Effects of thyroid hormone on norepinephrine signaling in brown adipose tissue. I. Beta 1- and beta 2-adrenergic receptors and cyclic adenosine 3',5'-monophosphate generation.
Effects of thyroid hormone on norepinephrine signaling in brown adipose tissue. I. Beta 1- and beta 2-adrenergic receptors and cyclic adenosine 3',5'-monophosphate generation.
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DOI：
10.1210/endo.136.8.7628360
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发表时间：
1995-08
期刊：
影响因子：
4.8
通讯作者：
A. Rubio;A. Raasmaja;A L Maia;K R Kim;J E Silva
中科院分区：
文献类型：
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作者：
A. Rubio;A. Raasmaja;A L Maia;K R Kim;J E Silva
棕色脂肪组织(BAT)产热是由交感神经系统激活的。在甲状腺功能减退症中，蝙蝠对去甲肾上腺素的反应是迟钝的，并被甲状腺激素迅速恢复。我们在大鼠中检测了甲状腺激素对BATβ1和β2肾上腺素能受体(AR)表达的影响，以及在肾上腺素能刺激下产生cAMP的能力。两者在甲状腺功能减退时都会减少。CAMP生成的减少等于或大于β1，2-AR的减少；去甲肾上腺素、选择性β3-AR激动剂或Forsklin刺激cAMP生成的情况相同；并且不受磷酸二酯酶抑制的影响。β1，2-AR和cAMP生成能力均被甲状腺激素缓慢纠正。T3使β-1，2-AR正常化1-2天，而cAMP生成的改善滞后1-2天。甲亢大鼠在30℃习服2天内，β-1，2-AR的数量达到正常甲状腺水平，而暴露于4℃则使这些受体减少。我们得出以下结论：1)甲状腺功能减退症患者BATβ1，2-AR和产生cAMP的能力降低；2)后者不能用β1，2-AR的减少来解释，而是反映了受体后水平的缺陷；3)β1.2-AR数量的减少主要是由甲状腺功能低下的代谢率引起的冷应激引起的；以及4)T3后受体数量和产生cAMP的能力恢复缓慢与这些缺陷不一致，这些缺陷是先前报道的甲减患者对肾上腺素能刺激的钝性解偶联蛋白反应的一个重要因素。
Brown adipose tissue (BAT) thermogenesis is activated by the sympathetic nervous system. BAT responses to norepinephrine are blunted in hypothyroidism and are rapidly restored by thyroid hormone. We examined in rats the effects of thyroid hormone on BAT beta 1- and beta 2-adrenergic receptors (AR) expression and capacity to generate cAMP in response to adrenergic stimulation. Both are reduced in hypothyroidism. The reduction in cAMP generation is equal to or greater than that in beta 1,2-AR; it is the same whether cAMP production is stimulated with norepinephrine, selective beta 3-AR agonists, or forskolin; and it is not affected by the inhibition of phosphodiesterase. Both beta 1,2-AR and the capacity to generate cAMP were slowly corrected by thyroid hormone. T3 normalized beta 1,2-AR between 1 and 2 days, whereas the improvement in cAMP generation lagged 1 or 2 days behind. Within 2 days of acclimation of athyreotic rats at 30 C, the number of beta 1,2-AR reached the euthyroid level, whereas exposure to 4 C decreased these receptors. We reached the following conclusions: 1) BAT beta 1,2-AR and capacity to generate cAMP are reduced in hypothyroidism; 2) the latter, however, is not explained by the reduction in beta 1,2-AR, but, rather, reflects a fault at the postreceptor level; 3) the reduction in beta 1.2-AR number is largely caused by the cold stress derived from the low metabolic rate of the hypothyroid state; and 4) the slow restoration of both receptor number and capacity to generate cAMP after T3 are not consistent with these defects being a significant factor in the previously reported blunted uncoupling protein responses to adrenergic stimulation in hypothyroidism.