Kisspeptin-10

What it is

Kisspeptin-10 (KP-10) is the shortest biologically active C-terminal decapeptide derived from the KISS1 gene product. It binds to its cognate G-protein-coupled receptor GPR54 (also designated KISS1R) expressed on GnRH neurons in the hypothalamus (PMID 23550004; PMID 41062590; PMID 23550004). GPR54 activation by KP-10 causes long-lasting membrane depolarization of GnRH neurons through inhibition of inwardly rectifying and A-type K⁺ currents and activation of nonselective cation (TRPC) currents, thereby increasing GnRH pulse frequency and amplitude. The resultant GnRH secretion drives pituitary release of LH and FSH, and downstream gonadal sex steroid production (PMID 21632807; PMID 42549827). KP-10 thus sits at the apex of the hypothalamic-pituitary-gonadal (HPG) axis. Sex steroid feedback (negative and positive) modulates the sensitivity of GnRH neurons to kisspeptin input (PMID 22956346; PMID 23550011). Beyond the HPG axis, KP-10 signals through GPR54/FAK pathways to regulate collagen and glycosaminoglycan metabolism in cardiac fibroblasts (PMID 37968564; PMID 42159865), exerts antiangiogenic effects via inhibition of endothelial proliferation and migration, induces vasoconstriction and plasma extravasation in peripheral microvasculature, and has demonstrated anti-metastatic and pro-apoptotic activity in several cancer cell lines (PMID 41062590; PMID 25420482; PMID 38401763). Neuroprotective effects against α-synuclein-mediated apoptosis have also been reported through a GPR54-independent mechanism.

Class: Endogenous neuropeptide / reproductive hormone (RF-amide family); C-terminal decapeptide fragment of kisspeptin-54, product of the KISS1 gene

What it's studied for

• Stimulation of gonadotropin (LH, FSH) and testosterone secretion in men Human RCT
  • Randomized single-blinded placebo-controlled study in 15 healthy men. Acute subcutaneous KP-10 infusions (1.25–10.0 nmol/kg/h) dose-dependently increased LH, FSH, and testosterone. Daily 8 h subcutaneous infusions at 150 nmol/h for 12 days sustained gonadotropin increases (mean LH increase day 1: +1.68 ± 0.25; day 12: PMID 42549827 Yeung et al., European Journal of Endocrinology (2026)
  • IV bolus KP-10 caused rapid dose-dependent LH rise; maximal stimulation at 1 µg/kg (4.1±0.4 to 12.4±1.7 IU/L at 30 min, P<0.001). Infusion at 1.5 µg/kg/h increased LH pulse frequency from 0.7±0.1 to 1.0±0.2 pulses/h. PMID 21632807 George et al., Journal of Clinical Endocrinology and Metabolism (2011)
  • Single IV bolus 1 µg/kg BW significantly increased plasma LH in adult, middle-aged, and advanced-aged men; plasma testosterone significantly elevated only in adult men. PMID 30590872 Ullah et al., Andrologia (2019)
• Stimulation of gonadotropin secretion in women and oocyte maturation triggering for IVF Human observational
  • IV bolus KP-10 stimulated LH and FSH in men and in women during the preovulatory phase (10 nmol/kg), but not during the follicular phase at doses up to 10 nmol/kg IV bolus, 32 nmol/kg SC bolus, or 720 pmol/kg/min IV infusion, demonstrating sexual and cycle-phase dimorphism. PMID 21976724 Jayasena et al., Journal of Clinical Endocrinology and Metabolism (2011)
  • IV KP-10 (0.3 µg/kg) stimulated LH in follicular-phase, post-menopausal, and progestogen-only contraceptive women; response was largest in post-menopausal women (ΔAUC LH 5.3±0.9 IU/l·h) and absent in women taking combined oral contraceptive pill. PMID 22956346 George et al., Human Reproduction (2012)
  • Review concludes KP-10 and KP-54 administration induces LH surge required for egg maturation and ovulation in animal and human studies; KP-54 successfully used as IVF oocyte maturation trigger. PMID 28393578 Kasum et al., Gynecological Endocrinology (2017)
• Differentiation of central precocious puberty from premature thelarche (biomarker use) Human observational
  • Prospective study in Indian girls aged 6–9 years (ICPP n=33, PT n=23, controls n=40). Kp-10/basal LH ratio <4.07 ng/mIU discriminated ICPP from PT with 72.7% sensitivity, 87.0% specificity, AUC 0.78–0.79. PMID 42364891 Banerjee et al., Clinica Chimica Acta (2027)
• Preeclampsia biomarker Human observational
  • Plasma KP-10 levels were significantly reduced in preeclamptic vs normotensive pregnant women (n=100). 3rd trimester ROC AUC 0.747, sensitivity 83.3%, specificity 67.5%. Low positive predictive value limits screening utility. PMID 32045961 Al-Kaabi et al., Journal of Obstetrics and Gynaecology Research (2020)
  • Plasma KP-10 lower in preeclamptic groups; inversely correlated with severity. Directly correlated with estimated fetal weight in severe preeclampsia. PMID 28040130 Ziyaraa et al., Taiwanese Journal of Obstetrics and Gynecology (2016)
• Anti-metastatic / anti-tumor activity in breast cancer In vitro only
  • KP-10 treatment of MDA-MB-231 and MDA-MB-468 TNBC cells significantly reduced cell viability and migration, upregulated KISS1 mRNA, reversed EMT markers (increased E-cadherin/β-catenin, decreased N-cadherin/CD44/Vimentin), and activated apoptotic pathways (upregulated CASP3/8/9, BAX; downregulated BCL2). PMID 41062590 Shah et al., Scientific Reports (2025)
  • KP-10 induced apoptosis and inhibited mobility of MDA-MB-231 and MDA-MB-157 cells in vitro; suppressed tumor growth in xenograft models and inhibited intratumoral microvessel formation; inhibited migration via EMT. PMID 25420482 Song and Zhao, Oncology Reports (2015)
  • KP-10 inhibited bone-directed migration of GPR54-positive breast cancer cells in a dose-window of 10⁻⁹ to 10⁻¹¹ M, associated with reduced CXCR4 expression and SDF-1 secretion. PMID 20832102 Olbrich et al., Gynecologic Oncology (2010)
• Anti-metastatic activity in endometrial cancer In vitro only
  • KP-10 reduced invasion of endometrial cancer cells through artificial basement membrane and inhibited SDF-1-induced invasion at a dose window of 10⁻¹³ to 10⁻¹¹ mol/L. PMID 24407584 Schmidt et al., International Journal of Gynecological Cancer (2014)
• Neuroprotection against α-synuclein toxicity In vitro only
  • KP-10 (0.1 µM) substantially suppressed wild-type and E46K mutant α-syn-mediated apoptosis and mitochondrial depolarization in cholinergic-differentiated SH-SY5Y neurons; co-administration with GPR54 antagonist KP-234 did not abrogate neuroprotection, indicating GPR54-independent mechanism. PMID 37047030 Simon et al., International Journal of Molecular Sciences (2023)
  • Low concentrations of KP-10 (0.01–1 µM) suppressed wild-type and E46K mutant α-syn-mediated cholinergic toxicity in SH-SY5Y cells; high concentration (10 µM) decreased viability. PMID 35563582 Simon et al., International Journal of Molecular Sciences (2022)
• Testicular antioxidant / redox protection in hypothyroidism Animal studies only
  • In hypothyroid adult male Wistar rats, KP-10 treatment reduced testicular apoptosis, reduced peroxynitrite production, increased SOD1 and GPX½ expression, and increased catalase enzymatic activity. KP-10 did not rescue downregulated UPR mediators caused by hypothyroidism. PMID 38338793 Santos et al., International Journal of Molecular Sciences (2024)
• Cardiac fibrosis and extracellular matrix remodelling In vitro only
  • KP-10 significantly increased intracellular collagen content in human cardiac fibroblasts, elevated phosphorylated FAK, increased procollagen type I and III propeptides, inhibited MMP-1/-2/-9 release, and elevated TIMP-1/-2/-4 secretion. FAK inhibition negated the stimulatory effect. TGF-β1 was not involved. PMID 37968564 Radwańska et al., Scientific Reports (2023)
  • KP-10 caused dose-dependent increase in glycosaminoglycan content in human cardiac fibroblast cells and medium via GPR54 and FAK signalling (not phospholipase C). KP-10 also increased decorin secretion but not decorin expression. PMID 42159865 Radwańska et al., Pharmacological Reports (2026)
• Antiangiogenic effects In vitro only
  • KP-10 inhibited new vessel sprouting from human placental arteries in Matrigel and tube-like structure formation by HUVEC in a concentration-dependent manner. KP-10 inhibited HUVEC proliferation and migration without affecting viability or apoptosis. PMID 20926586 Ramaesh et al., Endocrinology (2010)
  • KP-10 significantly impaired blood flow recovery and capillary growth in a rat hindlimb ischemia model. In HUVEC cultures, KP-10 inhibited tube formation and proliferation in a dose-dependent manner and induced cellular senescence (increased p53, decreased Sirt1). Y-27632 (Rho kinase inhibitor) partially reversed these PMID 24405415 Usui et al., Clinical Science (2014)
• Vasoconstriction and peripheral vascular effects Animal studies only
  • KP-10 caused dose-dependent oedema formation (0.3–10 nmol/injection site) and reduced peripheral blood flow (vasoconstriction) in dorsal skin of CD1 mice. Oedema inhibited by H1 receptor antagonist mepyramine; vasoconstriction partially inhibited by COX inhibitor indomethacin. PMID 21347414 Sawyer et al., PLoS One (2011)
  • KP-10 described as a potent vasoconstrictor; 4-week infusion in ApoE-knockout mice significantly accelerated aortic atherosclerotic lesion development with increased monocyte/macrophage infiltration; effects fully reversed by GPR54 antagonist P234. PMID 28411243 Sato et al., Journal of the American Heart Association (2017)
• Modulation of follicle maturation and gonadal steroids in fish (sturgeon) Animal studies only
  • Intraperitoneal injection or slow-release of human or Acipenser KP-10 in Sterlet sturgeon elevated plasma estradiol, oocyte and plasma vitellogenin, plasma calcium, mature follicle number, plasma glucose, plasma lipids, and cholesterol over 4 weeks. Testosterone levels were unaffected. PMID 38401763 Roosta et al., Comparative Biochemistry and Physiology Part A (2024)
• Pregnancy biomarker (threatened abortion / abortus imminens) Human observational
  • Maternal plasma KP-10 levels were significantly lower in pregnant women with early vaginal bleeding vs controls (p=0.01). KP-10 positively correlated with gestational week (p=0.02). PMID 21847585 Kavvasoglu et al., Archives of Gynecology and Obstetrics (2012)
• ICSI / embryo implantation biomarker Human observational
  • Serum kisspeptin levels on HCG day were significantly higher in women with clinical pregnancy vs non-pregnant after ICSI (P<0.001); AUC 0.784 for positive pregnancy prediction. PMID 27908602 Jamil et al., Reproductive Biomedicine Online (2017)
• Anti-Doping detection (urine screening) In vitro only
  • Validated LC-MS initial testing and confirmation procedures for KP-10 in urine. Metabolites y9, y8, y7, y5 identified after incubation in human serum. Rapid elimination (half-life ~30 min after injection in rats cited). A black-market KP-10 vial showed no unexpected impurities but had undergone more degradation than re PMID 38978171 Colpaert et al., Biomedical Chromatography (2024)

Community-reported dosing

Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.