KissPeptin-10 5mg

Kisspeptin-10 (KP-10) is the ten-residue C-terminal fragment of human kisspeptin, YNWNSFGLRF-NH2, and the shortest form that still activates the kisspeptin receptor, KISS1R, formerly called GPR54. This listing is the 5 mg vial of freeze-dried peptide, the main fill; a 10 mg vial is also sold. Research on kisspeptin-10 covers how the kisspeptins were found, how the receptor signals, their place upstream of GnRH neurons, small studies of LH release in healthy volunteers and the peptide’s very short half-life.

Specifications

Fills in this range

Kisspeptin-10 is sold in 2 fills. The compound and the testing are the same in every fill; only the amount in the vial changes.

The sequence, the amide and the numbering

The certificate gives the sequence as H-YNWNSFGLRF-NH2: a free N-terminal tyrosine and a C-terminal phenylalanine amide, the Arg-Phe-amide ending that every active kisspeptin shares. Formula C63H83N17O14, theoretical mass 1302.4 Da. A version ending in a free acid instead of the amide would weigh about one dalton more, so the LC-MS identity result on the certificate is worth reading closely against 1302.4.

The numbering explains the other names. The same ten residues are positions 45 to 54 of kisspeptin-54, hence metastin 45-54, and positions 112 to 121 when counted from the start of the 145-residue precursor. From the theoretical mass, 5 mg is about 3.8 µmol, slightly less once the water content on the certificate is allowed for. The sequence also contains two asparagines, at positions 2 and 4, a residue that can deamidate in solution.

What the research covers

Discovery and the receptor

Kisspeptins were identified in 2001 as the natural ligands of GPR54, then an orphan G protein-coupled receptor. Kotani and colleagues isolated peptides of 54, 14 and 13 residues from human placenta, all ending in the same RF-amide C-terminus and all derived from KiSS-1, a metastasis suppressor gene for melanoma cells¹. The peptides bound rat and human GPR54 with low nanomolar affinity and stimulated PIP2 hydrolysis, calcium mobilisation, arachidonic acid release and MAP kinase phosphorylation, while inhibiting cell proliferation¹. Human GPR54 was highly expressed in placenta, pituitary, pancreas and spinal cord, and kisspeptin given to rats stimulated oxytocin secretion¹.

The IUPHAR nomenclature committee later named the receptor the kisspeptin receptor, gene KISS1R². Its review describes kisspeptin-54 as cleaved from a 145-residue gene product and lists kisspeptin-10 as the smallest of the shorter fragments that remain biologically active². The receptor couples to Gq/11 and the phospholipase C pathway, mobilising calcium, and its sequence is more than 80% conserved between human, rat and mouse². Mutations in KISS1R cause hypogonadotropic hypogonadism, and mice with the gene disrupted reproduce that phenotype².

Upstream of GnRH

A 2012 review in Physiological Reviews placed kisspeptins, produced mainly by neurons in discrete hypothalamic nuclei, upstream of the neurons that make gonadotropin-releasing hormone³. It traced their involvement from sexual differentiation of the brain and the onset of puberty to adult gonadotropin secretion and the metabolic control of fertility, and set out the questions still contested³. The cell-line studies of hypothalamic neurons, granulosa cells and amyloid binding are summarised in the kisspeptin-10 (kisspeptin 45-54) guide.

Human volunteer studies

Kisspeptin-10 itself was first studied in men by George and colleagues in 2011. Healthy men received intravenous boluses of kisspeptin-10 or vehicle and, in a second phase, infusions lasting up to 22.5 hours, while LH pulse frequency and size were estimated by deconvolution analysis⁴. Serum LH rose quickly after a bolus; the response grew with the amount given up to a maximum and was smaller at the highest amount tested, and the infusions raised LH and testosterone⁴. Jayasena and colleagues compared men and women the same year, in groups of four or five⁵. LH and FSH rose in men, but women in the follicular phase of the menstrual cycle showed no change in gonadotropins by any of the routes tested, while women in the preovulatory phase did respond⁵.

A short half-life

Kisspeptin-10 is cleared quickly. In male mice, d’Anglemont de Tassigny and colleagues measured a half-life in the bloodstream of about 4 minutes for kisspeptin-10 against about 32 minutes for kisspeptin-54, and kisspeptin-54 sustained LH release far longer⁶. Repeating kisspeptin-10 at short intervals to make up for its clearance still did not reproduce the sustained rise, which suggested that clearance was not the whole explanation⁶.

What is not established

The human work consists of physiological experiments in groups of four to six, measuring hormones over hours⁴,⁵. Kotani’s binding data were obtained with the 54-, 14- and 13-residue peptides rather than kisspeptin-10¹, and the mouse comparison shows the short and long forms do not behave the same way in vivo⁶, so results for one form do not transfer automatically to another. The neuroprotection and appetite findings in the guide come from cell lines. None of the work used PrymaLab material.

How each lot is tested

Every lot is tested in PrymaLab’s own laboratory in Ashland, Kentucky before release: RP-HPLC for purity, LC-MS for identity, Karl Fischer titration for water, LAL for endotoxin and USP <71> for sterility. The results for the lot now shipping are in the certificate panel on this page, and the certificate number, key and QR code can be checked on the verify page. These are in-house results from PrymaLab Analytical, not an independent test, and the lab is not accredited to ISO 17025. The third-party testing guarantee on this page still applies: if any independent laboratory finds the wrong compound, or less than the stated purity or amount, the order is refunded and the cost of the test is reimbursed.

Frequently asked questions

References

1. 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(37):34631-6. DOI · PubMed
2. Kirby HR, Maguire JJ, Colledge WH, et al. International Union of Basic and Clinical Pharmacology. LXXVII. Kisspeptin receptor nomenclature, distribution, and function. Pharmacol Rev. 2010;62(4):565-78. DOI · PubMed
3. Pinilla L, Aguilar E, Dieguez C, et al. Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Physiol Rev. 2012;92(3):1235-316. DOI · PubMed
4. George JT, Veldhuis JD, Roseweir AK, et al. Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men. J Clin Endocrinol Metab. 2011;96(8):E1228-36. DOI · PubMed
5. Jayasena CN, Nijher GM, Comninos AN, et al. The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humans. J Clin Endocrinol Metab. 2011;96(12):E1963-72. DOI · PubMed
6. d'Anglemont de Tassigny X, Jayasena CN, Murphy KG, et al. Mechanistic insights into the more potent effect of KP-54 compared to KP-10 in vivo. PLoS One. 2017;12(5):e0176821. DOI · PubMed