Loireau A, Autissier N, Dumas P, Michel O, Jorgensen E C, Michel R
Biochem Pharmacol. 1986 May 15;35(10):1691-6. doi: 10.1016/0006-2952(86)90325-4.
3,5-Dimethyl-3'-isopropyl-L-thyronine (DIMIT) and 3,5-diiodo-3'-isopropylthyroacetic acid (IpTA2), two thyroid hormone analogs, have been tested in genetically obese Zucker rats and their lean littermates, in comparison with thyroxine (T4) and triiodothyronine (T3) for their thyromimetic activities on body weight gain and lipid levels in serum and liver. The compounds were administered for 9 weeks by orogastric tube to 6- to 8-week-old animals. While body weight gain remained practically unchanged in the lean rats, it decreased significantly in the obese individuals, especially with IpTA2. The serum lipid concentrations were also decreased in the obese rats in comparison with their lean littermates, especially with DIMIT. The connection observed between the structure of DIMIT and IpTA2 on one hand and their effects on the other is in good agreement with previous studies. Our results confirm that the iodine substituents are not necessary for thyromimetic activity and demonstrate that the isopropyl substituent in 3' plays an important role in the serum lipid-lowering effect of the thyroid hormone analogs tested.
两种甲状腺激素类似物3,5-二甲基-3'-异丙基-L-甲状腺素（DIMIT）和3,5-二碘-3'-异丙基甲状腺乙酸（IpTA2），已在遗传性肥胖的 Zucker 大鼠及其瘦的同窝仔鼠中进行了测试，并与甲状腺素（T4）和三碘甲状腺原氨酸（T3）比较，观察它们对体重增加以及血清和肝脏脂质水平的拟甲状腺活性。通过灌胃给6至8周龄的动物施用这些化合物，持续9周。在瘦大鼠中体重增加基本保持不变，而在肥胖个体中体重显著下降，尤其是使用IpTA2时。与它们的瘦同窝仔鼠相比，肥胖大鼠的血清脂质浓度也有所降低，尤其是使用DIMIT时。一方面观察到的DIMIT和IpTA2的结构与其作用之间的联系与先前的研究非常吻合。我们的结果证实，碘取代基对于拟甲状腺活性不是必需的，并表明3'位的异丙基取代基在所测试的甲状腺激素类似物的降低血清脂质作用中起重要作用。
