Clinical studies have suggested that prenatal alcohol exposure is associated with increased risk of tumorigenesis. Immune defects may account for this abnormality, since the immune system plays a pivotal role in cancer and infectious diseases (e.g. AIDS). Preliminary studies in this laboratory have shown that young adult rodents which were exposed to alcohol in utero display increased susceptibility to estrogen-induced pituitary tumors (prolactinoma) and a further enhancement of immune suppression. The mechanisms which underlie these abnormalities are not known, but the recognition of neuro-immune-endocrine interactions may be relevant. Thus, the long-term objective of this research proposal is to elucidate the neuroendocrine and immune mechanisms which underlie the increased susceptibility to tumor induction of offspring born to alcohol- abusing mothers. Specifically, the first aim of the proposed project is to further characterize the effects of prenatal alcohol exposure on the immunologic and neuroendocrine responses to short- and long-term estrogen treatments of the Fischer 344 rat. The second aim is to determine the persistency of pituitary tumors as well as of the immune and neuroendocrine responses following termination of estrogen treatments. Parameters to be measured include pituitary tumor size, cellular immune response and neuroendocrine variables such as prolactin and corticosterone. The proposed research will contribute to the understanding of mechanisms by which alcohol abuse during pregnancy elicits neuroendocrine and immune defects, thus compromising the well being of the offspring throughout life.