GnRH-driven FSH synthesis and secretion are modulated through circ-ptpn4 ceRNA sequestration of let-7b-5p miRNA,...

During animal growth and development, the reproductive system is tightly controlled by the central nervous system through a highly conserved, self-feedback loop-the hypothalamic-pituitary-gonadal (HPG) axis. Gonadotropin-releasing hormone (GnRH), which is produced in the hypothalamus and secreted into the hypophyseal portal circulation, serves as a master regulator of pituitary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) synthesis and secretion, thereby orchestrating growth and reproductive functions. We identified circ-ptpn4 as a GnRH-responsive circular RNA (circRNA) that sequesters let-7b-5p, thereby attenuating its suppression of ELK1. This decrease in let-7b-5p availability thus allows enhanced ELK1 expression, which ultimately stimulates FSH production. In summary, we revealed a novel competing endogenous RNA (ceRNA)-dependent pathway (circ-ptpn4/let-7b-5p/ELK1) underlying GnRH-induced FSH regulation.