Kawaguchi H, Pilbeam C C, Raisz L G
Department of Medicine, University of Connecticut Health Center, Farmington 06030.
Endocrinology. 1994 Sep;135(3):971-6. doi: 10.1210/endo.135.3.7520864.
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.
我们之前报道过，T3和三碘甲状腺乙酸（Triac）在器官培养中均能刺激骨吸收，且Triac的作用略强于T3。在本研究中，我们比较了T3和Triac对培养的新生小鼠颅骨中DNA和蛋白质合成的影响。预培养24小时后，经过72小时的处理（而非24或48小时），这些激素刺激了[3H]胸腺嘧啶核苷掺入。预培养72小时后，仅处理24小时就观察到了刺激作用。对于T3和Triac，这些作用在10^(-10) M时显著，在10^(-9) M时达到最大（处理组/对照组比值分别为2.2和2.0）。与它们对骨吸收的作用相反，T3在刺激[3H]胸腺嘧啶核苷掺入方面比Triac更有效。胰岛素样生长因子结合蛋白-3并未降低T3或Triac对DNA合成的刺激作用。培养基中胰岛素样生长因子-I的浓度低于10^(-10) M，且不受这些激素的调节。T3和Triac在相似程度上刺激了[3H]脯氨酸掺入胶原蛋白和非胶原蛋白中（在10^(-8) M时约为30%）。吲哚美辛并未改变T3和Triac对DNA或胶原蛋白合成的作用。阿非科林完全阻断了DNA合成，部分降低了甲状腺激素对胶原蛋白合成的作用。阿非科林对骨形成的作用小于之前观察到的对骨吸收的作用。我们推测甲状腺激素对骨形成以及骨吸收的作用可能部分依赖于它们的促有丝分裂作用。由于Triac在刺激吸收方面更有效，而在刺激形成方面效果较差，Triac可能比T3更具分解代谢作用。
