory A
GA
Bianco
Antonio C
AC
Gouveia
Cecilia H A
CH
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000139:chemically induced / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D005260:Female; D005269:Femur; D051381:Rats; D017208:Rats, Wistar; D011988:Receptors, Thyroid Hormone / Q000819:agonists* / Q000187:drug effects / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta; D013971:Thyrotoxicosis / Q000139:chemically induced / Q000150:complications; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives*
D011988:Receptors, Thyroid Hormone; D037042:Thyroid Hormone Receptors beta; D014284:Triiodothyronine; D013972:Thyrotropin; D002784:Cholesterol; D013974:Thyroxine