[Intragonadal regulation of human follicular genesis: facts and hypotheses]

In the mammalian ovary, the follicular growth is classically considered to be under the control of pituitary gonadotropins. In the human, three cycles (85 days) are required for a preantral follicle (approximately 0.15 mm in diameter) to attain the ovulatory size (approximately 20 mm in diameter). During this growing phase, follicular responsiveness to LH and especially to FSH exhibits strong changes. Up to diameter of approximately 2mm, follicles are unsensitive to cyclic changes in circulating levels of FSH, in terms of quality, growth rate and steroidogenesis (basal follicular growth). Follicles larger than 2 mm become responsive to FSH, in terms of quality and growth rate, but their ability to synthesize estrogen remains very low, they constitute the population of recruitable follicles. From its selection, the follicle destined to ovulate becomes mores and more responsive, first to FSH and then to LH; all the gonadotropin-induced functions are expressed during preovulatory maturation. The aim of this review is to clarify the intraovarian regulations involved: (a) in the inhibition of gonadotropin-induced functions (basal follicular growth); (b) in the acceleration of the growth rate of recruitable follicles and simultaneous acquisition of FSH responsiveness of their granulosa cells during the late luteal phase, as well as in the "selection" of one of them; (c) in the strong proliferation of granulosa cells paralleling with full expression of FSH-induced functions (preovulatory maturation before LH surge) and (d) in the inhibition of granulosa cell proliferation paralleling with full expression of FSH- and LH-induced functions (preovulatory maturation after the LH surge). Some peptides and proteins, such as growth factors (EGF, IGFs et IGFBPs, TGF-beta), the inhibin-activin-follistatin system and TNF-alpha, and synthesized by the follicular tissues, might be involved in both the inhibition and stimulation of follicular responsiveness to gonadotropins. Their possible role during maturation of the primate follicle has been analyzed in the light of the most recent findings.