Skip to content

Endocrine · Reference monograph

Full-length kisspeptin (metastin)

Reference compound — not available from Purity Peptides. Shown for research context.

Overview

Kisspeptin-54 is the full-length, 54-amino-acid peptide processed from the KISS1 gene product. The gene was first described in 1996 as a suppressor of metastasis in melanoma cell lines, and the mature peptide was later named metastin. Shorter fragments, including kisspeptin-14, -13 and -10, share the same C-terminal RF-amide decapeptide that is necessary for receptor activation.

The peptide's reproductive significance emerged in 2003, when two groups independently reported that loss-of-function mutations in its receptor, then called GPR54 and now KISS1R, cause hypogonadotropic hypogonadism in humans and mice. Kisspeptin is now regarded as a master upstream regulator of GnRH neurons and a key input to puberty onset. Kisspeptin-54 has been studied in clinical research settings, particularly at Imperial College London, as an experimental trigger of oocyte maturation in IVF and as a probe of LH pulsatility in conditions such as hypothalamic amenorrhoea. It is not approved by the FDA or EMA and remains an investigational research peptide.

Mechanism studied

  1. Kisspeptin-54
  2. KISS1R
  3. GnRH release
  4. LH surge

Kisspeptin-54 activates KISS1R, a Gq/11-coupled receptor expressed on hypothalamic GnRH neurons. Receptor activation stimulates phospholipase C, intracellular calcium release and depolarisation via TRPC-like channels and inhibition of potassium currents, producing robust GnRH release into the portal circulation and a downstream rise in LH and, to a lesser extent, FSH. In the arcuate nucleus, kisspeptin neurons co-expressing neurokinin B and dynorphin (KNDy neurons) are proposed as the GnRH pulse generator, while a separate population in the anteroventral periventricular region is implicated in the preovulatory surge in rodents. Kisspeptin-54 has a longer circulating half-life than kisspeptin-10.

Research highlights

  • 01KISS1 was identified in 1996 as a metastasis suppressor; its peptide product was characterised as metastin in 2001.
  • 02Human and mouse genetic studies in 2003 linked KISS1R mutations to absent puberty, redirecting the field toward reproduction.
  • 03Clinical research has examined kisspeptin-54 as an alternative trigger of oocyte maturation, including in women considered at risk of ovarian hyperstimulation.
  • 04Kisspeptin has been used as a probe to help distinguish constitutional delay of puberty from hypogonadotropic hypogonadism in research studies.
  • 05Open questions include receptor desensitisation with sustained exposure and kisspeptin's roles outside reproduction, such as in metabolism and behaviour.

Latest published research

241 papers on PubMed →

  1. Seminal Plasma Kisspeptin-1 and Kisspeptin-54 Levels Are Associated With Semen Parameters and Oxidative Stress in Male Infertility

    Korkmaz O et al. · Clinical endocrinology · 2026 Nov · PMID 42566672

  2. Follicular kisspeptin-VEGF axis in polycystic ovary syndrome and ovarian hyperstimulation syndrome

    Korkmaz O et al. · Journal of assisted reproduction and genetics · 2026 Aug 28 · PMID 42663893

  3. Kisspeptin-54 attenuates acute lung injury in septic mice through AMPK-mediated suppression of NLRP3 inflammasome

    Wang X et al. · Neuropeptides · 2026 Aug · PMID 42418889

  4. Kisspeptin-54 confers renal protection in diabetic nephropathy by ameliorating endothelial permeability through ZEB1 inhibition

    Gao L et al. · Tissue & cell · 2026 Aug · PMID 41950743

  5. Corrigendum to "Kisspeptin-54 attenuates oxidative stress and neuronal apoptosis in early brain injury after subarachnoid hemorrhage in rats via GPR54/ARRB2/AKT/GSK3β signaling pathway" [Free Radic Biol Med.171 (2021) 99-111]

    Huang Y et al. · Free radical biology & medicine · 2026 Aug 1 · PMID 41934061

  6. Dual rescue mission: P-G3 dendrimer addresses ovarian and neuroendocrine roots of obesity-linked subfertility

    Nie Y et al. · Journal of advanced research · 2026 Aug · PMID 41274638

  7. Analysis and Characterization of Kisspeptin and Its Analogues in Serum and Urine Samples by Liquid Chromatography-High-Resolution Mass Spectrometry for Doping Control Purposes

    Krombholz S et al. · Drug testing and analysis · 2026 Jul · PMID 42057309

  8. Therapeutic potential of nasal kisspeptin-54 for reducing α-synuclein accumulation and restoring hippocampal synaptic plasticity in a 6-hydroxydopamine-induced rat model of Parkinson's disease

    Gemici Sinen A et al. · Turkish journal of medical sciences · 2026 · PMID 42676968

Live feed from PubMed (NCBI) for “Kisspeptin-54”, updated 2026-10-30. Listing a paper is not an endorsement of its findings.

Registered studies

19 on ClinicalTrials.gov →

From the public ClinicalTrials.gov registry for “Kisspeptin-54”, updated 2026-10-30. Shown for research context only; Purity Peptides products are not for human use.

Key references

  1. [1]Abbara et al., 2015 — J Clin Endocrinol Metab
  2. [2]PubMed — reviews on kisspeptin-54 and IVF

FAQ

  • The KISS1 gene was discovered in a cancer-biology context as a suppressor of melanoma metastasis, and its peptide product was named metastin when the receptor was deorphanised in 2001. The name kisspeptin, referencing Hershey, Pennsylvania, where the gene was found, is now standard in reproductive research.

  • Both activate KISS1R through the shared C-terminal decapeptide. Kisspeptin-54 retains the longer N-terminal sequence, which appears to confer greater stability and a longer half-life in circulation. Kisspeptin-10 is shorter-lived and often used to study rapid, pulse-like activation of the reproductive axis.

  • KNDy neurons are arcuate nucleus cells that co-express kisspeptin, neurokinin B and dynorphin. Neurokinin B is thought to synchronise and start each burst while dynorphin terminates it, generating the pulsatile kisspeptin output that drives GnRH pulses. They are a major focus of reproductive neuroendocrinology.

FOR RESEARCH USE ONLY.Not for human or veterinary use. Not intended to diagnose, treat, cure, or prevent any disease.

Related compounds

WhatsApp