ANABOLIC EFFECTS OF 3,3',5-TRIIODOTHYRONINE AND TRIIODOTHYROACETIC ACID IN CULTURED NEONATAL MOUSE PARIETAL BONES

We previously reported that both T-3 and triiodothyroacetic acid (Tria c) stimulate bone resorption in organ culture, with Triac somewhat mor e potent than T-3. In this study we compared the effects of T-3 and Tr iac 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 [H-3]thymidine incorporation. After 72 h of preculture, stimulation was observed with only 24 h of treatment. The se effects were significant at 10(-10) M and maximal at 10(-9) M for b oth T-3 and Triac (treated/control ratios, 2.2 and 2.0, respectively). In contrast to their effects on bone resorption, T-3 was more potent than Triac in stimulating [H-3]thymidine incorporation. Insulin-like g rowth factor-binding protein-3 did not decrease the stimulation of DNA synthesis by T-3 or Triac. The medium insulin-like growth factor-I co ncentration was less than 10(-10) M and was not regulated by these hor mones. T-3 and Triac stimulated [H-3]proline incorporation into both c ollagen and noncollagen protein to a similar extent (similar to 30% at 10(-8) M). Indomethacin did not alter the effects of T-3 and Triac on DNA or collagen synthesis. Aphidicolin, which blocked DNA synthesis c ompletely, partially decreased the effects of thyroid hormones on coll agen synthesis. The effect of aphidicolin on bone formation was less t han that observed previously on bone resorption. We speculate that the effects of thyroid hormones on bone formation as well as bone resorpt ion 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 T-3.