The goal of the present proposal is to elucidate the role of Runx1, a nuclear transcription factor, in the ovary. We have recently identified that this transcription factor is dramatically and transiently induced in granulosa cells of periovulatory follicles after the LH [luteinizing hormone] surge. The periovulatory follicle undergoes rapid changes in the expression patterns of a myriad of genes to bring about ovulation and luteinization. Therefore, transcriptional regulators induced by the LH surge are believed to play an essential role in the ovulatory process and luteinization. We have preliminary data showing that knockdown of the LH-induced Runx1 expression in periovulatory granulosa cells resulted in a decrease in progesterone production, implicating the involvement of Runx1 in luteinization. We also found that Runx1 expression is regulated by the activation of the progesterone receptor and EGF [epidermal growth factor]-receptor, two known key mediators for the ovulatory process. Based on these novel findings, we hypothesize that Runx1 plays an important role(s) in ovulation and luteinization. The goal of this proposal is to: 1) demonstrate that the induction of Runx1 in periovulatory granulosa cells is essential for successful ovulation and luteinization and 2) determine the specific role(s) of Runx1 in periovulatory granulosa cells. To accomplish this goal, we will generate mice lacking functional Runx1 specifically in granulosa cells, and then examine the ovarian phenotype of these mutant mice (Specific Aim 1). Using the granulosa cell-specific Runx1 null mice, we will identify the genes down-stream of Runx1 action in periovulatory granulosa cells (Specific Aim 2). Information derived from this proposal will provide new insight into the mechanism(s) involved in ovulation and corpus luteum formation. Such knowledge can be applied for promoting or inhibiting these critical facets of ovarian physiology, thereby allowing us to better manage fertility, infertility, and ovarian-based disorders. ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
1R03HD051727-01
Application #
7018011
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Taymans, Susan
Project Start
2006-03-01
Project End
2008-02-29
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
1
Fiscal Year
2006
Total Cost
$73,209
Indirect Cost
Name
University of Kentucky
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506