Kisspeptin-10 Research, Specifications & Scientific Information

Introduction

Kisspeptin-10 is unusual among the compounds in this library in that nobody designed it. It is a fragment of a human peptide — the last ten residues of the protein encoded by the KISS1 gene, amidated at the C-terminus — prepared synthetically because that fragment carries the full activity of the parent.

The discovery history is worth knowing because it ran backwards. The receptor came first, as an orphan with no known ligand. In 2001 two groups independently reported that the products of KISS1, a gene until then studied as a metastasis suppressor, are its natural ligands ^{[1, 2]}. Two years later human genetics supplied the physiology: people carrying loss-of-function variants in that receptor fail to enter puberty ^{[3, 4]}. A cancer gene turned out to encode the ligand for the receptor that starts the reproductive axis.

What follows from that position in the pathway is the reason the decapeptide is studied at all. KISS1R sits on gonadotropin-releasing hormone neurons, upstream of the pituitary. Administering the peptide interrogates hypothalamic GnRH function specifically — something administering GnRH itself cannot do ^[13].

What Is Kisspeptin-10?

Kisspeptin-10 is the C-terminal decapeptide of the KISS1 gene product: residues 112 to 121 of the precursor, written in older metastin nomenclature as metastin 45-54, sequence YNWNSFGLRF-NH2.

The -NH2 is not decoration. Kisspeptins belong to the RFamide family, named for an arginine-phenylalanine-amide C-terminus, and that amide is part of what the receptor recognises. A preparation ending in a free carboxylic acid is roughly one dalton heavier, chromatographically similar and substantially less active. Any listing that writes this peptide as a bare ten-letter string has omitted the feature that determines whether the material is what it claims to be.

The gene produces several peptides sharing this C-terminus, of which the 54-residue kisspeptin-54 is the best characterised in human studies. The decapeptide is described in the literature as the minimal sequence with full intrinsic bioactivity ^[8], which is why it exists as a separate research compound rather than as a degradation product of interest.

Kisspeptin-10 has not been approved by the U.S. Food and Drug Administration for any indication, and no marketing application for it is on record in the United States. It is, however, under active registered clinical investigation: ClinicalTrials.gov records a phase 2 study in isolated hypogonadotropic hypogonadism ^[15] and a phase 1 study using the peptide to quantify GnRH neuronal function ^[16], both naming kisspeptin 112-121 explicitly as the investigational drug. Research-grade material supplied for laboratory use is not that drug.

Kisspeptin-10 Specifications

Kisspeptin-10 is the C-terminal decapeptide of the KISS1 gene product, corresponding to residues 112-121 of the precursor protein and written in the older metastin numbering as metastin 45-54. It is a fragment of a larger endogenous peptide rather than a designed analogue: the 54-residue kisspeptin-54 shares this same C-terminus, and the shorter peptide is described in the literature as the minimal sequence carrying full intrinsic bioactivity. The C-terminal phenylalanine is amidated, which is the defining feature of the RFamide family and is required for receptor activation — a preparation ending in a free carboxylic acid is a different and far less active molecule of almost identical mass. The single-letter string YNWNSFGLRF is therefore incomplete without the -NH2 notation. The identifiers here are the records held by PubChem (CID 25240297), which carries CAS registry number 374675-21-5 and FDA/NCATS UNII code FS1N52VS3S. Any figure on this page is a reference value: the certificate of analysis supplied with a laboratory order is the record for a given lot.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does Kisspeptin-10 Work?

The pathway is short and well mapped, which is rare among the compounds documented here.

KISS1R — formerly the orphan receptor GPR54, and also designated AXOR12 and hOT7T175 in the two independent 2001 deorphanisation papers — is a class A G protein-coupled receptor that signals through Gq/11. It is expressed on gonadotropin-releasing hormone neurons in the hypothalamus. Agonist binding there stimulates GnRH release; GnRH reaching the anterior pituitary through the portal circulation stimulates secretion of luteinising hormone and follicle-stimulating hormone; and those gonadotropins act on the gonads ^[6].

Two features of that arrangement give the peptide its research value. The first is the position: because the peptide acts on GnRH neurons rather than on the pituitary, a gonadotropin response to it demonstrates that hypothalamic GnRH neurons are functional — a distinction that matters diagnostically and cannot be made with GnRH itself ^[13]. The second is that the kisspeptin neurons are themselves the site where sex-steroid feedback and metabolic signals converge on the reproductive axis, which is why the response to exogenous peptide varies with the hormonal state of the person receiving it ^[9].

There is also a self-regulating element. A functional receptor-ligand system has been described within GnRH neurons themselves, implying autoregulation rather than a simple one-way input ^[7].

Kisspeptin-10 Mechanism of Action

In vitro research

Deorphanisation, twice over. In 2001 two groups reported independently that the KISS1 gene products activate the receptor then known as GPR54. One paper approached it as the characterisation of a novel human receptor designated AXOR12 ^[1]; the other approached it from the gene, reporting that the metastasis suppressor gene KiSS-1 encodes the kisspeptins and that these are the natural ligands of the orphan receptor ^[2].

Two independent groups arriving at the same ligand-receptor pairing in the same year is about as strong as a deorphanisation result gets, and it is the foundation everything else on this page rests on. It is also a useful contrast with several other compounds in this library, where the receptor was never found at all.

Autoregulation within GnRH neurons. A functional GPR54-kisspeptin system was subsequently described within hypothalamic gonadotropin-releasing hormone neurons themselves, indicating that these neurons both respond to kisspeptin and participate in its signalling ^[7]. That complicates the simple upstream-input picture and is relevant to interpreting desensitisation under sustained administration.

Findings in this section were obtained in receptor-expressing cells and in neuronal preparations. Nothing in them establishes anything about intact animals or about humans.

What Is Kisspeptin-10 Being Researched For?

• Physiology of the GnRH pulse generator — luteinising hormone pulse frequency and pulse mass in healthy men, resolved by deconvolution analysis ^[8].
• Sex-steroid feedback in women — gonadotrophin response across follicular, post-menopausal and contraceptive-suppressed states ^[9].
• Hypogonadism in metabolic disease — proof-of-concept work in men with type 2 diabetes and low testosterone ^[10].
• Chronic administration and desensitisation — continuous against intermittent subcutaneous administration over 5 and 12 days ^[14].
• Diagnostic use as a probe of hypothalamic function — in pubertal and reproductive disorders ^{[13, 16]} and in isolated hypogonadotropic hypogonadism ^[15].
• Interaction with neurokinin B — in mediating oestrogen feedback in healthy women ^[12].

Each of those is academic clinical or preclinical research conducted under a protocol. None of it is research into, or evidence about, research-grade material supplied for laboratory use.

Human Research on Kisspeptin-10

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

The human literature on this decapeptide is small in participant numbers and unusually precise in what it measures. These are endocrine physiology studies with hormone endpoints; none of them reports a clinical outcome.

Luteinising hormone pulsatility in healthy men

Population and design. Healthy men, given intravenous boluses across a range of administered amounts from 0.01 to 3.0 µg/kg together with vehicle, followed by infusions of up to 22.5 hours with pulse frequency and pulse size resolved by deconvolution analysis ^[8].

Result. Boluses produced a rapid rise in serum luteinising hormone that increased with the amount administered, reaching maximal stimulation at 1 µg/kg — from 4.1 ± 0.4 to 12.4 ± 1.7 IU/L at 30 minutes (p < 0.001, n = 6). At 3 µg/kg the response was smaller than at 1 µg/kg (p < 0.05). Infusion at 4 µg/kg per hour for 22.5 hours raised mean luteinising hormone from 5.4 ± 0.7 to 20.8 ± 4.9 IU/L (n = 4; p < 0.05) and serum testosterone from 16.6 ± 2.4 to 24.0 ± 2.5 nmol/L (p < 0.001). Pulses were obscured at that rate of secretion; a lower infusion rate of 1.5 µg/kg per hour raised mean luteinising hormone from 5.2 ± 0.8 to 14.1 ± 1.7 IU/L (n = 4; p < 0.01), pulse frequency from 0.7 ± 0.1 to 1.0 ± 0.2 pulses per hour (p < 0.05) and secretory burst mass from 3.9 ± 0.4 to 12.8 ± 2.6 IU/L (p < 0.05) ^[8].

Limitations. Four to six participants per arm. The non-monotonic response — a smaller effect at the highest amount than at a third of it — is the most important detail in the study and is consistent with receptor desensitisation rather than with a simple relationship between amount and effect.

Gonadotrophin response across sex-steroid states in women

Population. 24 women in four groups: 10 in the early follicular phase, 6 post-menopausal, and 8 receiving sex-steroid contraceptives (4 combined pill, 4 progestogen implant) with suppressed luteinising hormone secretion ^[9].

Endpoint. Area under the curve of gonadotrophin secretion sampled at 15-minute intervals over 60 minutes before and after a single intravenous administration of 0.3 µg/kg ^[9].

Result. Luteinising hormone rose in the follicular group (ΔAUC 2.3 ± 0.8 IU/L·h, p = 0.009), the post-menopausal group (5.3 ± 0.9, p = 0.002) and the progestogen group (2.6 ± 0.8, p = 0.05), but not in the combined-pill group (0.9 ± 0.4, p = 0.13). Follicle-stimulating hormone rose significantly only in post-menopausal women (ΔAUC 2.6 ± 0.8, p = 0.03), with changes under 0.5 IU/L·h in the other three groups. Both responses in post-menopausal women were significantly larger than in the other groups (p = 0.012 for LH, p = 0.001 for FSH) ^[9].

Limitations. The authors state their own principal one: the study assessed only acute responses to a single intravenous administration, and the effect of continuous exposure on pulse frequency in women remained unstudied. Group sizes are six to ten.

Men with type 2 diabetes and low testosterone

Population. Five men with type 2 diabetes and low testosterone (mean age 33.6 ± 3 years, BMI 40.6 ± 6.3, total testosterone 8.5 ± 1.0 nmol/L) and seven age-matched healthy men ^[10].

Result. After an intravenous administration of 0.3 µg/kg, mean luteinising hormone rose from 5.5 ± 0.8 to 13.9 ± 1.7 IU/L in healthy men (p < 0.001) and from 4.7 ± 0.7 to 10.7 ± 1.2 IU/L in the diabetes group (p = 0.02), with comparable increments between groups (p = 0.18). In a second experiment, an 11-hour infusion at 4 µg/kg per hour in four men with diabetes raised luteinising hormone from 3.9 ± 0.1 to 20.7 ± 1.1 IU/L (p = 0.03), testosterone from 8.5 ± 1.0 to 11.4 ± 0.9 nmol/L (p = 0.002), and pulse frequency from 0.6 ± 0.1 to 0.9 ± 0 pulses per hour (p = 0.05) ^[10].

Limitations. Five and four participants respectively. The authors label it a proof-of-concept study, and the comparison that carries the physiological argument — that the response is preserved in the diabetes group — is a negative finding on twelve people in total.

Chronic subcutaneous administration

Population and design. A randomised, single-blinded, placebo-controlled study in 15 healthy men across three protocols, with 12 men as controls: an acute 8-hour subcutaneous infusion across a range of rates; continuous subcutaneous infusion at 180 nmol/h for 5 days; and daily intermittent infusion — 8 hours on, 16 hours off — at 150 nmol/h for 12 days ^[14].

Result. Acute subcutaneous infusion raised luteinising hormone, follicle-stimulating hormone and testosterone against vehicle in proportion to the rate administered (p < 0.0001). After five days of continuous infusion, testosterone remained elevated but gonadotropin concentrations had returned to levels similar to vehicle. Daily 8-hour infusions over 12 days sustained the rise in gonadotropins, and a bolus given after those 12 days still produced a gonadotropin rise, indicating that the receptor remained functional ^[14].

Why this study matters more than its size suggests. It addresses the problem that the 2011 bolus work first hinted at. Continuous exposure to a KISS1R agonist desensitises the axis; intermittent exposure does not, at least over twelve days. That is a property of the receptor system rather than of any particular preparation, and it is the constraint that any sustained administration of a kisspeptin has to work around. Fifteen participants across three protocols, in healthy men only.

Preclinical Research on Kisspeptin-10

Animal research

The animal literature on kisspeptin signalling is far larger than what is cited here, and one strand of it bears directly on how the human results should be read.

Work in rodents examined not exogenous peptide but endogenous kisspeptin tone, and found it to be a critical excitatory component of spontaneous gonadotropin-releasing hormone activity as well as of the GnRH response to neuropeptide Y and to CART ^[11].

The significance for this page is a point about baseline. If endogenous kisspeptin is already a major excitatory input to GnRH neurons, then administering exogenous peptide is adding to an existing signal rather than switching on a silent one — which is consistent with the desensitisation seen under continuous administration in humans ^[14], and with the response varying by hormonal state ^[9].

Findings described in this section were observed in rodents. Nothing in them establishes anything about humans.

Other Areas of Kisspeptin-10 Research

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

The genetics that established the physiology. In 2003 two groups reported that loss-of-function variants in the kisspeptin receptor cause hypogonadotropic hypogonadism and failure of puberty ^{[3, 4]}. This is human evidence of a kind no administration study can provide: it establishes that the receptor is necessary for normal reproductive development, in people, from natural experiments rather than from an intervention. Every later study of an agonist at that receptor rests on it.

The first kisspeptin given to humans. The initial human administration work used kisspeptin-54, not the decapeptide, and reported stimulation of the hypothalamic-pituitary-gonadal axis in human males ^[5]. The distinction matters throughout this literature: a great deal of frequently quoted human kisspeptin research — including work in in-vitro fertilisation and in emotional and brain-imaging paradigms — used the 54-residue peptide. Results obtained with it are not results for the decapeptide, which differs in pharmacokinetics even though it shares the active C-terminus.

Interaction with neurokinin B. Kisspeptin neurons of the arcuate nucleus co-express neurokinin B and dynorphin, and the interaction between kisspeptin and neurokinin B signalling in mediating oestrogen feedback has been examined directly in healthy women ^[12]. That work locates the peptide within a network rather than treating it as an isolated input.

Use as a diagnostic probe. The most developed current direction is not treatment but measurement: using the peptide as a test of hypothalamic function in pubertal and reproductive disorders, where the clinical problem is distinguishing a hypothalamic cause from a pituitary one ^[13]. Registered studies pursuing exactly that use kisspeptin 112-121 by name ^{[16, 15]}.

That is a modest ambition compared with what is claimed for several other compounds in this library, and it is supported by a correspondingly better-defined evidence base.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Kisspeptin-10 vs Related Compounds

Against kisspeptin-54

Same gene, same amidated C-terminal decapeptide, same receptor. Kisspeptin-54 carries 44 further residues ahead of that sequence and differs in pharmacokinetics. Kisspeptin-10 is described as the minimal sequence with full intrinsic bioactivity ^[8]. Much of the widely quoted human kisspeptin literature used the 54-residue peptide ^[5], and those results do not transfer.

Against GnRH and its analogues

Gonadorelin is GnRH itself and triptorelin a GnRH receptor agonist; both act at the pituitary. Kisspeptin-10 acts one step upstream, on the hypothalamic neurons that release GnRH. That difference is the whole basis of its diagnostic use: a response to it demonstrates functioning GnRH neurons in a way a pituitary-level agent cannot ^[13].

Continuous versus intermittent exposure

GnRH agonists are known for the paradox that continuous administration suppresses the axis it acutely stimulates. The kisspeptin system shows a related pattern: five days of continuous subcutaneous infusion returned gonadotropins to vehicle levels while intermittent daily infusion sustained them over twelve days ^[14].

Endogenous fragment, not an analogue

Unlike most compounds documented here, this is a naturally occurring human sequence prepared synthetically, with no D-amino acids, no non-proteinogenic residues and no stabilising modification beyond the amidation the natural peptide already carries.

Regulatory position

Not approved by the U.S. Food and Drug Administration for any indication. Registered academic studies naming kisspeptin 112-121 are recruiting ^{[15, 16]}; a registered study is not an approval.

No comparison of effect between these compounds is made on this page.

Chemical & Molecular Characteristics

Kisspeptin-10 is a ten-residue peptide with a free N-terminus and an amidated C-terminus. PubChem carries it as compound identifier 25240297, with CAS registry number 374675-21-5 and FDA/NCATS UNII code FS1N52VS3S, molecular formula C63H83N17O14 and average mass 1302.4 g/mol.

The C-terminal amide is the compound. The RFamide motif — Arg-Phe-NH2 — is what the receptor recognises. The free-acid form differs by about one dalton, which is within the noise of a low-resolution mass measurement and invisible on many methods, and it is substantially less active. Confirming amidation is therefore a specific and necessary analytical question for this peptide, not a general one.

Two asparagines in a short sequence. Asparagine at positions 2 and 4 makes this peptide susceptible to deamidation, in which an asparagine converts to aspartate or isoaspartate. The mass change is about one dalton — the same magnitude as the amidation question above, in the opposite direction — so a single mass figure can be consistent with more than one molecule. Separation, not mass alone, resolves it.

One tryptophan, at position 3. This is the peptide's only strong ultraviolet chromophore at 280 nm, which makes quantification straightforward, and it is also the residue most vulnerable to oxidation and photodegradation.

Strongly basic, and sticky. A single arginine against no acidic residue gives net positive charge at physiological pH, and the sequence is hydrophobic enough through tryptophan, phenylalanine and leucine to adsorb readily to glass and plastic. Adsorption losses are a recognised practical difficulty with peptides of this composition and are a reason that nominal and delivered amounts can diverge in a way a certificate of analysis does not capture.

A natural sequence, with the consequences that implies. There are no D-amino acids, no non-proteinogenic residues and no protecting groups beyond the amide. The molecule is therefore a normal substrate for peptidases, which is consistent with the short-lived responses reported after bolus administration in the human studies above.

Analytical Specifications

Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.

Frequently Asked Questions

Scientific References

1. Muir AI, Chamberlain L, Elshourbagy NA, et al.. AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1 The Journal of biological chemistry; 2001. PMID 11387329 doi:10.1074/jbc.M102743200
2. 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 The Journal of biological chemistry; 2001. PMID 11457843 doi:10.1074/jbc.M104847200
3. de Roux N, Genin E, Carel JC, et al.. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54 Proceedings of the National Academy of Sciences of the United States of America; 2003. PMID 12944565 doi:10.1073/pnas.1834399100
4. Seminara SB, Messager S, Chatzidaki EE, et al.. The GPR54 gene as a regulator of puberty The New England journal of medicine; 2003. PMID 14573733 doi:10.1056/NEJMoa035322
5. Dhillo WS, Chaudhri OB, Patterson M, et al.. Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males The Journal of clinical endocrinology and metabolism; 2005. PMID 16174713 doi:10.1210/jc.2005-1468
6. Dhillo WS, Murphy KG, Bloom SR. The neuroendocrine physiology of kisspeptin in the human Reviews in endocrine & metabolic disorders; 2007. PMID 17323132 doi:10.1007/s11154-007-9029-1
7. Quaynor S, Hu L, Leung PK, et al.. Expression of a functional g protein-coupled receptor 54-kisspeptin autoregulatory system in hypothalamic gonadotropin-releasing hormone neurons Molecular endocrinology (Baltimore, Md.); 2007. PMID 17698953 doi:10.1210/me.2007-0207
8. George JT, Veldhuis JD, Roseweir AK, et al.. Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men The Journal of clinical endocrinology and metabolism; 2011. PMID 21632807 doi:10.1210/jc.2011-0089
9. George JT, Anderson RA, Millar RP. Kisspeptin-10 stimulation of gonadotrophin secretion in women is modulated by sex steroid feedback Human reproduction (Oxford, England); 2012. PMID 22956346 doi:10.1093/humrep/des326
10. George JT, Veldhuis JD, Tena-Sempere M, et al.. Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: kisspeptin-10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism Clinical endocrinology; 2013. PMID 23153270 doi:10.1111/cen.12103
11. Verma S, Kirigiti MA, Millar RP, et al.. Endogenous kisspeptin tone is a critical excitatory component of spontaneous GnRH activity and the GnRH response to NPY and CART Neuroendocrinology; 2014. PMID 25011649 doi:10.1159/000365419
12. Skorupskaite K, George JT, Veldhuis JD, et al.. Interactions Between Neurokinin B and Kisspeptin in Mediating Estrogen Feedback in Healthy Women The Journal of clinical endocrinology and metabolism; 2016. PMID 27636018 doi:10.1210/jc.2016-2132
13. Pierret ACS, Patel AH, Daniels E, et al.. Kisspeptin as a test of hypothalamic dysfunction in pubertal and reproductive disorders Andrology; 2026. PMID 39834030 doi:10.1111/andr.13843
14. Yeung AC, Phylactou M, Koysombat K, et al.. Chronic subcutaneous kisspeptin-10 stimulates gonadotropin secretion for 12 days in healthy men European journal of endocrinology; 2026. PMID 42549827 doi:10.1093/ejendo/lvag134
15. Kisspeptin Administration Subcutaneously to Patients With IHH 2023. NCT05896293
16. Kisspeptin to Quantify GnRH Neuronal Function in Health and Disease 2026. NCT07224490

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Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.

Related laboratory reagent: Kisspeptin-10 specifications and lot documentation