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Androgens, FSH, anti-Mullerian hormone (AMH) and estradiol (E2) are essential in human ovarian folliculogenesis. However, the interactions between these four players is not fully understood. The purpose of this review is to highlight the chronological sequence of the appearance and function of androgens, FSH, AMH and E2 and to discuss controversies in the relationship between FSH and AMH. A better understanding of this interaction could supplement our current knowledge about the pathophysiology of the polycystic ovary syndrome (PCOS). During the pre-antral ("gonadotropin-independent") follicle growth, FSH is already active and promotes follicle growth in synergy with theca cell-derived androgens. Conversely, AMH is inhibitory by counteracting FSH. We challenge the hypothesis that AMH is regulated by androgens and propose rather an indirect effect through an androgen-dependent amplification of FSH action on granulosa cells (GCs) from small growing follicles. This hypothesis implies that FSH stimulates AMH expression. During the antral ("gonadotropin-dependent") follicle growth, E2 production results from FSH-dependent activation of aromatase. Conversely, AMH is inhibitory but the decline of its expression, amplified by E2, allows full expression of aromatase, characteristic of the large antral follicles. We propose a theoretical scheme made up of two triangles that follow each other chronologically. In PCOS, pre-antral follicle growth is excessive (triangle 1) because of intrinsic androgen excess that renders GCs hypersensitive to FSH, with consequently excessive AMH expression. Antral follicle growth and differentiation are disturbed (triangle 2) because of the abnormally persisting inhibition of FSH effects by AMH that blocks aromatase. Beside anovulation, this scenario may also serve to explain the higher receptiveness to gonadotropin therapy and the increased risk of ovarian hyperstimulation syndrome (OHSS) in patients with PCOS. Within GCs, the balance between FSH and AMH effects is pivotal in the shift from androgen- to estrogen- driven follicles. Our two triangles hypothesis, based on updated data from the literature, offers a pedagogic template for the understanding of folliculogenesis in the normal and polycystic ovary. It opens new avenues for the treatment of anovulation due to PCOS. [ABSTRACT FROM AUTHOR]

The good progress of the folliculogenesis is fundamental for obtaining an oocyte capable of generating an embryo having a good implanting potential. During this follicular development, the oocyte has a special relationship with the cumulus cells surrounding it and with which it forms a cumulo-oocyte complex. A dialogue is thus established inside the follicle, thanks to communicating junctions and paracrine signals allowing the oocyte to control certain functions of the cumulus cells in order to ensure its own survival. This interaction is expressed by the expression of key genes, which are themselves regulated by short RNA fragments, about 19-25 nucleotides, called microRNAs. The identification of microRNAs involved in the intrafollicular dialogue should lead to obtaining non-invasive tests to assess the oocyte quality. [ABSTRACT FROM AUTHOR]