Kisspeptin is the brain signal that switches on the chain of reproductive hormones. Research asks how that first step is controlled, and what happens when it is given.
Kisspeptin · Upstream reproductive signalling peptide
Reproductive hormones are released in a chain. The brain sends a releasing signal to the pituitary gland, the pituitary signals the ovaries or testes, and those organs make oestrogen or testosterone. Kisspeptin is a key upstream regulator of the first link, which is why researchers use it to ask how the chain is switched on and paced. Evidence in people comes from small clinical studies.
Kisspeptins are a family of peptides cut from one larger precursor encoded by the KISS1 gene. The main forms are named by length: kisspeptin-54 and shorter fragments such as kisspeptin-10, all sharing the same active end of the sequence. They act on a single receptor, KISS1R (formerly GPR54), a cellular receiver on the neurons that make gonadotropin-releasing hormone, or GnRH, the brain’s releasing signal to the pituitary.
The gene came first. KISS1 was identified in 1996 as a suppressor of melanoma spread, and its product was called metastin (Lee et al., 1996). Only in 2001 did two groups show that the gene encodes peptides that activate GPR54 (Ohtaki et al., 2001; Kotani et al., 2001). The reproductive role emerged in 2003, when people with inactivating mutations in the receptor were found not to enter puberty. The gene’s name, a nod to the Hershey, Pennsylvania campus where it was characterised, is a footnote to that biology.
The founding human evidence is genetic. Two independent groups reported in 2003 that loss-of-function mutations in GPR54 cause hypogonadotropic hypogonadism, a failure of the brain-to-gonad chain, in affected families (Seminara et al., 2003; de Roux et al., 2003).
Administration studies followed, mostly from one London group. In healthy men, an intravenous infusion of kisspeptin-54 raised luteinising hormone, follicle-stimulating hormone and testosterone in the blood (Dhillo et al., 2005). Kisspeptin-10 given intravenously to healthy men also stimulated luteinising hormone and increased its pulse frequency (George et al., 2011). In women undergoing IVF, a single subcutaneous injection of kisspeptin-54 was tested as the trigger for final egg maturation in a 53-participant study, which measured mature eggs retrieved and subsequent pregnancies (Jayasena et al., 2014). Separate work has examined the peptide in women with hypothalamic amenorrhoea, where the chain is switched off, and found that repeated dosing can blunt the response.
Kisspeptin-54 and kisspeptin-10 act on the same receptor but differ in size and in how long they persist in blood, so findings for one form do not automatically describe the other, and the form supplied matters when reading any study. The human studies are small and short: hormone measurements in volunteers, and egg-maturation and pregnancy outcomes in one 53-woman IVF study that was a research protocol rather than an approved use. None establishes a treatment. Responses differ between men, women at different cycle stages and people whose axis is suppressed, and the blunting seen with repeated administration is not fully understood.
Kisspeptin is not an approved medicine in Australia and is not separately listed in the Poisons Standard (June 2026). No regulator has approved a kisspeptin medicine. In sport, kisspeptin and its agonist analogues are listed under S2.2.1 (testosterone-stimulating peptides in males) of the 2026 WADA Prohibited List, prohibited at all times in males.
Sources and status checked 2026-09-23
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