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.
