Elks M L, Manganiello V C
Endocrinology. 1985 Sep;117(3):947-53. doi: 10.1210/endo-117-3-947.
We have used cultured 3T3-L1 adipocytes to assess direct effects of T3 on beta-adrenergic-mediated regulation of lipolysis and adenylate cyclase and phosphodiesterase activities. Differentiated 3T3-L1 adipocytes were maintained under four conditions: in the presence of medium containing serum from a hypothyroid calf (hypothyroid medium), hypothyroid medium supplemented with T3 (T3-supplemented hypothyroid medium), medium with serum from a normal calf (control medium), and control medium supplemented with excess T3 (hyperthyroid medium). Compared to the two control groups, i.e. cells maintained in control medium or T3-supplemented hypothyroid medium, cells maintained in hypothyroid medium exhibited lower basal rates of lipolysis and lower sensitivity to isoproterenol. Hyperthyroid cells exhibited higher basal rates of lipolysis and higher sensitivity to isoproterenol. In the presence of maximally effective concentrations of isoproterenol, rates of lipolysis were similar in the four groups. Similarly, basal cAMP content and cAMP accumulation in the presence of isoproterenol were reduced in hypothyroid and increased in hyperthyroid adipocytes compared to those adipocytes maintained in control or T3-supplemented hypothyroid medium. Basal adenylate cyclase activity was similar in the four groups. Sensitivity to isoproterenol and maximal isoproterenol-stimulated cyclase activity were diminished in membrane preparations from hypothyroid adipocytes and increased in preparations from hyperthyroid adipocytes. Cyclase activity in the presence of NaF, however, was similar in preparations from cells maintained in hypothyroid, T3-supplemental hypothyroid, or control medium. NaF-stimulated activity was increased in preparations from hyperthyroid adipocytes. Thyroid status did not affect beta-receptor number of affinity for iodohydroxybenzylpindolol. Compared to control cells or cells maintained in T3-supplemented hypothyroid medium, both soluble and particulate cAMP phosphodiesterase activities were increased in hypothyroid cells and decreased in hyperthyroid cells. These results indicated that in 3T3-L1 adipocytes, some of the effects of thyroid hormone on cAMP content and lipolysis can be explained by alterations in both production and degradation of cAMP.
我们使用培养的3T3-L1脂肪细胞来评估T3对β-肾上腺素能介导的脂肪分解调节以及腺苷酸环化酶和磷酸二酯酶活性的直接影响。分化的3T3-L1脂肪细胞在四种条件下培养：存在来自甲状腺功能减退小牛血清的培养基（甲状腺功能减退培养基）、补充T3的甲状腺功能减退培养基（T3补充的甲状腺功能减退培养基）、含有正常小牛血清的培养基（对照培养基）以及补充过量T3的对照培养基（甲状腺功能亢进培养基）。与两个对照组（即培养在对照培养基或T3补充的甲状腺功能减退培养基中的细胞）相比，培养在甲状腺功能减退培养基中的细胞脂肪分解的基础速率较低，对异丙肾上腺素的敏感性也较低。甲状腺功能亢进的细胞脂肪分解的基础速率较高，对异丙肾上腺素的敏感性也较高。在存在最大有效浓度异丙肾上腺素的情况下，四组中的脂肪分解速率相似。同样，与培养在对照或T3补充的甲状腺功能减退培养基中的脂肪细胞相比，甲状腺功能减退的脂肪细胞中基础cAMP含量以及在异丙肾上腺素存在下的cAMP积累减少，而甲状腺功能亢进的脂肪细胞中则增加。四组中的基础腺苷酸环化酶活性相似。甲状腺功能减退脂肪细胞膜制剂对异丙肾上腺素的敏感性以及最大异丙肾上腺素刺激的环化酶活性降低，而甲状腺功能亢进脂肪细胞膜制剂中的则增加。然而，在存在NaF的情况下，培养在甲状腺功能减退、T3补充的甲状腺功能减退或对照培养基中的细胞制剂中的环化酶活性相似。甲状腺功能亢进脂肪细胞制剂中NaF刺激的活性增加。甲状腺状态不影响碘羟基苄基吲哚洛尔的β受体数量或亲和力。与对照细胞或培养在T3补充的甲状腺功能减退培养基中的细胞相比，甲状腺功能减退细胞中可溶性和颗粒性cAMP磷酸二酯酶活性均增加，而甲状腺功能亢进细胞中则降低。这些结果表明，在3T3-L1脂肪细胞中，甲状腺激素对cAMP含量和脂肪分解的一些影响可以通过cAMP产生和降解的改变来解释。
