The development of hyperplasia and tumors in rat pituitary glands will be investigated using morphological, immunohistochemical, and biochemical methods. Morphological studies at the light and electron microscope level and immunohistochemical methods with antisera to pituitary hormones will be utilized to distinguish between normal, hyperplastic, and neoplastic pituitary tissues. The transplantable pituitary tumor M+T/W15 will be analyzed concurrently as a model of pituitary neoplasia. Differences in dopamine receptor levels in normal, hyperplastic, and neoplastic tissues will be analyzed; and the effects of specific drugs such as bromocriptine, pergolide, estrogens, and luteinizing hormone releasing hormone (LHRH) on tumor progression and regression and on dopamine receptor levels will be examined. The biosynthesis of rat PRL mRNA in these tissues will also be studied with in situ hybridization methods to analyze for changes in PRL biosynthesis at the cellular level during the progression from normal pituitaries to pituitary tumors. Preliminary studies have shown that DES-implants lead to PRL cell proliferation and that this effect is partially reversible after removing the DES-implant or with daily injections of bromocriptine for 2 weeks. DES-implants in animals with M+T/W15 tumors led to an inhibition in the development of transplantable tumors with concomitant hyperplasia of the animal's own pituitary. This research is designed to understand the sequence of progression from normal to hyperplastic and neoplastic pituitary tissues. Goals include: (1)\understanding the progression in the development of pituitary tumors using rat pituitary tumor models; (2)\utilization of these models to produce effective means of arresting and reversing hyperplasia and tumor development; and (3)\development of more refined and specific methods to understand the biosynthesis of PRL at the cellular level in normal and neoplastic pituitary tissues. (S)