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)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R23)
Project #
5R23CA037238-02
Application #
3446549
Study Section
Pathology B Study Section (PTHB)
Project Start
1984-03-01
Project End
1987-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Lloyd, R V; Schmidt, K; Coleman, K et al. (1986) Prolactin and growth hormone synthesis and thymidine incorporation in dissociated rat pituitary tumor cells. Proc Soc Exp Biol Med 181:18-23
Lloyd, R V; Landefeld, T D (1986) Detection of prolactin messenger RNA in rat anterior pituitary by in situ hybridization. Am J Pathol 125:35-44
Lloyd, R V; Schmidt, K; Nath, V (1985) Effects of pergolide on diethylstilbestrol-induced rat pituitary hyperplasia. Am J Pathol 121:486-95
Lloyd, R V; Landefeld, T D; Maslar, I et al. (1985) Diethylstilbestrol inhibits tumor growth and prolactin production in rat pituitary tumors. Am J Pathol 118:379-86