Receptor identification and signalling
Kisspeptins were isolated from human placenta as GPR54 agonists, and receptor binding, second-messenger signalling and tissue expression of GPR54 were characterised1,2.
Research Peptide · For laboratory research use only
Kisspeptin-10
Also known as Metastin (45-54), KP-10
- Formula
- C63H83N17O14
- CAS
- 374675-21-5
Overview
Kisspeptin-10 (metastin 45-54, KP-10) is the C-terminal decapeptide of the kisspeptins, Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2, equivalent to residues 112-121 of the KiSS-1 precursor7. The kisspeptins were identified in 2001 as products of KiSS-1, a metastasis suppressor gene, and as the endogenous ligands of the orphan receptor GPR54, now also called KISS1R1,2.
Genetic work in 2003 linked GPR54 to the onset of puberty in humans and mice3, and kisspeptin-10 has since been used widely as a research probe of the hypothalamic-pituitary-gonadal axis in rodents, sheep and non-human primates4,5,6,7.
Mechanism of action
As described in the research literature
As described in the research literature, kisspeptins bound rat and human GPR54 expressed in CHO-K1 cells with low nanomolar affinity and stimulated PIP2 hydrolysis, calcium mobilisation, arachidonic acid release, and ERK1/2 and p38 MAP kinase phosphorylation2. Metastin inhibited chemotaxis and invasion of receptor-transfected CHO cells in vitro1.
Within the reproductive axis, GPR54 transcripts were found in mouse hypothalamic GnRH neurons, kisspeptin had no effect on LH and FSH release in gpr54 knockout mice, and kisspeptin released GnRH into the cerebrospinal fluid in sheep5. Kisspeptin evoked a potent, long-lasting depolarisation of more than 90% of GnRH neurons in adult mice, with smaller proportions responding in juvenile and prepubertal animals6. In rat hypothalamic explants kisspeptin-10 stimulated LHRH release, whereas it did not affect LH or FSH release from pituitary fragments, pointing to a hypothalamic site of action4.
Research areas
What published studies have examined
GPR54 and the onset of puberty
Genetic studies in a consanguineous family and in Gpr54-deficient mice examined the receptor's role in hypogonadotropic hypogonadism3. Electrophysiology across postnatal development examined how GnRH neuron responsiveness to kisspeptin changes towards puberty, alongside in situ hybridisation for KiSS-1 and GPR54 transcripts6.
Gonadotrophin release in animal models
Kisspeptin-10 in adult male rats was examined for effects on plasma LH, FSH and testosterone, alongside in vitro hypothalamic and pituitary preparations4. GnRH release was measured directly in sheep cerebrospinal fluid, and responses were compared in wild-type and gpr54 knockout mice5.
Receptor desensitisation
In agonadal juvenile male rhesus monkeys, continuous exposure to human metastin 45-54 was followed by a fall in LH despite ongoing exposure, and responses to further challenges were used to localise the desensitisation to GPR547.
Sources [7]
Specifications
- Sequence
- Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2 (YNWNSFGLRF-NH2)
- Molecular formula
- C63H83N17O14
- Molecular weight
- 1302.4 g/mol
- CAS number
- 374675-21-5
Vial
- Form
- White to off-white lyophilised powder in a sealed vial (10 mg)
- Storage
- Store lyophilised powder at -20 °C, protected from light and moisture. Once reconstituted, keep refrigerated at 2 to 8 °C and protect from light.
- Solubility and reconstitution
- Reconstitute with bacteriostatic water. Add the diluent slowly down the inside wall of the vial and swirl gently until clear; do not shake.
Mist Applicator
- Form
- 10 mg in a vial fitted with a 10 mL mist applicator
- Storage
- Store as directed on the product label, protected from light.
- Solubility and reconstitution
- Prepare and use as directed on the product label.
References
- 1
Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.
Ohtaki T, Shintani Y, Honda S, et al. Nature, 2001.
- 2
The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54.
Kotani M, Detheux M, Vandenbogaerde A, et al. The Journal of Biological Chemistry, 2001.
- 3
The GPR54 gene as a regulator of puberty.
Seminara SB, Messager S, Chatzidaki EE, et al. The New England Journal of Medicine, 2003.
- 4
Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis.
Thompson EL, Patterson M, Murphy KG, et al. Journal of Neuroendocrinology, 2004.
- 5
Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54.
Messager S, Chatzidaki EE, Ma D, et al. Proceedings of the National Academy of Sciences of the United States of America, 2005.
- 6
Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty.
Han SK, Gottsch ML, Lee KJ, et al. The Journal of Neuroscience, 2005.
- 7
Continuous human metastin 45-54 infusion desensitizes G protein-coupled receptor 54-induced gonadotropin-releasing hormone release monitored indirectly in the juvenile male Rhesus monkey (Macaca mulatta): a finding with therapeutic implications.
Seminara SB, Dipietro MJ, Ramaswamy S, et al. Endocrinology, 2006.
This page is provided for research and educational reference only. It does not constitute medical advice, dosing guidance, or a recommendation for use. All compounds are strictly for laboratory and in-vitro research purposes.