This research proposal seeks new information about the basic cellular mechanisms involved in hormone storage and release by the human and mammalian adenohypophysis. Dynamic alterations in secretory cell populations and organelles associated with various human disease states, with altered physiological states such as pregnancy, and with neoplastic transformation will be determined. Biochemical analyses will include cell fractionation, nucleic acid determinations, and hormone measurements using radioimmunoassays. Primary emphasis will be placed on morphologic techniques, including differential staining, electron microscopy, immunocytochemistry, and quantitative morphometry. Combined ultrastructural, biochemical, and dynamic secretory studies will employ in vitro cell culture systems using dispersed cells from rat pituitary glands, from estrogen-induced rat pituitary tumors, and from spontaneous human and rat pituitary adenomas. A rat model will be developed to study sequential changes in vivo during estrogen-induced pituitary neoplasia. Attention will be directed to the isolation, identification and characterization of pituitary microfilaments and their possible relatedness to actomyosin or other contractile proteins as well as their potential role in hormone secretion and release. The biochemical composition and enzymatic activities of isolated secretory granules and their membranes will be studied by chromatographic, electrophoretic, and radioimmunoassay methodology to establish their potential role in hormone packaging and release.