Kisspeptin-54 (Metastin)

Research-Grade

Kisspeptin-54 (originally named metastin for its metastasis-suppressor activity) is the full-length bioactive product of the KISS1 gene, cleaved from a 145-amino-acid precursor. It acts on the KISS1R receptor (formerly GPR54) expressed on hypothalamic GnRH neurons in the arcuate and anteroventral periventricular nuclei. Binding of kisspeptin-54 to KISS1R is the most potent known physiological stimulus for GnRH secretion, and loss-of-function mutations in either KISS1 or KISS1R cause hypogonadotropic hypogonadism and absent puberty in humans — establishing this pathway as the gatekeeper of the reproductive endocrine axis. Kisspeptin integrates metabolic, circadian, and stress signals to modulate GnRH pulse frequency and amplitude, making it the critical link between energy status and fertility. Human clinical studies at Imperial College London and elsewhere have demonstrated that intravenous kisspeptin-54 infusion potently stimulates LH release in healthy volunteers, and that it can safely trigger oocyte maturation in women undergoing in-vitro fertilization — with a dramatically lower risk of ovarian hyperstimulation syndrome (OHSS) compared to hCG triggers, because kisspeptin's effect is physiological and self-limiting rather than supraphysiological. Additional human trials have explored kisspeptin-54 as a diagnostic agent for distinguishing hypothalamic from pituitary causes of reproductive dysfunction, and as a potential therapeutic for hypoactive sexual desire disorder given KISS1R expression in limbic brain regions. The peptide has a plasma half-life of approximately 28 minutes after IV administration, necessitating infusion protocols for sustained effect.