Each of the cell types of the anterior pituitary gland may give rise to adenomas which hypersecrete specific hormones, including prolactin (PRL), growth hormone (GH), adrenocorticotropin (ACTH) glycoprotein hormones or their subunits. Excessive hormone secretion may result in infertility, growth disorders or metabolic dysfunctions. The local pituitary mass may also impinge on surrounding vital structures causing visual defects, cranial nerve palsies or sinus invasion. Although several mechanisms have been proposed for the etiology of pituitary adenomas, including hypothalamic dysfunction, peripheral hormone (e.g. estrogen) action and pituitary vascular abnormalities, no direct pathogenetic mechanism for pituitary tumorigenesis is known. This proposal aims to study the molecular pathogenesis of these tumors. Firstly, the clonal origin of the various pituitary adenomas will be determined by X-chromosome inactivation analysis in female patients using the X-chromosome genes, HPRT and PGK as probes. DNA extracted from pituitary tumor tissue obtained at surgery will be used to transfect mouse NIH-3t3 cells in order to test for the presence of transforming genes. After enrichment of the tertiary transfectants will be cloned into a phage library, and sequence. We show preliminary data describing the standardization of the transformation assay, as well as successful transformation induced by DNA extracted from 4 pituitary adenomas. Evidence will be provided suggesting that the putative transforming gene is not a member of the ras gene family. The transforming gene(s) will be sought and characterized in each of the pituitary tumor cell types, including PRL-cell, GH-cell, Cushing's, alpha subunit and non- functioning tumors. These studies will provide further insight into the pathogenesis of the cell-specific anterior pituitary adenomas.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK041906-01A1
Application #
3242861
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1990-01-01
Project End
1992-12-31
Budget Start
1990-01-01
Budget End
1990-12-31
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048
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