Kisspeptin-10 is a ten-residue peptide that activates KISS1R, the receptor that sits at the top of the reproductive hormone cascade in mammals. It is the shortest fragment of the kisspeptin family that keeps full receptor activity in vitro, which makes it the default agonist for laboratory studies of how the brain switches on gonadotropin-releasing hormone (GnRH) release.
Kisspeptin research has an unusual history: the gene was first studied by cancer biologists, and only later did human genetics reveal its role in puberty. The sections below follow that path, then cover the receptor signaling, the main experimental models and the questions that remain open.
At a glance
- Class: Decapeptide; C-terminal fragment of kisspeptin; KISS1R (GPR54) agonist
- Origin: KISS1 described as a melanoma metastasis suppressor in 1996; peptide products identified as GPR54 ligands in 2001
- Structure: Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 (human); C63H83N17O14; MW 1302.4 g/mol; CAS 374675-21-5
- Main research areas: GnRH neuron physiology, puberty and the hypothalamic-pituitary-gonadal axis, receptor pharmacology, glucose homeostasis, tumor biology
- Regulatory status: Not approved by the FDA for any use; research reagent only
Structure and origin
The KISS1 gene was cloned in 1996 by researchers in Hershey, Pennsylvania, who were looking for genes that kept melanoma cells from spreading; the name nods to the town’s best-known chocolate. The gene encodes a 145-amino-acid precursor that is cut into several peptides. In 2001, Ohtaki and colleagues purified a 54-residue product from human placenta, named it metastin, and showed that it was the natural ligand of the orphan receptor GPR54 and that it reduced metastasis of tumor cells in a mouse model (Ohtaki et al., 2001).
Kisspeptin-54, -14, -13 and -10 all end in the same amidated sequence, and the shared C-terminal decapeptide, Arg-Phe-NH2 included, is enough to bind and activate the receptor. That places kisspeptins in the wider RF-amide peptide family. The amidated C-terminal phenylalanine is important for receptor activation. Because Kisspeptin-10 is short and linear, it is cleared quickly in vivo, and much structure-activity work has aimed at analogs that resist peptidases.
Mechanism: what the research shows
KISS1R is a class A G protein-coupled receptor that signals mainly through Gq/11. Receptor activation stimulates phospholipase C, generating inositol trisphosphate and diacylglycerol, releasing intracellular calcium and activating protein kinase C and the ERK1/2 pathway. In GnRH neurons, this leads to prolonged depolarization and increased firing (Xie et al., 2022).
Messager and colleagues showed that GnRH neurons express GPR54 and that kisspeptin acts on them directly to stimulate GnRH release, placing the peptide immediately upstream of the GnRH system (Messager et al., 2005). In rodents, two hypothalamic populations of kisspeptin neurons, in the arcuate nucleus and the anteroventral periventricular area, relay negative and positive sex-steroid feedback to GnRH neurons, a model reviewed in detail by Xie and colleagues (Xie et al., 2022).
Key areas of study
Puberty genetics
The field changed in 2003, when two groups independently linked loss-of-function mutations in GPR54 to hypogonadotropic hypogonadism, a failure to enter puberty. Seminara and colleagues described affected families and showed that mice lacking the receptor had a comparable reproductive phenotype (Seminara et al., 2003). These findings established kisspeptin signaling as a gatekeeper upstream of GnRH.
GnRH neuron physiology
Kisspeptin-10 is a standard stimulus in hypothalamic slice electrophysiology, explant hormone-release assays and immortalized GnRH cell lines. Studies in rodent and sheep models used it to map how kisspeptin neurons drive GnRH pulses and the preovulatory surge (Messager et al., 2005; Xie et al., 2022).
Glucose homeostasis
KISS1R is also expressed outside the brain, including in pancreatic islets. Studies in isolated islets and rodent models have examined effects of kisspeptin on glucose-stimulated insulin secretion, with results that differ between species, preparations and experimental conditions (Izzi-Engbeaya et al., 2019). This area links reproductive signaling to energy balance.
Tumor biology
The original metastasis-suppressor work continues in tumor cell lines and xenograft models, where investigators study how KISS1R signaling affects cell migration, invasion and matrix metalloproteinase activity (Ohtaki et al., 2001).
What the evidence does not show
Much of what is known about kisspeptin control of GnRH comes from rodents and sheep, and the anatomy of kisspeptin neuron populations differs between species. Kisspeptin-10 has a much shorter duration of action in vivo than kisspeptin-54, so results with one form do not automatically carry over to the other. Continuous exposure to kisspeptin agonists can desensitize the axis, which makes timing a major variable in experimental design. Metabolic findings are mixed, and the metastasis-suppressor role varies by tumor type. Kisspeptin peptides have been studied in clinical research, but no kisspeptin drug product is approved, and those studies do not describe the material sold here.
Regulatory status
Kisspeptin-10 is not approved by the FDA for any use. Kisspeptin peptides have been evaluated in clinical research studies, but no kisspeptin drug product is approved. The material sold by Rogue Compounds is a research reagent only.
Handling and storage in the lab
Lyophilized Kisspeptin-10 should be kept sealed and refrigerated at 2–8°C (36–46°F), protected from light. Keep the vial closed until use to limit exposure to moisture.
Sourcing and documentation
Rogue Compounds has Kisspeptin-10 made in small batches. Every vial carries a batch number and a QR code that opens the independent U.S. testing lab’s own report for that batch. The same batch COA is posted on the product page and in the COA Library.
View Kisspeptin-10 on Rogue Compounds
References
- Ohtaki T, et al. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature. 2001;411(6837):613-617. PMID 11385580
- Seminara SB, et al. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003;349(17):1614-1627. PMID 14573733
- Messager S, et al. Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci USA. 2005;102(5):1761-1766. PMID 15665093
- Izzi-Engbeaya C, Hill TG, Bowe JE. Kisspeptin and glucose homeostasis. Semin Reprod Med. 2019;37(3):141-146. PMID 31869842
- Xie Q, et al. The role of kisspeptin in the control of the hypothalamic-pituitary-gonadal axis and reproduction. Front Endocrinol (Lausanne). 2022;13:925206. PMID 35837314
Research use only. Rogue Compounds products are sold strictly for laboratory research. They are not for human or veterinary use, and nothing in this article is medical advice. The studies cited here describe published research, not this product or any use of it.