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转录因子催乳素调节元件结合蛋白介导促甲状腺素释放激素诱导的 GH3 细胞中催乳素的转录。

The transcription factor prolactin regulatory element-binding protein mediates prolactin transcription induced by thyrotropin-releasing hormone in GH3 cells.

机构信息

Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan.

出版信息

Endocrine. 2010 Aug;38(1):53-9. doi: 10.1007/s12020-010-9343-3. Epub 2010 May 5.

Abstract

The prolactin regulatory element-binding protein (PREB) is a transcription factor that regulates prolactin (PRL) promoter activity in the rat anterior pituitary. PRL gene expression and secretion are regulated by various hormones and growth factors, including dopamine, epidermal growth factor, and thyrotropin-releasing hormone (TRH). We examined the effect of TRH on PREB expression in pituitary cells. Western blots probed with a PREB-specific antiserum showed that the relative abundance of PREB in GH3 cells increased on treatment with TRH in a dose-dependent manner. The relative abundance of PREB mRNA also increased in a dose-dependent manner after treatment with TRH. TRH induced the expression of the luciferase reporter protein under the PREB promoter control. We used inhibitors of certain signal transduction pathways to show that TRH-induced PREB induction is sensitive to the protein kinase A (PKA) inhibitor. TRH stimulated the activity of the wild-type PRL promoter, whereas mutation of the PREB core-binding element on the PRL promoter reduced this ability. In summary, we have shown that TRH stimulated PREB expression in GH3 cells via the PKA pathway. PREB can function as a transcriptional regulator of PRL promoter activity and might be involved in TRH-induced PRL gene transcription.

摘要

催乳素调节元件结合蛋白(PREB)是一种转录因子,可调节大鼠前垂体中的催乳素(PRL)启动子活性。PRL 基因的表达和分泌受各种激素和生长因子的调节,包括多巴胺、表皮生长因子和促甲状腺素释放激素(TRH)。我们研究了 TRH 对垂体细胞中 PREB 表达的影响。用 PREB 特异性抗血清进行的 Western blot 分析表明,GH3 细胞中 PREB 的相对丰度在 TRH 处理下呈剂量依赖性增加。用 TRH 处理后,PREB mRNA 的相对丰度也呈剂量依赖性增加。TRH 诱导 PREB 启动子控制下的荧光素酶报告蛋白的表达。我们使用某些信号转导途径的抑制剂表明,TRH 诱导的 PREB 诱导对蛋白激酶 A(PKA)抑制剂敏感。TRH 刺激野生型 PRL 启动子的活性,而 PRL 启动子上 PREB 核心结合元件的突变降低了这种能力。总之,我们已经表明,TRH 通过 PKA 途径刺激 GH3 细胞中 PREB 的表达。PREB 可以作为 PRL 启动子活性的转录调节因子,并且可能参与 TRH 诱导的 PRL 基因转录。

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