Estradiol Signaling at the Heart of Folliculogenesis: Its Potential Deregulation in Human Ovarian Pathologies

Estradiol (E2) is a major hormone controlling women fertility, in particular folliculogenesis. This steroid, which is locally produced by granulosa cells (GC) within ovarian follicles, controls the development and selection of dominant preovulatory follicles. E2 effects rely on a complex set of nuclear and extra-nuclear signal transduction pathways principally triggered by its nuclear receptors, ER alpha and ER beta. These transcription factors are differentially expressed within follicles, with ER beta being the predominant ER in GC. Several ER beta splice isoforms have been identified and display specific structural features, which greatly complicates the nature of ER beta-mediated E2 signaling. This review aims at providing a concise overview of the main actions of E2 during follicular growth, maturation, and selection in human. It also describes the current understanding of the various roles of ER beta splice isoforms, especially their influence on cell fate. We finally discuss how E2 signaling deregulation could participate in two ovarian pathogeneses characterized by either a follicular arrest, as in polycystic ovary syndrome, or an excess of GC survival and proliferation, leading to granulosa cell tumors. This review emphasizes the need for further research to better understand the molecular basis of E2 signaling throughout folliculogenesis and to improve the efficiency of ovarian-related disease therapies.

Automated summary

This review provides a comprehensive overview of the role of E2 in female folliculogenesis and the various effects of ERβ splice isoforms. It also discusses how deregulation of E2 signaling can lead to two ovarian pathologies and emphasizes the need for further research.