Kisspeptin: Complete Guide
Kisspeptin is a neuropeptide encoded by the KISS1 gene that serves as the master regulator of the hypothalamic-pituitary-gonadal (HPG) axis. By activating GPR54 (KISS1R) receptors on GnRH neurons, kisspeptin controls the release of gonadotropin-releasing hormone, which in turn regulates LH, FSH, testosterone, and estrogen production. It is researched for fertility, puberty disorders, hypogonadism, and as a diagnostic tool for reproductive function.
Last updated: 2026-01-29
Quick Facts
- Category
- therapeutic
- Also Known As
- Kisspeptin-10, Kisspeptin-54, Metastin
- Related Goals
- sexual health
Who Researches Kisspeptin?
Kisspeptin is researched by people interested in reproductive health, fertility, and hormonal regulation. It's relevant for fertility researchers studying IVF protocols (kisspeptin can trigger oocyte maturation with lower OHSS risk than hCG), those investigating sexual function and desire, and men researching alternatives to testosterone replacement for maintaining natural HPG axis function. It's particularly interesting as a comparison to gonadorelin (GnRH) — kisspeptin acts one step upstream, at the level that controls GnRH release itself.
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What Is Kisspeptin?
Kisspeptin was originally identified as metastin — a metastasis suppressor gene product. Its reproductive role was discovered in 2003 when researchers found that inactivating mutations in GPR54 (the kisspeptin receptor) caused hypogonadotropic hypogonadism — failure of puberty and reproductive function. This discovery identified kisspeptin as the key upstream regulator of the entire reproductive hormone cascade.
The KISS1 gene produces a 145-amino-acid precursor that is cleaved into kisspeptin-54, which can be further processed into shorter active fragments (kisspeptin-14, kisspeptin-13, kisspeptin-10). All fragments share the same C-terminal 10-amino-acid sequence (kisspeptin-10) required for receptor activation.
Mechanism of Action
Kisspeptin activates GPR54 (KISS1R) on GnRH neurons in the hypothalamus, triggering the reproductive hormone cascade:
- Kisspeptin → GnRH release: Direct activation of GnRH neurons
- GnRH → LH + FSH: GnRH stimulates pituitary gonadotroph cells
- LH/FSH → Testosterone/Estrogen: Gonadotropins drive gonadal steroidogenesis
Beyond reproductive hormones, kisspeptin also activates limbic brain circuits involved in sexual arousal and attraction, which is why it enhances both reproductive hormones and sexual desire simultaneously.
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Dosage Overview
| Form | Dose | Route | Application |
|---|---|---|---|
| Kisspeptin-54 | 1–6.4 nmol/kg | IV or SC | Clinical research |
| Kisspeptin-10 | 0.1–1 mcg/kg | IV or SC | Research protocols |
Most clinical research has used IV bolus or infusion of kisspeptin-54. Subcutaneous protocols are being developed for more practical administration. Kisspeptin-10 has a shorter half-life and is used in acute stimulation studies.
Side Effects & Safety
- Generally well-tolerated: Clinical studies report a favorable safety profile
- Injection site reactions: Mild, transient
- No reported OHSS: A key advantage over hCG in IVF protocols — kisspeptin triggers oocyte maturation without the sustained LH-like activity that causes ovarian hyperstimulation syndrome
- Transient hormonal effects: LH and testosterone increases are short-lived and dose-dependent
- Potential desensitization: Continuous kisspeptin exposure can desensitize GnRH neurons, paradoxically suppressing reproductive hormones — pulsatile administration is important