Growth factors of endocrine and/or paracrine origin play determinant r
oles in antral follicular development. They modulate survival, prolife
ration and differentiation of follicular cells, acting in interaction
with gonadotropins. It is thought that factors belonging to the famili
es of the insulin-like growth factor (IGF-I and -II), epidermal growth
factor (EGF and TGF-alpha) and fibroblast growth factor (FGF) can sup
port growth of small antral follicles by enhancing granulosa cell prol
iferation. During terminal follicular development, i.e. development of
large antral follicles strictly dependent on gonadotropin supply, fac
tors such as IGFs and inhibin potentiate the differentiation-promoting
actions of gonadotropins on granulosa and thecal cells, respectively.
In addition, binding proteins modulate bioavailability of these growt
h factors in follicles. In particular, terminal follicular development
in domestic ruminants is accompanied by important decreases in intraf
ollicular concentrations of the IGF-binding proteins IGFBP-2, -4 and -
5, due to both a decrease in their synthesis by follicular cells and a
n increase in their degradation by specific intrafollicular proteinase
s. As a result, IGF bioavailability increases in large antral follicle
s, enhancing the amplification of gonadotropin action on follicular ce
lls. In contrast, atresia is characterized by an increase in the expre
ssion of IGFBP-2, -4 and -5 mRNAs and a decrease in proteolytic degrad
ation of the corresponding proteins, resulting in an increase in their
intrafollicular concentrations and a decrease in IGF bioavailability.
All these intrafollicular mechanisms, in addition to the privileged e
ndocrine dialogue that establishes between the dominant follicle(s) an
d the hypothalamo-pituitary complex, contribute to ensuring its (their
) final development and to triggering off atresia of the gonadotropin
dependent follicles of the cohort. (C) 1996 by Elsevier Science Inc.