NORMAL AND NEOPLASTIC HUMAN PITUITARY TISSUE

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DESCRIPTION: Pituitary neoplasms are associated with a great deal of morbidity because of excessive hormone production and/or as space occupying lesions. The mechanisms regulating pituitary tumor growth in humans are poorly understood. This proposal will examine the regulation of hormone production and cell growth in normal and neoplastic human pituitary gland tissues using morphological, immunohistochemical, biochemical and hybridization methods. The role of chromogranins (Cg)/secretogranins (Sg) and their proteolytic products on hormone secretion and on cell growth will be investigated. Preliminary studies have shown that x:u, which is derived from CgA, is secreted by pituitary cells in culture in response to hypothalamic peptides and that chromostatin and ate regulate hormone secretion in cultured pituitary tumors. The role of the proconvertases PC2 and PC3 in the processing of Cg/Sg will be analyzed in pituitary tumors. The possible autocrine/paracrine role of prolactin (PRL) and its receptor (PRL-R) in the growth and hormone secretion in pituitary tumors will be investigated and the effects of basic fibroblast growth factor (bFGF) and its receptors in pituitary cell and tumor function will be examined using immunohistochemical techniques and the reverse hemolytic plaque assay to assess release of bFGF by pituitary cells in the presence or absence of specific hypothalamic peptides. Preliminary studies have shown that hypothalamic peptides can increase bFGF mRNA in pituitary cells. Dr. Lloyd will establish cell lines from pituitary tumors using SV40 recombinants to infect pituitary cells and induce cell proliferation in order to obtain cell lines to perform large series of experiments for the same tumors. The long term objectives o this study are to analyze the mechanisms by which hormones and growth factors influence growth and hormone secretion in pituitary cells which may lead to a better understanding about the development of pituitary tumors and to more effective treatment modalities.