Growth of the ovarian follicle is a developmental program dependent on stage-specific gene expression that is responsible for controlling granulosa cell fate, proliferation and differentiation. FSH and IGF-1 have been shown to act independently and synergistically to regulate this gene expression and follicular development. Recent evidence suggests that FSH impacts the PI3-K pathway and is able to mediate a proportion of the effects ascribed to IGF-1 in this pathway via the recently identified cAMP-dependent guanine nucleotide exchange factors (cAMP-GEFs). In addition, recent studies have demonstrated that the forkhead family of transcription factors are expressed in granulosa cells in the rodent ovary and that one of these factors FKHR, a known target of IGF-1 via the PI3-K pathway, responds to FSH in the granulosa cell. Therefore, it is my intention to determine whether FSH is able to activate cAMP-GEFS in granulosa cells and to determine what impact this may have on the PI3-K pathway. Secondly, I intend to determine how FSH is able to regulate FKHR expression and activity and what the functional role FKHR pays in the rodent ovary.
|Wayne, Chad M; Fan, Heng-Yu; Cheng, Xiaodong et al. (2007) Follicle-stimulating hormone induces multiple signaling cascades: evidence that activation of Rous sarcoma oncogene, RAS, and the epidermal growth factor receptor are critical for granulosa cell differentiation. Mol Endocrinol 21:1940-57|