Cellular interactions that control primordial follicle development and folliculogenesis.

Specific factors that mediate local cell--cell interactions in the ovary related to the initiation and progression of follicle development will be discussed. Recently, several factors produced locally by the primordial follicle have been shown to induce primordial follicle development from a quiescent state to promote follicle development. Kit ligand/stem cell factor (KL/SCF) produced by the immature granulosa cells appears to promote theca cell organization. Basic fibroblast growth factor produced predominately by the oocyte, but by all cells at reduced levels, also was found to induce primordial follicle development similar to KL. It is likely that numerous locally produced factors will mediate cellular interactions and interact between each other to control the induction of primordial follicle development and influence processes such as the onset of puberty and menopause. After follicle development has been induced, theca cells and granulosa cells interact through classical mesenchymal-epithelial type interactions to influence the progression of follicle development. Mesenchymally derived theca cells have been shown to produce transforming growth factor alpha (TGF-alpha), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and transforming growth factor beta to regulate granulosa cell growth and function. The epithelial granulosa cells have been show to produce KL/SCF that can feed back on the theca cells to regulate theca cell growth and stimulate the production of the theca cell factors (TGF-alpha, KGF, and HGF). Therefore, a positive feedback loop between the theca cells and granulosa cells appears to exist to promote the dramatic cell growth required during folliculogenesis. Interestingly, hormones such as estrogen and gonadotropins stimulate the expression of these paracrine growth factors. Therefore, the actions of hormones to stimulate follicle development and growth are mediated in part through altering these local cell--cell interactions. In summary, the locally produced paracrine factors that mediate cell-cell interactions involved in primordial follicle development and the progression of follicle development during folliculogenesis are starting to be elucidated.