Wahrenberg H, Wennlund A, Arner P
Department of Medicine, Huddinge University Hospital, Karolinska Institute, Sweden.
J Clin Endocrinol Metab. 1994 Apr;78(4):898-903. doi: 10.1210/jcem.78.4.8157718.
The influence of thyroid hormones on the adrenergic regulation of lipolysis was studied in isolated adipocytes removed from the gluteal region of hyper- and hypothyroid women and compared in adipocytes from euthyroid normal women. Noradrenaline significantly enhanced lipolysis in hyperthyroid patients, whereas noradrenaline inhibited lipolysis in hypothyroid patients compared to that in controls. Moreover, beta-adrenergic sensitivity and responsiveness were 10- and 2-fold increased, respectively, in hyperthyroid patients. In hypothyroid patients, beta-adrenoceptor responsiveness was reduced by 50%, whereas beta-adrenergic sensitivity remained unchanged compared with that in controls. Furthermore, the alpha 2-adrenergic and adenosine-induced antilipolytic effects were similar in all thyroid states. The lowered beta-adrenergic responsiveness seen in hypothyroidism could be mimicked by agents acting at the levels of phosphodiesterase (enprofylline), adenylate cyclase (forskolin) and protein kinase (dibutyryl cAMP). In hyperthyroidism, the increased beta-adrenergic sensitivity and responsiveness were not seen when lipolysis was stimulated at the adenylate cyclase, phosphodiesterase, or protein kinase levels. There was no change in the numbers of adipocyte beta- and alpha 2-adrenoceptors in hypothyroidism. However, the number of beta-adrenergic binding sites was doubled, whereas the fraction and affinities of isoprenaline high affinity sites remained unchanged in hyperthyroidism. Thus, the influence of thyroid hormone on catecholamine-stimulated lipolysis in man acts through different mechanisms when adipocytes are exposed to high or low levels of thyroid hormones. In hyperthyroidism, lipolysis adapts to increasing energy demands through an increase in the beta-adrenoceptor number and, thus, a more effective coupling of the adenylate-cyclase complex. In hypothyroidism, the low lipolytic effect of catecholamines seems to be mainly due to an impairment at the protein kinase level or to the hormone-sensitive lipase itself.
研究了甲状腺激素对取自甲状腺功能亢进和减退女性臀区的分离脂肪细胞中肾上腺素能调节脂肪分解的影响，并与甲状腺功能正常的正常女性的脂肪细胞进行了比较。去甲肾上腺素显著增强甲状腺功能亢进患者的脂肪分解，而与对照组相比，去甲肾上腺素抑制甲状腺功能减退患者的脂肪分解。此外，甲状腺功能亢进患者的β-肾上腺素能敏感性和反应性分别增加了10倍和2倍。在甲状腺功能减退患者中，β-肾上腺素能受体反应性降低了50%，而与对照组相比，β-肾上腺素能敏感性保持不变。此外，在所有甲状腺状态下，α2-肾上腺素能和腺苷诱导的抗脂解作用相似。甲状腺功能减退时β-肾上腺素能反应性降低可被作用于磷酸二酯酶（恩丙茶碱）、腺苷酸环化酶（福斯高林）和蛋白激酶（二丁酰环磷腺苷）水平的药物模拟。在甲状腺功能亢进时，当在腺苷酸环化酶、磷酸二酯酶或蛋白激酶水平刺激脂肪分解时，未观察到β-肾上腺素能敏感性和反应性增加。甲状腺功能减退时脂肪细胞β-和α2-肾上腺素能受体数量没有变化。然而，β-肾上腺素能结合位点数量增加了一倍，而在甲状腺功能亢进时，异丙肾上腺素高亲和力位点的比例和亲和力保持不变。因此，当脂肪细胞暴露于高水平或低水平甲状腺激素时，甲状腺激素对人体儿茶酚胺刺激的脂肪分解的影响通过不同机制起作用。在甲状腺功能亢进时，脂肪分解通过增加β-肾上腺素能受体数量来适应能量需求的增加，从而使腺苷酸环化酶复合物的偶联更有效。在甲状腺功能减退时，儿茶酚胺的低脂解作用似乎主要是由于蛋白激酶水平或激素敏感性脂肪酶本身的损伤。
