title: Comparison of the effects of 3,5,3'-triiodothyroacetic acid and triiodothyronine on bone resorption in cultured fetal rat long bones and neonatal mouse calvariae.
abstract: Thyroid hormones can stimulate bone resorption both directly and indirectly by increasing endogenous prostaglandin (PG) synthesis. Because 3,5,3'-triiodothyroacetic acid (Triac, Tiratricol) can bind to nuclear thyroid hormone receptors with high affinity, we compared the effects of Triac and 3,5,3'-triiodothyronine (T3) on bone resorption. 45Ca release was measured at 2, 5, and 8 days from 19-day-old-fetal rat long bones in the presence or absence of calcitonin, indomethacin, aphidicolin (APC), cortisol, or interleukin-1 receptor antagonist (IL-1ra). Both Triac and T3 stimulated 45Ca release in a dose-dependent manner. The maximal treated/control ratio (T/C) for Triac (10(-7) M) was 1.6 +/- 0.1 at 2 days and 2.5 +/- 0.1 at 5 days and, for T3 (10(-7) M), 1.5 +/- 0.1 at 2 days and 2.6 +/- 0.1 at 5 days. These responses were smaller and slower than that to PTH. Significant stimulation of resorption was observed at 10(-8), 10(-9), and 10(-10) M for Triac but only at 10(-8) and 10(-9) M for T3. Indomethacin (10(-6) M) and IL-1ra (1 microgram/ml) did not decrease the effects of Triac or T3. In contrast, calcitonin (10(-9) M), APC (30 microM), and cortisol could all block the response to these hormones. These results indicated that the resorptive responses were not mediated by endogenous PG or IL-1 but were osteoclast mediated and dependent on DNA synthesis, suggesting that these hormones acted by stimulating replication of osteoclast precursors or other supporting cells. Thyroid hormones were less effective in 7-day-old neonatal mouse calvariae.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Connecticut Health Center, Farmington.
authors.forename: H
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: C C
authors.initials: CC
authors.lastname: Pilbeam
authors.forename: F N
authors.initials: FN
authors.lastname: Woodiel
authors.forename: L G
authors.initials: LG
authors.lastname: Raisz
mesh_terms: D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D001862:Bone Resorption / Q000139:chemically induced*; D001842:Bone and Bones / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D002116:Calcitonin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005333:Fetus; D006854:Hydrocortisone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D051379:Mice; D009924:Organ Culture Techniques; D010010:Osteoclasts / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology; D014284:Triiodothyronine / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014284:Triiodothyronine; C010642:3,3',5-triiodothyroacetic acid; D016590:Aphidicolin; D002116:Calcitonin; D002118:Calcium; D006854:Hydrocortisone; D007213:Indomethacin