Bhat N R, Rao G S, Pieringer R A
J Biol Chem. 1981 Feb 10;256(3):1167-71.
L-3,5,3'-Triiodothyronine (T3) has been shown to influence the synthesis of myelin-associated lipids in cultures of cells dissociated from brains of embryonic mice (Bhat, N. R., Sarlieve, L., Subba Rao, G., and Pieringer, R. A. (1979) J. Biol. Chem. 254, 9342-9344). This culture system was used in the present study to gain additional information on the regulation of the synthesis of myelin lipids by thyroid hormone. The rate of synthesis of the myelin associated sulfolipids remained drastically diminished throughout a 70-day developmental period when cells were grown in the presence of hypothyroid calf serum (T3 < 25 ng/100 ml; thyroxine (T4), 1.2 microgram/ml). However, the activity could be restored to normal levels after 72 h of exposure to deficient medium supplemented with exogenous T3. Half-maximal effects were obtained with 2 X 10(-9) M T3 and 6.25 X 10(-7) M T4. T3 does not alter the synthesis of sulfated mucopolysaccharides, which share adenosine 3'-phosphate, 5'-phosphosulfate (PAPS), as a common precursor, with sulfolipids. This observation argues against the hormone altering the entry of sulfate or the synthesis of PAPS. Rather, T3 acts by changing the activity of the glycolipid:PAPS sulfotransferase(s) in direct proportion to the concentration of T3 in the growth medium. The activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, another myelin marker was also found to be T3 dependent. The response of sulfolipid synthesis to varying amounts of T3 was also observed in a serum-free medium, which suggests that T3 can function independently of other hormones and serum factors in exerting a relatively specific effect on the regulation of myelination.
已证明L-3,5,3'-三碘甲状腺原氨酸（T3）可影响从胚胎小鼠脑中分离的细胞培养物中髓鞘相关脂质的合成（Bhat, N. R., Sarlieve, L., Subba Rao, G., and Pieringer, R. A. (1979) J. Biol. Chem. 254, 9342 - 9344）。本研究使用该培养系统来获取有关甲状腺激素对髓鞘脂质合成调节的更多信息。当细胞在甲状腺功能减退的小牛血清（T3 < 25 ng/100 ml；甲状腺素（T4），1.2微克/毫升）存在下生长时，在整个70天的发育期间，髓鞘相关硫脂的合成速率仍急剧下降。然而，在暴露于补充有外源性T3的缺乏培养基72小时后，活性可恢复到正常水平。用2×10⁻⁹ M T3和6.25×10⁻⁷ M T4可获得半数最大效应。T3不会改变硫酸化粘多糖的合成，硫酸化粘多糖与硫脂共享3'-磷酸腺苷5'-磷酸硫酸酯（PAPS）作为共同前体。这一观察结果表明该激素不会改变硫酸盐的进入或PAPS的合成。相反，T3通过直接改变糖脂：PAPS磺基转移酶的活性起作用，该活性与生长培养基中T3的浓度成正比。另一种髓鞘标记物2',3'-环核苷酸3'-磷酸水解酶的活性也被发现依赖于T3。在无血清培养基中也观察到硫脂合成对不同量T3的反应，这表明T3在对髓鞘形成的调节发挥相对特异性作用时可以独立于其他激素和血清因子发挥作用。
