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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA042951-06
Application #
3184717
Study Section
Pathology A Study Section (PTHA)
Project Start
1986-07-01
Project End
1995-05-31
Budget Start
1991-06-01
Budget End
1992-05-31
Support Year
6
Fiscal Year
1991
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
Jin, L; Burguera, B G; Couce, M E et al. (1999) Leptin and leptin receptor expression in normal and neoplastic human pituitary: evidence of a regulatory role for leptin on pituitary cell proliferation. J Clin Endocrinol Metab 84:2903-11
Kulig, E; Jin, L; Qian, X et al. (1999) Apoptosis in nontumorous and neoplastic human pituitaries: expression of the Bcl-2 family of proteins. Am J Pathol 154:767-74
Oka, H; Jin, L; Kulig, E et al. (1999) Pituitary adenylate cyclase-activating polypeptide inhibits transforming growth factor-beta1-induced apoptosis in a human pituitary adenoma cell line. Am J Pathol 155:1893-900
Lloyd, R V; Erickson, L A; Jin, L et al. (1999) p27kip1: a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers. Am J Pathol 154:313-23
Jin, L; Thompson, C A; Qian, X et al. (1999) Analysis of anterior pituitary hormone mRNA expression in immunophenotypically characterized single cells after laser capture microdissection. Lab Invest 79:511-2
Jin, L; Kulig, E; Qian, X et al. (1999) Distribution and regulation of proconvertases PC1 and PC2 in human pituitary adenomas. Pituitary 1:187-95
Liang, Y; Wang, A; Belyantseva, I A et al. (1999) Characterization of the human and mouse unconventional myosin XV genes responsible for hereditary deafness DFNB3 and shaker 2. Genomics 61:243-58
Oka, H; Jin, L; Reubi, J C et al. (1998) Pituitary adenylate-cyclase-activating polypeptide (PACAP) binding sites and PACAP/vasoactive intestinal polypeptide receptor expression in human pituitary adenomas. Am J Pathol 153:1787-96
Qian, X; Jin, L; Kulig, E et al. (1998) DNA methylation regulates p27kip1 expression in rodent pituitary cell lines. Am J Pathol 153:1475-82
Sanno, N; Jin, L; Qian, X et al. (1997) Gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor messenger ribonucleic acids expression in nontumorous and neoplastic pituitaries. J Clin Endocrinol Metab 82:1974-82

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