Regulation of Pituitary Somatotroph Differentiation by Zn-16

这个项目旨在了解因子如何调节选定细胞类型中特定激素的产生。位于脑下垂体的促生长激素细胞在大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骼生长。虽然已知一种名为Pit-1的蛋白质对生长激素基因的表达是必不可少的，但与另一种名为锌-16的蛋白质的组合相互作用对于生长激素表达的正常协同调节是必要的。实验将研究和操纵生长激素细胞中的锌-16，以评估对生长激素基因RNA转录的影响。将在生长激素缺乏的侏儒大鼠和小鼠中测量锌-16的表达，无论是成年后还是在垂体腺分化的关键阶段。生长激素抑制剂对大鼠生长激素细胞株中锌-16水平的影响将在体外进行研究。最后，可以由生长激素细胞形成的肿瘤将被进行基因操作，以研究体内锌-16的活性。建立关于生长激素调控的准确信息将加强对控制细胞分化和成熟的分子机制的理解。这些实验需要一系列分子生物学技术，特别是聚合酶链式反应，并将验证使用新的试剂来检测锌-16蛋白。除了确定锌-16在生长激素调节中的作用外，这些研究还将产生更广泛的影响，为本科生提供培训，发表他们的发现，并将这些主题整合到课堂上。特别是，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，该联盟由杜兰大学的合作者亨利·巴特博士共同指导。

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.