A NEW GLUCOCORTICOID RECEPTOR SPECIES - RELATION TO INDUCTION OF TRYPTOPHAN DIOXYGENASE BY GLUCOCORTICOIDS

A NEW GLUCOCORTICOID RECEPTOR SPECIES - RELATION TO INDUCTION OF TRYPTOPHAN DIOXYGENASE BY GLUCOCORTICOIDS
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DOI:
10.1210/endo-117-5-1788
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发表时间:
1985-01-01
期刊:
影响因子:
4.8
通讯作者:
TANAKA, T
TANAKA, T
中科院分区:
医学2区
文献类型:
--
作者:
HIROTA, T;HIROTA, K;TANAKA, T

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当用高剂量(≥20μg/100g BW)地塞米松处理大鼠时,它们的肝细胞溶质在二乙氨基乙基纤维素色谱上显示用0.13-0.14M NaCl洗脱的糖皮质激素特异性结合蛋白的主峰。另一方面,当用低剂量(约2μg/100g BW)地塞米松治疗大鼠时,胞质溶胶仅显示与未治疗大鼠相同的峰,这被广泛认为是典型的糖皮质激素受体的峰。新结合峰的出现取决于激素的剂量和地塞米松治疗后的时间(从30分钟到20小时);治疗后40小时消失。用高剂量激素处理后,与细胞质中相似的峰也出现在核部分中。糖皮质激素诱导酶、色氨酸双加氧酶[(TO) EC 1.13.11.11]和酪氨酸转氨酶(EC 2.6.1.5)被测定作为受体功能的生理标志物。 TO 诱导与新结合峰的出现在糖皮质激素的剂量和时间依赖性方面具有良好的相关性,而酪氨酸转氨酶诱导则不然。因此,在细胞质和核部分中检测到的糖皮质激素结合蛋白的新峰可能代表参与 TO 诱导、应激下生理变化以及高剂量糖皮质激素治疗后药理变化的糖皮质激素受体种类。
When rats were treated with a high dose (.gtoreq. 20 .mu.g/100 g BW) of dexamethasone, their liver cytosol showed a predominant peak of specific binding protein of glucocorticoid eluting with 0.13-0.14 M NaCl on diethylaminoethyl cellulose chromatography. On the other hand, when rats were treated with a low dose (.apprx. 2 .mu.g/100 g BW) of dexamethasone, the cytosol showed only the same peak as that of untreated rats, which is widely thought to be that of the typical glucocorticoid receptor. The appearance of the new binding peak depended both on the dose of hormone and the time (from 30 min to 20 h) after dexamethasone treatment; it disappeared 40 h after treatment. A peak similar to that in the cytosol also appeared in the nuclear fraction after treatment with a high dose of hormone. The glucocorticoid-inducible enzymes, tryptophan dioxygenase [(TO) EC 1.13.11.11] and tyrosine aminotransferase (EC 2.6.1.5) were assayed as physiological markers of receptors function. TO induction correlated well with the appearance of the new binding peak in terms of dose-and time dependence on glucocorticoid, whereas tyrosine aminotransferase induction did not. The new peak of glucocorticoid-binding protein detected in the cytosol and nuclear fractions may thus represent the glucocorticoid receptor species involved in TO induction, physiological changes under stress, and pharmacological changes after therapy with high doses of glucocorticoid hormones.