Transcriptional regulation of the tyrosine hydroxylase gene by glucocorticoid and cyclic AMP.
Transcriptional regulation of the tyrosine hydroxylase gene by glucocorticoid and cyclic AMP.
复制标题
糖皮质激素和环AMP对酪氨酸羟化酶基因的转录调节。
DOI：
10.1073/pnas.84.11.3550
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发表时间：
1987
影响因子：
11.1
通讯作者：
Chikaraishi,DM
中科院分区：
文献类型：
--
作者：
Lewis,EJ;Harrington,CA;Chikaraishi,DM
糖皮质激素和环 AMP 会增加嗜铬细胞瘤培养物中酪氨酸羟化酶 (TH) 的活性和 mRNA 水平。当用合成糖皮质激素地塞米松或增加细胞内环 AMP 的药物（如毛喉素和 8-BrcAMP）处理培养物时，通过核连载试验测量的 TH 基因的转录活性也会增加。两种诱导剂均在治疗后 10 分钟内影响转录变化，对于毛喉素而言，在 30 分钟后达到最大，对于地塞米松而言，在 60 分钟后达到最大。 TH 基因的 5' 侧翼序列与细菌基因氯霉素乙酰转移酶 (CAT) 融合，并将杂合基因转染到嗜铬细胞瘤培养物和 GH4 垂体细胞中。在这两种细胞系中，TH 基因中包含碱基 -272 至 +27 的区域可通过环 AMP 诱导 CAT，但不能通过糖皮质激素诱导。当使用包含-773至+27的TH基因区域时，发现了相同的结果。因此，环AMP诱导TH所需的序列包含在5'侧翼序列的272个碱基内，但足以进行糖皮质激素调节的序列不包含在773个碱基内。
Glucocorticoid and cyclic AMP increase tyrosine hydroxylase (TH) activity and mRNA levels in pheochromocytoma cultures. The transcriptional activity of the TH gene, as measured by nuclear run-on assay, is also increased when cultures are treated with the synthetic glucocorticoid dexamethasone or agents that increase intracellular cyclic AMP, such as forskolin and 8-BrcAMP. Both inducers effect transcriptional changes within 10 min after treatment and are maximal after 30 min for forskolin and after 60 min for dexamethasone. The 5' flanking sequences of the TH gene were fused to the bacterial gene chloramphenicol acetyltransferase (CAT), and the hybrid gene was transfected into pheochromocytoma cultures and GH4 pituitary cells. In both cell lines, a region of the TH gene containing bases -272 to +27 conferred induction of CAT by cyclic AMP, but not by glucocorticoid. The same results were found when a region of the TH gene containing -773 to +27 was used. Thus, the sequences required for induction of TH by cyclic AMP are contained within 272 bases of 5' flanking sequence, but sequences sufficient for glucocorticoid regulation are not contained within 773 bases.