This project will prepare the awardee for a career combining independent biomedical research and medical specialization. A program of research training, advanced graduate course work and continued exposure to pathology has been prepared to accomplish this goal as evidenced by the completion of a Ph.D. and eligibility for board certification. Mechanisms of evaluation and coordination of training components, a mentor and research project have been put in place. Criteria for advancement have been determined. A phosphorylated variant of bovine prolactin (bPRL) has been isolated by our laboratory from pituitaries. Phosphorylation appears to be at serine 34 and associated with an altered folding pattern. The relationship between the structure and biological function of this bPRL variant needs to be determined and will constitute the focus of this project. The central hypothesis of these studies is that several forms of bPRL, each having unique biological actions, can be synthesized and secreted in a regulated manner from the pituitary. The specific objectives in Phase I are: 1) compare the biological actions of native and phosphorylated bPRL in several bioassays, 2) determine the relationship between bPRL phosphorylation and associated folding patterns by biological assay and physical/chemical methods, 3) determine if human decidual cells synthesize phosphorylated human PRL. Phase II specific objectives are: 4) determine the differential regulation of synthesis and secretion of native and phosphorylated bPRL within the bovine pituitary, and 5) determine the chronology of biochemical mechanisms that convert bPRL from a highly polymerized storage from to either a native or phosphorylated monomer during secretion.
