Anabolic effects of 3,3',5-triiodothyronine and triiodothyroacetic acid in cultured neonatal mouse parietal bones.

Abstract

We previously reported that both T3 and triiodothyroacetic acid (Triac) stimulate bone resorption in organ culture, with Triac somewhat more potent than T3. In this study we compared the effects of T3 and Triac on DNA and protein synthesis in cultured neonatal mouse calvariae. After 24 h of preculture, with 72 h of treatment, but not 24 or 48 h, these hormones stimulated [3H]thymidine incorporation. After 72 h of preculture, stimulation was observed with only 24 h of treatment. These effects were significant at 10(-10) M and maximal at 10(-9) M for both T3 and Triac (treated/control ratios, 2.2 and 2.0, respectively). In contrast to their effects on bone resorption, T3 was more potent than Triac in stimulating [3H]thymidine incorporation. Insulin-like growth factor-binding protein-3 did not decrease the stimulation of DNA synthesis by T3 or Triac. The medium insulin-like growth factor-I concentration was less than 10(-10) M and was not regulated by these hormones. T3 and Triac stimulated [3H]proline incorporation into both collagen and noncollagen protein to a similar extent (approximately 30% at 10(-8) M). Indomethacin did not alter the effects of T3 and Triac on DNA or collagen synthesis. Aphidicolin, which blocked DNA synthesis completely, partially decreased the effects of thyroid hormones on collagen synthesis. The effect of aphidicolin on bone formation was less than that observed previously on bone resorption. We speculate that the effects of thyroid hormones on bone formation as well as bone resorption may be partially dependent on their mitogenic effects. As Triac is more potent in stimulating resorption and less potent in stimulating formation, Triac may be more catabolic than T3.