Kisspeptin-10 is a ten-amino-acid peptide derived from the KISS1 gene and one of the most frequently used tools in research on the hypothalamic-pituitary-gonadal (HPG) axis. The wider kisspeptin family was first studied in cancer biology before a pair of 2003 genetic studies placed it at the centre of reproductive neuroendocrinology. This article covers where kisspeptin-10 comes from, its structure, its receptor and how it has been used in published research.
For laboratory research use only. Not for human or veterinary use. See our research use only policy.
Kisspeptin-10 belongs to our cluster on hypothalamic-pituitary signalling peptides. For the growth hormone side of that cluster, see our guide to CJC-1295 and ipamorelin in research.
At a glance: kisspeptin-10
- Name: Kisspeptin-10
- Synonyms: Kp-10, metastin (45-54), KISS1 (112-121) amide
- Sequence: Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2
- Molecular formula: C63H83N17O14
- Molecular weight: 1302.4 g/mol
- CAS number: 374675-21-5
- Form: Lyophilised powder
- Purity: >99% (HPLC)
- Storage: 2-8°C, dark, upright, do not freeze. Keep sealed until use.
From metastasis suppressor to reproductive regulator
The KISS1 gene was described in 1996 by Lee and colleagues, working at Penn State in Hershey, who identified it as a gene whose expression suppressed metastasis of human melanoma cells. In 2001, three groups independently identified the peptide products of KISS1 as ligands for an orphan G protein-coupled receptor, GPR54. Ohtaki and colleagues named the 54-residue peptide metastin, while Kotani and colleagues and Muir and colleagues used the kisspeptin terminology.
The decisive link to reproduction came in 2003. Seminara and colleagues, and separately de Roux and colleagues, reported that loss-of-function mutations in GPR54 were associated with idiopathic hypogonadotropic hypogonadism, a condition in which puberty does not occur normally. Mouse models lacking the receptor showed a comparable reproductive phenotype. These findings positioned kisspeptin signalling upstream of gonadotropin-releasing hormone (GnRH) neurones.
Structure and processing
KISS1 encodes a 145-amino-acid precursor. Proteolytic processing yields kisspeptin-54, and shorter forms kisspeptin-14, kisspeptin-13 and kisspeptin-10 have also been described. All share the same C-terminus, ending in an arginine-phenylalanine amide (an RF-amide motif). This places the kisspeptins within the broader RF-amide peptide family, which also includes neuropeptide FF and prolactin-releasing peptide.
Kisspeptin-10 corresponds to residues 112 to 121 of the human precursor, and to the final ten residues of kisspeptin-54. Structure-activity studies reported that this decapeptide is sufficient for full agonist activity at the receptor in vitro, which is why it is often chosen as a compact, synthetically convenient research ligand.
Notable residues
- Tyr1: the N-terminal tyrosine of the human decapeptide, a convenient site in iodination and labelling work.
- Trp3 and Phe6: aromatic residues implicated in receptor interaction in structure-activity work.
- Arg9-Phe10-NH2: the C-terminal RF-amide, the C-terminal amide is reported to be important for activity, and the free acid form is reported to be largely inactive.
The kisspeptin receptor, KISS1R
KISS1R, formerly GPR54, is a class A G protein-coupled receptor. On ligand binding it signals predominantly through Gq/11, activating phospholipase C, generating inositol trisphosphate and diacylglycerol and mobilising intracellular calcium. In the hypothalamus, the receptor is expressed by GnRH neurones, and kisspeptin-producing neurones are found in the arcuate nucleus and, in rodents, the anteroventral periventricular nucleus.
Rodent studies, including work by Gottsch and colleagues published in 2004, reported that intracerebroventricular kisspeptin was followed by GnRH-dependent release of luteinising hormone, a response that was absent when GnRH receptor signalling was blocked. This work helped establish kisspeptin as a regulator acting through GnRH rather than directly on the pituitary.
Kisspeptin-10 in the research literature
Kisspeptin-10 has been investigated in a range of experimental settings, including in vitro receptor pharmacology, GnRH neurone electrophysiology in brain slice preparations and studies of the neuroendocrine control of puberty and seasonal breeding in several species. Its short length makes it convenient for labelling and for structure-activity work, although its reported plasma half-life is short. Academic clinical research groups have also used kisspeptin isoforms in physiological studies. None of this work establishes any approved use, and our material is not a medicine.
Kisspeptin in context with other hypothalamic peptides
Kisspeptin sits in the reproductive arm of hypothalamic-pituitary signalling, alongside GnRH. The growth hormone arm uses GHRH, analogues of which include CJC-1295 no DAC and tesamorelin, and ghrelin receptor agonists such as ipamorelin. Each acts at a distinct receptor, which is why they are useful as separate tools for probing different axes.
Storage and handling
Kisspeptin-10 is supplied as a lyophilised powder in a sealed vial. We recommend storage at 2-8°C, in the dark, upright and not frozen, with the vial kept sealed until use. The tryptophan residue is susceptible to oxidation, so limiting light and air exposure is sensible. See our guide on how to store lyophilised peptides.
View kisspeptin-10 in the catalogue.
Frequently asked questions
What is kisspeptin-10?
Kisspeptin-10 is a ten-residue peptide amide corresponding to the C-terminal portion of the kisspeptin precursor encoded by the KISS1 gene. It is the shortest naturally occurring kisspeptin isoform reported to retain full activity at the kisspeptin receptor.
What receptor does kisspeptin act on?
Kisspeptins act at KISS1R, a G protein-coupled receptor originally known as GPR54. It couples mainly through Gq/11 proteins and phospholipase C signalling.
How is kisspeptin-10 related to kisspeptin-54?
Kisspeptin-54, also called metastin, is the longest processed form of the precursor. Kisspeptin-14, -13 and -10 are shorter forms. All share the same C-terminal RF-amide sequence, which is the region required for receptor activation.
Why was the gene called KISS1?
KISS1 was identified in 1996 at the Penn State College of Medicine in Hershey, Pennsylvania, and the name is widely reported to reference Hershey's Kisses chocolates. The gene was first studied as a suppressor of metastasis in melanoma cell lines.
Is kisspeptin-10 an approved medicine?
No kisspeptin product holds a marketing authorisation. Compound Cave supplies kisspeptin-10 only as a laboratory research material.
References
- 1. Lee JH, Miele ME, Hicks DJ, et al. KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst. 1996;88:1731-1737.
- 2. Ohtaki T, Shintani Y, Honda S, et al. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature. 2001;411:613-617.
- 3. Kotani M, Detheux M, Vandenbogaerde A, 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;276:34631-34636.
- 4. Seminara SB, Messager S, Chatzidaki EE, et al. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003;349:1614-1627.
- 5. de Roux N, Genin E, Carel JC, et al. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci USA. 2003;100:10972-10976.
- 6. Gottsch ML, Cunningham MJ, Smith JT, et al. A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology. 2004;145:4073-4077.
For laboratory research use only. Not for human or veterinary use. See our research use only policy.