Fox tales: Regulation of gonadotropin gene expression by forkhead transcription factors

• Loss of FOXD1 in the pituitary mesenchyme results in decreased Lhb transcription.
• FOXL2 is essential for activin-induced Fshb transcription and FSH production.
• FOXL2 also regulates follistatin, Gnrhr and Cga gene expression.
• FOXO1 suppresses Lhb and Fshb transcription, potentially via PITX1, SF1 and EGR1.
• FOXP3 is required for gonadotropin hormone synthesis and fertility in male mice.

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are produced by pituitary gonadotrope cells and are required for steroidogenesis, the maturation of ovarian follicles, ovulation, and spermatogenesis. Synthesis of LH and FSH is tightly regulated by a complex network of signaling pathways activated by hormones including gonadotropin-releasing hormone, activin and sex steroids. Members of the forkhead box (FOX) transcription factor family have been shown to act as important regulators of development, homeostasis and reproduction. In this review, we focus on the role of four specific FOX factors (FOXD1, FOXL2, FOXO1 and FOXP3) in gonadotropin hormone production and discuss our current understanding of the molecular function of these factors derived from studies in mouse genetic and cell culture models.