Nuclear triiodothyronine receptor binding characteristics and occupancy in obese (ob/ob) mice.
Nuclear triiodothyronine receptor binding characteristics and occupancy in obese (ob/ob) mice.
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肥胖 (ob/ob) 小鼠的核三碘甲状腺原氨酸受体结合特征和占据。
DOI：
10.1152/ajpendo.1987.252.3.e414
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Romsos,DR
中科院分区：
文献类型：
--
作者：
Hillgartner,FB;Romsos,DR
肥胖(ob/ob)小鼠表现出与甲状腺激素作用受损相关的适应性产热减少。通过比较瘦小鼠和肥胖小鼠肝脏中溶解的3，5，3‘-三碘甲腺原氨酸(T3)受体的结合特性和占有率，探讨后者缺陷的机制。Scatchard分析表明，在4周龄和8-10周龄时，Bmax和Kd在表型之间的差异很小，这表明肥胖小鼠肝脏甲状腺激素表达的减少不是由于核受体浓度或亲和力的变化造成的。相比之下，4周龄和8至10周龄肥胖小鼠的细胞核T3受体占有率(与特定受体相关的内源性T3除以Bmax)分别低14%和23%。再加上报道的肝脏甲状腺激素敏感酶的变化，这些数据与启动肥胖小鼠甲状腺激素作用的核T3信号减弱是一致的。核内T_3受体占有率降低可能是由于血浆T_3向核池转运减少所致。总而言之，肥胖小鼠的肝脏甲状腺激素作用受损至少部分是通过核内T3受体占有率的减少来调节的。
Obese (ob/ob) mice exhibit reduced adaptive thermogenesis associated with an impairment of thyroid hormone action. The mechanism underlying the latter defect was investigated by comparing the binding characteristics and occupancy of solubilized nuclear 3,5,3'-triiodothyronine (T3) receptors from livers of lean and obese mice. Scatchard analysis showed minimal differences in Bmax and Kd between phenotypes at both 4 and 8–10 wk of age, indicating that reduced hepatic thyroid hormone expression in obese mice is not caused by alterations in nuclear receptor concentration or affinity. In contrast, nuclear T3 receptor occupancy (endogenous T3 associated with the specific receptor divided by Bmax) was 14 and 23% lower in 4- and 8- to 10-wk-old obese mice, respectively. Together with reported changes in hepatic thyroid hormone-sensitive enzymes, these data are consistent with a diminished nuclear T3 signal initiating thyroid hormone action in obese mice. Decreased nuclear T3 receptor occupancy may be secondary to a low transport of plasma T3 to the nuclear pool. In conclusion, impaired hepatic thyroid hormone action in obese mice is mediated in part at least by a reduction in nuclear T3 receptor occupancy.