A hypothalamic neuropeptide that stimulates GnRH release and is being investigated for fertility and hypogonadism.
Kisspeptin is a family of neuropeptides encoded by the KISS1 gene, produced primarily in the arcuate nucleus and anteroventral periventricular nucleus of the hypothalamus. The most studied form for research purposes is Kisspeptin-10 (KP-10), the C-terminal decapeptide. Kisspeptin is recognized as the master regulator of the hypothalamic-pituitary-gonadal (HPG) axis — without kisspeptin signaling, puberty does not occur and reproductive function is absent. It has been investigated in Phase I and II clinical trials for hypogonadotropic hypogonadism, female infertility, and as a diagnostic tool for HPG axis assessment. Kisspeptin levels are regulated by sex steroids (both positive and negative feedback), metabolic status (leptin, insulin), and stress, making it a key integrator of reproductive and metabolic signaling.
* Benefits based on preclinical/animal research unless otherwise noted.
Kisspeptin binds to the KISS1 receptor (KISS1R, also known as GPR54) — a Gq/11-coupled GPCR expressed on GnRH neurons in the hypothalamus. KISS1R activation triggers the PLC-IP3-DAG pathway, increasing intracellular calcium and depolarizing GnRH neurons, which triggers pulsatile GnRH release into the hypothalamic-pituitary portal circulation. GnRH then binds to GnRH receptors on gonadotroph cells in the anterior pituitary, stimulating the synthesis and pulsatile secretion of LH and FSH. LH acts on Leydig cells in the testes to stimulate testosterone synthesis, while FSH supports spermatogenesis and follicular development. The pulsatile nature of kisspeptin-GnRH-LH signaling is critical: continuous kisspeptin stimulation leads to receptor desensitization and gonadotropin suppression, while pulsatile administration maintains or restores reproductive function.
Protocol Notes: Pulsatile administration mimics natural GnRH release. Requires careful monitoring of LH, FSH, and sex hormones.
Add 1 mL bacteriostatic water to 1 mg vial → 1000 mcg/mL
When sourcing Kisspeptin for research purposes, the following quality benchmarks should be verified before use.
Lyophilized: refrigerate. Reconstituted: refrigerate and use within 14 days.
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Moderate Evidence — Multiple animal studies and/or early human trials. Reasonable confidence in mechanism, but human data is limited.
Peptides commonly used alongside Kisspeptin for synergistic effects.
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