Leseney A M, Benmiloud M, Befort N, Befort J J
Mol Cell Endocrinol. 1987 Jul;52(1-2):1-10. doi: 10.1016/0303-7207(87)90090-6.
We have previously reported that hypothyroidism is accompanied by modifications of the cytosolic rat liver glucocorticoid receptors. In the present study we have used molybdate, which stabilizes the glucocorticoid receptor from hypothyroid rats, allowing its characterization. We confirm a decrease in the number of glucocorticoid binding sites in the liver of hypothyroid rats as compared to that in normal rats (8000 per cell versus 23,000 per cell for normal rats). At 22 degrees C and in the absence of molybdate, thermal activation shows the same kinetics in both complexes from normal and hypothyroid rats, though activated hormone-receptor complexes from hypothyroid rats are progressively degraded (t 1/2 = 230 min). At the same temperature the dissociation rate of native complexes from hypothyroid rats is slower (k-1 = 8 X 10(-3) min-1) than normal (k-1 = 16 X 10(-3) min-1). Competitive dissociation studies using [3H]dexamethasone indicate that native complexes from hypothyroid rats show altered affinities for agonist and antagonist. Hypothyroidism decreases the number of rat liver glucocorticoid receptors and alters their properties, as evidenced by their greater instability and differences in steroid binding. These effects may be due to regulating factors and/or slight, probably post-transcriptional, modifications of the binding protein.
我们之前曾报道，甲状腺功能减退症伴有大鼠肝脏胞质糖皮质激素受体的改变。在本研究中，我们使用了钼酸盐，它可稳定甲状腺功能减退大鼠的糖皮质激素受体，从而对其进行表征。我们证实，与正常大鼠相比，甲状腺功能减退大鼠肝脏中糖皮质激素结合位点的数量减少（正常大鼠每细胞23,000个，甲状腺功能减退大鼠每细胞8000个）。在22摄氏度且不存在钼酸盐的情况下，热激活在正常和甲状腺功能减退大鼠的两种复合物中显示出相同的动力学，尽管甲状腺功能减退大鼠的活化激素 - 受体复合物会逐渐降解（t1/2 = 230分钟）。在相同温度下，甲状腺功能减退大鼠天然复合物的解离速率（k-1 = 8×10-3分钟-1）比正常大鼠慢（k-1 = 16×10-3分钟-1）。使用[3H]地塞米松进行的竞争性解离研究表明，甲状腺功能减退大鼠的天然复合物对激动剂和拮抗剂的亲和力发生了改变。甲状腺功能减退症会减少大鼠肝脏糖皮质激素受体的数量并改变其特性，这可通过其更大的不稳定性和类固醇结合差异来证明。这些影响可能是由于调节因子和/或结合蛋白的轻微（可能是转录后）修饰所致。
