Kisspeptin
Kisspeptin, signalling through the KISS1R (GPR54) receptor, is a key upstream regulator of gonadotropin-releasing hormone (GnRH) neurons; loss-of-function mutations in its receptor cause absent puberty. Human experimental-medicine studies, notably kisspeptin-54 to trigger oocyte maturation in IVF and to probe reproductive disorders, have shown promising physiology, but kisspeptin remains investigational and unapproved.
Mechanism
In plain terms, kisspeptin is the switch that turns on the reproductive hormone system, prompting the brain to release the hormones that drive the ovaries and testes. Technically, kisspeptin binds KISS1R (GPR54), a Gq/11-coupled receptor on hypothalamic GnRH neurons, stimulating GnRH release; this in turn drives pituitary secretion of luteinising hormone (LH) and follicle-stimulating hormone (FSH). Its central role in initiating puberty and regulating fertility underlies its study as a more physiological trigger of the reproductive axis.
Regulatory Status by Region
- United States (FDA)Not approved for any indication; investigational and studied only in clinical research.
- Australia (TGA)Not on the Australian Register of Therapeutic Goods (ARTG); an unapproved substance with no registered therapeutic product.
- European Union (EMA)No EMA marketing authorisation; not an approved medicine in the EU.
- WADAProhibited in males under Section S2: WADA added kisspeptin to the 2024 Prohibited List as an example of a testosterone-stimulating peptide (a luteinising-hormone releasing factor); it is prohibited in males only, not in females.
Key Studies
- The GPR54 gene as a regulator of puberty (loss-of-function mutations in the kisspeptin receptor cause absent puberty) (Seminara SB, et al. N Engl J Med. 2003.)
- Kisspeptin-54 stimulates the hypothalamic-pituitary-gonadal axis in human males (Dhillo WS, et al. J Clin Endocrinol Metab. 2005.)
- Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization (Jayasena CN, et al. (Dhillo group). J Clin Invest. 2014.)