Kisspeptin-10research overview.

Overview

Kisspeptins are peptides derived from the KISS1 gene, first studied as a metastasis suppressor gene in melanoma cells. In 2001, two groups independently reported that its products are the natural ligands of an orphan G-protein-coupled receptor, GPR54, now called KISS1R. Ohtaki et al. isolated a 54-residue C-terminally amidated peptide from human placenta and named it metastin ¹. Kotani et al. isolated 54-, 14- and 13-residue forms and named them kisspeptins ².

In 2003, two groups linked loss-of-function mutations in GPR54 to hypogonadotropic hypogonadism, a condition in which puberty does not begin ^3,4. This placed kisspeptin signalling upstream of gonadotropin-releasing hormone (GnRH).

Kisspeptin-10 is the shortest form, the C-terminal ten residues shared by the longer kisspeptins. George et al. (2011) describe it as the minimal sequence with full intrinsic activity ⁵. Kisspeptin has been named on the World Anti-Doping Agency Prohibited List since 2024, as a testosterone-stimulating peptide prohibited in male athletes under section S2 ⁶.

Structure and chemistry

Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH₂ (YNWNSFGLRF-NH₂). Molecular formula C63H83N17O14, molecular weight 1302.4 g/mol, CAS 374675-21-5.

It is a linear peptide of L-amino acids. Its C-terminus is Arg-Phe-NH₂, the RF-amide motif shared by all the kisspeptins and by the wider RF-amide peptide family. Kotani et al. noted this common RF-amide C-terminus across the 54-, 14- and 13-residue forms ². Native kisspeptins are amidated at the C-terminus, and the synthetic decapeptide keeps the amide.

With one arginine and no acidic side chains, the peptide carries a small net positive charge at neutral pH. Its two asparagines can deamidate over time in solution, a general property of Asn-containing peptides.

Mechanisms investigated

Research has focused on KISS1R signalling in cells and on the reproductive hormone axis in animals and people.

• Receptor signalling. Kotani et al. (2001) reported low-nanomolar binding of kisspeptins to rat and human GPR54 expressed in CHO cells. They also reported PIP2 hydrolysis, calcium mobilisation, arachidonic acid release and ERK1/2 and p38 MAP kinase phosphorylation ².
• Cell migration. Ohtaki et al. (2001) reported that metastin inhibited chemotaxis and invasion of GPR54-transfected CHO cells in vitro, and measured pulmonary metastasis of transfected B16-BL6 melanoma cells in mice ¹.
• Human genetics. Seminara et al. (2003) and de Roux et al. (2003) identified GPR54 mutations in families with hypogonadotropic hypogonadism, and Seminara et al. also characterised Gpr54-deficient mice ^3,4.
• Healthy men. George et al. (2011) measured serum LH, LH pulse frequency and testosterone in healthy men given kisspeptin-10. They reported a rise in LH and, with prolonged administration, in testosterone ⁵.

Research areas

• Identification of KISS1 products as GPR54 ligands (in vitro and animal) ^1,2
• GPR54 mutations in hypogonadotropic hypogonadism (human genetics and animal) ^3,4
• LH pulsatility and testosterone in healthy men (human) ⁵

Limits of the evidence

Most of the receptor and signalling work used the longer kisspeptins or metastin ^1,2. Kisspeptin-10 shares their receptor-binding C-terminus, but its pharmacokinetics differ, so findings for one form should not be assumed to apply to another.

The human kisspeptin-10 data cited here come from small physiology studies in healthy men, measuring hormone levels over hours ⁵. They are not long-term outcome studies.

OzPept’s kisspeptin-10 is a research chemical, not a medicine, and is not for human use.

Key studies

1. 2001In vitro

   Metastin identified as the GPR54 ligand ¹

2. 2001In vitro

   Kisspeptins and GPR54 signalling ²

3. 2003Human

   GPR54 mutations and puberty ³

4. 2003Human

   GPR54 loss of function in a consanguineous family ⁴

5. 2011Human

   LH and testosterone in healthy men ⁵

Questions

References

1. Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K, et al. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature. 2001;411(6837):613-617. Source
2. Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001;276(37):34631-34636. Source
3. Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS, Shagoury JK, et al. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003;349(17):1614-1627. Source
4. de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A. 2003;100(19):10972-10976. Source
5. George JT, Veldhuis JD, Roseweir AK, Newton CL, Faccenda E, Millar RP, et al. Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men. J Clin Endocrinol Metab. 2011;96(8):E1228-E1236. Source
6. US Anti-Doping Agency. Explanation of key changes on the 2024 WADA Prohibited List. Athlete advisory. Accessed October 2026. Source