Abstract
Follicular development and ovulation process are complex events in which a sequential process is started by two pituitary hormones, FSH and LH. Recent studies using microarray analysis have shown that numerous endocrine factors are expressed and specifically activate the signal transduction cascades to upregulate or downregulate the expression of target genes in granulosa cells and cumulus cells. Especially, the PI 3-kinase-AKT pathway during the follicular development stage and the ERK1/2 pathway after LH surge are essential for initiating the dramatic changes in follicular function. The proliferation of granulosa cells and cell survival are dependent on the FSH-induced PI 3-kinase-AKT pathway in a c-Src-EGFR dependent manner. On the other hand, the transient activation of ERK1/2 by LH surge is dependent on de-novo transcription and translation. EGF-like factors, especially amphiregulin, that are expressed in a cAMP-PKA-CREB dependent manner, act on EGFR expressed on granulosa cells and cumulus cells. The phosphorylated EGFR induces the RAS-cRAF-MEK-ERK1/2 pathway in both cell types. One of the ERK1/2 target molecules is C/EBP that is a member of transcription factors increasing the expression of genes involved in granulosa cell luteinization, cumulus expansion and oocyte maturation. These signaling cascades upregultaed by FSH or LH in granulosa cells play important roles in follicular development and ovulation process.
