What is kisspeptin-10?

Kisspeptin-10 is a chain of ten amino acids with an amide group in place of the usual free acid at its end. In the body it is one of several fragments cut from a single precursor protein. For research it is made by solid-phase chemical synthesis and supplied as a freeze-dried salt.

One precursor, several kisspeptins

The KISS1 gene, located on the long arm of chromosome 1, encodes a precursor of 145 amino acids. Enzymes trim this protein into peptides of different lengths that are named after the number of residues they contain:

• Kisspeptin-54 (residues 68–121): the longest form, first isolated from human placenta in 2001 and also called metastin.
• Kisspeptin-14 and kisspeptin-13: intermediate fragments found in the same placental extracts.
• Kisspeptin-10 (residues 112–121): the shortest fragment with full activity at the receptor; under the metastin numbering it is metastin 45–54.

All of these share the same final ten residues, so the differences between them lie in the extra length at the front of the molecule rather than in the part that touches the receptor.

The RF-amide tail

The sequence ends in arginine and phenylalanine with a C-terminal amide (Arg-Phe-NH₂). This motif places kisspeptins in the wider RF-amide peptide family, which is found from invertebrates to mammals. The amide matters: it is part of how the peptide is recognised, and laboratory reports describe KP-10 as the minimal sequence that keeps the full intrinsic activity of the longer forms.

The KISS1R receptor

KISS1R belongs to class A of the G protein-coupled receptors, the largest receptor family in the human genome. Its gene sits on the short arm of chromosome 19. Before its ligand was known it was an orphan receptor called GPR54, noted for sharing about 40% of its sequence with the galanin receptors. Industrial groups gave it other names along the way, including AXOR12 and hOT7T175.

• Main signalling route: through Gq/11 proteins, activating phospholipase C, breaking down the membrane lipid PIP₂ and releasing calcium inside the cell.
• Further pathways: phosphorylation of the ERK1/2 and p38 kinases, and in 2024 structural work also showed coupling to Gi/o proteins.
• Where it is expressed: notably in the brain, pituitary, placenta, pancreas and spinal cord, and in the smooth muscle of some blood vessels.

What the receptor structures show

In 2024 two groups solved cryo-electron microscopy structures of KISS1R bound to its ligands. One captured the receptor with kisspeptin-10 itself and with the synthetic analogue TAK-448, showing that both insert into the receptor in the same way and lean on its extracellular loops. The same study described an unusual 40° shift at the inner end of the sixth transmembrane helix, compared with other Gq-coupled receptors, where the receptor engages its G protein.

Where kisspeptin is made in the body

Kisspeptin-producing neurons are clustered in the hypothalamus, chiefly in the arcuate nucleus and the preoptic region. Their fibres reach the GnRH neurons, which carry KISS1R. The placenta makes very large amounts during pregnancy, which is why the first peptides were purified from placental tissue.

Short and long forms compared

KP-10 is handy for experiments because it is small, but its brevity has a cost. In mice its half-life in the blood was about 4 minutes, compared with about 32 minutes for kisspeptin-54, and the longer peptide sustained the hormone response far longer. In a study of healthy men given each form by intravenous infusion, the two produced similar gonadotropin responses at the rates tested, while GnRH itself was more potent than either.

In short

• A ten-residue peptide with an amidated Arg-Phe end, cut from the KISS1 precursor.
• The smallest fragment that fully activates KISS1R, the former GPR54.
• Cleared from the blood much faster than kisspeptin-54.
• A research reagent, not an approved medicine.