Overview
Kisspeptin-10, KP-10, metastin 45-54: the same substance
| Designation | Origin |
|---|---|
| Kisspeptin-10 | After its length of ten amino acids |
| KP-10 | Common short form |
| Metastin 45-54 | Original name plus position in the precursor protein |
| KISS1 (45-54) | After the coding gene |
There is a risk of confusion with kisspeptin-54, the longer fragment from the same studies. Both are active; the material offered here is the ten amino acid form.
Origin and reason for development
The story of kisspeptin begins in an unexpected place. In 1996 a group in Hershey, Pennsylvania, described a gene that suppressed metastasis of melanoma cells. They named it KISS1 and the gene product metastin.
Only in 2003 did it become clear that its real significance lay elsewhere. Two independent groups, Seminara in Boston and de Roux in Paris, studied families with absent puberty and both found the same genetic defect: an inactive receptor, GPR54. The matching ligand was kisspeptin.
That identified a previously unknown, higher-order switch of the reproductive axis. In the published models kisspeptin acts upstream of GnRH, making it one of the few cases in which endocrinology found an entirely new level of regulation.
Mechanism of action in the literature
GPR54 activation. Kisspeptin-10 binds the G protein-coupled receptor GPR54 on GnRH neurons in the hypothalamus. The described consequence is a release of GnRH, which in turn triggers the secretion of LH and FSH from the pituitary.
Pulsatility. The literature stresses that the signalling is pulsatile. In the published models continuous exposure leads to desensitization of the receptor, a pattern familiar from other endocrine axes.
State of research 2026
Kisspeptin is among the better studied peptides on this list. Human studies on gonadotropin release exist, for instance by Dhillo and colleagues, alongside a broad body of basic literature on the regulation of puberty.
In research the substance is examined among other things as a diagnostic tool for the function of the hypothalamic-pituitary axis. There is no marketing authorization as a medicinal product.
From a cancer gene to a regulator of puberty
The story of kisspeptin is one of the most unexpected in recent endocrinology, and it explains its name.
In 1996 a group in Pennsylvania was looking for genes that suppress metastasis in melanoma. It found one and called it KiSS-1. The allusion was local: Hershey Kisses are made in Hershey, Pennsylvania. The peptide is therefore named kisspeptin because of a confectionery, not because of reproduction.
For five years KiSS-1 remained a metastasis suppressor gene. Then in 2001 the group around Ohtaki showed that the gene in fact encodes the ligand of a then orphan G protein-coupled receptor, GPR54, since renamed KISS1R.
The turn came in 2003. Seminara and colleagues described in the New England Journal of Medicine families with inactivating mutations of GPR54. Those patients presented with hypogonadotropic hypogonadism, that is an absence of puberty. A gene studied in cancer research turned out to be a key point of sexual development.
The precise place in the hypothalamic-pituitary-gonadal axis
This is the point most accounts miss, and it determines everything that follows.
Kisspeptin does not act at the gonads. It acts further upstream, at the GnRH neurons of the hypothalamus, which express KISS1R. The described cascade runs as follows:
- Kisspeptin neurons, among others in the arcuate nucleus, release the peptide.
- Kisspeptin binds KISS1R on the GnRH neurons.
- Those neurons release GnRH in pulses.
- The pituitary answers with the secretion of LH and FSH.
- The gonads respond to LH and FSH.
The practical consequence matters: kisspeptin sits at the head of the cascade, where physiological regulation remains intact. That distinguishes it from exogenous administration of gonadotropins, which bypasses the control steps.
Kisspeptin-10 compared with the longer forms
The KISS1 gene encodes a precursor of 145 amino acids that is cleaved into several active fragments. The naming simply follows the length.
| Form | Length | Note |
|---|---|---|
| Kisspeptin-54 | 54 amino acids | Metastin, the originally isolated long form |
| Kisspeptin-14 | 14 amino acids | Intermediate fragment |
| Kisspeptin-13 | 13 amino acids | Intermediate fragment |
| Kisspeptin-10 | 10 amino acids | Smallest active C-terminal fragment |
All share the same C-terminal end, which carries the activity at the receptor. Kisspeptin-10 is the shortest fragment with full affinity for KISS1R.
In the published work the short forms show a shorter half-life than kisspeptin-54, which has immediate consequences for the design of an experimental protocol.
Documented fields of research
- Reproductive neuroendocrinology. By far the dominant field. Control of puberty, pulsatility of GnRH, seasonal regulation in animal models.
- Oncology. The historical function as a metastasis suppressor remains an active topic, separate from the reproductive function.
- Metabolism. More recent work describes effects on enteroendocrine cells and pancreatic islets in mouse models.
- Aquaculture and animal science. The use in fish models for follicular maturation is an active field usually overlooked in human-centred accounts.
Regulatory placement
Kisspeptin-10 is not authorized as a medicinal product in any jurisdiction. Within the EU the competent authority for medicinal products is the EMA.
Buying kisspeptin-10: what to look for
When buying kisspeptin-10 the deciding factor is not price but the verifiability of quality. A research peptide is only ever as good as its certificate of analysis. These five criteria separate serious suppliers from grey-market sellers, because from the outside lyophilized powder looks identical.
1. HPLC purity, documented rather than claimed
HPLC purity states what proportion of the powder is actually kisspeptin-10 and not a by-product of synthesis. Serious suppliers document the figure with a chromatogram. A purity number without an attached chromatogram is a claim, not evidence.
2. Batch-specific certificate of analysis (CoA)
The most important document. A batch-specific CoA belongs to exactly the batch you receive: with batch number, date of analysis and purity value, issued by an independent laboratory. Rule of thumb: if a supplier cannot show the CoA for the specific batch immediately, do not buy there.
3. LC-MS identity confirmation
Purity tells you how much of a substance is present. LC-MS tells you which substance it is. Through the molecular mass it confirms the correct identity and rules out cheaper, mislabeled material having been shipped.
4. Origin and EU dispatch with traceability
A supplier with a warehouse in the EU and full batch traceability has the advantage over grey imports: shorter transport routes, no customs risk, a documented path from synthesis to vial.
5. The correct delivery form: lyophilizate
Quality material is supplied as a lyophilizate, freeze-dried powder, not as a premixed solution. In dry form the substance is considerably more stable and is reconstituted only immediately before use.
Legal notice: Kisspeptin-10 is a research material and not an authorized medicinal product. It is supplied exclusively for scientific laboratory research and is not intended for human or animal consumption. It has no approved therapeutic use.
Science & studies
Key publications
Lee J.H., Miele M.E., Hicks D.J., Phillips K.K., Trent J.M., Weissman B.E., Welch D.R. (1996). KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst. 88(23):1731 to 1737. PubMed 8944003 The discovery of the gene, five years before anyone made a connection to reproduction.
Ohtaki T., Shintani Y., Honda S. et al. (2001). Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature. 411(6837):613 to 617. PubMed 11385580 The pairing of ligand and receptor. The pivot of the whole story.
Seminara S.B., Messager S., Chatzidaki E.E. et al. (2003). The GPR54 gene as a regulator of puberty. N Engl J Med. 349(17):1614 to 1627. PubMed 14573733 The publication that made kisspeptin a subject of endocrinology. Human genetics, not an animal model.
Thompson E.L., Patterson M., Murphy K.G. et al. (2004). Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis. J Neuroendocrinol. 16(10):850 to 858. PubMed 15500545 The paper dealing specifically with administered kisspeptin-10 rather than with the gene.
Colledge W.H. (2004). GPR54 and puberty. Trends Endocrinol Metab. 15(9):448 to 453. PubMed 15519892 A contemporary review of the 2003 findings, useful for the overall frame.
Studies in detail
▸ Study 1: the discovery of the gene
Citation: Lee J.H. et al. KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst, 1996. PubMed 8944003
What they did: the group was searching for metastasis suppressor genes, working with melanoma cell hybrids, a classic approach of somatic genetics.
What they found: a gene whose expression reduced the metastatic capacity of the melanoma cells, named KiSS-1.
Why it counts: because the function described here has nothing to do with reproduction. That is a useful reminder that a peptide can have several biological roles with no discernible connection, and that the oncological field of kisspeptin continues.
▸ Study 2: the ligand and its receptor
Citation: Ohtaki T. et al. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature, 2001. PubMed 11385580
What they did: a deorphanization strategy. GPR54 was a G protein-coupled receptor whose natural ligand was unknown. The group searched for the endogenous molecule that activates it.
What they found: the product of the KiSS-1 gene binds GPR54 with high affinity. The C-terminal fragment suffices for activation, which is what justifies the existence of kisspeptin-10 in the first place.
Why it counts: this article is what makes kisspeptin-10 relevant. Without it nobody would know that the C-terminal decapeptide is the effective part.
▸ Study 3: the demonstration in humans
Citation: Seminara S.B. et al. The GPR54 gene as a regulator of puberty. N Engl J Med, 2003. PubMed 14573733
What they did: the genetic investigation of consanguineous families in which several members presented with idiopathic hypogonadotropic hypogonadism, that is an absence of puberty without any discernible anatomical cause.
What they found: inactivating mutations of GPR54 in the affected individuals, with a segregation matching the phenotype.
Why it counts: it is a demonstration in humans, delivered by genetics rather than by administering a substance. Loss of receptor function blocks puberty. This level of evidence sits well above the average of the peptide field.
▸ Study 4: administration of the decapeptide
Citation: Thompson E.L. et al. Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis. J Neuroendocrinol, 2004. PubMed 15500545
What they did: administration of kisspeptin-10 by two separate routes, central and peripheral, in an animal model, with measurement of the gonadotropins.
What they found: stimulation of the axis by both routes, with a rise in LH. That the peripheral route works was the remarkable result, since for a peptide acting on hypothalamic neurons that was not a given.
Why it counts: it is the most directly relevant paper for a protocol with kisspeptin-10, as opposed to investigations of the gene or the receptor.
Storage
Store lyophilized powder at 2 to 8 °C protected from light, at −20 °C for long-term storage. In dry form the substance stays stable for years that way. After reconstitution the solution belongs in the fridge, protected from light, and according to the literature should be used within 28 days. Avoid repeated freezing and thawing, which degrades peptides measurably.
Reconstitution
First bring the lyophilizate and the bacteriostatic water to room temperature. Let the solvent run slowly down the inner wall of the vial held at 45°, never squirt it directly onto the powder. Do not shake, swirl gently until everything has dissolved. Foaming indicates denaturation.
The exact volume for your target concentration is calculated by the peptide calculator. A suitable solvent is bacteriostatic water with 0.9 % benzyl alcohol, which allows withdrawals over several weeks after the first puncture.
Volumes for various final concentrations
| Amount in the vial | Solvent added | Final concentration |
|---|---|---|
| 5 mg | 2 ml | 2.5 mg/ml |
| 5 mg | 5 ml | 1 mg/ml |
| 10 mg | 5 ml | 2 mg/ml |
| 10 mg | 10 ml | 1 mg/ml |
A note specific to kisspeptin-10
Kisspeptin-10 is a short decapeptide without a stabilizing modification. Two practical consequences follow.
First, the half-life described for the short forms is short compared with kisspeptin-54. A protocol designed for the long form cannot be transferred unchanged.
Second, as with any short unmodified peptide, repeated freeze-thaw cycles are the most important avoidable degradation factor. Dividing into single-use aliquots immediately after reconstitution solves the problem once and for all.
The reconstituted solution stays clear. Any cloudiness or visible precipitate points to a problem with the solvent or the storage, and the solution must not be used for quantitative work.
Pre-order
Kisspeptin-10 is currently available for pre-order. You reserve the quantity you want without obligation, and we confirm the batch and delivery date by email. No payment is taken at reservation.
Stacking tips: substances from the same field
Kisspeptin-10 occupies a special position: it acts at the head of an endocrine cascade. The references that make sense in research are therefore mostly comparisons rather than potentiations.
Gonadotropins and GnRH
In the published protocols kisspeptin is more often compared with GnRH than combined with it. The logic is plain: both act on the same cascade at different levels, and joint administration makes the analysis harder.
Metabolic peptides
The more recent work on enteroendocrine cells and pancreatic islets places kisspeptin in a metabolic field, far from its historical reproductive one. References to GLP-1 receptor agonists belong in that field, which is young and whose evidence base remains limited.
A methodological note
Combining several peptides that act on the same axis almost always renders the result uninterpretable. For kisspeptin, whose appeal lies precisely in its upstream position, this holds to a particular degree.
Key scientific figures and citations
“Mutations in the GPR54 gene are associated with idiopathic hypogonadotropic hypogonadism, identifying this signalling pathway as a regulator of puberty.” After Seminara S.B. et al. (2003), New England Journal of Medicine 349(17):1614 to 1627 PubMed 14573733
Core figures from the literature
- Discovery of the KiSS-1 gene: 1996, Lee and colleagues, in the melanoma field
- Identification of the ligand of GPR54: 2001, Ohtaki and colleagues, Nature
- Demonstration of the role in human puberty: 2003, Seminara and colleagues, NEJM
- Length of the precursor encoded by KISS1: 145 amino acids
- Described active fragments: kisspeptin 54, 14, 13 and 10
- Receptor: KISS1R, formerly GPR54, a G protein-coupled receptor
- Site of action: GnRH neurons of the hypothalamus
- Origin of the name: the Hershey Kisses from Hershey, Pennsylvania
- WADA prohibited list: not currently affected
Figures from the cited studies
- Discovery of the gene (Lee 1996, J Natl Cancer Inst 88(23):1731 to 1737): transferring human chromosome 6 into the C8161 and MelJuSo melanoma lines suppressed their ability to metastasise by at least 95 % without affecting tumorigenicity. The cDNA named KiSS-1 was isolated from exactly these cells
- Identification of the peptide (Ohtaki 2001, Nature 411(6837):613 to 617): KiSS-1 encodes a C-terminally amidated peptide of 54 amino acids, isolated from human placenta and named metastin. It is the endogenous ligand of the orphan receptor hOT7T175, today KISS1R
- The genetics of puberty (Seminara 2003, NEJM 349(17):1614 to 1627): a consanguineous family carried a homozygous L148S mutation in GPR54, and an unrelated proband carried R331X and X399R. Transfecting COS-7 cells with the mutant constructs produced significantly less inositol phosphate accumulation
- Where the peptide acts (Thompson 2004, J Neuroendocrinol 16(10):850 to 858): in adult male rats an i.c.v. dose of 3 nmol kisspeptin-10 raised plasma LH at 10, 20 and 60 minutes, FSH at 60 minutes and total testosterone at 20 and 60 minutes
- In the same work, concentrations of 100 to 1000 nM kisspeptin-10 had no effect on LH or FSH release from pituitary fragments in vitro. The action is therefore hypothalamic rather than pituitary, and that is the whole difference from giving gonadotropins
- GPR54-null mice (Colledge 2004, Trends Endocrinol Metab 15(9):448 to 453) fail to go through puberty and have immature reproductive organs and low sex steroids, yet normal hypothalamic GnRH levels. Marketing authorisation: none
Reference sources (PubMed)
- Lee J.H. et al. (1996). KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst 88(23):1731 to 1737. PubMed 8944003
- Ohtaki T. et al. (2001). Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature 411(6837):613 to 617. PubMed 11385580
- Seminara S.B. et al. (2003). The GPR54 gene as a regulator of puberty. N Engl J Med 349(17):1614 to 1627. PubMed 14573733
- Thompson E.L. et al. (2004). Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis. J Neuroendocrinol 16(10):850 to 858. PubMed 15500545
- Colledge W.H. (2004). GPR54 and puberty. Trends Endocrinol Metab 15(9):448 to 453. PubMed 15519892
Regulatory status: Kisspeptin-10 is not authorized as a medicinal product in any jurisdiction. It is the subject of clinical research in reproductive endocrinology, which is not the same as an authorization. Within the EU the competent authority for medicinal products is the EMA. The product offered here is a reagent exclusively for scientific laboratory research (RUO).
Frequently asked questions about kisspeptin-10
What is kisspeptin-10?
Kisspeptin-10 is the shortest fully active fragment of the peptide hormone kisspeptin, encoded by the KISS1 gene. It comprises amino acids 45 to 54 of the precursor and binds the receptor GPR54, also called KISS1R.
Why is it called kisspeptin?
The name goes back to the place of discovery: the KISS1 gene was described in 1996 in Hershey, Pennsylvania, as a metastasis suppressor gene, named after the Hershey’s Kisses produced there. The original designation metastin comes from that context.
What role does kisspeptin play in research?
The 2003 work by Seminara and de Roux showed that defects in the GPR54 receptor lead to absent puberty. Kisspeptin was thereby identified as a higher-order switch of the gonadotropin axis, upstream of GnRH.
Is kisspeptin-10 authorized?
No. Kisspeptin-10 is not an authorized medicinal product and is supplied exclusively as research material for laboratory research.
How do kisspeptin-10 and kisspeptin-54 differ?
They are two fragments of the same precursor with the same active C-terminal end. Kisspeptin-54, also metastin, is the originally isolated long form. Kisspeptin-10 is the shortest fragment with retained receptor affinity. The described half-lives differ, which matters for the design of a protocol.
Why does this peptide carry such an odd name?
Because the gene was discovered in Hershey, Pennsylvania, where Hershey Kisses are made. The name has no bearing whatsoever on the biological function.
Does kisspeptin act at the gonads?
No, not directly. It acts on the GnRH neurons of the hypothalamus, that is at the head of the cascade. The gonads then respond to the gonadotropins from the pituitary.
What is GPR54?
The former name of the kisspeptin receptor, today KISS1R. Until 2001 it was an orphan receptor whose natural ligand was unknown.
Is the level of evidence robust?
For the role in puberty it is unusually robust for this field: it rests on human genetics, with loss-of-function mutations and a clear phenotype. That says nothing, however, about the effect of an exogenous dose in a healthy person, for which the evidence is far thinner.
