Recent Advances in the Understanding of Gonadotrope Lineage Differentiation in the Developing Pituitary

Background: The pituitary gland is a vital endocrine organ regulating body homoeostasis through six hormone-secreting cell types. Among these, pituitary gonadotrope cells are essential for reproductive function. Throughout pituitary ontogenesis, gonadotrope cells differentiate in a stepwise process, involving both morphogenic cues and transcription factors, which drives specification of progenitor cells into specialised endocrine cells. It is crucial to understand the mechanisms underlying gonadotrope differentiation, as developmental defects and abnormalities in this process can lead to many reproductive pathologies. Summary: This review offers a detailed overview of the latest advances in gonadotrope cell differentiation. We addressed this question with a specific focus on three important aspects of gonadotrope differentiation: the identification of the progenitor population giving rise to gonadotrope cells, the early mechanisms that initiate Nr5a1 expression and thus gonadotrope fate commitment, and finally, the mechanisms driving the formation of physical and functional gonadotrope networks. Key Messages: Overall, this review aimed to provide new insights into three aspects of the gonadotrope differentiation process by reconsidering pioneering studies in the light of data gained from latest technological developments. Firstly, we re-investigated the long debated developmental trajectory of pituitary gonadotrope cells. Secondly, we reported new regulatory mechanisms of Nr5a1 expression, focusing on the involvement of ER alpha. Finally, we highlighted the molecular and cellular mechanisms driving gonadotrope network formation during embryogenesis, a process that seems essential for regulation of gonadotrope activity.