Multifactorial Regulation of Granulosa Cell (GC) Proliferation: Interactions Among Polypeptide Growth Factors

Abstract

Proliferation of the mural granulosa cells is a requisite component of the folliculogenic process. Our understanding of the regulation of this process at the level of the cell is limited. Although FSH and estradiol stimulate granulosa cell proliferation in vivo, they have a limited effect in vitro which suggests that they may act indirectly by stimulating the production of local, intraovarian mitogens, i.e., growth factors. Indeed, the ovary may be a site for the production of insulin-like growth factor-I (IGF-I,1,2), epidermal growth factor (EGF, 3,4), and transforming growth factor-beta (TGF β, 5). Studies by Gospodarowicz and colleagues suggested that EGF and fibroblast growth factor (FGF) were mitogens for many but not all granulosa cells (6–8). The actions of these growth factors could be enhanced markedly by serum which suggested that other factors, perhaps other growth factors, could synergize with EGF and FGF to promote granulosa cell proliferation. Accordingly, studies were initiated in this laboratory to investigate interactions among growth factors with respect to the regulation of granulosa cell proliferation.