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Kisspeptin-10

Category: Peptides · Last updated

Kisspeptin-10 (also written kp-10) is a synthetic 10-amino-acid peptide corresponding to the C-terminal active fragment of the human KISS1 gene product. It is the principal upstream activator of the hypothalamic gonadotropin-releasing-hormone (GnRH) axis and is studied as a research tool in reproductive endocrinology and as a candidate therapy for hypogonadism, infertility, and sexual function.

Peppudex card: see the mechanism + evidence-grade summary at [Peppudex / Kisspeptin-10](https://peppudex.com/peptides/kisspeptin-10).

Overview

Kisspeptin signaling was first identified as a metastasis-suppressor pathway (the KISS1 gene was named for Hershey, Pennsylvania, where the work was done) and later recognized as the master regulator of GnRH neuron firing. Mutations in KISS1 or its receptor KISS1R/GPR54 cause hypogonadotropic hypogonadism in humans. The active peptide is the 10-amino-acid C-terminal fragment; longer kisspeptin variants (54, 14, 13) all reduce to this active core in vivo.

The sequence is Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH₂.

Mechanism

Kisspeptin-10 binds the KISS1R / GPR54 receptor on hypothalamic GnRH neurons, triggering Gαq signaling, depolarization, and downstream GnRH secretion. The result is a pulse of LH and FSH from the anterior pituitary, increasing gonadal steroid production (testosterone in males, estradiol/progesterone in females).

See: Growth_hormone (orthogonal pituitary-axis context).

Evidence

Clinical research in the reproductive-medicine space:

  • GnRH activation in healthy men · Single subcutaneous kisspeptin-10 doses produce LH/FSH pulses in healthy men (Dhillo et al., J Clin Endocrinol Metab 2005; PMID 15883247).
  • Female fertility / IVF · Kisspeptin-54 has been studied to trigger oocyte maturation as an alternative to hCG in IVF protocols (Abbara et al., JCI Insight 2017).
  • Hypogonadism research · Kisspeptin restores LH pulsatility in patients with hypothalamic amenorrhea and isolated hypogonadotropic hypogonadism.

Dosing literature

Research literature has used subcutaneous boluses of 1-10 nmol/kg or fixed doses of 50-300 µg. The compound is not registered for clinical use. The wiki does not recommend any human dose.

Pharmacokinetics

Kisspeptin-10 has a plasma half-life of approximately 4 minutes after intravenous administration, the C-terminal decapeptide being rapidly cleaved by ubiquitous proteases. Published trials use either continuous infusion or repeated bolus subcutaneous dosing. The short half-life is suited to the pulsatile pharmacodynamic effect on GnRH neurons that mirrors physiological kisspeptin signaling.

Storage

Lyophilized kisspeptin-10 is stable at –20 °C for at least 24 months. Once reconstituted with bacteriostatic water, store at 2-8 °C and use within 14-21 days. Kisspeptin-10 is shorter than typical research peptides and degrades faster in solution.

Regulatory status

  • United States. Research-use only. Not FDA-approved.
  • WADA. Not listed on the 2024 Prohibited List. GnRH-axis-active compounds (e.g., hCG, GnRH analogs) are prohibited for male athletes under S2; kisspeptin is not yet specifically named but may fall under regulator discretion.

Side effects (from published clinical literature)

The Dhillo and Abbara group Phase 1/2 trials report a benign safety profile. No major adverse-event signals beyond transient mild headache and injection-site discomfort. Theoretical concern around prolonged HPG-axis stimulation and downstream sex-steroid effects exists for chronic high-dose research scenarios but is not seen in short-course published protocols.

See also

References

  • Dhillo WS, et al. "Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males." J Clin Endocrinol Metab. 2005;90(12):6609-15. PMID 15883247.
  • Abbara A, et al. "Kisspeptin: a novel physiological trigger for oocyte maturation in in-vitro fertilisation treatment." Lancet. 2014;383(9924):1361. PMID 24725563.
  • de Roux N, et al. "Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54." Proc Natl Acad Sci U S A. 2003;100(19):10972-6. PMID 12944565.
Research framing only. Peppu Wiki documents the published research literature surrounding peptide compounds. Articles describe in-vitro and animal-model evidence, regulatory status, and community-reported protocols. Nothing on this site is medical advice, a recommendation for human use, or a substitute for consultation with a qualified clinician. All compounds discussed are research-use only. Citations should be verified at the source before relying on any quantitative claim.
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