Description): The major objective of this project is to utilize transgenic technology to develop immortalized granulosa cell (GC) lines which will maintain functional Follicle-stimulating hormone receptor (FSHR). In pilot studies, the investigators prepared a FSHR gene-promoter-SV40-T-antigen cDNA construct which targeted T-antigen (Tag) mRNA expression specifically to the gonads of the F1 mice. Their rationale is based upon the transgenic approach of Windle et al (Mol Endo 4:597,1990) in which LH alpha-subunit gene promoter-SV40-T-antigen cDNA constructs produced anterior pituitary tumors, from which immortalized LH-secreting cell lines were derived. They propose to develop FSHR-expressing GC lines in the same manner, but have extended the approach to the F2 generation because GC tumors did not develop in their hemizygous F1 offspring. The objectives will be to: 1) accelerate the development of tumors in the homozygous mice by neonatal DES treatment; and 2) develop and characterize GC lines from the Tag-induced and/or DES-Tag-induced ovarian tumors in terms of FSHR expression and responsiveness. FSHR- expressing cells will provide a powerful tool to study folliculogenesis at the molecular level. Their availability may allow the investigators in an expanded application to determine the mechanism(s) by which the pathways of mitosis and apoptosis in GC are uniquely regulated by FSH. They may also provide a critically important resource for molecular biological studies of ovarian cellular function.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
1R03HD035135-01A1
Application #
2761838
Study Section
Special Emphasis Panel (ZHD1-DRG-A (04))
Program Officer
De Paolo, Louis V
Project Start
1999-01-01
Project End
2000-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Duke University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705