Summary

Kisspeptin is a neuropeptide that plays a central role in regulating the hypothalamic-pituitary-gonadal (HPG) axis, acting upstream of gonadotropin-releasing hormone (GnRH). It has been studied in human clinical trials for its effects on reproductive hormone signalling, with potential research applications in hypogonadism, fertility, and testosterone modulation. Evidence is moderate, supported by Phase 1/2 human studies.

Mechanism

Kisspeptin binds to the KISS1R (GPR54) receptor on GnRH neurons in the hypothalamus, triggering GnRH release into the hypothalamic-pituitary portal system. GnRH then stimulates the anterior pituitary to secrete LH and FSH, which in turn act on the gonads (testes in males, ovaries in females) to produce sex steroids (testosterone, oestradiol) and gametes. Kisspeptin is thus positioned at the apex of the HPG axis — upstream of GnRH — making it one of the most potent known physiological stimulants of reproductive hormone secretion. The KISS1 gene product is cleaved into several bioactive fragments, with kisspeptin-54 (metastin) being the longest and kisspeptin-10 the shortest commonly studied form.

Evidence base

Human clinical evidence (Phase 1/2) supports kisspeptin's stimulatory effect on LH, FSH, and sex steroids. Key studies include Jayasena et al. (2014) demonstrating dose-dependent LH/testosterone increases in men, and IVF maturation studies (Jayasena et al., 2014, JCI). Evidence is primarily from one research group (Imperial College London). No Phase 3 trials completed.

Protocols

Research protocols from published studies: SC bolus 0.1–1.0 nmol/kg (kisspeptin-54) or 1 nmol/kg (kisspeptin-10). Acute administration only in published literature. No established chronic dosing protocol. Research use only — not medical dosing advice.

Legal to purchase and possess for research purposes in the UK. Not a licensed medicine. Not scheduled under the Misuse of Drugs Act. Not MHRA-licensed for any therapeutic indication. All human studies conducted under clinical trial authorisations.

Vendor notes

Kisspeptin is available from select UK research chemical suppliers. As with all peptides, verify COA availability and third-party purity testing before purchase. See our Vendor Vetting Guide for evaluation criteria.

References

  1. Seminara SB, et al. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003;349(17):1614-1627.
  2. Jayasena CN, et al. Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea. J Clin Endocrinol Metab. 2013;98(9):E1557-E1564.
  3. Jayasena CN, et al. Increasing LH pulsatility in women with hypothalamic amenorrhea using subcutaneous kisspeptin-54. J Clin Endocrinol Metab. 2014;99(6):E1190-E1198.
  4. George JT, et al. Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men. J Clin Endocrinol Metab. 2015;100(2):E262-E269.
  5. Dhillo WS, et al. Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab. 2005;90(12):6609-6615.
  6. Jayasena CN, et al. Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilisation. J Clin Invest. 2014;124(8):3667-3677.