STUDIES OF NORMAL AND NEOPLASTIC HUMAN PITUITARY TISSUE

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Although pituitary neoplasms are associated with a great deal of morbidity because of excessive hormone production and/or as space occupying lesions, very little is known about the mechanisms regulating the development of pituitary hyperplasia and neoplasia in humans. The regulation of hormone production and differentiation in normal and neoplastic human pituitary gland tissues will be investigated using morphological, immunochemical, biochemical and in situ hybridization methods. Morphological studies at the light and electron microscopic level, immunochemical methods with specific antibodies and in situ hybridization analyses with oligonucleotide, cDNA and riboprobes will be used to study normal pituitaries, prolactin (PRL), growth hormone (GH)-producing and null cell or undifferentiated adenomas. Cell culture on extracellular matrix with serum free media will be used to analyze the effects of specific hypothalamic hormones such as thyrotropin releasing hormone, gonadotropin releasing hormone, corticotropin releasing hormone and somatostatin, as well as phorbol esters on hormone production and differentiation. Receptor autoradiography and biochemical analysis for specific receptors will be performed in these tissues and correlated with the effects of various secretagogues on cell differentiation. The role of specific growth factors, such as epidermal growth factor and basic fibroblast growth factor on pituitary cell differentiation will be examined. The regulation of estrogen receptor, chromogranins and pituitary transcription factor messenger RNA levels in normal and neoplastic pituitary cells will be analyzed. The long-term objectives are to understand the morphological and biochemical differences and similarities between normal and neoplastic human pituitary tissues and to gain more insight into the biology of normal and neoplastic pituitary cells. The data from these studies may lead to a better understanding of the biology of normal and neoplastic pituitary cells in humans and to the development of methods to treat these tumors more effectively.