Though a number of hormones become elevated during the physiological response to stress, most studies have focused on the effects of elevated cortisol and catecholamines. The significance and effects of stress-induced prolactin (Prl) elevation remain largely unknown, despite many reports showing that stress increases Prl. Preliminary studies using an in vitro endothelial injury model show that added Prl alters cell shape, motility and the actin cytoskeleton in cells migrating to close the wound space. The purpose here is to further investigate these novel observations and elucidate the effects of increased Prl on wounded endothelial cells. Using injury models, the investigators will 1) Determine if the responses of cultured endothelial cells to Prl after injury are due to the 23 kD Prl hormone, which would be novel, or instead a 16 kD fragment of Prl, with known anti-angiogenic properties, perhaps formed by enzymes released from injured cells; 2) Determine the effects of Prl on cultured endothelial cells migrating into wounds, particularly cell shape and motility, the cytoskeleton and associated proteins, and cell junctions; 3) Investigate the effects of added Prl on mitosis and gap closure during late stages of wound repair in vitro. Mitosis and gap closure are needed for endothelial barrier function; 4) Test the in vivo relevance of the in vitro studies on Prl and injured endothelial cells by examining Prl binding and Prl receptor labeling in rat aortic endothelium in situ. State-of-the-art imaging techniques, including light microscopy and electron microscopy, and biochemical methods, e.g. the polymerase chain reaction and Western blot analysis, will be employed.
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