For normal folliculogenesis and oogenesis to occur many intrinsic and extrinsic factors are needed, i.e. positive feedback of hormone secretion and local ovarian-follicular growth factors distribution. During follicle formation, granulosa cells (GCs) change their morphology and physiological properties. The factors needed for GCs to differentiate within each layer are transforming growth factor beta (TGFB) and insulin-like growth factor (IGF), as well as the activation and modification of biochemical pathways involved in folliculogenesis. Physiological alterations occur when GC genes are characterized by several differences in their gene expression profile. Studies in recent years indicate a variety of processes involved in follicle morphology and biochemical remodeling during growth and development. It was demonstrated that IGFs play a central role in the differentiation of GCs both in vivo and in vitro. Moreover, the primary role of FSH and LH in the formation of the ovarian follicle, was also described. Our review article characterizes the most important pathways involved in the differentiation of GCs and the effect of various factors on gene expression in GCs during folliculogenesis.