Hellström L, Wahrenberg H, Reynisdottir S, Arner P
Department of Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
J Clin Endocrinol Metab. 1997 Jan;82(1):159-66. doi: 10.1210/jcem.82.1.3664.
Increased lipid mobilization in thyrotoxicosis is attributed to amplification of catecholamine action in fat cells by thyroid hormones. We investigated the adrenergic regulation of lipolysis in isolated sc abdominal fat cells obtained from 14 patients with thyrotoxicosis and 18 control subjects. Ten of the hyperthyroid subjects were also reinvestigated after antithyroid treatment. The thyrotoxic state was associated with a 3-fold increase in maximum norepinephrine-induced lipolysis (P < 0.005), unaltered sensitivity to dobutamine (selective beta 1-adrenoceptor agonist) and clonidine (selective alpha 2-adrenoceptor agonist), but 15 times enhanced sensitivity to terbutaline (selective beta 2-adrenoceptor agonist; P < 0.01). Moreover, thyrotoxicosis was accompanied by a 3-fold increase in beta 2-adrenoceptor number (P < 0.005), but unchanged beta 1-adrenoceptor levels. Further, the lipolytic effects of dibutyryl cAMP (activating protein kinase A and thereby hormone-sensitive lipase) and forskolin (activating adenylate cyclase) were about 60% enhanced (P < 0.005). No change in the maximum activity of the hormone-sensitive lipase could be demonstrated in the hyperthyroid state compared to that in the euthyroid state. The observed abnormalities in lipolysis and beta 2-adrenoceptor number were normalized after antithyroid treatment. It is concluded that in human hyperthyroidism, the interactions between thyroid hormone and catecholamines in adipocytes involve abnormalities at both receptor and postreceptor levels. The former mechanism seems to be a selective increase in the expression of the beta 2-adrenoceptors. The latter mechanism involves increased ability of cAMP to activate hormone-sensitive lipase, but not a change in maximum enzyme capacity.
甲状腺毒症时脂质动员增加归因于甲状腺激素对脂肪细胞中儿茶酚胺作用的放大。我们研究了从14例甲状腺毒症患者和18例对照者获取的离体腹直肌脂肪细胞中脂解的肾上腺素能调节。10例甲状腺功能亢进患者在接受抗甲状腺治疗后也再次接受了研究。甲状腺毒症状态与去甲肾上腺素诱导的最大脂解增加3倍相关（P<0.005），对多巴酚丁胺（选择性β1肾上腺素能受体激动剂）和可乐定（选择性α2肾上腺素能受体激动剂）的敏感性未改变，但对特布他林（选择性β2肾上腺素能受体激动剂；P<0.01）的敏感性增强了15倍。此外，甲状腺毒症伴有β2肾上腺素能受体数量增加3倍（P<0.005），但β1肾上腺素能受体水平未改变。此外，二丁酰环磷腺苷（激活蛋白激酶A从而激活激素敏感性脂肪酶）和福斯可林（激活腺苷酸环化酶）的脂解作用增强了约60%（P<0.005）。与甲状腺功能正常状态相比，甲状腺功能亢进状态下未发现激素敏感性脂肪酶的最大活性有变化。抗甲状腺治疗后，观察到的脂解和β2肾上腺素能受体数量异常恢复正常。结论是，在人类甲状腺功能亢进症中，脂肪细胞中甲状腺激素与儿茶酚胺之间的相互作用涉及受体和受体后水平的异常。前一种机制似乎是β2肾上腺素能受体表达的选择性增加。后一种机制涉及环磷腺苷激活激素敏感性脂肪酶的能力增强，但最大酶活性没有变化。
