Kisspeptin-10

Molecular identity

Sequence

Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH₂

Formula

C63H83N17O14

Molecular weight

1302.4 g/mol

CAS

374675-21-5

PubChem CID

25240297

What it acts on

• KISS1R (GPR54) — the cognate seven-transmembrane receptor for kisspeptins; the cited reviews report that homozygous or compound heterozygous loss-of-function mutations in this receptor have been identified in familial and sporadic patients with isolated hypogonadotropic hypogonadism without olfactory abnormalities, and that mice with targeted deletion of Kiss1 or Gpr54 show a similar failure of sexual maturation.
• Gq/11–phospholipase C branch — receptor occupancy is read out in cell-based systems as inositol-trisphosphate and diacylglycerol generation, intracellular calcium mobilisation and ERK/MAPK phosphorylation; the 2024 astrocyte paper reports only that kisspeptin activated canonical intracellular signalling pathways in cultured glia, without naming the individual readouts in its abstract.
• KISS1R on hypothalamic GnRH neurons — the reviews describe kisspeptin binding here as stimulating neuronal activity and supplying what one chapter calls an obligatory signal for GnRH secretion, placing the decapeptide upstream of gonadotropin release.
• Astrocytic Kiss1r and prostaglandin-E2 synthesis — in the 2024 mouse study, conditional deletion of Kiss1r in GFAP-positive cells altered expression of key PGE2-synthesis genes and disturbed astrocyte–GnRH neuronal appositions.
• KISS1 expression under gonadal steroid feedback — the reviews report KISS1 as a target of gonadal steroid regulation in both sexes, with the pubertal rise in hypothalamic kisspeptin expression treated as part of reproductive-axis maturation.

What the studies report

Each item below summarises the paper it is numbered to, written from that paper's own abstract. The badge says how the evidence was produced.

1. 1.
   reviewIn Vivo (2011)

   A 2011 narrative review of the kisspeptin/GPR54 system in reproduction. It traces the field's two origins — cancer biology, where loss of KISS1 expression was associated with poor prognosis in several malignancies, and human genetics, where two independent groups analysing large consanguineous pedigrees linked inactivating GPR54 mutations to idiopathic hypogonadotropic hypogonadism — and reviews the coupling of kisspeptin to the gonadal steroid feedback loop and to the triggering of puberty onset. It is a secondary source that summarises other groups' data rather than reporting new experiments.

2. 2.
   animal modelJ Clin Invest (2024)

   A mouse study with supporting astrocyte cultures from human, rat and mouse. Hypothalamic proteomic profiling after kisspeptin stimulation flagged glial and astrocyte markers as regulated; the authors then confirmed Kiss1r expression in mouse astrocytes in vivo and canonical intracellular signalling in astrocyte culture, with Kiss1r co-expression with GFAP and S100-β occurring across brain regions and at a higher percentage in Kiss1- and GnRH-enriched areas. Conditional ablation of Kiss1r in GFAP-positive cells altered astrocytic PGE2-synthesis gene expression, perturbed astrocyte–GnRH neuronal appositions, changed LH responses to kisspeptin and LH pulsatility, and altered reproductive responses to high-fat-diet metabolic stress, including female pubertal onset and estrous cyclicity. The evidence comes from genetic ablation in mice: it addresses whether the pathway is required, not what administering this decapeptide does.

3. 3.
   reviewFront Horm Res (2010)

   A 2010 review of the kisspeptin–GPR54 system in the human reproductive axis. It reports kisspeptins as a powerful stimulus for GnRH-driven gonadotropin secretion, KISS1 as a target of gonadal steroid regulation in both sexes, and the pubertal rise in hypothalamic kisspeptin expression as believed to contribute to maturation of the axis. The human evidence it rests on is loss-of-function GPR54 mutations in familial and sporadic isolated hypogonadotropic hypogonadism without olfactory abnormalities, mirrored by mice with targeted deletion of Kiss1 or Gpr54. The argument is built from mutation and knockout phenotypes — that is, from loss of signalling — rather than from controlled administration studies.

4. 4.
   reviewAdv Exp Med Biol (2013)

   A book-chapter review of kisspeptin antagonists rather than of the agonist decapeptide. It restates that kisspeptin binds KISS1R on GnRH neurons and provides an obligatory signal for GnRH secretion, and that the system is itself regulated by steroid hormone feedback and by nutritional and metabolic input; it then surveys attempts to block that receptor, noting that at the time of writing only four peptide antagonists and one small-molecule antagonist had been designed. The authors frame peripherally active antagonists as a possible route for hormone-dependent disorders of reproduction — a prospective argument about different molecules, which says nothing about the agonist's own effects.

Used in research on