Regulation of Pituitary Somatotroph Differentiation by Zn-16

该项目旨在了解因子如何调节特定细胞类型中特定激素的产生。 位于脑垂体的促生长细胞在脑下丘脑神经元的控制下产生生长激素（GH），以调节肌肉发育和骨生长。 虽然已知一种名为Pit-1的蛋白质对于GH基因的表达是必需的，但与另一种名为Zn-16的蛋白质的组合相互作用对于GH表达的正常协同调节是必需的。 实验将研究和操纵Zn-16在生长激素细胞中，以评估对GH基因RNA转录的影响。 Zn-16的表达将在GH缺乏的侏儒大鼠和小鼠中测量，无论是作为成年人还是在垂体分化的关键阶段。 将在体外大鼠生长激素细胞系中研究GH抑制剂对Zn-16水平的影响。 最后，可以形成生长激素细胞的肿瘤将被遗传操纵，以研究体内Zn-16的活性。 建立精确的信息调节生长激素将提高理解的分子机制控制细胞如何分化和成熟。 这些实验需要一系列分子生物学技术，特别是聚合酶链反应，并将验证使用新试剂来检测Zn-16蛋白。 除了确定Zn-16在GH调节中的作用外，这些研究还将产生更广泛的影响，包括为本科生提供培训，发表他们的研究结果，并将这些主题融入课堂。 特别是，由杜兰大学的合作者亨利巴特博士共同指导的路易斯安那州少数民族参与联盟的学生将被鼓励参与这些项目。

This project aims to understand how factors regulate the production of a specific hormone in a selected cell type. Somatotroph cells located in the pituitary gland make growth hormone (GH) under the control of the hypothalamic neurons of the brain in order to regulate muscle development and bone growth. While one protein, named Pit-1, is known to be essential for expression of the gene for GH, combinatorial interactions with another protein named Zn-16 are necessary for normal synergistic regulation of GH expression. Experiments will study and manipulate Zn-16 in somatotrophs to assess effects on the transcription of RNA from the GH gene. Zn-16 expression will be measured in GH-deficient dwarf rats and mice, either as adults or during critical stages of pituitary differentiation. Effects of GH inhibitors on Zn-16 levels will be studied in rat somatotroph cell lines in vitro. Finally, tumors that can be formed form somatotrophs will be manipulated genetically to study the activity of Zn-16 in vivo. Establishing precise information about regulation of GH will enhance understanding of the molecular mechanisms controlling how cells differentiate and mature. These experiments require an array of molecular biology techniques, especially polymerase chain reaction, and will validate the use of new reagents to detect the Zn-16 protein. Beyond determining the role of Zn-16 in GH regulation, these studies will have the broader impacts of providing training of undergraduate students, publishing their findings, and integrating these topics into the classroom. In particular, students in the Louisiana Alliance for Minority Participation, co-directed by collaborator Dr. Henry Bart at Tulane University, will be encouraged to work on these projects.