Kisspeptin for Research in Canada

Kisspeptin-10 is the ten-residue C-terminal fragment (Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH₂) of the peptides encoded by the human KISS1 gene — a gene cloned in 1996 from melanoma cells that had lost the ability to metastasise^[1], and whose products were shown in 2001 to be the natural ligands of the orphan receptor GPR54, now called KISS1R^{[2, 3]}. Two years later, families in which puberty never started were found to carry loss-of-function mutations in that receptor^{[4, 5]}, and kisspeptin moved from cancer biology to the centre of reproductive neuroendocrinology. The decapeptide is the shortest fragment with full receptor activity^{[15, 12]}, which is why it is the form most laboratories use as a reference agonist. Kisspeptin peptides have been studied in mice, rats, sheep, monkeys and — unusually for peptides sold for research — in a series of small controlled human studies. None of that makes the vial on this page a medicine: it is lyophilized research-grade material for laboratory use only.

Key facts

• Sequence: YNWNSFGLRF-NH₂, residues 112–121 of the 138-residue KISS1 precursor^{[16, 18]}; the C-terminal Arg-Phe-amide (“RF-amide”) motif is shared by kisspeptin-54, -14 and -13^[3]
• Formula and weight: C₆₃H₈₃N₁₇O₁₄, 1302.4 g/mol (PubChem CID 25240297); ChEMBL376756 lists 1302.46 — the databases agree
• Identifiers: CAS 374675-21-5; synonyms KP-10, metastin (45–54), human kisspeptin 10F (PubChem)
• Receptor: KISS1R (GPR54), a G-protein-coupled receptor that signals through phosphoinositide hydrolysis and intracellular calcium^{[3, 5]}; kisspeptins bind it with low-nanomolar affinity^[3], and human and rat kisspeptin-10 give EC₅₀ values in the 10⁻⁸ M range in receptor-transfected cells^[12]
• Where it acts: on GnRH neurons in the hypothalamus — the receptor is co-expressed with GnRH, kisspeptin releases GnRH directly, and a GnRH antagonist abolishes its effect on LH in mice, rats and monkeys^{[7, 6, 11, 9]}
• Human genetics: inactivating mutations in KISS1R^{[4, 5]} and in KISS1 itself^[17] cause hypogonadotropic hypogonadism — puberty does not start
• Human studies: small controlled studies in healthy men and in women with reproductive disorders^{[8, 15, 16, 13, 20, 21]}; ChEMBL records a maximum development phase of 3 for kisspeptin-10
• Regulatory status: no approved drug form in Canada, the US or the EU; 2025–2026 reviews describe kisspeptin as a candidate diagnostic and therapeutic tool still under investigation^{[22, 24]}
• Format on this site: one 10mg vial of lyophilized powder, laboratory research only — the “10” in kisspeptin-10 counts amino acids; the “10mg” is the labelled vial content

Where does kisspeptin come from?

The name is a pun on Hershey, Pennsylvania. Lee and colleagues at the Hershey Medical Center were looking for the gene on chromosome 6 that stopped human melanoma cells metastasising; subtractive hybridisation gave them a cDNA expressed only in the non-metastatic hybrids, encoding a 164-residue hydrophilic protein with its strongest expression in placenta, which they called KiSS-1^[1]. Five years later two groups working on orphan G-protein-coupled receptors converged on the same gene: Ohtaki’s group purified a 54-residue C-terminally amidated peptide from human placenta as the ligand of receptor hOT7T175 and named it metastin, showing it blocked chemotaxis and invasion of receptor-transfected cells and reduced lung metastases of transfected melanoma in mice^[2]; Kotani’s group isolated 54-, 14- and 13-residue RF-amide peptides from placenta, named them kisspeptins, and showed they bound rat and human GPR54 at low nanomolar affinity, mobilised calcium and activated MAP kinases while inhibiting cell proliferation^[3].

The reproductive role arrived through genetics. In 2003 de Roux’s group mapped isolated hypogonadotropic hypogonadism in a consanguineous family to a homozygous 155-nucleotide deletion in GPR54^[4], and Seminara’s group reported the L148S and compound R331X/X399R mutations in other pedigrees, showed the mutant receptors accumulated less inositol phosphate in COS-7 cells, and created Gpr54-deficient mice with small testes, delayed vaginal opening and no follicular maturation yet normal hypothalamic GnRH content^[5]. The 2012 description of an inactivating KISS1 mutation with the same phenotype completed the picture: both the ligand and its receptor are required for puberty in humans^[17].

Chemical identity

Species matter for this peptide. Human and rat kisspeptin-10 differ in sequence yet give similar EC₅₀ values at rat KISS1R^[12]; a certificate of analysis should therefore name the species form as well as the mass, and a mass-spectrometry match to 1302.4 identifies the human decapeptide.

What has been studied in the laboratory?

Receptor pharmacology (cell culture)

In CHO-K1 cells expressing rat or human GPR54, kisspeptins triggered PIP₂ hydrolysis, calcium mobilisation, arachidonic-acid release, ERK1/2 and p38 phosphorylation and stress-fibre formation while inhibiting proliferation^[3]. In receptor-transfected cells, alanine scanning of rat kisspeptin-10 showed that positions 6 and 10 carry most of the activity: substituting either raised the EC₅₀ from the 10⁻⁸ M range to above 6 × 10⁻⁶ M and slowed the response^[12]. Investigational analogues TAK-448 and TAK-683 matched natural Kp-10 for binding affinity and full agonism at rat KISS1R^[19].

GnRH and gonadotrophin release (mouse, rat, sheep, monkey)

Delivered into the cerebral ventricles of mice, kisspeptin-54 and kisspeptin-10 both stimulated LH, and kisspeptin-54 stimulated LH and FSH at femtomolar amounts; acyline, a GnRH antagonist, blocked the effect, and KiSS-1 mRNA mapped to the anteroventral periventricular, periventricular and arcuate nuclei^[6]. GPR54 transcripts co-localise with GnRH neurons, kisspeptin has no effect on LH or FSH in Gpr54-null mice, and in sheep it produced a large release of GnRH into cerebrospinal fluid with a parallel LH rise — direct evidence that the peptide acts at the level of GnRH release^[7]. In ovariectomised rats with recording electrodes in the arcuate nucleus, kisspeptin-10 increased LH dose-dependently and cetrorelix blocked it, but the multiunit electrical volleys that mark each GnRH pulse did not change frequency^[11]. In juvenile agonadal rhesus monkeys, hourly kisspeptin-10 for 48 hours produced a sustained train of GnRH-dependent LH discharges, supporting the idea that GPR54 activation triggers primate puberty^[9]. A 2013 review lists rats, mice, hamsters, sheep, pigs, goats, cows, horses and monkeys among species in which acute kisspeptin stimulates gonadotrophins, LH more than FSH, and notes that continuous exposure desensitises the response in some species^[18].

Steroid feedback and season (ewe)

In the ewe, KiSS-1 mRNA in the arcuate nucleus rose after ovariectomy and fell back with estradiol replacement, and partly with progesterone; about 86% of arcuate kisspeptin cells carried progesterone receptors, and expression was lower in the non-breeding season — placing kisspeptin neurons in the negative-feedback and seasonal control of GnRH^[10].

Chronic exposure, analogues and testicular effects (rat)

The stimulatory picture reverses with time. In prepubertal male rats given pulsatile kisspeptin-10 for 12 days, plasma LH and testosterone fell at the higher doses tested, sperm production and Sertoli-cell support capacity decreased, and seminiferous tubules showed degeneration with multinucleated giant cells and disrupted germ cells^[14]. Continuous exposure of adult male rats to the analogues TAK-448 or TAK-683 caused a transient testosterone rise followed within days by castrate-level testosterone and prostate and seminal-vesicle atrophy, sustained for four weeks and faster than leuprolide; TAK-683 also lowered PSA in an androgen-dependent prostate-cancer model^[19]. These are the pharmacology behind the rule that continuous kisspeptin signalling suppresses, rather than drives, the axis.

Human studies

Kisspeptin is unusual among research peptides in having a genuine, if small, controlled human literature, all of it academic and none of it a product approval. In six healthy men, kisspeptin-54 exposure raised LH, FSH and testosterone against saline, with a plasma half-life of about 28 minutes^[8]. Kisspeptin-10 itself raised LH in healthy men dose-dependently with a bell-shaped curve — the highest exposure tested produced a smaller response than the one below it — and prolonged exposure increased LH pulse frequency, pulse mass and testosterone^[15]. A single exposure in 13 men triggered an immediate LH pulse larger than endogenous pulses, implied roughly 17 minutes of sustained GnRH release, and reset the timing of the next endogenous pulse^[16]. In women with hypothalamic amenorrhoea, the first exposure to kisspeptin-54 produced strong LH and FSH rises, but after two weeks of repeated exposure the responses had shrunk markedly — tachyphylaxis^[13]. In 53 women undergoing IVF, a single exposure to kisspeptin-54 across the doses tested induced oocyte maturation dose-dependently, with fertilisation and embryo transfer in 92% and clinical pregnancy in 23%^[20]. Functional MRI in 29 healthy men showed kisspeptin enhanced limbic responses to sexual and couple-bonding images and reduced negative mood^[21]. The 2025 Physiological Reviews article and 2025–2026 reviews frame these findings as the basis for kisspeptin as a possible IVF trigger and as a test of hypothalamic function — proposals, not approved uses^{[22, 23, 24]}.

Stress and metabolism (animal models)

A 2026 review of animal work describes kisspeptin neurons in the arcuate nucleus as integrators of glucocorticoid and serotonergic signals: stress lowers serotonin and 5-HT₇ receptor expression on those neurons and, with glucocorticoids, suppresses kisspeptin, GnRH and gonadotrophin output^[25]. That is a description of the endogenous system, not of what an exogenous decapeptide does.

Study summary

What the evidence does not show

• No approved use. Every human study cited here was an academic physiology or proof-of-concept study. Kisspeptin-10 is not an approved medicine in Canada, the US or the EU; the reviews describing its clinical potential are explicit that trials are still needed^{[22, 24]}.
• “Stimulates the axis” is an acute finding. Repeated or continuous kisspeptin desensitises the response — in women over two weeks^[13], in several animal species^[18], and to the point of castrate-level testosterone with continuous analogue exposure in rats^[19]. Direction depends entirely on the pattern of exposure.
• Testicular effects in immature animals were harmful. Twelve days of kisspeptin-10 in prepubertal rats reduced LH, testosterone and sperm production and produced degenerative changes in the seminiferous tubules^[14].
• Not a fertility, libido or testosterone product. The human LH and testosterone data come from a handful of healthy men under controlled conditions in a research unit^{[8, 15, 16]}; the brain-imaging result is a 29-man fMRI study^[21]. None tested a commercial product, none was designed to show benefit, and no dose or regimen is described on this site.
• The metastasis story is preclinical. The anti-metastatic effect of kisspeptin-54 was shown in receptor-transfected cells and transfected melanoma in mice^[2]; it has no clinical translation.
• Species and fragment matter. Most human studies used kisspeptin-54, not the decapeptide^{[8, 13, 20]}; rat and human kisspeptin-10 differ in sequence^[12]. Findings do not transfer automatically between fragments or species.

Batch documentation

No batch-specific certificate of analysis for the Kisspeptin-10 10mg vial is posted in the COA library at the time of this review, and we have not substituted another product’s report. When an independent report for a kisspeptin-10 lot is issued, the product page will embed it and this page will quote the measured content and purity. A report worth relying on should state the species form (human kisspeptin-10), an HPLC purity figure and a mass-spectrometry identity result matching C₆₃H₈₃N₁₇O₁₄ (1302.4).

Kisspeptin-10 is one of the compounds on the page where you can buy peptides online in Canada; every listing there is sold under the same research-use-only terms.

Handling and storage in the laboratory

• Form: lyophilized powder in a sealed vial. The decapeptide is a C-terminal amide with an N-terminal tyrosine and a tryptophan, both oxidation-sensitive residues; keep it dry and dark.
• Storage: the site’s guidance is −20 °C for the sealed vial over the long term (stated stability up to 24 months) and cool, dry, dark conditions for short holds; avoid repeated freeze–thaw.
• Stability in circulation: kisspeptin-54 had a plasma half-life of about 28 minutes in men^[8]; the decapeptide is generally regarded as shorter-lived still, which is one reason analogues such as TAK-448 were developed^[19]. Solutions should be prepared fresh for each experiment.
• Documentation: record the species form, the batch, the receipt date and the opening date; match the batch to its certificate before use.
• Protocols: the researcher’s responsibility. Shop Peptides Online publishes no dosing, reconstitution or administration guidance.

References

All references were retrieved from PubMed (NCBI) on 30 September 2026 and cross-checked against Europe PMC; identity data from PubChem and ChEMBL (EMBL-EBI) on the same date.

1. Lee JH, Miele ME, Hicks DJ et al. (1996). KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst 88(23):1731-7. PMID 8944003
2. 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):613-7. PMID 11385580
3. Kotani M, Detheux M, Vandenbogaerde A et al. (2001). The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem 276(37):34631-6. PMID 11457843
4. de Roux N, Genin E, Carel JC et al. (2003). Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A 100(19):10972-6. PMID 12944565
5. Seminara SB, Messager S, Chatzidaki EE et al. (2003). The GPR54 gene as a regulator of puberty. N Engl J Med 349(17):1614-27. PMID 14573733
6. Gottsch ML, Cunningham MJ, Smith JT et al. (2004). A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology 145(9):4073-7. PMID 15217982
7. Messager S, Chatzidaki EE, Ma D et al. (2005). Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci U S A 102(5):1761-6. PMID 15665093
8. Dhillo WS, Chaudhri OB, Patterson M et al. (2005). Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab 90(12):6609-15. PMID 16174713
9. Plant TM, Ramaswamy S, Dipietro MJ (2006). Repetitive activation of hypothalamic G protein-coupled receptor 54 with intravenous pulses of kisspeptin in the juvenile monkey (Macaca mulatta) elicits a sustained train of gonadotropin-releasing hormone discharges. Endocrinology 147(2):1007-13. PMID 16282350
10. Smith JT, Clay CM, Caraty A et al. (2007). KiSS-1 messenger ribonucleic acid expression in the hypothalamus of the ewe is regulated by sex steroids and season. Endocrinology 148(3):1150-7. PMID 17185374
11. Kinsey-Jones JS, Li XF, Luckman SM et al. (2008). Effects of kisspeptin-10 on the electrophysiological manifestation of gonadotropin-releasing hormone pulse generator activity in the female rat. Endocrinology 149(3):1004-8. PMID 18063679
12. Gutiérrez-Pascual E, Leprince J, Martínez-Fuentes AJ et al. (2009). In vivo and in vitro structure-activity relationships and structural conformation of Kisspeptin-10-related peptides. Mol Pharmacol 76(1):58-67. PMID 19389922
13. Jayasena CN, Nijher GM, Chaudhri OB et al. (2009). Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis. J Clin Endocrinol Metab 94(11):4315-23. PMID 19820030
14. Ramzan F, Qureshi IZ (2011). Intraperitoneal kisspeptin-10 administration induces dose-dependent degenerative changes in maturing rat testes. Life Sci 88(5-6):246-56. PMID 21112339
15. George JT, Veldhuis JD, Roseweir AK et al. (2011). Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men. J Clin Endocrinol Metab 96(8):E1228-36. PMID 21632807
16. Chan YM, Butler JP, Pinnell NE et al. (2011). Kisspeptin resets the hypothalamic GnRH clock in men. J Clin Endocrinol Metab 96(6):E908-15. PMID 21470997
17. Topaloglu AK, Tello JA, Kotan LD et al. (2012). Inactivating KISS1 mutation and hypogonadotropic hypogonadism. N Engl J Med 366(7):629-35. PMID 22335740
18. Abbara A, Ratnasabapathy R, Jayasena CN et al. (2013). The effects of kisspeptin on gonadotropin release in non-human mammals. Adv Exp Med Biol 784:63-87. PMID 23550002
19. Matsui H, Masaki T, Akinaga Y et al. (2014). Pharmacologic profiles of investigational kisspeptin/metastin analogues, TAK-448 and TAK-683, in adult male rats in comparison to the GnRH analogue leuprolide. Eur J Pharmacol 735:77-85. PMID 24747751
20. Jayasena CN, Abbara A, Comninos AN et al. (2014). Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization. J Clin Invest 124(8):3667-77. PMID 25036713
21. Comninos AN, Wall MB, Demetriou L et al. (2017). Kisspeptin modulates sexual and emotional brain processing in humans. J Clin Invest 127(2):709-719. PMID 28112678
22. Koysombat K, Tsoutsouki J, Patel AH et al. (2025). Kisspeptin and neurokinin B: roles in reproductive health. Physiol Rev 105(2):707-764. PMID 39813600
23. Mills EG, Tsoutsouki J, Pierret ACS et al. (2025). The Neuroendocrine Regulation of Reproductive Behavior and Emotional Control by Kisspeptin. J Clin Endocrinol Metab 110(6):e1747-e1758. PMID 39880372
24. Pierret ACS, Patel AH, Daniels E et al. (2026). Kisspeptin as a test of hypothalamic dysfunction in pubertal and reproductive disorders. Andrology 14(4):1002-1016. PMID 39834030
25. Chisupa CO, Manchishi SM (2026). Stress as a Neuroendocrine Modulator of the Reproductive Axis: Roles of Glucocorticoids, Kisspeptin, and Serotonergic Signalling in Animal Models. Neuroendocrinology :1-22. PMID 42371829