Progesterone Receptor Regulation of the Gene Networks That Control Ovulation in Mice

152 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008.In a pubertal human female, the mid-cycle surge of luteinizing hormone (LH) induces ovulation, releasing a fertilizable egg from a mature ovarian follicle. Although ovulation is a physiologically well-characterized event, the underlying molecular processes remain poorly understood. Based on research performed over the past twenty years, the steroid hormone progesterone, which exerts its biological effects through the progesterone receptors (PR), has emerged as a key regulator of ovulation. The development of progesterone receptor (PR)-null mice, which are unable to ovulate, revealed a critical role of this receptor in the control of follicular rupture. This animal model has presented a unique opportunity to study the molecular pathways underlying ovulation. Using these PR-null mice, my research has uncovered novel gene networks, which act downstream of PR to control ovulation. Most notably, my study has identified several factors such as the peroxisome proliferator-activator receptor gamma (PPARgamma), hypoxia-inducible factors (HIFs), and interleukin-6 (IL-6) as critical regulators of ovulation. These factors function as the downstream mediators of the PR signal to bring about the rupture of a mature ovarian follicle. The knowledge gained from this study would help us better understand the molecular mechanisms underlying ovulation. This research may also allow the development of new contraceptives with improved efficacy and reduced side effects. In addition, our findings may also aid in the understanding of infertility disorders, such as polycystic ovarian syndrome (PCOS), which is a complex disease that displays an anovulation phenotype.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD