GROWTH HORMONE AND PROLACTIN GENE REGULATORY MECHANISMS

生长激素和催乳素基因调控机制

• 批准号: 3291413
• 负责人: F C BANCROFT
• 金额: $ 26.36万
• 依托单位: MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-01-01 至 1994-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3291413
• 关键词: DNA binding protein; active sites; biological signal transduction; cell type; epidermal growth factor; gene expression; genetic promoter element; genetic regulation; genetic transcription; hormone binding protein; hormone regulation /control mechanism; laboratory rat; molecular cloning; neoplastic cell culture for noncancer research; phorbols; prolactin; somatotropin; thyrotropin releasing hormone; tissue /cell culture; transcription factor; transfection; vasoactive intestinal peptide; DNA binding protein; active sites; biological signal transduction; cell type; epidermal growth factor; gene expression; genetic promoter element; genetic regulation; genetic transcription; hormone binding protein; hormone regulation /control mechanism; laboratory rat; molecular cloning; neoplastic cell culture for noncancer research; phorbols; prolactin; somatotropin; thyrotropin releasing hormone; tissue /cell culture; transcription factor; transfection; vasoactive intestinal peptide

The research described involves two major projects. The central aims of these two projects are to elucidate: 1. The cell-specific mechanisms that direct expression of the growth hormone (GH) and prolactin (PRL) genes to different cell types. 2. The signal transduction pathways employed by peptide hormones to regulate pituitary expression of the PRL gene. These studies will be performed with the GH3 rat pituitary cells and other cell lines. One of the aims of Project 1 is to further investigate cell- specific repression of the GH gene. To do this we will investigate whether transcription in vitro of chromatinized templates can be employed to study GH promoter repression; further investigate a recently characterized GH promoter repressor sequence and its DNA-binding proteins; and pursue the use of F9 embryonal carcinoma cells as a model for early embryogenic repression of the PRL and GH genes. Two other aims of Project 1 are to characterize further the regulatory properties of multiple sites in the promoters of these genes that bind the transcription factor pit-1; and to employ a genetic technique, recently developed with L. Chasin (Columbia University), to attempt to clone genes involved, directly or indirectly, in developmental regulation of the PRL gene. The immediate aim of Project 2 is based on our recent finding that the proximal pit-1 binding site in the PRL promoter is also a response element for thyrotropin-releasing hormone (TRH). We are now investigating how pit-1 mediates the action of this peptide hormone, and whether TRH can also regulate the PRL promoter independently of pit-1. In similar studies, directed to understanding the complex hormonal regulation of the PRL gene, the actions of the phorbol ester TPA, and of two other peptide hormones (epidermal growth factor and vasoactive intestinal peptide) on the PRL promoter will be further investigated.

描述的研究涉及两个主要项目。 中心目标 这两个项目是为了阐明：1。 生长激素（GH）和催乳素（PRL）基因的直接表达 不同的细胞类型。 2。由 肽激素调节PRL基因的垂体表达。 这些 研究将使用GH3大鼠垂体细胞和其他细胞进行研究 线。 项目1的目的之一是进一步研究细胞 - GH基因的具体抑制。 为此，我们将调查是否 可以在体外转录染色化模板来研究 GH启动子抑制；进一步研究最近表征的GH 启动子阻遏序列及其DNA结合蛋白；并追求 使用F9胚胎癌细胞作为早期胚胎的模型 抑制PRL和GH基因。 项目1的其他两个目标是 进一步表征了多个位点的调节特性 这些结合转录因子pit-1的基因的启动子；然后 采用最近用L. chasin开发的遗传技术（哥伦比亚 大学），试图直接或间接地克隆基因在 PRL基因的发育调节。 项目2的直接目标 是基于我们最近的发现，即近端PIT-1结合位点 PRL启动子也是甲状腺蛋白释放激素的响应元件 （TRH）。 我们现在正在研究PIT-1如何介导此操作 肽激素以及TRH是否也可以调节PRL启动子 独立于Pit-1。 在类似的研究中，旨在理解 PRL基因的复杂激素调节，佛波的作用 酯TPA和另外两种肽激素（表皮生长因子和 PRL启动子上的血管活性肠肽）将进一步 调查。