Inhibition of nuclear T3 binding by fatty acids.
Inhibition of nuclear T3 binding by fatty acids.
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脂肪酸抑制核 T3 结合。
DOI：
10.1016/0026-0495(88)90159-x
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Teco,GN
中科院分区：
文献类型：
--
作者：
Wiersinga,WM;Chopra,IJ;Teco,GN
本研究旨在探讨脂质对T3与大鼠肝细胞核受体结合的调节作用。不饱和脂肪酸是[125 I] T3与离体大鼠肝细胞核结合的有效抑制剂。导致核T3结合抑制50%的剂量（μmol/L）为棕榈油酸10、亚油酸11、油酸22、花生四烯酸24和亚麻酸37。其他脂质具有较少或没有抑制活性。不饱和脂肪酸使T3与核受体结合的亲和力常数（Ka）降低到对照组的57.4% ± 11.0（平均值± SE 1.04 ± 0.14 v1.97 ± 0.23 109 L/M，n = 5;P<0.02），但不影响最大结合容量（MBC）（1.47 ± 0.20 v1.55 ± 0.10 10− 10 M/L; NS）。用磷脂酶A2预处理大鼠肝匀浆5 ~ 20分钟（从磷脂中释放不饱和脂肪酸）的蒸发乙醚提取物与未处理大鼠肝匀浆的乙醚提取物相比，随着时间的推移，显示出对核T3结合的进行性抑制（F= 16.1;P<0.01）。蒸发，富含脂肪酸的乙醚提取物的人血清引起的剂量依赖性抑制[125 I] T3的核T3受体的结合。22例非甲状腺疾病（NTI）患者血清（0.1 mL-Eq等分试样）提取物存在时，核T3结合率为正常血清（100% ± 6.2%，n = 9，P<0.0005）的58.9% ± 4.9%（平均值± SE;范围17%-107%）; 12例（55%）患者比正常平均值低2SD以上。NTI血清对核T3结合的抑制与这些血清中甲状腺素结合抑制剂（THBI）的存在相关（r= 0.89;P<0.0005）。NTI血清的挥发性乙醚提取物使T3与核受体结合的Ka值降低到正常血清的47.5% ± 10.8%（n = 4;P<0.01），而对MBC无影响。这些不同的数据表明，不饱和脂肪酸可以调节甲状腺激素结合其核受体在体外。脂肪酸是否在体内发挥类似的作用目前尚不清楚。
Studies were performed to evaluate a possible modulatory role of lipids on the binding of T3to rat liver nuclear receptors in vitro. Unsaturated fatty acids were potent inhibitors of the binding of [125I] T3to isolated rat liver nuclei. Doses (in μmol/L) causing a 50% inhibition of nuclear T3binding were 10 for palmitoleic acid, 11 for linoleic acid, 22 for oleic acid, 24 for arachidonic acid, and 37 for linolenic acid. Other lipids had less or no inhibitory activity. Unsaturated fatty acids reduced the affinity constant (Ka) of the binding of T3to nuclear receptors to 57.4% ± 11.0% that of controls (mean ± SE1.04 ± 0.14v1.97 ± 0.23 109L/M, n = 5;P< .02) but did not affect the maximal binding capacity (MBC) (1.47 ± 0.20v1.55 ± 0.10 10−10M/L; NS). Evaporated ether extracts of rat liver homogenate pretreated with phospholipase A2for five to 20 minutes (that liberates unsaturated fatty acids from phospholipids) demonstrated a progressive inhibition of nuclear T3binding with time when compared with ether extracts of untreated rat liver homogenate (F= 16.1;P< .01). Evaporated, fatty-acid-rich ether extracts of human sera caused a dose-dependent inhibition in the binding of [125I] T3to nuclear T3receptors. Nuclear T3binding in the presence of extracts of 22 sera (0.1 mL-Eq aliquots) of patients with nonthyroidal illness (NTI) was 58.9% ± 4.9% (mean ± SE; range 17% to 107%) that of normal sera (100% ± 6.2%, n = 9,P< .0005); it was more that 2 SD below the normal mean in 12 (55%) patients. Inhibition of nuclear T3binding by NTI sera was correlated with the presence of a thyroid hormone-binding inhibititor (THBI) in these sera (r= .89;P< .0005). Evaporated ether extracts of NTI sera reduced the Kavalues of the binding of T3to nuclear receptors to 47.5% ± 10.8% that of normal sera (n = 4;P< .01), without an effect on MBC. These various data suggest that unsaturated fatty acids can modulate thyroid hormone binding to its nuclear receptor in vitro. Whether or not fatty acids exert a similar effect in vivo is presently unknown.