The long-term goal of this project is to find the cause and develop a treatment for human pituitary gonadotroph adenomas.
The specific aim for the next 4 years is to determine if absence of follistatin plays a role in the development of gonadotroph adenomas. The rationale for this aim is that these adenomas underexpress follistatin mRNA and peptide, and follistatin has been shown in a variety of tissues to inhibit the action of activin, which is to stimulate FSH secretion. The first approach will be to transfect gonadotroph adenoma cells with a sense follistatin cDNA to determine if increasing follistatin expression in those cells will decrease FSH secretion and cell division, and to transfect cultured nonadenomatous gonadotrophs with an antisense follistatin cDNA to determine if decreasing follistatin will increase FSH secretion and cell division. The second approach will be to construct transgenic mice whose gonadotroph cells, and only gonadotroph cells, underexpress follistatin. If the pituitaries of mice carrying the transgene do express the antisense transgene and underexpress sense follistatin mRNA and peptide, other F1 mice will be used to establish lines which will be observed for the development of gonadotroph adenomas.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK042139-06
Application #
2518293
Study Section
Reproductive Endocrinology Study Section (REN)
Program Officer
Sato, Sheryl M
Project Start
1990-07-01
Project End
1999-08-31
Budget Start
1997-09-20
Budget End
1998-08-31
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Djerassi, A; Coutifaris, C; West, V A et al. (1995) Gonadotroph adenoma in a premenopausal woman secreting follicle-stimulating hormone and causing ovarian hyperstimulation. J Clin Endocrinol Metab 80:591-4
Daiter, E; Braunstein, G D; Snyder, P J et al. (1994) Gonadotropin-releasing hormone-dependent chorionic gonadotropin secretion in a menopausal woman. J Clin Endocrinol Metab 78:1293-7
Haddad, G; Penabad, J L; Bashey, H M et al. (1994) Expression of activin/inhibin subunit messenger ribonucleic acids by gonadotroph adenomas. J Clin Endocrinol Metab 79:1399-403
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