Kisspeptin-10

Kisspeptin-10 (Kp-10) is the 10-amino acid C-terminal fragment of kisspeptin (the protein product of the KISS1 gene, also historically called metastin), spanning residues 112–121 of the full 145-residue precursor. It is the shortest kisspeptin isoform that retains full agonist activity at the GPR54 receptor (also known as KISS1R). All kisspeptin isoforms (Kp-54, Kp-14, Kp-13, Kp-10) share the same C-terminal RF-amide motif required for GPR54 binding; Kp-10 is the minimal pharmacophore. Kisspeptin signalling through GPR54 on hypothalamic GnRH neurons is not merely modulatory but obligatory for reproductive axis function: loss-of-function mutations in GPR54 in humans cause absent puberty and idiopathic hypogonadotropic hypogonadism (IHH) with near-complete absence of LH and FSH. This established the kisspeptin/GPR54 system as an essential gatekeeper of the hypothalamic-pituitary-gonadal (HPG) axis. Kp-10 has been studied in a meaningful number of human clinical pharmacology studies — primarily at the Imperial College London group (Dhillo, Murphy, Jayasena and colleagues) — demonstrating dose-dependent LH, FSH, and sex hormone responses in healthy men and women (in the appropriate hormonal milieu), and restoration of gonadotropin pulsatility in patients with IHH and hyperprolactinemia-induced amenorrhea. Despite substantial human pharmacology data, Kp-10 is not approved as a drug in any jurisdiction. It remains investigational, with ongoing clinical trials. It is sold and discussed as a research compound only. This entry summarises available evidence for scientific reference and is not medical advice.