Scientists discovered that a circular RNA called circ‑ptpn4 reacts to the hormone GnRH and pulls away a tiny regulator (let‑7b‑5p), which lets another protein (ELK1) increase and boost the production of the reproductive hormone FSH. This adds a new layer to how the brain tells the pituitary to make FSH, but it doesn’t change how we currently use GnRH‑based peptides.

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.