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The upstream switch for puberty and fertility — kisspeptin tells GnRH neurons when to fire.
Also known as: KISS1 peptide · metastin · kisspeptin-10 (fragment) · KISS-1 metastasis suppressor
Part of the Neuropeptides & signaling cluster
Overview
Kisspeptin is a hypothalamic neuropeptide encoded by the KISS1 gene that binds the kisspeptin receptor (KISS1R, formerly GPR54) on GnRH neurons and is an obligatory signal for gonadotrophin-releasing hormone secretion, and so for puberty and reproduction. It is an endogenous hormone rather than a drug; investigational uses in hypogonadotropic hypogonadism, hypothalamic amenorrhoea and IVF are in phase 1–2 trials as of September 2026.
Source & context
Biological / chemical source: Product of the KISS1 gene; secreted by hypothalamic kisspeptin (KNDy) neurons
Primary research or clinical context: Endogenous hormone; investigational in reproductive medicine (hypogonadotropic hypogonadism, hypothalamic amenorrhoea, IVF oocyte maturation)
What kisspeptin is
Kisspeptin is a neuropeptide produced from the KISS1 gene, originally identified as a metastasis suppressor (hence the alias metastin) before its central role in reproduction was recognised. It binds the kisspeptin receptor KISS1R, also called GPR54, on gonadotrophin-releasing hormone (GnRH) neurons and stimulates GnRH secretion, which in turn drives luteinising hormone and follicle-stimulating hormone release from the pituitary — the hypothalamic–pituitary–gonadal axis (Xie et al., Frontiers in Endocrinology 2022). Shorter fragments such as the C-terminal decapeptide kisspeptin-10 retain receptor activity and are the forms used experimentally; the IUPHAR record for kisspeptin-10 (ligand 3711) lists mouse and rat data.
Mechanism: the KNDy neuron and GnRH
Kisspeptin neurons in the arcuate nucleus co-express neurokinin B and dynorphin — the so-called KNDy neurons — and act as the pulse generator for GnRH (Xie et al., 2022). Because kisspeptin signalling is an obligatory step for GnRH release, it gates every downstream reproductive event, and it is the point at which steroid-hormone feedback, nutrition and metabolic state are integrated (Roseweir & Millar, Advances in Experimental Medicine and Biology 2013). A 2024 study extended the picture to astrocytes, showing kisspeptin signalling in glial cells also modulates the reproductive axis (Torres et al., Journal of Clinical Investigation 2024).
Metabolism and reproduction
Sufficient energy reserves are required for reproduction, and kisspeptin neurons are the site where that requirement is enforced: metabolic signals tightly control kisspeptin synthesis and release, linking energy balance to fertility (Navarro, Nature Reviews Endocrinology 2020). Elevated prolactin suppresses kisspeptin secretion, which explains prolactin-associated hypogonadotropic hypogonadism and infertility (Grattan & Szawka, Seminars in Reproductive Medicine 2019). Kisspeptin may also influence glucose homeostasis: human studies associate circulating levels with insulin secretion and resistance, and the single published interventional study found kisspeptin enhanced glucose-stimulated insulin secretion (Izzi-Engbeaya et al., Seminars in Reproductive Medicine 2019).
Clinical research
Kisspeptin is not an approved medicine. Its investigational uses follow from its biology: in health it induces normal puberty and modulates ovulation, and hypothalamic kisspeptin expression is reduced in several functional reproductive disorders, making replacement conceptually attractive (Tsoutsouki et al., Current Opinion in Pharmacology 2022). The same review notes that kisspeptin can induce a more physiological degree of oocyte maturation during IVF. ClinicalTrials.gov lists 36 studies naming kisspeptin as of September 2026, including phase 2 trials of pulsatile and subcutaneous kisspeptin in hypogonadotropic hypogonadism (NCT04648969, NCT05896293) and hypothalamic amenorrhoea (NCT07224438), and a phase 1 study using kisspeptin to quantify GnRH neuronal function (NCT07224490).
Antagonists and other directions
Because kisspeptin drives the reproductive axis, blocking it is also of interest: peripherally active kisspeptin antagonists have been proposed for hormone-dependent conditions such as precocious puberty, endometriosis and metastatic prostate cancer (Roseweir & Millar, 2013), and a 2024 narrative review examines altered kisspeptin signalling in endometriosis (Meczekalski et al., Journal of Clinical Medicine 2024).
Kisspeptin and the grey market
Kisspeptin-10 is sold online as a research peptide with claims about testosterone and libido. None of that use is approved, the human trials to date are small phase 1–2 studies in specific reproductive disorders, and vial contents are unverified. This profile is educational and is not guidance on obtaining or using any product. The gonadorelin (GnRH) profile on this site covers the hormone kisspeptin acts upon.
Structure & chemistry
Molecular identity & reference confidence
Reference mass unavailable
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Encoded by KISS1; shorter C-terminal fragments such as kisspeptin-10 retain receptor activity
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- Receptors
- Kisspeptin receptor KISS1R (GPR54), a G-protein-coupled receptor on GnRH neurons
- Backbone
- Encoded by KISS1; shorter C-terminal fragments such as kisspeptin-10 retain receptor activity
- Status
- Endogenous hormone — not an approved product; investigational in reproductive medicine
Chemistry values: curated profile.
Clinical development snapshot
ClinicalTrials.gov lists 36 registered studies with “Kisspeptin” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT04648969 | Prolonged Pulsatile Kisspeptin Administration in Hypogonadotropic Hypogonadism | Phase 2 | completed | 2026-08-26 |
| NCT07224490 | Kisspeptin to Quantify GnRH Neuronal Function in Health and Disease | Phase 1 | recruiting | 2026-07-13 |
| NCT07224438 | Kisspeptin Administration Subcutaneously to Patients With Hypothalamic Amenorrhea | Phase 2 | recruiting | 2026-07-13 |
| NCT05896293 | Kisspeptin Administration Subcutaneously to Patients With IHH | Phase 2 | recruiting | 2026-07-13 |
| NCT05971836 | The Molecular Basis of Inherited Reproductive Disorders | — | completed | 2026-07-13 |
| NCT06501729 | Kissing as a Protective Factor Against Acidic pH in Saliva | Not applicable | completed | 2026-04-24 |
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- TrialsClinicalTrials.gov snapshot added: 36 registered studies, highest phase 3.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Kisspeptin
What is Kisspeptin?+
Kisspeptin is a hypothalamic neuropeptide encoded by the KISS1 gene that binds the kisspeptin receptor (KISS1R, formerly GPR54) on GnRH neurons and is an obligatory signal for gonadotrophin-releasing hormone secretion, and so for puberty and reproduction. It is an endogenous hormone rather than a drug; investigational uses in hypogonadotropic hypogonadism, hypothalamic amenorrhoea and IVF are in phase 1–2 trials as of September 2026.
What Canadian product status is recorded for Kisspeptin?+
Canadian product status for Kisspeptin has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Kisspeptin?+
Kisspeptin is not a classic amino-acid chain peptide in the same sense; see the profile for classification details.
What is kisspeptin?+
A hypothalamic neuropeptide from the KISS1 gene that activates KISS1R on GnRH neurons and is required for GnRH release — the upstream signal for puberty and fertility.
What does kisspeptin do?+
It stimulates GnRH secretion, which drives LH and FSH release. It also integrates metabolic and hormonal signals into reproductive function, and may enhance glucose-stimulated insulin secretion.
Is kisspeptin approved as a drug?+
No. It is an endogenous hormone; clinical use in hypogonadotropic hypogonadism, hypothalamic amenorrhoea and IVF is investigational (phase 1–2) as of September 2026.
What is kisspeptin-10?+
The C-terminal 10-residue fragment of kisspeptin, which retains receptor activity and is the form most used in experiments.
Related peptides
References & further reading
- 1.Xie et al. (2022). The Role of Kisspeptin in the Control of the Hypothalamic-Pituitary-Gonadal Axis and Reproduction. Frontiers in Endocrinology
- 2.Navarro (2020). Metabolic regulation of kisspeptin — the link between energy balance and reproduction. Nature Reviews Endocrinology
- 3.Tsoutsouki et al. (2022). Novel therapeutic avenues for kisspeptin. Current Opinion in Pharmacology
- 4.Torres et al. (2024). Kisspeptin signaling in astrocytes modulates the reproductive axis. Journal of Clinical Investigation
- 5.Izzi-Engbeaya et al. (2019). Kisspeptin and Glucose Homeostasis. Seminars in Reproductive Medicine
- 6.Roseweir & Millar (2013). Kisspeptin antagonists. Advances in Experimental Medicine and Biology
- 7.PubChem — compound summary for Kisspeptin (CID 71306396)