Reproductive neuropeptide; KISS1 gene product and endogenous agonist of the kisspeptin receptor (KISS1R/GPR54); upstream stimulator of GnRH neurons
Kisspeptin
Investigationalaka Kisspeptin-54, Metastin, KP-54, KISS1
Kisspeptin, signalling through the KISS1R (GPR54) receptor, is a key upstream regulator of gonadotropin-releasing hormone (GnRH) neurons; loss-of-function mutations in its receptor cause absent puberty. Human experimental-medicine studies, notably kisspeptin-54 to trigger oocyte maturation in IVF and to probe reproductive disorders, have shown promising physiology, but kisspeptin remains investigational and unapproved.
Mechanism
In plain terms, kisspeptin is the switch that turns on the reproductive hormone system, prompting the brain to release the hormones that drive the ovaries and testes. Technically, kisspeptin binds KISS1R (GPR54), a Gq/11-coupled receptor on hypothalamic GnRH neurons, stimulating GnRH release; this in turn drives pituitary secretion of luteinising hormone (LH) and follicle-stimulating hormone (FSH). Its central role in initiating puberty and regulating fertility underlies its study as a more physiological trigger of the reproductive axis.
Regulatory Status by Region
- United States (FDA)Not approved for any indication; investigational and studied only in clinical research.
- Australia (TGA)Not on the Australian Register of Therapeutic Goods (ARTG); an unapproved substance with no registered therapeutic product.
- European Union (EMA)No EMA marketing authorisation; not an approved medicine in the EU.
- WADAProhibited in males under Section S2: WADA added kisspeptin to the 2024 Prohibited List as an example of a testosterone-stimulating peptide (a luteinising-hormone releasing factor); it is prohibited in males only, not in females.
Key Studies
- The GPR54 gene as a regulator of puberty (loss-of-function mutations in the kisspeptin receptor cause absent puberty) (opens in a new tab) (Seminara SB, et al. N Engl J Med. 2003.)
- Kisspeptin-54 stimulates the hypothalamic-pituitary-gonadal axis in human males (opens in a new tab) (Dhillo WS, et al. J Clin Endocrinol Metab. 2005.)
- Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization (opens in a new tab) (Jayasena CN, et al. (Dhillo group). J Clin Invest. 2014.)
Related Clinical Trials
- Kisspeptin to Quantify GnRH Neuronal Function in Health and DiseasePhase 1 · Recruiting
- Kisspeptin Administration Subcutaneously to Patients With Hypothalamic AmenorrheaPhase 2 · Recruiting
- Functional Proteins in Polycystic Ovary SyndromeN/A · Recruiting
- Kissing as a Protective Factor Against Acidic pH in SalivaN/A · Completed
- A Prospective Cohort Study on the Serum Kisspeptin Levels Throughout Pregnancy in PCOSN/A · Unknown
- Recall by Genotype: Neuropeptide StimulationPhase 1 · Terminated
- Dampening the Reproductive Axis With Continuous KisspeptinPhase 1 · Completed
- Evaluation of Some Puberty-related Hormones Among Children and Adolescents With Chronic Kidney DiseasesN/A · Unknown
Related News & Research
- This Week in Peptide Research: GLP-1 Mechanism Studies, LL-37 Engineering Advances, and Kisspeptin's Reach Beyond Reproduction
- This Week in Peptide Research: A Kisspeptin Reproductive-Axis Cluster, Survodutide's Liver Mechanism, and Teriparatide's Cost Question
- This Week in Peptide Research: Bone-Building Peptide Mechanisms, Real-World GLP-1 Data, and a Reproductive-Axis Cluster
Latest research
- SLC32A1 regulates puberty onset in female mice by modulating GnRH neuron function through Kisspeptin and GABA-GABA(B) receptor signaling. (opens in a new tab)
Theriogenology · Oct 9, 2026
- Comparison of the effects of atypical antipsychotics on decreased libido in zebrafish and their mechanisms. (opens in a new tab)
Behavioural brain research · Oct 2, 2026
- Early neuroendocrine signatures of polyendocrine metabolic ovarian syndrome risk: Pubertal programming, social brain signals, and novel therapeutic targets. (opens in a new tab)
Journal of neuroendocrinology · Oct 1, 2026
- Functional interactions between anteroventral periventricular kisspeptin neurons and gonadotropin-releasing hormone neurons in female mice. (opens in a new tab)
Journal of neuroendocrinology · Oct 1, 2026
Common Questions
- What is Kisspeptin?
- Kisspeptin is a natural reproductive neuropeptide (the product of the KISS1 gene) that acts as a master activator of the hormonal axis controlling puberty and fertility. It is investigational: it is being studied in human reproductive medicine (for example, as a trigger for egg maturation in IVF and in disorders of reproduction) but is not approved as a medicine by any regulator.
- Is Kisspeptin approved for medical use?
- Kisspeptin is investigational: it is being studied in clinical research and is not an approved medicine. United States (FDA): Not approved for any indication; investigational and studied only in clinical research. European Union (EMA): No EMA marketing authorisation; not an approved medicine in the EU. Australia (TGA): Not on the Australian Register of Therapeutic Goods (ARTG); an unapproved substance with no registered therapeutic product.
- How does Kisspeptin work?
- In plain terms, kisspeptin is the switch that turns on the reproductive hormone system, prompting the brain to release the hormones that drive the ovaries and testes. Technically, kisspeptin binds KISS1R (GPR54), a Gq/11-coupled receptor on hypothalamic GnRH neurons, stimulating GnRH release; this in turn drives pituitary secretion of luteinising hormone (LH) and follicle-stimulating hormone (FSH).
- Is Kisspeptin legal in Australia?
- Kisspeptin in Australia (TGA): Not on the Australian Register of Therapeutic Goods (ARTG); an unapproved substance with no registered therapeutic product.
- Is Kisspeptin banned in sport?
- Kisspeptin under the World Anti-Doping Agency (WADA) code: Prohibited in males under Section S2: WADA added kisspeptin to the 2024 Prohibited List as an example of a testosterone-stimulating peptide (a luteinising-hormone releasing factor); it is prohibited in males only, not in females.