Kisspeptin-10

Kisspeptin-10 is the C-terminal decapeptide (Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2) of full-length Kisspeptin-54, the most biologically active of the kisspeptin family processed from the KISS1 gene product. It is the minimal active fragment retaining high-affinity GPR54 (Kiss1R, KISS1R) agonist activity and is the standard research tool for kisspeptin receptor pharmacology and HPG axis research.

The discovery of kisspeptin's fundamental role in reproductive biology came through the simultaneous identification of KISS1 and GPR54 loss-of-function mutations in humans causing idiopathic hypogonadotropic hypogonadism — absent puberty, absent GnRH pulsatility, and infertility without other developmental abnormalities. Seminara et al. (NEJM, 2003) and de Roux et al. (PNAS, 2003) independently published these findings, establishing kisspeptin/GPR54 as the gate-keeping system for pubertal onset and reproductive axis activation. These foundational clinical genetics observations drove intense research into kisspeptin pharmacology for which Kisspeptin-10 is the primary tool compound.

GPR54 is a Gq/11-coupled class A GPCR. Kisspeptin-10 binding activates phospholipase C-beta, generating IP3 (calcium release from ER) and DAG (PKC activation). In GnRH neurons, this calcium signal drives action potential firing and GnRH peptide release from axon terminals in the median eminence into the hypophyseal portal circulation. GnRH pulses in the portal blood then activate GnRHR on pituitary gonadotrophs, driving LH and FSH secretion and downstream gonadal steroidogenesis.

The KNDy neuron network in the hypothalamic arcuate nucleus is the physiological source of kisspeptin for pulsatile GnRH regulation. KNDy neurons co-express Kisspeptin (KISS1), Neurokinin B (TAC3), and Dynorphin (PDYN) — three neuropeptides with autocrine/paracrine interactions that generate rhythmic kisspeptin release driving the GnRH pulse generator. Neurokinin B (acting via NK3R) activates KNDy neurons to release kisspeptin (GnRH pulse initiation); Dynorphin (acting via KOR) suppresses KNDy neuron activity, creating the refractory period between pulses. This self-contained oscillator produces GnRH pulses approximately every 60-90 minutes in women and every 90-120 minutes in men.

A separate kisspeptin population in the anteroventral periventricular nucleus (AVPV) mediates the positive oestrogen feedback that triggers the pre-ovulatory LH surge — responding to rising late follicular phase oestradiol by massively activating GPR54 on GnRH neurons, producing the surge that induces ovulation. The same GPR54 receptor is activated by both arcuate KNDy (pulsatile GnRH control) and AVPV kisspeptin neurons (LH surge generation) — but the physiological outcome differs based on the pattern of kisspeptin release and the hormonal context.

Research applications: GPR54 binding assays and calcium mobilisation (FLIPR assay) in GPR54-expressing HEK293 cells; GnRH neuron electrophysiology in hypothalamic slice preparations (GT1-7 cells, primary GnRH neurons); HPG axis challenge comparing Kisspeptin-10 response (complete hypothalamic-pituitary relay) with Gonadorelin response (pituitary-only) to dissect hypothalamic versus pituitary contributions; and reproductive cycle research in rodent models examining LH pulse frequency and the kisspeptin-GnRH-LH signal chain.

MW: 1302.49 g/mol. CAS: 374683-26-8. Molecular formula: C63H83N15O13. Contains tryptophan — protect from UV light throughout handling and storage. Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C in amber container. For laboratory and analytical research purposes only.

GPR54 calcium mobilisation assay protocol: load GPR54-HEK293 cells with Fluo-4 AM (4uM, 60 min, 37°C) in HEPES-buffered saline. Wash and transfer to FLIPR plate reader. Inject Kisspeptin-10 at 0.01-1000nM (8-point dose-response). Record fluorescence for 120 seconds. Calculate area under the curve for each concentration. Use GPR54-selective antagonist Kp-234 (if available) or scrambled Kisspeptin-10 peptide as negative controls. Primary rat anterior pituitary cells provide a physiological model where Kisspeptin-10-induced LH secretion (measured by ELISA at 15-60 minutes) can be used as a functional endpoint upstream of Gonadorelin's GnRHR-mediated LH response. MW: 1302.49 g/mol. Contains tryptophan. Store lyophilised at -20°C, amber container. For laboratory and analytical research purposes only.